Datasets:

google

/

FACTS-grounding-public

like 12

Follow

Google 5.87k

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> [user request] <TEXT> [context document]

List the travel bags referenced in the text in order, from the one that holds the most items to the one that holds the least. Describe what it is about these bags that makes them preferable to other travel bags, and include the colors when referencing them, if given.

What is the Best Purse to Travel With | Shop the Post Top: SoCo Vintage (old, similar) // Jeans: Loft (old, similar) // Purse: Coach (old, similar) // Sunglasses: Coach (old,similar) // Purse: kate spade new york (in black) What is the Best Purse to Travel With | How to Pick If there is one accessory I love, it is a good purse. I love how they are practical, but can make an entire outfit look put together. I have a lot of purses...too many probably! But I get a lot out of each one of them. There are so many different kinds of purses and so many different ways to use them. I will be talking a lot about other purses in later posts, but today I want to talk about the best purses to take when you are traveling. I personally think that a good cross-body bag is the best kind of bag to have when traveling. They are so versatile and they allow you to have your hands free while still storing your necessities in style. What is the Best Purse to Travel With | My Favorites In Turkey, I was touting a Coach Mini Willis cross body. I have this bag in three different colors and it's a great bag for traveling! While it is on the smaller side, it is big enough to hold a small wallet, phone, chapstick and sunglasses. It is perfect for when you are touring a city but don't want to take a lot with you. It's also really nice because you can easily move it to hang in front of you so you can ward off pickpockets! For my birthday last year, my mom gave me the Michael Kors Large Jet Set Traveler in gray. That is a pretty awesome bag. It fits perfectly into my Michael Kors computer bag so I can throw it in there right before I get on a plane and I can pull it back out when I get off. I love that the color goes with just about anything and it fits a LOT of stuff! The last trip I took it on, I got a wallet, glasses, sunglasses, phone, planner, notebook and some pens in there. I have been really happy with how well it has worn too. The leather isn't my favorite but it has a coating on it that keeps stains and water off. Here you can glimpse my newest cross-body obsession from kate spade new york. I took this on my recent trip to Jordan and I loved it! It is much bigger than the Coach bag, and has more room in it than the Michael Kors. It also has a zipper pocket that folds down across the top. The leather on this bag is so soft and I love how pink it is. I found this beauty for a steal at a kate spade outlet sale. The entire store was 50% off with an additional 20% bags. It was a great buy! I will keep an eye out for their next outlet sale and make sure I update you all on it!

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> List the travel bags referenced in the text in order, from the one that holds the most items to the one that holds the least. Describe what it is about these bags that makes them preferable to other travel bags, and include the colors when referencing them, if given. <TEXT> What is the Best Purse to Travel With | Shop the Post Top: SoCo Vintage (old, similar) // Jeans: Loft (old, similar) // Purse: Coach (old, similar) // Sunglasses: Coach (old,similar) // Purse: kate spade new york (in black) What is the Best Purse to Travel With | How to Pick If there is one accessory I love, it is a good purse. I love how they are practical, but can make an entire outfit look put together. I have a lot of purses...too many probably! But I get a lot out of each one of them. There are so many different kinds of purses and so many different ways to use them. I will be talking a lot about other purses in later posts, but today I want to talk about the best purses to take when you are traveling. I personally think that a good cross-body bag is the best kind of bag to have when traveling. They are so versatile and they allow you to have your hands free while still storing your necessities in style. What is the Best Purse to Travel With | My Favorites In Turkey, I was touting a Coach Mini Willis cross body. I have this bag in three different colors and it's a great bag for traveling! While it is on the smaller side, it is big enough to hold a small wallet, phone, chapstick and sunglasses. It is perfect for when you are touring a city but don't want to take a lot with you. It's also really nice because you can easily move it to hang in front of you so you can ward off pickpockets! For my birthday last year, my mom gave me the Michael Kors Large Jet Set Traveler in gray. That is a pretty awesome bag. It fits perfectly into my Michael Kors computer bag so I can throw it in there right before I get on a plane and I can pull it back out when I get off. I love that the color goes with just about anything and it fits a LOT of stuff! The last trip I took it on, I got a wallet, glasses, sunglasses, phone, planner, notebook and some pens in there. I have been really happy with how well it has worn too. The leather isn't my favorite but it has a coating on it that keeps stains and water off. Here you can glimpse my newest cross-body obsession from kate spade new york. I took this on my recent trip to Jordan and I loved it! It is much bigger than the Coach bag, and has more room in it than the Michael Kors. It also has a zipper pocket that folds down across the top. The leather on this bag is so soft and I love how pink it is. I found this beauty for a steal at a kate spade outlet sale. The entire store was 50% off with an additional 20% bags. It was a great buy! I will keep an eye out for their next outlet sale and make sure I update you all on it! https://breezingthrough.com/blog/what-is-the-best-purse-to-travel-with

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. [user request] [context document]

Describe the different types of hydrogen, how the hydrogen is produced and how each type of hydrogen is relevant in the context of climate change.

Grey hydrogen and blue hydrogen The grey hydrogen considered in this study is produced by SMR technology, and the production starts with hydrogen purging with natural gas feedstock to break long hydrocarbon chains. This step is followed by sulphur removal by chemical absorption on a ZnO bed because even a small amount of sulphur present in natural gas poisons the catalyst. Then, methane is fed to the steam reformer together with steam. The subsequent reaction is a strongly endothermic reaction and produces a mixture containing hydrogen and carbon monoxide. The required steam is assumed to be produced from natural gas. Next, the produced syngas and steam go to a water gas shift reactor to produce more hydrogen and some carbon dioxide from the carbon monoxide. Subsequently, the pressure swing adsorbent (PSA) process is used to separate hydrogen and CO2 and the hydrogen is stored with a compression to 60 bar.19 Unrecovered hydrogen, methane, CO and other compounds go to the furnace to produce heat for the reformer.20 A study by Alhamdani et al. (2017) showed that the fugitive emission from the SMR process is equal to 0.004 kg CO2 eq. per kg H2 and does not have a major impact.21 In view of the low level of fugitive emissions, their effects are neglected in this study. An overview of a typical SMR process is given in Fig. 3. The production process for blue hydrogen is the same as that for grey hydrogen, except that carbon dioxide is captured from the plant, stored and sequestered as shown in Fig. 3. Fig. 3 Grey hydrogen (SMR) and blue hydrogen (SMR-CCS) production (modified from Petrescu et al., 2014).19 2.3.2. Turquoise hydrogen TDM consumes less natural gas than SMR for hydrogen production and has lower total environmental impact.22 This superior environmental performance is because the TDM process does not release carbon dioxide to air. Moreover, since carbon dioxide is in a solid form, carbon gas cannot escape from the process, and a large amount of carbon dioxide can be captured with little impact on the environment. Typically, TDM is a form of pyrolysis of methane at a high temperature of 1500 K. There are two alternate routes in this process: one involving the use of a catalyst, which requires a lower temperature of around 1000 K, and the other without a catalyst, which requires a higher temperature of 1500 K.23 One of the advantages of pyrolysis of methane is that the only reaction products are hydrogen and solid carbon, thereby preventing the formation of CO2 during the reaction.24 Consequently, TDM is considered a promising alternative method for hydrogen production and can be seen in Fig. 4. The produced solid carbon can be utilised in many applications, such as chemical and industrial use.5 The benefit of using TDM is that it does not depend on CCS development and the infrastructure since the output carbon is in the solid form.25 Fig. 4 Turquoise hydrogen (TDM) production (modified from Keipi et al., 2018).25 2.3.3. Green hydrogen Electrolysis of water to split water into oxygen and hydrogen using renewable energy as an electricity source is currently considered the most promising method for carbon-free hydrogen production. Electrolyzers range in size from small apparatus-sized devices suitable for small-scale decentralized production of hydrogen to large centralized production facilities that could be directly connected to renewable or other zero-emission forms of electricity generation. A number of different electrolyzer types exist that operate on different principles: polymer electrolyte membrane (PEM) electrolyzers, alkaline electrolyzers and solid electrolyzers.26 An overview of the general process of water electrolysis for hydrogen production is given in Fig. 5. By-product oxygen from water hydrolysis can be used in combustion processes in the form of oxygen-enriched air to overcome mass transfer limitations and increase the flame speed and temperature.

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. Describe the different types of hydrogen, how the hydrogen is produced and how each type of hydrogen is relevant in the context of climate change. Grey hydrogen and blue hydrogen The grey hydrogen considered in this study is produced by SMR technology, and the production starts with hydrogen purging with natural gas feedstock to break long hydrocarbon chains. This step is followed by sulphur removal by chemical absorption on a ZnO bed because even a small amount of sulphur present in natural gas poisons the catalyst. Then, methane is fed to the steam reformer together with steam. The subsequent reaction is a strongly endothermic reaction and produces a mixture containing hydrogen and carbon monoxide. The required steam is assumed to be produced from natural gas. Next, the produced syngas and steam go to a water gas shift reactor to produce more hydrogen and some carbon dioxide from the carbon monoxide. Subsequently, the pressure swing adsorbent (PSA) process is used to separate hydrogen and CO2 and the hydrogen is stored with a compression to 60 bar.19 Unrecovered hydrogen, methane, CO and other compounds go to the furnace to produce heat for the reformer.20 A study by Alhamdani et al. (2017) showed that the fugitive emission from the SMR process is equal to 0.004 kg CO2 eq. per kg H2 and does not have a major impact.21 In view of the low level of fugitive emissions, their effects are neglected in this study. An overview of a typical SMR process is given in Fig. 3. The production process for blue hydrogen is the same as that for grey hydrogen, except that carbon dioxide is captured from the plant, stored and sequestered as shown in Fig. 3. Fig. 3 Grey hydrogen (SMR) and blue hydrogen (SMR-CCS) production (modified from Petrescu et al., 2014).19 2.3.2. Turquoise hydrogen TDM consumes less natural gas than SMR for hydrogen production and has lower total environmental impact.22 This superior environmental performance is because the TDM process does not release carbon dioxide to air. Moreover, since carbon dioxide is in a solid form, carbon gas cannot escape from the process, and a large amount of carbon dioxide can be captured with little impact on the environment. Typically, TDM is a form of pyrolysis of methane at a high temperature of 1500 K. There are two alternate routes in this process: one involving the use of a catalyst, which requires a lower temperature of around 1000 K, and the other without a catalyst, which requires a higher temperature of 1500 K.23 One of the advantages of pyrolysis of methane is that the only reaction products are hydrogen and solid carbon, thereby preventing the formation of CO2 during the reaction.24 Consequently, TDM is considered a promising alternative method for hydrogen production and can be seen in Fig. 4. The produced solid carbon can be utilised in many applications, such as chemical and industrial use.5 The benefit of using TDM is that it does not depend on CCS development and the infrastructure since the output carbon is in the solid form.25 Fig. 4 Turquoise hydrogen (TDM) production (modified from Keipi et al., 2018).25 2.3.3. Green hydrogen Electrolysis of water to split water into oxygen and hydrogen using renewable energy as an electricity source is currently considered the most promising method for carbon-free hydrogen production. Electrolyzers range in size from small apparatus-sized devices suitable for small-scale decentralized production of hydrogen to large centralized production facilities that could be directly connected to renewable or other zero-emission forms of electricity generation. A number of different electrolyzer types exist that operate on different principles: polymer electrolyte membrane (PEM) electrolyzers, alkaline electrolyzers and solid electrolyzers.26 An overview of the general process of water electrolysis for hydrogen production is given in Fig. 5. By-product oxygen from water hydrolysis can be used in combustion processes in the form of oxygen-enriched air to overcome mass transfer limitations and increase the flame speed and temperature. https://pubs.rsc.org/en/content/articlelanding/2024/gc/d3gc02410e

Respond succinctly and directly. Refer only to the provided document. After your answer, provide any relevant quotes from the source document in italics.

Using only the context document, what are the 4 plant-based diet indexes?

**Plant‐Based Diets Are Associated With a Lower Risk of Incident Cardiovascular Disease, Cardiovascular Disease Mortality, and All‐Cause Mortality in a General Population of Middle‐Aged Adults** Abstract Background Previous studies have documented the cardiometabolic health benefits of plant‐based diets; however, these studies were conducted in selected study populations that had narrow generalizability. Methods and Results We used data from a community‐based cohort of middle‐aged adults (n=12 168) in the ARIC (Atherosclerosis Risk in Communities) study who were followed up from 1987 through 2016. Participants’ diet was classified using 4 diet indexes. In the overall plant‐based diet index and provegetarian diet index, higher intakes of all or selected plant foods received higher scores; in the healthy plant‐based diet index, higher intakes of only the healthy plant foods received higher scores; in the less healthy plant‐based diet index, higher intakes of only the less healthy plant foods received higher scores. In all indexes, higher intakes of animal foods received lower scores. Results from Cox proportional hazards models showed that participants in the highest versus lowest quintile for adherence to overall plant‐based diet index or provegetarian diet had a 16%, 31% to 32%, and 18% to 25% lower risk of cardiovascular disease, cardiovascular disease mortality, and all‐cause mortality, respectively, after adjusting for important confounders (all P<0.05 for trend). Higher adherence to a healthy plant‐based diet index was associated with a 19% and 11% lower risk of cardiovascular disease mortality and all‐cause mortality, respectively, but not incident cardiovascular disease (P<0.05 for trend). No associations were observed between the less healthy plant‐based diet index and the outcomes. Conclusions Diets higher in plant foods and lower in animal foods were associated with a lower risk of cardiovascular morbidity and mortality in a general population. Clinical Perspective What Is New? • Plant‐based diets, diets that emphasize higher intakes of plant foods and lower intakes of animal foods, are associated with a lower risk of incident cardiovascular disease, cardiovascular disease mortality, and all‐cause mortality in a general US adult population. • Healthful plant‐based diets, diets higher in nutrient‐dense plant foods and lower in refined carbohydrates and animal foods, are associated with a lower risk of cardiovascular disease mortality and all‐cause mortality, but not incident cardiovascular disease. What Are the Clinical Implications? • Our results suggest that dietary patterns that are relatively higher in plant foods and relatively lower in animal foods may confer benefits for cardiovascular health. • Future research examining whether the quality of plant foods (healthful versus less healthful) within the framework of an overall plant‐based diet is associated with cardiovascular disease and all‐cause mortality is warranted. Introduction Plant‐based diets are dietary patterns that emphasize higher intakes of plant foods and are low in animal foods. Vegetarian diets, a type of plant‐based diet, with a focus on restriction of different types of animal foods (meat, poultry, or fish), have been associated with a lower risk of cardiovascular risk factors, such as obesity, hypertension, type 2 diabetes mellitus, and ischemic heart disease.1, 2, 3 However, prospective cohort studies have shown mixed results on the associations with cardiovascular disease mortality and all‐cause mortality.4, 5, 6 These previous studies were conducted in selected study populations that were mostly composed of Seventh‐Day Adventists, vegetarians, or health‐conscious individuals; thus, they had relatively narrow generalizability.4, 5, 7, 8, 9 Although prior studies have characterized participants’ diets using a relatively simple classification method based on frequency of animal food consumption,4, 5, 6 there have since been more comprehensive attempts to assess an individual's diet using plant‐based diet indexes.10, 11, 12, 13 These indexes give higher scores for higher consumption of plant foods and lower consumption of animal foods, allowing researchers to examine whether the degree of adherence to an overall plant‐based diet is associated with health outcomes. Studies that used such indexes (ie, an overall plant‐based diet index [PDI] or a provegetarian diet index) found that greater adherence to these diets was associated with a lower risk of type 2 diabetes mellitus, coronary heart disease, and all‐cause mortality.10, 11, 12 In addition, some plant‐based indexes separately scored healthful (whole grains, vegetables, and plant proteins) and unhealthful (refined carbohydrates and sugar) plant sources of food. Healthful plant‐based diets, which scored higher intakes of only healthful plant foods higher, were more strongly inversely associated with type 2 diabetes mellitus and coronary heart disease than the overall plant‐based diets.11, 12 In contrast, greater adherence to less healthful (unhealthful) plant‐based diets, which scored higher intakes of only less healthful plant foods higher, were associated with a higher risk of these conditions.11, 12 Given the limited evidence on plant‐based diets in the general population and recent developments in plant‐based diet scores, the objectives of the present study were as follows: (1) to evaluate whether overall plant‐based diets are associated with a lower risk of incident cardiovascular disease, cardiovascular disease mortality, and all‐cause mortality in a general US population; and (2) to assess if the association differed by adherence to healthful and less healthful plant‐based diets using 4 a priori defined plant‐based diet scores (overall plant‐based diet, healthy plant‐based diet, less healthy plant‐based diet, and provegetarian diet indexes). Study Design We used data from a community‐based cohort of middle‐aged men and women (45–64 years of age at baseline, n=15 792) in the ARIC study. From 1987 to 1989, participants from 4 US communities (Washington County, Maryland; Forsyth County, North Carolina; Minneapolis, MN; and Jackson, MS) were enrolled in the study. Follow‐up visits occurred in 1990 to 1992 (visit 2), 1993 to 1995 (visit 3), 1996 to 1998 (visit 4), 2011 to 2013 (visit 5), and 2016 to 2017 (visit 6).14 The Institutional Review Board at each study site approved the study protocol, and participants provided informed consent. Dietary Assessment At baseline and visit 3, participants’ usual intake of foods and beverages was assessed by trained interviewers using a modified version of the 66‐item semiquantitative Willett food frequency questionnaire. Participants indicated the frequency with which they consumed foods and beverages of a defined serving size in the previous year. Visual guides, such as glasses and measuring cups, were provided for participants to estimate portion size. The reliability of the food frequency questionnaire was assessed in a random sample of ARIC study participants (n=419) from all 4 study sites at visit 2.15 Nutrient and total energy intakes were derived through multiplying consumption of food by nutrient content of each item in the food frequency questionnaire. Plant‐Based Diet Scores The ARIC study did not assess whether participants were following a plant‐based diet. We used established plant‐based diet scores (PDI, healthy plant‐based diet index [hPDI], less healthy [unhealthy] plant‐based diet index [uPDI], and provegetarian diet index) to assess participants’ degree of adherence to plant‐based diets on the basis of their reported dietary intake on the food frequency questionnaire. We used these 4 plant‐based diet indexes to provide comprehensive and nuanced characterization of dietary intakes because the indexes differed from each other in scoring of food groups within the indexes. For instance, the PDI was more comprehensive than the provegetarian index in that the PDI assessed dietary intakes of plant foods high in refined carbohydrates (fruit juices, sugar‐sweetened beverages, sweets, and desserts). Consistent with some ethically motivated dietary patterns that are focused on the exclusion of animal sources of food and have less of an emphasis on the quality of plant foods, the provegetarian diet index provides a more simplistic score of the diet in that these refined carbohydrate food groups were not assessed. Further details on differences and construction of the scores have been published previously and are available in Data S1.10, 11, 12, 13, 16 The PDI, hPDI, and uPDI had a possible range from 17 to 85, and the provegetarian diet index had a possible range from 11 to 55. All scores were divided into quintiles for analyses. Outcome Assessment Incident cardiovascular disease events and deaths (cardiovascular and all cause) were ascertained through annual telephone calls with participants or proxies, active surveillance of local hospital discharge records and state death records, and linkage to the National Death Index from baseline to December 31, 2016. Incident cardiovascular disease was defined as a composite outcome of coronary heart disease, stroke, and heart failure. Incident coronary heart disease was defined as hospitalized myocardial infarction or fatal coronary heart disease.17 Incident stroke was defined as definite or probable stroke, which was adjudicated.18 Incident heart failure was defined as hospitalization or death, with International Classification of Diseases, Ninth Revision (ICD‐9), code 428 or International Classification of Diseases, Tenth Revision (ICD‐10), code I50.19 All‐cause mortality was defined as deaths attributable to any cause, and cardiovascular disease mortality was defined as deaths with ICD‐9 codes 390 to 459 or ICD‐10 codes I00 to I99. Covariate Assessment At baseline, participants’ sociodemographic information (age, sex, race/ethnicity, and education), health behaviors (cigarette smoking, frequency and duration of physical activity, alcohol intake, and margarine intake), medication use (lipid‐lowering medication use, antihypertensive medication use, or diabetes mellitus medication use), and health conditions (diagnosis of diseases) were collected by self‐reports. Trained staff measured participants’ weight and height, which was used to calculate body mass index (BMI; kg/m2). Those whose BMI was ≤25 kg/m2 were classified as normal weight, those whose BMI was from 25 to <30 kg/m2 were classified as overweight, and those whose BMI was ≥30 kg/m2 were classified as obese. An enzymatic method was used to measure total cholesterol concentration.20 A certified technician measured participants’ blood pressure 3 times, and the second and third measurements were averaged. The modified hexokinase/glucose‐6‐phosphate dehydrogenase method was used to measure blood glucose concentrations. Baseline kidney function (estimated glomerular filtration rate) was estimated from serum creatinine measurement using the 2009 Chronic Kidney Disease Epidemiology Collaboration equation.21 We defined hypertension as systolic blood pressure of ≥140 mm Hg, diastolic blood pressure of ≥90 mm Hg, or antihypertensive medication use in the past 2 weeks. We defined diabetes mellitus as fasting glucose concentration of ≥126 mg/dL, nonfasting blood glucose concentration of ≥200 mg/dL, self‐reported physician's diagnosis of diabetes mellitus, or diabetes mellitus medication use in the past 2 weeks.

{Task Information} ================== Respond succinctly and directly. Refer only to the provided document. After your answer, provide any relevant quotes from the source document in italics. ================ {Query} ================== Using only the context document, what are the 4 plant-based diet indexes? ================ {Passage} ================== **Plant‐Based Diets Are Associated With a Lower Risk of Incident Cardiovascular Disease, Cardiovascular Disease Mortality, and All‐Cause Mortality in a General Population of Middle‐Aged Adults** Abstract Background Previous studies have documented the cardiometabolic health benefits of plant‐based diets; however, these studies were conducted in selected study populations that had narrow generalizability. Methods and Results We used data from a community‐based cohort of middle‐aged adults (n=12 168) in the ARIC (Atherosclerosis Risk in Communities) study who were followed up from 1987 through 2016. Participants’ diet was classified using 4 diet indexes. In the overall plant‐based diet index and provegetarian diet index, higher intakes of all or selected plant foods received higher scores; in the healthy plant‐based diet index, higher intakes of only the healthy plant foods received higher scores; in the less healthy plant‐based diet index, higher intakes of only the less healthy plant foods received higher scores. In all indexes, higher intakes of animal foods received lower scores. Results from Cox proportional hazards models showed that participants in the highest versus lowest quintile for adherence to overall plant‐based diet index or provegetarian diet had a 16%, 31% to 32%, and 18% to 25% lower risk of cardiovascular disease, cardiovascular disease mortality, and all‐cause mortality, respectively, after adjusting for important confounders (all P<0.05 for trend). Higher adherence to a healthy plant‐based diet index was associated with a 19% and 11% lower risk of cardiovascular disease mortality and all‐cause mortality, respectively, but not incident cardiovascular disease (P<0.05 for trend). No associations were observed between the less healthy plant‐based diet index and the outcomes. Conclusions Diets higher in plant foods and lower in animal foods were associated with a lower risk of cardiovascular morbidity and mortality in a general population. Clinical Perspective What Is New? • Plant‐based diets, diets that emphasize higher intakes of plant foods and lower intakes of animal foods, are associated with a lower risk of incident cardiovascular disease, cardiovascular disease mortality, and all‐cause mortality in a general US adult population. • Healthful plant‐based diets, diets higher in nutrient‐dense plant foods and lower in refined carbohydrates and animal foods, are associated with a lower risk of cardiovascular disease mortality and all‐cause mortality, but not incident cardiovascular disease. What Are the Clinical Implications? • Our results suggest that dietary patterns that are relatively higher in plant foods and relatively lower in animal foods may confer benefits for cardiovascular health. • Future research examining whether the quality of plant foods (healthful versus less healthful) within the framework of an overall plant‐based diet is associated with cardiovascular disease and all‐cause mortality is warranted. Introduction Plant‐based diets are dietary patterns that emphasize higher intakes of plant foods and are low in animal foods. Vegetarian diets, a type of plant‐based diet, with a focus on restriction of different types of animal foods (meat, poultry, or fish), have been associated with a lower risk of cardiovascular risk factors, such as obesity, hypertension, type 2 diabetes mellitus, and ischemic heart disease.1, 2, 3 However, prospective cohort studies have shown mixed results on the associations with cardiovascular disease mortality and all‐cause mortality.4, 5, 6 These previous studies were conducted in selected study populations that were mostly composed of Seventh‐Day Adventists, vegetarians, or health‐conscious individuals; thus, they had relatively narrow generalizability.4, 5, 7, 8, 9 Although prior studies have characterized participants’ diets using a relatively simple classification method based on frequency of animal food consumption,4, 5, 6 there have since been more comprehensive attempts to assess an individual's diet using plant‐based diet indexes.10, 11, 12, 13 These indexes give higher scores for higher consumption of plant foods and lower consumption of animal foods, allowing researchers to examine whether the degree of adherence to an overall plant‐based diet is associated with health outcomes. Studies that used such indexes (ie, an overall plant‐based diet index [PDI] or a provegetarian diet index) found that greater adherence to these diets was associated with a lower risk of type 2 diabetes mellitus, coronary heart disease, and all‐cause mortality.10, 11, 12 In addition, some plant‐based indexes separately scored healthful (whole grains, vegetables, and plant proteins) and unhealthful (refined carbohydrates and sugar) plant sources of food. Healthful plant‐based diets, which scored higher intakes of only healthful plant foods higher, were more strongly inversely associated with type 2 diabetes mellitus and coronary heart disease than the overall plant‐based diets.11, 12 In contrast, greater adherence to less healthful (unhealthful) plant‐based diets, which scored higher intakes of only less healthful plant foods higher, were associated with a higher risk of these conditions.11, 12 Given the limited evidence on plant‐based diets in the general population and recent developments in plant‐based diet scores, the objectives of the present study were as follows: (1) to evaluate whether overall plant‐based diets are associated with a lower risk of incident cardiovascular disease, cardiovascular disease mortality, and all‐cause mortality in a general US population; and (2) to assess if the association differed by adherence to healthful and less healthful plant‐based diets using 4 a priori defined plant‐based diet scores (overall plant‐based diet, healthy plant‐based diet, less healthy plant‐based diet, and provegetarian diet indexes). Study Design We used data from a community‐based cohort of middle‐aged men and women (45–64 years of age at baseline, n=15 792) in the ARIC study. From 1987 to 1989, participants from 4 US communities (Washington County, Maryland; Forsyth County, North Carolina; Minneapolis, MN; and Jackson, MS) were enrolled in the study. Follow‐up visits occurred in 1990 to 1992 (visit 2), 1993 to 1995 (visit 3), 1996 to 1998 (visit 4), 2011 to 2013 (visit 5), and 2016 to 2017 (visit 6).14 The Institutional Review Board at each study site approved the study protocol, and participants provided informed consent. Dietary Assessment At baseline and visit 3, participants’ usual intake of foods and beverages was assessed by trained interviewers using a modified version of the 66‐item semiquantitative Willett food frequency questionnaire. Participants indicated the frequency with which they consumed foods and beverages of a defined serving size in the previous year. Visual guides, such as glasses and measuring cups, were provided for participants to estimate portion size. The reliability of the food frequency questionnaire was assessed in a random sample of ARIC study participants (n=419) from all 4 study sites at visit 2.15 Nutrient and total energy intakes were derived through multiplying consumption of food by nutrient content of each item in the food frequency questionnaire. Plant‐Based Diet Scores The ARIC study did not assess whether participants were following a plant‐based diet. We used established plant‐based diet scores (PDI, healthy plant‐based diet index [hPDI], less healthy [unhealthy] plant‐based diet index [uPDI], and provegetarian diet index) to assess participants’ degree of adherence to plant‐based diets on the basis of their reported dietary intake on the food frequency questionnaire. We used these 4 plant‐based diet indexes to provide comprehensive and nuanced characterization of dietary intakes because the indexes differed from each other in scoring of food groups within the indexes. For instance, the PDI was more comprehensive than the provegetarian index in that the PDI assessed dietary intakes of plant foods high in refined carbohydrates (fruit juices, sugar‐sweetened beverages, sweets, and desserts). Consistent with some ethically motivated dietary patterns that are focused on the exclusion of animal sources of food and have less of an emphasis on the quality of plant foods, the provegetarian diet index provides a more simplistic score of the diet in that these refined carbohydrate food groups were not assessed. Further details on differences and construction of the scores have been published previously and are available in Data S1.10, 11, 12, 13, 16 The PDI, hPDI, and uPDI had a possible range from 17 to 85, and the provegetarian diet index had a possible range from 11 to 55. All scores were divided into quintiles for analyses. Outcome Assessment Incident cardiovascular disease events and deaths (cardiovascular and all cause) were ascertained through annual telephone calls with participants or proxies, active surveillance of local hospital discharge records and state death records, and linkage to the National Death Index from baseline to December 31, 2016. Incident cardiovascular disease was defined as a composite outcome of coronary heart disease, stroke, and heart failure. Incident coronary heart disease was defined as hospitalized myocardial infarction or fatal coronary heart disease.17 Incident stroke was defined as definite or probable stroke, which was adjudicated.18 Incident heart failure was defined as hospitalization or death, with International Classification of Diseases, Ninth Revision (ICD‐9), code 428 or International Classification of Diseases, Tenth Revision (ICD‐10), code I50.19 All‐cause mortality was defined as deaths attributable to any cause, and cardiovascular disease mortality was defined as deaths with ICD‐9 codes 390 to 459 or ICD‐10 codes I00 to I99. Covariate Assessment At baseline, participants’ sociodemographic information (age, sex, race/ethnicity, and education), health behaviors (cigarette smoking, frequency and duration of physical activity, alcohol intake, and margarine intake), medication use (lipid‐lowering medication use, antihypertensive medication use, or diabetes mellitus medication use), and health conditions (diagnosis of diseases) were collected by self‐reports. Trained staff measured participants’ weight and height, which was used to calculate body mass index (BMI; kg/m2). Those whose BMI was ≤25 kg/m2 were classified as normal weight, those whose BMI was from 25 to <30 kg/m2 were classified as overweight, and those whose BMI was ≥30 kg/m2 were classified as obese. An enzymatic method was used to measure total cholesterol concentration.20 A certified technician measured participants’ blood pressure 3 times, and the second and third measurements were averaged. The modified hexokinase/glucose‐6‐phosphate dehydrogenase method was used to measure blood glucose concentrations. Baseline kidney function (estimated glomerular filtration rate) was estimated from serum creatinine measurement using the 2009 Chronic Kidney Disease Epidemiology Collaboration equation.21 We defined hypertension as systolic blood pressure of ≥140 mm Hg, diastolic blood pressure of ≥90 mm Hg, or antihypertensive medication use in the past 2 weeks. We defined diabetes mellitus as fasting glucose concentration of ≥126 mg/dL, nonfasting blood glucose concentration of ≥200 mg/dL, self‐reported physician's diagnosis of diabetes mellitus, or diabetes mellitus medication use in the past 2 weeks.

Write your response in a table containing bullet points of information. Ensure to answer the question using only the information provided in the context block. If it is not possible to fully answer the question with the text provided, say, “I’m sorry, I cannot answer that question due to lack of context”.

Summarise and simplify how a hash works and explain how this is different from a nonce, each in two to five sentences.

Cryptocurrency Mining There are three primary approaches to gaining ownership of Bitcoin: purchase Bitcoin directly by exchanging conventional money and a paying an exchange fee; earn Bitcoin in return for a product or service; or create Bitcoin through mining. 5 Bitcoin and other cryptocurrencies each implement their own blockchain: mining is the creation and publication of a new block in a blockchain.6 Early cryptocurrency platforms, like Bitcoin, required the use of mining to validate transactions. In blockchain platforms generally, miners—those seeking to add a block to a blockchain—are incentivized to improve their value in that blockchain through either a monetary, reputational, or stake award, for example. New blocks may be added to a blockchain through a variety of methods. For Bitcoin, new blocks are added to the blockchain through proof-of-work (PoW). Under PoW, miners are presented a difficult computational problem, or puzzle. PoW identifies a numeric value (called a nonce), which is used to generate an authenticator (hash value). Hash values are used to ensure the integrity of data, in this case, that a block of data in the blockchain has not been modified. Hashes are determined by submitting the data through an algorithm that will output a string of characters. By inserting the nonce into the algorithm, miners seek to change the hashvalue. The problem Bitcoin miners are trying to solve is the creation of a hash value for a given block which begins with a certain number of zeros. They add data to the block through changing the nonce in order to change the hash value and discover the solution. Identifying these valid nonces and hashes is computationally intensive, and the essence of mining.7 The security properties of hash algorithms are such that a miner tests nonces until a valid hash is found for a block.

Summarise and simplify how a hash works and explain how this is different from a nonce, each in two to five sentences. Write your response in a table containing bullet points of information. Ensure to answer the question using only the information provided in the context block. If it is not possible to fully answer the question with the text provided, say, “I’m sorry, I cannot answer that question due to lack of context”. Cryptocurrency Mining There are three primary approaches to gaining ownership of Bitcoin: purchase Bitcoin directly by exchanging conventional money and a paying an exchange fee; earn Bitcoin in return for a product or service; or create Bitcoin through mining. 5 Bitcoin and other cryptocurrencies each implement their own blockchain: mining is the creation and publication of a new block in a blockchain.6 Early cryptocurrency platforms, like Bitcoin, required the use of mining to validate transactions. In blockchain platforms generally, miners—those seeking to add a block to a blockchain—are incentivized to improve their value in that blockchain through either a monetary, reputational, or stake award, for example. New blocks may be added to a blockchain through a variety of methods. For Bitcoin, new blocks are added to the blockchain through proof-of-work (PoW). Under PoW, miners are presented a difficult computational problem, or puzzle. PoW identifies a numeric value (called a nonce), which is used to generate an authenticator (hash value). Hash values are used to ensure the integrity of data, in this case, that a block of data in the blockchain has not been modified. Hashes are determined by submitting the data through an algorithm that will output a string of characters. By inserting the nonce into the algorithm, miners seek to change the hashvalue. The problem Bitcoin miners are trying to solve is the creation of a hash value for a given block which begins with a certain number of zeros. They add data to the block through changing the nonce in order to change the hash value and discover the solution. Identifying these valid nonces and hashes is computationally intensive, and the essence of mining.7 The security properties of hash algorithms are such that a miner tests nonces until a valid hash is found for a block.

Answer in a single sentence. Use only the document as your source.

According to the above article what causes heart disease?

** Heart Disease** The human heart beats about 2.5 billion times over an average lifetime, pushing millions of gallons of blood throughout the body. This steady blood flow carries oxygen, hormones, and other compounds. It also whisks away the waste products of metabolism. Given the heart's never-ending workload, it's a wonder it performs so well for so long. But it can also fail, brought down by poor diet, lack of exercise, smoking, infection, unfavorable genes, and more. Heart disease and cardiovascular disease are two of the most significant heart health issues. They are often used interchangeably, but they are not the same. Heart disease refers to diseases of the heart, such as coronary artery disease, heart failure, heart valve abnormalities, and abnormal heart rhythms. Cardiovascular disease is a catch-all term for all heart and blood vessel diseases. It includes heart disease, but also stroke. Does a coronary stent make sense for stable angina? What are the different types of heart disease? Heart disease refers to diseases that affect the function and condition of the heart. There are several kinds of heart disease, including: cardiomyopathy: a heart muscle disease that causes the heart to become abnormally enlarged, thickened, and/or stiffened. congenital heart disease: heart disease or abnormalities in the heart's structure that are present at birth. coronary artery disease: accumulation of cholesterol-filled plaques, which clog the arteries that supply blood and oxygen to the heart. endocarditis: infection and inflammation of the heart valves and the inner lining of the heart chambers, called the endocardium. heart attack (myocardial infarction): the sudden stopping of blood flow to part of the heart muscle heart failure: the inability of the heart to pump as forcefully or efficiently as needed to supply the body with oxygenated blood. heart rhythm disorders (arrhythmias): heartbeats that are too fast, too slow, or irregular. heart valve disorders: problems with the valves that control blood flow from one part of the heart to another part of the heart or to the body. myocarditis: inflammation of the myocardium, the middle layer of the heart wall, that decreases the ability of the heart to pump blood normally. pericarditis: inflammation of the pericardium, a thin sac surrounding the heart. sudden cardiac arrest: the sudden cessation of the heartbeat. You might also be interested in... Controlling Your Blood Pressure An alarming one in three American adults has high blood pressure. Known medically as hypertension, many people don't even know they have it, because high blood pressure has no symptoms or warning signs. But when elevated blood pressure is accompanied by abnormal cholesterol and blood sugar levels, the damage to your arteries, kidneys, and heart accelerates exponentially. Fortunately, high blood pressure is easy to detect and treat. In the Special Health Report, Controlling Your Blood Pressure, find out how to keep blood pressure in a healthy range simply by making lifestyle changes, such as losing weight, increasing activity, and eating more healthfully. READ MORE What causes heart disease? The most common type of heart disease is coronary artery disease (CAD), and the leading cause of CAD is atherosclerosis, the buildup of cholesterol plaque inside the coronary arteries. Too much plaque limits blood flow through the arteries that supply blood to the heart. Restricted blood flow can cause chest pain or pressure (known as angina) and requires immediate medical attention. When plaque ruptures, it can form a blood clot that stops blood flow and triggers a heart attack. The risk factors for atherosclerosis (and thus CAD) include: High total blood cholesterol level High level of LDL (bad) cholesterol High levels of triglycerides High levels of lipoprotein(a) High blood pressure (hypertension) Diabetes Family history of heart disease Smoking Obesity Physical inactivity Inflammation Stroke: Strategies to prevent, treat, and recover from a "brain attack" Protect your brain: That’s the strategy that Harvard doctors recommend in this report on preventing and treating stroke. Whether you’ve already had a mini-stroke or a major stroke, or have been warned that your high blood pressure might cause a future stroke, Stroke: Strategies to prevent, treat, and recover from a "brain attack" provides help and advice. READ MORE Heart disease symptoms A variety of symptoms and signs may indicate heart disease. If you experience any of the following for no apparent reason, immediately report them to your doctor. Fatigue. Fatigue can be caused by many illnesses and medicines. But constant, new fatigue can sometimes signal two kinds of heart disease: heart failure and coronary artery disease. Unexplained aches or pains. Blockage of blood to the heart muscle can cause pain or pressure in the chest, shoulders, arms, back, jaw, or abdomen, primarily when pain in these locations occurs with exercise and disappears with rest. Shortness of breath. Unexplained shortness of breath that occurs with small amounts of activity. Swollen legs, feet, or ankles. The kind of swelling that leaves an indentation if you press your finger into it could be a sign of heart failure. Heart palpitations. Palpitations refers to a heartbeat that feels irregular or rapid. Most palpitations may be caused by anxiety, caffeine intake, or dehydration. But sometimes they indicate a heart problem. You might also be interested in... Managing Your Cholesterol Managing Your Cholesterol offers up-to-date information to help you or a loved one keep cholesterol in check. The report spells out what are healthy and unhealthy cholesterol levels, and offers specific ways to keep cholesterol in line. It covers cholesterol tests and the genetics of cholesterol. The report also focuses on treatments based on the latest scientific evidence, including the pros and cons of statins and other medications, and provides the lowdown on other substances advertised to lower cholesterol. Managing Your Cholesterol can also help you work with your doctor to individualize your treatment. READ MORE How can you prevent heart disease? The best way to prevent heart disease is to adopt heart-healthy habits. These include managing blood pressure and cholesterol levels, eating a plant-based diet, adopting regular exercise, maintaining a proper weight, getting enough sleep, and not smoking. Blood pressure. High blood pressure makes the heart work harder, which can weaken the heart muscle over time. Blood pressure is measured in millimeters of mercury (mm Hg) and is categorized as follows: Normal: Less than 120/80 mm Hg Elevated: 120/less than 80 to 129/less than 80 mm Hg Stage 1 hypertension: 130/80 to 139/89 mm Hg Stage 2 hypertension: 140/90 mm Hg and above Cholesterol. There are two main types: “bad” low-density lipoprotein (LDL) and “good” high-density lipoprotein (HDL). Ideally, most adults should keep their LDL below 100 milligrams per deciliter (mg/dL) and their HDL above 40 mg/dL. However, your ideal numbers may differ based on your health, risk factors for heart disease, and individual goals, as determined in consultation with your doctor. Diet. Following a plant-based diet is known to protect against heart disease. The plant diets that have been most studied for heart health are the Mediterranean diet and the DASH (Dietary Approaches to Stop Hypertension) diet. Each emphasizes eating foods associated with heart-healthy benefits, such as whole grains, fruits, vegetables, legumes, nuts and seeds, fatty fish, and healthy oils like olive oil, and reducing the intake of red meat and processed foods. Exercise. Guidelines recommend that adults engage in at least 150 minutes of moderate-intensity aerobic activity per week, which breaks down to 30 minutes daily, five days a week. But this is the minimum. Evidence suggests that doing more is better. Weight. About 30% of American adults are classified as overweight. While it’s natural for people’s weight to increase somewhat with age, even five to 10 pounds over your ideal number is associated with an increased risk of heart disease. Check with your doctor to determine your weight range for your gender, age, and body type. Sleep. Experts recommend that adults get at least seven hours of sleep per night. Studies have found that less than this amount is associated with heart disease risk factors like higher stress levels, increased inflammation, high blood pressure, and weight gain. Smoking. Smokers have a much higher heart disease risk than never-smokers and two to three times the risk of early death. Certain medications and nicotine replacement therapies can help people quit. Speak with your doctor about these or other options.

[Task Instructions] ================== Answer in a single sentence. Use only the document as your source. ================ [Query] ================== According to the above article what causes heart disease? ================ [Text] ================== ** Heart Disease** The human heart beats about 2.5 billion times over an average lifetime, pushing millions of gallons of blood throughout the body. This steady blood flow carries oxygen, hormones, and other compounds. It also whisks away the waste products of metabolism. Given the heart's never-ending workload, it's a wonder it performs so well for so long. But it can also fail, brought down by poor diet, lack of exercise, smoking, infection, unfavorable genes, and more. Heart disease and cardiovascular disease are two of the most significant heart health issues. They are often used interchangeably, but they are not the same. Heart disease refers to diseases of the heart, such as coronary artery disease, heart failure, heart valve abnormalities, and abnormal heart rhythms. Cardiovascular disease is a catch-all term for all heart and blood vessel diseases. It includes heart disease, but also stroke. Does a coronary stent make sense for stable angina? What are the different types of heart disease? Heart disease refers to diseases that affect the function and condition of the heart. There are several kinds of heart disease, including: cardiomyopathy: a heart muscle disease that causes the heart to become abnormally enlarged, thickened, and/or stiffened. congenital heart disease: heart disease or abnormalities in the heart's structure that are present at birth. coronary artery disease: accumulation of cholesterol-filled plaques, which clog the arteries that supply blood and oxygen to the heart. endocarditis: infection and inflammation of the heart valves and the inner lining of the heart chambers, called the endocardium. heart attack (myocardial infarction): the sudden stopping of blood flow to part of the heart muscle heart failure: the inability of the heart to pump as forcefully or efficiently as needed to supply the body with oxygenated blood. heart rhythm disorders (arrhythmias): heartbeats that are too fast, too slow, or irregular. heart valve disorders: problems with the valves that control blood flow from one part of the heart to another part of the heart or to the body. myocarditis: inflammation of the myocardium, the middle layer of the heart wall, that decreases the ability of the heart to pump blood normally. pericarditis: inflammation of the pericardium, a thin sac surrounding the heart. sudden cardiac arrest: the sudden cessation of the heartbeat. You might also be interested in... Controlling Your Blood Pressure An alarming one in three American adults has high blood pressure. Known medically as hypertension, many people don't even know they have it, because high blood pressure has no symptoms or warning signs. But when elevated blood pressure is accompanied by abnormal cholesterol and blood sugar levels, the damage to your arteries, kidneys, and heart accelerates exponentially. Fortunately, high blood pressure is easy to detect and treat. In the Special Health Report, Controlling Your Blood Pressure, find out how to keep blood pressure in a healthy range simply by making lifestyle changes, such as losing weight, increasing activity, and eating more healthfully. READ MORE What causes heart disease? The most common type of heart disease is coronary artery disease (CAD), and the leading cause of CAD is atherosclerosis, the buildup of cholesterol plaque inside the coronary arteries. Too much plaque limits blood flow through the arteries that supply blood to the heart. Restricted blood flow can cause chest pain or pressure (known as angina) and requires immediate medical attention. When plaque ruptures, it can form a blood clot that stops blood flow and triggers a heart attack. The risk factors for atherosclerosis (and thus CAD) include: High total blood cholesterol level High level of LDL (bad) cholesterol High levels of triglycerides High levels of lipoprotein(a) High blood pressure (hypertension) Diabetes Family history of heart disease Smoking Obesity Physical inactivity Inflammation Stroke: Strategies to prevent, treat, and recover from a "brain attack" Protect your brain: That’s the strategy that Harvard doctors recommend in this report on preventing and treating stroke. Whether you’ve already had a mini-stroke or a major stroke, or have been warned that your high blood pressure might cause a future stroke, Stroke: Strategies to prevent, treat, and recover from a "brain attack" provides help and advice. READ MORE Heart disease symptoms A variety of symptoms and signs may indicate heart disease. If you experience any of the following for no apparent reason, immediately report them to your doctor. Fatigue. Fatigue can be caused by many illnesses and medicines. But constant, new fatigue can sometimes signal two kinds of heart disease: heart failure and coronary artery disease. Unexplained aches or pains. Blockage of blood to the heart muscle can cause pain or pressure in the chest, shoulders, arms, back, jaw, or abdomen, primarily when pain in these locations occurs with exercise and disappears with rest. Shortness of breath. Unexplained shortness of breath that occurs with small amounts of activity. Swollen legs, feet, or ankles. The kind of swelling that leaves an indentation if you press your finger into it could be a sign of heart failure. Heart palpitations. Palpitations refers to a heartbeat that feels irregular or rapid. Most palpitations may be caused by anxiety, caffeine intake, or dehydration. But sometimes they indicate a heart problem. You might also be interested in... Managing Your Cholesterol Managing Your Cholesterol offers up-to-date information to help you or a loved one keep cholesterol in check. The report spells out what are healthy and unhealthy cholesterol levels, and offers specific ways to keep cholesterol in line. It covers cholesterol tests and the genetics of cholesterol. The report also focuses on treatments based on the latest scientific evidence, including the pros and cons of statins and other medications, and provides the lowdown on other substances advertised to lower cholesterol. Managing Your Cholesterol can also help you work with your doctor to individualize your treatment. READ MORE How can you prevent heart disease? The best way to prevent heart disease is to adopt heart-healthy habits. These include managing blood pressure and cholesterol levels, eating a plant-based diet, adopting regular exercise, maintaining a proper weight, getting enough sleep, and not smoking. Blood pressure. High blood pressure makes the heart work harder, which can weaken the heart muscle over time. Blood pressure is measured in millimeters of mercury (mm Hg) and is categorized as follows: Normal: Less than 120/80 mm Hg Elevated: 120/less than 80 to 129/less than 80 mm Hg Stage 1 hypertension: 130/80 to 139/89 mm Hg Stage 2 hypertension: 140/90 mm Hg and above Cholesterol. There are two main types: “bad” low-density lipoprotein (LDL) and “good” high-density lipoprotein (HDL). Ideally, most adults should keep their LDL below 100 milligrams per deciliter (mg/dL) and their HDL above 40 mg/dL. However, your ideal numbers may differ based on your health, risk factors for heart disease, and individual goals, as determined in consultation with your doctor. Diet. Following a plant-based diet is known to protect against heart disease. The plant diets that have been most studied for heart health are the Mediterranean diet and the DASH (Dietary Approaches to Stop Hypertension) diet. Each emphasizes eating foods associated with heart-healthy benefits, such as whole grains, fruits, vegetables, legumes, nuts and seeds, fatty fish, and healthy oils like olive oil, and reducing the intake of red meat and processed foods. Exercise. Guidelines recommend that adults engage in at least 150 minutes of moderate-intensity aerobic activity per week, which breaks down to 30 minutes daily, five days a week. But this is the minimum. Evidence suggests that doing more is better. Weight. About 30% of American adults are classified as overweight. While it’s natural for people’s weight to increase somewhat with age, even five to 10 pounds over your ideal number is associated with an increased risk of heart disease. Check with your doctor to determine your weight range for your gender, age, and body type. Sleep. Experts recommend that adults get at least seven hours of sleep per night. Studies have found that less than this amount is associated with heart disease risk factors like higher stress levels, increased inflammation, high blood pressure, and weight gain. Smoking. Smokers have a much higher heart disease risk than never-smokers and two to three times the risk of early death. Certain medications and nicotine replacement therapies can help people quit. Speak with your doctor about these or other options.

Use only the provided context for your response, without relying on external information.

How much does a pair of Diamond 210 cost?

Title: Wharfedale Diamonds Shine Even Brighter Wharfedale's classic Diamond lineage of high-performance, high-value speakers reaches new heights with the Diamond 200 Series Huntingdon, England -- For more than 30 years, Wharfedale’s famous Diamond speakers have served as the classic entry point to true high-fidelity sound, their exceptional value for money earning dozens of awards around the globe. Now, with the introduction of the all-new Diamond 200 Series, Wharfedale has once again raised the bar for affordable, high-performance loudspeakers. Replacing the critically acclaimed Diamond 100 Series, Diamond 200 comprises two standmount speakers and three floorstanding models, plus a center speaker for home cinema use. Given that the speakers’ predecessors were so highly rated for their sound quality, Wharfedale's engineers took an evolutionary approach, precisely targeting key areas to improve in order to make an already great loudspeaker range deliver even better value for money. Enhancements across the range include: New cabinet construction – a sandwich of particleboard between MDF, which has enabled improvements both aesthetic and sonic. New lacquered baffle design further enhances aesthetic qualities. Improved bass motor system with larger magnets makes the speakers easier to drive and boosts transient acoustic power. Enhanced 'Slot-Loaded Distributed Port' – improved airflow control lowers turbulence and hence reduces low-frequency distortion. Upgraded crossover networks further improve the integration between the drive units. The Wharfedale Diamond 200 Series in full The first Diamond 200 Series model to launch is the Diamond 220. Available now, this pivotal model is the latest evolution of Wharfedale’s classic Diamond standmount speaker – a neatly proportioned design with a 130mm mid/bass driver. It is the direct replacement for the best-selling Diamond 121 from the outgoing Diamond 100 Series, benefitting from all the enhancements described above, yet Wharfedale has managed to shave £30 off the RRP – the Diamond 220 has an RRP of just £199.95 per pair. The remaining Diamond 200 Series models arrive this month. These include the Diamond 210, an ultra-compact speaker for rear/surround duties or stereo applications where space is at a premium (£149.95 per pair), plus three floorstanders – the Diamond 230 (£499.95 per pair), Diamond 240 (£699.95 per pair), and Diamond 250 (£999.95 per pair). The Diamond 220C home cinema center speaker (£199.95) completes the range. Anyone wishing to compile a 5.1 or 7.1 surround sound package from the Diamond 200 Series can add an active subwoofer from Wharfedale’s highly rated PowerCube SPC range, selecting an appropriate model to suit their room. Many of the speakers’ core features are unchanged from the Diamond 100 Series. The bass and midrange cones are fashioned from woven Kevlar and incorporate semi-elliptical ‘break-up’ areas – visible as raised ‘V’ shapes on the cone’s surface – that smooth the response throughout the audible range. The dust cap is blended and treated to provide a smooth transition with the treble unit, which incorporates an advanced ferrite magnet system and a carefully constructed waveguide around the fabric dome for optimal dispersion. Bass performance is enhanced by a newly refined version of the Slot-Loaded Distributed Port, first introduced in the outgoing Diamond 100 Series. Instead of the usual circular reflex port, all Diamond 200 Series models incorporate a port that exits at the base of the speaker cabinet, loaded by a slot that is created by the plinth. This equalizes the air pressure to mimic that inside the cabinet, allowing smooth transition between the pressure variation in the cabinet and the low-frequency sound developed in the room. The result is deep, articulate and well-integrated bass, without the ‘chuffing’ that is often associated with regular front- or rear-mounted ports. It also allows the speakers to be placed closer to a rear wall than is appropriate with most competing designs, making them easier to position in an average room. No other speaker range at such affordable price points implements an advanced bass loading system of this kind. All Wharfedale Diamond 200 Series speakers come in a choice of four finishes – black, white, walnut, and rosewood – adding to their smart aesthetics and excellent value for money. Designer’s notes: Peter Comeau, Wharfedale’s Director of Acoustic Design Peter Comeau, Wharfedale’s Director of Acoustic Design, describes the improvements he and his team have brought to the Diamond 200 Series: When Wharfedale launched the very first Diamond in 1981, the company defined a new class of speaker that delivered genuine hi-fi accuracy and musical brio at a remarkably affordable price. Since then, every iteration of the famous Diamond line has adhered to that tradition but improved upon it. Our challenge with the Diamond 200 Series was to further enhance every model across the range, whilst maintaining the traditionally affordable retail prices that embody the Diamond ethos – no mean feat at a time when other manufacturers are being forced to raise the prices of equivalent ranges. It is no coincidence that research from loudspeakers further up the Wharfedale range has crept downwards into the Diamond 200 Series. Whilst higher retail price points permit the advanced research that lets Wharfedale engineers investigate cutting-edge performance in acoustic technology, the trick is to use the benefits of this research and apply it to materials that can be produced in higher quantities with the benefit of lower cost to production. That’s no more apparent than in the Diamond 200 Series’ new cabinet material. Research undertaken for Wharfedale’s upmarket Jade Series yielded a matrix of materials called Crystalam, which reduced the audibility of panel resonance and what our engineers call ‘cabinet hear-through’. This research showed that coherent materials, like raw MDF, have peak resonances (particularly in the midrange) that let sound out of a cabinet at volume levels that interfere with the sound from the drive units. Not surprisingly, this ‘hear-through’ causes a distinct coloration and character to the sound of such cabinets. In Jade’s Crystalam, Wharfedale put together a matrix of non-coherent materials comprising differing densities of particleboard and MDF, substantially reducing both panel resonance and cabinet hear-through. For the Diamond 200 Series, we found that a simpler ‘sandwich’ combination of particleboard and MDF, whilst not quite reaching to the absolute standards of Crystalam, yielded similar reductions in coloration at considerably lower cost. In addition, the inner and outer layers of MDF allow a superior finish to the cabinet veneers, enhancing the aesthetic quality of the speakers in comparison to the outgoing Diamond 100 Series. Topping this new cabinet material is a simple, one-piece baffle lacquered to a highly polished finish that cosmetically matches the silver-colored, diamond-cut drive unit surrounds. The result is an attractive appearance, with or without grilles, that makes Diamond 200 Series speakers look more expensive than they actually are, adding to their exceptional value for money. Additional improvements inside the speakers enhance sound quality in comparison to the already highly acclaimed Diamond 100 Series. Bass unit motor systems have been further refined, with corresponding increases in magnet size, making the speakers easier to drive and boosting transient acoustic power. Furthermore, we have taken note of how most users are placing their speakers in their rooms. These days, loudspeakers are often expected to blend into room furnishings rather than take up a significant amount of space. This is particularly true of low-cost speakers like those in the Diamond 200 Series, which are expected to fit seamlessly into average-size living rooms. For this reason, the ability to be positioned close to a rear wall is important. The balance of the Diamond 200 Series takes this into account, with the standmount speakers having a recommended minimum of 50mm to the rear wall, alongside a minimum of 200mm for the floorstanders – considerably closer positioning than is possible with many similar-sized designs. This freedom of positioning is aided by the Slot-Loaded Distributed Port, again grown out of our research into the Jade Aperiodic bass loading system. While the Diamond 200 Series bass system is strictly bass reflex, with its attendant bonus of high sensitivity, the slot-loaded port, which uses a gap between the plinth and the port exit in the base of the cabinet, aids the pressure differential between the port and the air in the room, increasing the energy transfer and making the system more efficient. Attendant with the increase in bass driver power, Diamond 200 Series speakers now have an added degree of airflow control to the port exit, which effectively reduces turbulence in this region and reduces low-frequency distortion. Finally, but not least of the Diamond 200 Series improvements, the crossovers have been refined over hundreds of hours of listening tests to further improve the integration between the drive units and herald a new level of realism to instruments and voices. The result of all these technical endeavors is, we feel, the best Diamond Series yet, delivering loudspeakers which reveal a whole new level of musical detail and transient attack, drawing the listener into the musical performance in a way that is normally only expected from speakers at a considerably higher price level.

[Query] How much does a pair of Diamond 210 cost? ================ [Task Description] Use only the provided context for your response, without relying on external information. ================ [Document] Title: Wharfedale Diamonds Shine Even Brighter Wharfedale's classic Diamond lineage of high-performance, high-value speakers reaches new heights with the Diamond 200 Series Huntingdon, England -- For more than 30 years, Wharfedale’s famous Diamond speakers have served as the classic entry point to true high-fidelity sound, their exceptional value for money earning dozens of awards around the globe. Now, with the introduction of the all-new Diamond 200 Series, Wharfedale has once again raised the bar for affordable, high-performance loudspeakers. Replacing the critically acclaimed Diamond 100 Series, Diamond 200 comprises two standmount speakers and three floorstanding models, plus a center speaker for home cinema use. Given that the speakers’ predecessors were so highly rated for their sound quality, Wharfedale's engineers took an evolutionary approach, precisely targeting key areas to improve in order to make an already great loudspeaker range deliver even better value for money. Enhancements across the range include: New cabinet construction – a sandwich of particleboard between MDF, which has enabled improvements both aesthetic and sonic. New lacquered baffle design further enhances aesthetic qualities. Improved bass motor system with larger magnets makes the speakers easier to drive and boosts transient acoustic power. Enhanced 'Slot-Loaded Distributed Port' – improved airflow control lowers turbulence and hence reduces low-frequency distortion. Upgraded crossover networks further improve the integration between the drive units. The Wharfedale Diamond 200 Series in full The first Diamond 200 Series model to launch is the Diamond 220. Available now, this pivotal model is the latest evolution of Wharfedale’s classic Diamond standmount speaker – a neatly proportioned design with a 130mm mid/bass driver. It is the direct replacement for the best-selling Diamond 121 from the outgoing Diamond 100 Series, benefitting from all the enhancements described above, yet Wharfedale has managed to shave £30 off the RRP – the Diamond 220 has an RRP of just £199.95 per pair. The remaining Diamond 200 Series models arrive this month. These include the Diamond 210, an ultra-compact speaker for rear/surround duties or stereo applications where space is at a premium (£149.95 per pair), plus three floorstanders – the Diamond 230 (£499.95 per pair), Diamond 240 (£699.95 per pair), and Diamond 250 (£999.95 per pair). The Diamond 220C home cinema center speaker (£199.95) completes the range. Anyone wishing to compile a 5.1 or 7.1 surround sound package from the Diamond 200 Series can add an active subwoofer from Wharfedale’s highly rated PowerCube SPC range, selecting an appropriate model to suit their room. Many of the speakers’ core features are unchanged from the Diamond 100 Series. The bass and midrange cones are fashioned from woven Kevlar and incorporate semi-elliptical ‘break-up’ areas – visible as raised ‘V’ shapes on the cone’s surface – that smooth the response throughout the audible range. The dust cap is blended and treated to provide a smooth transition with the treble unit, which incorporates an advanced ferrite magnet system and a carefully constructed waveguide around the fabric dome for optimal dispersion. Bass performance is enhanced by a newly refined version of the Slot-Loaded Distributed Port, first introduced in the outgoing Diamond 100 Series. Instead of the usual circular reflex port, all Diamond 200 Series models incorporate a port that exits at the base of the speaker cabinet, loaded by a slot that is created by the plinth. This equalizes the air pressure to mimic that inside the cabinet, allowing smooth transition between the pressure variation in the cabinet and the low-frequency sound developed in the room. The result is deep, articulate and well-integrated bass, without the ‘chuffing’ that is often associated with regular front- or rear-mounted ports. It also allows the speakers to be placed closer to a rear wall than is appropriate with most competing designs, making them easier to position in an average room. No other speaker range at such affordable price points implements an advanced bass loading system of this kind. All Wharfedale Diamond 200 Series speakers come in a choice of four finishes – black, white, walnut, and rosewood – adding to their smart aesthetics and excellent value for money. Designer’s notes: Peter Comeau, Wharfedale’s Director of Acoustic Design Peter Comeau, Wharfedale’s Director of Acoustic Design, describes the improvements he and his team have brought to the Diamond 200 Series: When Wharfedale launched the very first Diamond in 1981, the company defined a new class of speaker that delivered genuine hi-fi accuracy and musical brio at a remarkably affordable price. Since then, every iteration of the famous Diamond line has adhered to that tradition but improved upon it. Our challenge with the Diamond 200 Series was to further enhance every model across the range, whilst maintaining the traditionally affordable retail prices that embody the Diamond ethos – no mean feat at a time when other manufacturers are being forced to raise the prices of equivalent ranges. It is no coincidence that research from loudspeakers further up the Wharfedale range has crept downwards into the Diamond 200 Series. Whilst higher retail price points permit the advanced research that lets Wharfedale engineers investigate cutting-edge performance in acoustic technology, the trick is to use the benefits of this research and apply it to materials that can be produced in higher quantities with the benefit of lower cost to production. That’s no more apparent than in the Diamond 200 Series’ new cabinet material. Research undertaken for Wharfedale’s upmarket Jade Series yielded a matrix of materials called Crystalam, which reduced the audibility of panel resonance and what our engineers call ‘cabinet hear-through’. This research showed that coherent materials, like raw MDF, have peak resonances (particularly in the midrange) that let sound out of a cabinet at volume levels that interfere with the sound from the drive units. Not surprisingly, this ‘hear-through’ causes a distinct coloration and character to the sound of such cabinets. In Jade’s Crystalam, Wharfedale put together a matrix of non-coherent materials comprising differing densities of particleboard and MDF, substantially reducing both panel resonance and cabinet hear-through. For the Diamond 200 Series, we found that a simpler ‘sandwich’ combination of particleboard and MDF, whilst not quite reaching to the absolute standards of Crystalam, yielded similar reductions in coloration at considerably lower cost. In addition, the inner and outer layers of MDF allow a superior finish to the cabinet veneers, enhancing the aesthetic quality of the speakers in comparison to the outgoing Diamond 100 Series. Topping this new cabinet material is a simple, one-piece baffle lacquered to a highly polished finish that cosmetically matches the silver-colored, diamond-cut drive unit surrounds. The result is an attractive appearance, with or without grilles, that makes Diamond 200 Series speakers look more expensive than they actually are, adding to their exceptional value for money. Additional improvements inside the speakers enhance sound quality in comparison to the already highly acclaimed Diamond 100 Series. Bass unit motor systems have been further refined, with corresponding increases in magnet size, making the speakers easier to drive and boosting transient acoustic power. Furthermore, we have taken note of how most users are placing their speakers in their rooms. These days, loudspeakers are often expected to blend into room furnishings rather than take up a significant amount of space. This is particularly true of low-cost speakers like those in the Diamond 200 Series, which are expected to fit seamlessly into average-size living rooms. For this reason, the ability to be positioned close to a rear wall is important. The balance of the Diamond 200 Series takes this into account, with the standmount speakers having a recommended minimum of 50mm to the rear wall, alongside a minimum of 200mm for the floorstanders – considerably closer positioning than is possible with many similar-sized designs. This freedom of positioning is aided by the Slot-Loaded Distributed Port, again grown out of our research into the Jade Aperiodic bass loading system. While the Diamond 200 Series bass system is strictly bass reflex, with its attendant bonus of high sensitivity, the slot-loaded port, which uses a gap between the plinth and the port exit in the base of the cabinet, aids the pressure differential between the port and the air in the room, increasing the energy transfer and making the system more efficient. Attendant with the increase in bass driver power, Diamond 200 Series speakers now have an added degree of airflow control to the port exit, which effectively reduces turbulence in this region and reduces low-frequency distortion. Finally, but not least of the Diamond 200 Series improvements, the crossovers have been refined over hundreds of hours of listening tests to further improve the integration between the drive units and herald a new level of realism to instruments and voices. The result of all these technical endeavors is, we feel, the best Diamond Series yet, delivering loudspeakers which reveal a whole new level of musical detail and transient attack, drawing the listener into the musical performance in a way that is normally only expected from speakers at a considerably higher price level.

Rely only on the context document, with no outside information.

According to this document you shouldn't use which two things in conjunction on the same CPU or memory sticks?

**Best practices for performance and scaling for small to medium workloads in Azure Kubernetes Service (AKS):** This article focuses on general best practices for small to medium workloads. For best practices specific to large workloads, see Performance and scaling best practices for large workloads in Azure Kubernetes Service (AKS). As you deploy and maintain clusters in AKS, you can use the following best practices to help you optimize performance and scaling. In this article, you learn about: Tradeoffs and recommendations for autoscaling your workloads. Managing node scaling and efficiency based on your workload demands. Networking considerations for ingress and egress traffic. Monitoring and troubleshooting control plane and node performance. Capacity planning, surge scenarios, and cluster upgrades. Storage and networking considerations for data plane performance. Application autoscaling vs. infrastructure autoscaling Application autoscaling Application autoscaling is useful when dealing with cost optimization or infrastructure limitations. A well-configured autoscaler maintains high availability for your application while also minimizing costs. You only pay for the resources required to maintain availability, regardless of the demand. For example, if an existing node has space but not enough IPs in the subnet, it might be able to skip the creation of a new node and instead immediately start running the application on a new pod. Horizontal Pod autoscaling Implementing horizontal pod autoscaling is useful for applications with a steady and predictable resource demand. The Horizontal Pod Autoscaler (HPA) dynamically scales the number of pod replicas, which effectively distributes the load across multiple pods and nodes. This scaling mechanism is typically most beneficial for applications that can be decomposed into smaller, independent components capable of running in parallel. The HPA provides resource utilization metrics by default. You can also integrate custom metrics or leverage tools like the Kubernetes Event-Driven Autoscaler (KEDA) (Preview). These extensions allow the HPA to make scaling decisions based on multiple perspectives and criteria, providing a more holistic view of your application's performance. This is especially helpful for applications with varying complex scaling requirements. Note If maintaining high availability for your application is a top priority, we recommend leaving a slightly higher buffer for the minimum pod number for your HPA to account for scaling time. Vertical Pod autoscaling Implementing vertical pod autoscaling is useful for applications with fluctuating and unpredictable resource demands. The Vertical Pod Autoscaler (VPA) allows you to fine-tune resource requests, including CPU and memory, for individual pods, enabling precise control over resource allocation. This granularity minimizes resource waste and enhances the overall efficiency of cluster utilization. The VPA also streamlines application management by automating resource allocation, freeing up resources for critical tasks. Warning You shouldn't use the VPA in conjunction with the HPA on the same CPU or memory metrics. This combination can lead to conflicts, as both autoscalers attempt to respond to changes in demand using the same metrics. However, you can use the VPA for CPU or memory in conjunction with the HPA for custom metrics to prevent overlap and ensure that each autoscaler focuses on distinct aspects of workload scaling. Note The VPA works based on historical data. We recommend waiting at least 24 hours after deploying the VPA before applying any changes to give it time to collect recommendation data. Infrastructure autoscaling Cluster autoscaling Implementing cluster autoscaling is useful if your existing nodes lack sufficient capacity, as it helps with scaling up and provisioning new nodes. When considering cluster autoscaling, the decision of when to remove a node involves a tradeoff between optimizing resource utilization and ensuring resource availability. Eliminating underutilized nodes enhances cluster utilization but might result in new workloads having to wait for resources to be provisioned before they can be deployed. It's important to find a balance between these two factors that aligns with your cluster and workload requirements and configure the cluster autoscaler profile settings accordingly. The Cluster Autoscaler profile settings apply universally to all autoscaler-enabled node pools in your cluster. This means that any scaling actions occurring in one autoscaler-enabled node pool might impact the autoscaling behavior in another node pool. It's important to apply consistent and synchronized profile settings across all relevant node pools to ensure that the autoscaler behaves as expected. Overprovisioning Overprovisioning is a strategy that helps mitigate the risk of application pressure by ensuring there's an excess of readily available resources. This approach is especially useful for applications that experience highly variable loads and cluster scaling patterns that show frequent scale ups and scale downs. To determine the optimal amount of overprovisioning, you can use the following formula: txt Copy 1-buffer/1+traffic For example, let's say you want to avoid hitting 100% CPU utilization in your cluster. You might opt for a 30% buffer to maintain a safety margin. If you anticipate an average traffic growth rate of 40%, you might consider overprovisioning by 50%, as calculated by the formula: txt Copy 1-30%/1+40%=50% An effective overprovisioning method involves the use of pause pods. Pause pods are low-priority deployments that can be easily replaced by high-priority deployments. You create low priority pods that serve the sole purpose of reserving buffer space. When a high-priority pod requires space, the pause pods are removed and rescheduled on another node or a new node to accommodate the high priority pod. The following YAML shows an example pause pod manifest: yml Copy apiVersion: scheduling.k8s.io/v1 kind: PriorityClass metadata: name: overprovisioning value: -1 globalDefault: false description: "Priority class used by overprovisioning." --- apiVersion: apps/v1 kind: Deployment metadata: name: overprovisioning namespace: kube-system spec: replicas: 1 selector: matchLabels: run: overprovisioning template: metadata: labels: run: overprovisioning spec: priorityClassName: overprovisioning containers: - name: reserve-resources image: your-custome-pause-image resources: requests: cpu: 1 memory: 4Gi Node scaling and efficiency Best practice guidance: Carefully monitor resource utilization and scheduling policies to ensure nodes are being used efficiently. Node scaling allows you to dynamically adjust the number of nodes in your cluster based on workload demands. It's important to understand that adding more nodes to a cluster isn't always the best solution for improving performance. To ensure optimal performance, you should carefully monitor resource utilization and scheduling policies to ensure nodes are being used efficiently. Node images Best practice guidance: Use the latest node image version to ensure that you have the latest security patches and bug fixes. Using the latest node image version provides the best performance experience. AKS ships performance improvements within the weekly image releases. The latest daemonset images are cached on the latest VHD image, which provide lower latency benefits for node provisioning and bootstrapping. Falling behind on updates might have a negative impact on performance, so it's important to avoid large gaps between versions. Azure Linux The Azure Linux Container Host on AKS uses a native AKS image and provides a single place for Linux development. Every package is built from source and validated, ensuring your services run on proven components. Azure Linux is lightweight, only including the necessary set of packages to run container workloads. It provides a reduced attack surface and eliminates patching and maintenance of unnecessary packages. At its base layer, it has a Microsoft-hardened kernel tuned for Azure. This image is ideal for performance-sensitive workloads and platform engineers or operators that manage fleets of AKS clusters. Ubuntu 2204 The Ubuntu 2204 image is the default node image for AKS. It's a lightweight and efficient operating system optimized for running containerized workloads. This means that it can help reduce resource usage and improve overall performance. The image includes the latest security patches and updates, which help ensure that your workloads are protected from vulnerabilities. The Ubuntu 2204 image is fully supported by Microsoft, Canonical, and the Ubuntu community and can help you achieve better performance and security for your containerized workloads. Virtual machines (VMs) Best practice guidance: When selecting a VM, ensure the size and performance of the OS disk and VM SKU don't have a large discrepancy. A discrepancy in size or performance can cause performance issues and resource contention. Application performance is closely tied to the VM SKUs you use in your workloads. Larger and more powerful VMs, generally provide better performance. For mission critical or product workloads, we recommend using VMs with at least an 8-core CPU. VMs with newer hardware generations, like v4 and v5, can also help improve performance. Keep in mind that create and scale latency might vary depending on the VM SKUs you use. Use dedicated system node pools For scaling performance and reliability, we recommend using a dedicated system node pool. With this configuration, the dedicated system node pool reserves space for critical system resources such as system OS daemons. Your application workload can then run in a user node pool to increase the availability of allocatable resources for your application. This configuration also helps mitigate the risk of resource competition between the system and application.

<Task Information> ================== Rely only on the context document, with no outside information. <Passage> ================== **Best practices for performance and scaling for small to medium workloads in Azure Kubernetes Service (AKS):** This article focuses on general best practices for small to medium workloads. For best practices specific to large workloads, see Performance and scaling best practices for large workloads in Azure Kubernetes Service (AKS). As you deploy and maintain clusters in AKS, you can use the following best practices to help you optimize performance and scaling. In this article, you learn about: Tradeoffs and recommendations for autoscaling your workloads. Managing node scaling and efficiency based on your workload demands. Networking considerations for ingress and egress traffic. Monitoring and troubleshooting control plane and node performance. Capacity planning, surge scenarios, and cluster upgrades. Storage and networking considerations for data plane performance. Application autoscaling vs. infrastructure autoscaling Application autoscaling Application autoscaling is useful when dealing with cost optimization or infrastructure limitations. A well-configured autoscaler maintains high availability for your application while also minimizing costs. You only pay for the resources required to maintain availability, regardless of the demand. For example, if an existing node has space but not enough IPs in the subnet, it might be able to skip the creation of a new node and instead immediately start running the application on a new pod. Horizontal Pod autoscaling Implementing horizontal pod autoscaling is useful for applications with a steady and predictable resource demand. The Horizontal Pod Autoscaler (HPA) dynamically scales the number of pod replicas, which effectively distributes the load across multiple pods and nodes. This scaling mechanism is typically most beneficial for applications that can be decomposed into smaller, independent components capable of running in parallel. The HPA provides resource utilization metrics by default. You can also integrate custom metrics or leverage tools like the Kubernetes Event-Driven Autoscaler (KEDA) (Preview). These extensions allow the HPA to make scaling decisions based on multiple perspectives and criteria, providing a more holistic view of your application's performance. This is especially helpful for applications with varying complex scaling requirements. Note If maintaining high availability for your application is a top priority, we recommend leaving a slightly higher buffer for the minimum pod number for your HPA to account for scaling time. Vertical Pod autoscaling Implementing vertical pod autoscaling is useful for applications with fluctuating and unpredictable resource demands. The Vertical Pod Autoscaler (VPA) allows you to fine-tune resource requests, including CPU and memory, for individual pods, enabling precise control over resource allocation. This granularity minimizes resource waste and enhances the overall efficiency of cluster utilization. The VPA also streamlines application management by automating resource allocation, freeing up resources for critical tasks. Warning You shouldn't use the VPA in conjunction with the HPA on the same CPU or memory metrics. This combination can lead to conflicts, as both autoscalers attempt to respond to changes in demand using the same metrics. However, you can use the VPA for CPU or memory in conjunction with the HPA for custom metrics to prevent overlap and ensure that each autoscaler focuses on distinct aspects of workload scaling. Note The VPA works based on historical data. We recommend waiting at least 24 hours after deploying the VPA before applying any changes to give it time to collect recommendation data. Infrastructure autoscaling Cluster autoscaling Implementing cluster autoscaling is useful if your existing nodes lack sufficient capacity, as it helps with scaling up and provisioning new nodes. When considering cluster autoscaling, the decision of when to remove a node involves a tradeoff between optimizing resource utilization and ensuring resource availability. Eliminating underutilized nodes enhances cluster utilization but might result in new workloads having to wait for resources to be provisioned before they can be deployed. It's important to find a balance between these two factors that aligns with your cluster and workload requirements and configure the cluster autoscaler profile settings accordingly. The Cluster Autoscaler profile settings apply universally to all autoscaler-enabled node pools in your cluster. This means that any scaling actions occurring in one autoscaler-enabled node pool might impact the autoscaling behavior in another node pool. It's important to apply consistent and synchronized profile settings across all relevant node pools to ensure that the autoscaler behaves as expected. Overprovisioning Overprovisioning is a strategy that helps mitigate the risk of application pressure by ensuring there's an excess of readily available resources. This approach is especially useful for applications that experience highly variable loads and cluster scaling patterns that show frequent scale ups and scale downs. To determine the optimal amount of overprovisioning, you can use the following formula: txt Copy 1-buffer/1+traffic For example, let's say you want to avoid hitting 100% CPU utilization in your cluster. You might opt for a 30% buffer to maintain a safety margin. If you anticipate an average traffic growth rate of 40%, you might consider overprovisioning by 50%, as calculated by the formula: txt Copy 1-30%/1+40%=50% An effective overprovisioning method involves the use of pause pods. Pause pods are low-priority deployments that can be easily replaced by high-priority deployments. You create low priority pods that serve the sole purpose of reserving buffer space. When a high-priority pod requires space, the pause pods are removed and rescheduled on another node or a new node to accommodate the high priority pod. The following YAML shows an example pause pod manifest: yml Copy apiVersion: scheduling.k8s.io/v1 kind: PriorityClass metadata: name: overprovisioning value: -1 globalDefault: false description: "Priority class used by overprovisioning." --- apiVersion: apps/v1 kind: Deployment metadata: name: overprovisioning namespace: kube-system spec: replicas: 1 selector: matchLabels: run: overprovisioning template: metadata: labels: run: overprovisioning spec: priorityClassName: overprovisioning containers: - name: reserve-resources image: your-custome-pause-image resources: requests: cpu: 1 memory: 4Gi Node scaling and efficiency Best practice guidance: Carefully monitor resource utilization and scheduling policies to ensure nodes are being used efficiently. Node scaling allows you to dynamically adjust the number of nodes in your cluster based on workload demands. It's important to understand that adding more nodes to a cluster isn't always the best solution for improving performance. To ensure optimal performance, you should carefully monitor resource utilization and scheduling policies to ensure nodes are being used efficiently. Node images Best practice guidance: Use the latest node image version to ensure that you have the latest security patches and bug fixes. Using the latest node image version provides the best performance experience. AKS ships performance improvements within the weekly image releases. The latest daemonset images are cached on the latest VHD image, which provide lower latency benefits for node provisioning and bootstrapping. Falling behind on updates might have a negative impact on performance, so it's important to avoid large gaps between versions. Azure Linux The Azure Linux Container Host on AKS uses a native AKS image and provides a single place for Linux development. Every package is built from source and validated, ensuring your services run on proven components. Azure Linux is lightweight, only including the necessary set of packages to run container workloads. It provides a reduced attack surface and eliminates patching and maintenance of unnecessary packages. At its base layer, it has a Microsoft-hardened kernel tuned for Azure. This image is ideal for performance-sensitive workloads and platform engineers or operators that manage fleets of AKS clusters. Ubuntu 2204 The Ubuntu 2204 image is the default node image for AKS. It's a lightweight and efficient operating system optimized for running containerized workloads. This means that it can help reduce resource usage and improve overall performance. The image includes the latest security patches and updates, which help ensure that your workloads are protected from vulnerabilities. The Ubuntu 2204 image is fully supported by Microsoft, Canonical, and the Ubuntu community and can help you achieve better performance and security for your containerized workloads. Virtual machines (VMs) Best practice guidance: When selecting a VM, ensure the size and performance of the OS disk and VM SKU don't have a large discrepancy. A discrepancy in size or performance can cause performance issues and resource contention. Application performance is closely tied to the VM SKUs you use in your workloads. Larger and more powerful VMs, generally provide better performance. For mission critical or product workloads, we recommend using VMs with at least an 8-core CPU. VMs with newer hardware generations, like v4 and v5, can also help improve performance. Keep in mind that create and scale latency might vary depending on the VM SKUs you use. Use dedicated system node pools For scaling performance and reliability, we recommend using a dedicated system node pool. With this configuration, the dedicated system node pool reserves space for critical system resources such as system OS daemons. Your application workload can then run in a user node pool to increase the availability of allocatable resources for your application. This configuration also helps mitigate the risk of resource competition between the system and application. <Question> ================== According to this document you shouldn't use which two things in conjunction on the same CPU or memory sticks?

Use only the provided text for your answers.

What are some current challenges with our DHCP system as it stands?

Authentication for DHCP Messages Status of this Memo This document specifies an Internet standards track protocol for the Internet community, and requests discussion and suggestions for improvements. Please refer to the current edition of the "Internet Official Protocol Standards" (STD 1) for the standardization state and status of this protocol. Distribution of this memo is unlimited. Copyright Notice Copyright (C) The Internet Society (2001). All Rights Reserved. Abstract This document defines a new Dynamic Host Configuration Protocol (DHCP) option through which authorization tickets can be easily generated and newly attached hosts with proper authorization can be automatically configured from an authenticated DHCP server. DHCP provides a framework for passing configuration information to hosts on a TCP/IP network. In some situations, network administrators may wish to constrain the allocation of addresses to authorized hosts. Additionally, some network administrators may wish to provide for authentication of the source and contents of DHCP messages. 1. Introduction DHCP [1] transports protocol stack configuration parameters from centrally administered servers to TCP/IP hosts. Among those parameters are an IP address. DHCP servers can be configured to dynamically allocate addresses from a pool of addresses, eliminating a manual step in configuration of TCP/IP hosts. Some network administrators may wish to provide authentication of the source and contents of DHCP messages. For example, clients may be subject to denial of service attacks through the use of bogus DHCP servers, or may simply be misconfigured due to unintentionally instantiated DHCP servers. Network administrators may wish to constrain the allocation of addresses to authorized hosts to avoid denial of service attacks in "hostile" environments where the network Droms & Arbaugh Standards Track [Page 1] RFC 3118 Authentication for DHCP Messages June 2001 medium is not physically secured, such as wireless networks or college residence halls. This document defines a technique that can provide both entity authentication and message authentication. The current protocol combines the original Schiller-Huitema-Droms authentication mechanism defined in a previous work in progress with the "delayed authentication" proposal developed by Bill Arbaugh. 1.1 DHCP threat model The threat to DHCP is inherently an insider threat (assuming a properly configured network where BOOTP ports are blocked on the enterprise’s perimeter gateways.) Regardless of the gateway configuration, however, the potential attacks by insiders and outsiders are the same. The attack specific to a DHCP client is the possibility of the establishment of a "rogue" server with the intent of providing incorrect configuration information to the client. The motivation for doing so may be to establish a "man in the middle" attack or it may be for a "denial of service" attack. There is another threat to DHCP clients from mistakenly or accidentally configured DHCP servers that answer DHCP client requests with unintentionally incorrect configuration parameters. The threat specific to a DHCP server is an invalid client masquerading as a valid client. The motivation for this may be for "theft of service", or to circumvent auditing for any number of nefarious purposes. The threat common to both the client and the server is the resource "denial of service" (DoS) attack. These attacks typically involve the exhaustion of valid addresses, or the exhaustion of CPU or network bandwidth, and are present anytime there is a shared resource. In current practice, redundancy mitigates DoS attacks the best. 1.2 Design goals These are the goals that were used in the development of the authentication protocol, listed in order of importance: 1. Address the threats presented in Section 1.1. 2. Avoid changing the current protocol. Droms & Arbaugh Standards Track [Page 2] RFC 3118 Authentication for DHCP Messages June 2001 3. Limit state required by the server. 4. Limit complexity (complexity breeds design and implementation errors). 1.3 Requirements Terminology The key words "MUST", "MUST NOT", "REQUIRED", "SHALL", "SHALL NOT", "SHOULD", "SHOULD NOT", "RECOMMENDED", "MAY" and "OPTIONAL" in this document are to be interpreted as described in RFC 2119 [5]. 1.4 DHCP Terminology This document uses the following terms: o "DHCP client" A DHCP client or "client" is an Internet host using DHCP to obtain configuration parameters such as a network address. o "DHCP server" A DHCP server or "server" is an Internet host that returns configuration parameters to DHCP clients. The code for the authentication option is 90, and the length field contains the length of the protocol, RDM, algorithm, Replay Detection fields and authentication information fields in octets.The protocol field defines the particular technique for authentication used in the option. New protocols are defined as described in Section 6. The algorithm field defines the specific algorithm within the technique identified by the protocol field. The Replay Detection field is per the RDM, and the authentication information field is per the protocol in use. The Replay Detection Method (RDM) field determines the type of replay detection used in the Replay Detection field. If the RDM field contains 0x00, the replay detection field MUST be set to the value of a monotonically increasing counter. Using a counter value such as the current time of day (e.g., an NTP-format timestamp [4]) can reduce the danger of replay attacks. This method MUST be supported by all protocols. 3. Interaction with Relay Agents Because a DHCP relay agent may alter the values of the ’giaddr’ and ’hops’ fields in the DHCP message, the contents of those two fields MUST be set to zero for the computation of any hash function over the message header. Additionally, a relay agent may append the DHCP relay agent information option 82 [7] as the last option in a message to servers. If a server finds option 82 included in a received message, the server MUST compute any hash function as if the option were NOT included in the message without changing the order of options. Whenever the server sends back option 82 to a relay agent, the server MUST not include the option in the computation of any hash function over the message. will be defined as separate protocols. 5. Delayed authentication If the protocol field is 1, the message is using the "delayed authentication" mechanism. In delayed authentication, the client requests authentication in its DHCPDISCOVER message and the server replies with a DHCPOFFER message that includes authentication information. This authentication information contains a nonce value generated by the source as a message authentication code (MAC) to provide message authentication and entity authentication. This document defines the use of a particular technique based on the HMAC protocol [3] using the MD5 hash [2]. 5.1 Management Issues The "delayed authentication" protocol does not attempt to address situations where a client may roam from one administrative domain to another, i.e., interdomain roaming. This protocol is focused on solving the intradomain problem where the out-of-band exchange of a shared secret is feasible. Replay Detection - as defined by the RDM field K - a secret value shared between the source and destination of the message; each secret has a unique identifier (secret ID) secret ID - the unique identifier for the secret value used to generate the MAC for this message HMAC-MD5 - the MAC generating function [3, 2]. The sender computes the MAC using the HMAC generation algorithm [3] and the MD5 hash function [2]. The entire DHCP message (except as noted below), including the DHCP message header and the options field, is used as input to the HMAC-MD5 computation function. The ’secret ID’ field MUST be set to the identifier of the secret used to generate the MAC. DISCUSSION: Algorithm 1 specifies the use of HMAC-MD5. Use of a different technique, such as HMAC-SHA, will be specified as a separate protocol. Delayed authentication requires a shared secret key for each client on each DHCP server with which that client may wish to use the DHCP protocol. Each secret key has a unique identifier that can be used by a receiver to determine which secret was used to generate the MAC in the DHCP message. Therefore, delayed authentication may not scale well in an architecture in which a DHCP client connects to multiple administrative domains. 5.3 Message validation To validate an incoming message, the receiver first checks that the value in the replay detection field is acceptable according to the replay detection method specified by the RDM field. Next, the receiver computes the MAC as described in [3]. The receiver MUST set the ’MAC’ field of the authentication option to all 0s for computation of the MAC, and because a DHCP relay agent may alter the values of the ’giaddr’ and ’hops’ fields in the DHCP message, the contents of those two fields MUST also be set to zero for the computation of the MAC. If the MAC computed by the receiver does not match the MAC contained in the authentication option, the receiver MUST discard the DHCP message. Section 3 provides additional information on handling messages that include option 82 (Relay Agents). 5.4 Key utilization Each DHCP client has a key, K. The client uses its key to encode any messages it sends to the server and to authenticate and verify any messages it receives from the server. The client’s key SHOULD be initially distributed to the client through some out-of-band mechanism, and SHOULD be stored locally on the client for use in all authenticated DHCP messages. Once the client has been given its key, it SHOULD use that key for all transactions even if the client’s configuration changes; e.g., if the client is assigned a new network address. Each DHCP server MUST know, or be able to obtain in a secure manner, the keys for all authorized clients. If all clients use the same key, clients can perform both entity and message authentication for all messages received from servers. However, the sharing of keys is strongly discouraged as it allows for unauthorized clients to masquerade as authorized clients by obtaining a copy of the shared key. To authenticate the identity of individual clients, each client MUST be configured with a unique key. Appendix A describes a technique for key management. 5.5 Client considerations This section describes the behavior of a DHCP client using delayed authentication. 5.5.1 INIT state When in INIT state, the client uses delayed authentication as follows: 1. The client MUST include the authentication request option in its DHCPDISCOVER message along with a client identifier option [6] to identify itself uniquely to the server. 2. The client MUST perform the validation test described in section 5.3 on any DHCPOFFER messages that include authentication information. If one or more DHCPOFFER messages pass the validation test, the client chooses one of the offered configurations. Client behavior if no DHCPOFFER messages include authentication information or pass the validation test is controlled by local policy in the client. According to client policy, the client MAY choose to respond to a DHCPOFFER message that has not been authenticated. The decision to set local policy to accept unauthenticated messages should be made with care. Accepting an unauthenticated DHCPOFFER message can make the client vulnerable to spoofing and other attacks. If local users are not explicitly informed that the client has accepted an unauthenticated DHCPOFFER message, the users may incorrectly assume that the client has received an authenticated address and is not subject to DHCP attacks through unauthenticated messages. A client MUST be configurable to decline unauthenticated messages, and SHOULD be configured by default to decline unauthenticated messages. A client MAY choose to differentiate between DHCPOFFER messages with no authentication information and DHCPOFFER messages that do not pass the validation test; for example, a client might accept the former and discard the latter. If a client does accept an unauthenticated message, the client SHOULD inform any local users and SHOULD log the event. 3. The client replies with a DHCPREQUEST message that MUST include authentication information encoded with the same secret used by the server in the selected DHCPOFFER message. 4. If the client authenticated the DHCPOFFER it accepted, the client MUST validate the DHCPACK message from the server. The client MUST discard the DHCPACK if the message fails to pass validation and MAY log the validation failure. If the DHCPACK fails to pass validation, the client MUST revert to INIT state and returns to step 1. The client MAY choose to remember which server replied with a DHCPACK message that failed to pass validation and discard subsequent messages from that server. If the client accepted a DHCPOFFER message that did not include authentication information or did not pass the validation test, the client MAY accept an unauthenticated DHCPACK message from the server. 5.5.2 INIT-REBOOT state When in INIT-REBOOT state, the client MUST use the secret it used in its DHCPREQUEST message to obtain its current configuration to generate authentication information for the DHCPREQUEST message. The client MAY choose to accept unauthenticated DHCPACK/DHCPNAK messages if no authenticated messages were received. The client MUST treat the receipt (or lack thereof) of any DHCPACK/DHCPNAK messages as specified in section 3.2 of [1]. 5.5.3 RENEWING state When in RENEWING state, the client uses the secret it used in its initial DHCPREQUEST message to obtain its current configuration to generate authentication information for the DHCPREQUEST message. If client receives no DHCPACK messages or none of the DHCPACK messages pass validation, the client behaves as if it had not received a DHCPACK message in section 4.4.5 of the DHCP specification [1]. 5.5.4 REBINDING state When in REBINDING state, the client uses the secret it used in its initial DHCPREQUEST message to obtain its current configuration to generate authentication information for the DHCPREQUEST message. If client receives no DHCPACK messages or none of the DHCPACK messages pass validation, the client behaves as if it had not received a DHCPACK message in section 4.4.5 of the DHCP specification [1]. 5.5.5 DHCPINFORM message Since the client already has some configuration information, the client may also have established a shared secret value, K, with a server. Therefore, the client SHOULD use the authentication request as in a DHCPDISCOVER message when a shared secret value exists. The client MUST treat any received DHCPACK messages as it does DHCPOFFER messages, see section 5.5.1. 5.5.6 DHCPRELEASE message Since the client is already in the BOUND state, the client will have a security association already established with the server. Therefore, the client MUST include authentication information with the DHCPRELEASE message. 5.6 Server considerations This section describes the behavior of a server in response to client messages using delayed authentication. 5.6.1 General considerations Each server maintains a list of secrets and identifiers for those secrets that it shares with clients and potential clients. This information must be maintained in such a way that the server can: * Identify an appropriate secret and the identifier for that secret for use with a client that the server may not have previously communicated with * Retrieve the secret and identifier used by a client to which the server has provided previous configuration information Each server MUST save the counter from the previous authenticated message. A server MUST discard any incoming message which fails the replay detection check as defined by the RDM avoid replay attacks. DISCUSSION: The authenticated DHCPREQUEST message from a client in INIT-REBOOT state can only be validated by servers that used the same secret in their DHCPOFFER messages. Other servers will discard the DHCPREQUEST messages. Thus, only servers that used the secret selected by the client will be able to determine that their offered configuration information was not selected and the offered network address can be returned to the server’s pool of available addresses. The servers that cannot validate the DHCPREQUEST message will eventually return their offered network addresses to their pool of available addresses as described in section 3.1 of the DHCP specification [1]. 5.6.2 After receiving a DHCPDISCOVER message The server selects a secret for the client and includes authentication information in the DHCPOFFER message as specified in section 5, above. The server MUST record the identifier of the secret selected for the client and use that same secret for validating subsequent messages with the client. 5.6.3 After receiving a DHCPREQUEST message The server uses the secret identified in the message and validates the message as specified in section 5.3. If the message fails to pass validation or the server does not know the secret identified by the ’secret ID’ field, the server MUST discard the message and MAY choose to log the validation failure. If the message passes the validation procedure, the server responds as described in the DHCP specification. The server MUST include authentication information generated as specified in section 5.2. 5.6.4 After receiving a DHCPINFORM message The server MAY choose to accept unauthenticated DHCPINFORM messages, or only accept authenticated DHCPINFORM messages based on a site policy. When a client includes the authentication request in a DHCPINFORM message, the server MUST respond with an authenticated DHCPACK message. If the server does not have a shared secret value established with the sender of the DHCPINFORM message, then the server MAY respond with an unauthenticated DHCPACK message, or a DHCPNAK if the server does not accept unauthenticated clients based on the site policy, or the server MAY choose not to respond to the DHCPINFORM message. 6. IANA Considerations Section 2 defines a new DHCP option called the Authentication Option, whose option code is 90. This document specifies three new name spaces associated with the Authentication Option, which are to be created and maintained by IANA: Protocol, Algorithm and RDM. Initial values assigned from the Protocol name space are 0 (for the configuration token Protocol in section 4) and 1 (for the delayed authentication Protocol in section 5). Additional values from the Protocol name space will be assigned through IETF Consensus, as defined in RFC 2434 [8]. The Algorithm name space is specific to individual Protocols. That is, each Protocol has its own Algorithm name space. The guidelines for assigning Algorithm name space values for a particular protocol should be specified along with the definition of a new Protocol. For the configuration token Protocol, the Algorithm field MUST be 0. For the delayed authentication Protocol, the Algorithm value 1 is assigned to the HMAC-MD5 generating function as defined in section 5. Additional values from the Algorithm name space for Algorithm 1 will be assigned through IETF Consensus, as defined in RFC 2434. The initial value of 0 from the RDM name space is assigned to the use of a monotonically increasing value as defined in section 2. Additional values from the RDM name space will be assigned through IETF Consensus, as defined in RFC 2434. 7. References [1] Droms, R., "Dynamic Host Configuration Protocol", RFC 2131, March 1997. [2] Rivest, R., "The MD5 Message-Digest Algorithm", RFC 1321, April 1992.[3] Krawczyk H., Bellare, M. and R. Canetti, "HMAC: Keyed-Hashing for Message Authentication", RFC 2104, February 1997. [4] Mills, D., "Network Time Protocol (Version 3)", RFC 1305, March 1992. [5] Bradner, S., "Key words for use in RFCs to Indicate Requirement Levels", RFC 2219, March 1997. [6] Alexander, S. and R. Droms, "DHCP Options and BOOTP Vendor Extensions", RFC 2132, March 1997. [7] Patrick, M., "DHCP Relay Agent Information Option", RFC 3046, January 2001. [8] Narten, T. and H. Alvestrand, "Guidelines for Writing and IANA Considerations Section in RFCs", BCP 26, RFC 2434, October 1998. 8. Acknowledgments Jeff Schiller and Christian Huitema developed the original version of this authentication protocol in a terminal room BOF at the Dallas IETF meeting, December 1995. One of the editors (Droms) transcribed the notes from that discussion, which form the basis for this document. The editors appreciate Jeff’s and Christian’s patience in reviewing this document and its earlier drafts. The "delayed authentication" mechanism used in section 5 is due to Bill Arbaugh. The threat model and requirements in sections 1.1 and 1.2 come from Bill’s negotiation protocol proposal. The attendees of an interim meeting of the DHC WG held in June, 1998, including Peter Ford, Kim Kinnear, Glenn Waters, Rob Stevens, Bill Arbaugh, Baiju Patel, Carl Smith, Thomas Narten, Stewart Kwan, Munil Shah, Olafur Gudmundsson, Robert Watson, Ralph Droms, Mike Dooley, Greg Rabil and Arun Kapur, developed the threat model and reviewed several alternative proposals. The replay detection method field is due to Vipul Gupta. Other input from Bill Sommerfield is gratefully acknowledged. Thanks also to John Wilkins, Ran Atkinson, Shawn Mamros and Thomas Narten for reviewing earlier drafts of this document. 9. Security Considerations This document describes authentication and verification mechanisms for DHCP. 9.1 Protocol vulnerabilities The configuration token authentication mechanism is vulnerable to interception and provides only the most rudimentary protection against inadvertently instantiated DHCP servers. The delayed authentication mechanism described in this document is vulnerable to a denial of service attack through flooding with DHCPDISCOVER messages, which are not authenticated by this protocol. Such an attack may overwhelm the computer on which the DHCP server is running and may exhaust the addresses available for assignment by the DHCP server. Delayed authentication may also be vulnerable to a denial of service attack through flooding with authenticated messages, which may overwhelm the computer on which the DHCP server is running as the authentication keys for the incoming messages are computed. 9.2 Protocol limitations Delayed authentication does not support interdomain authentication. A real digital signature mechanism such as RSA, while currently computationally infeasible, would provide better security. Appendix A - Key Management Technique To avoid centralized management of a list of random keys, suppose K for each client is generated from the pair (client identifier [6], subnet address, e.g., 192.168.1.0), which must be unique to that client. That is, K = MAC(MK, unique-id), where MK is a secret master key and MAC is a keyed one-way function such as HMAC-MD5. Without knowledge of the master key MK, an unauthorized client cannot generate its own key K. The server can quickly validate an incoming message from a new client by regenerating K from the client-id. For known clients, the server can choose to recover the client’s K dynamically from the client-id in the DHCP message, or can choose to precompute and cache all of the Ks a priori. By deriving all keys from a single master key, the DHCP server does not need access to clear text passwords, and can compute and verify the keyed MACs without requiring help from a centralized authentication server. To avoid compromise of this key management system, the master key, MK, MUST NOT be stored by any clients. The client SHOULD only be given its key, K. If MK is compromised, a new MK SHOULD be chosen and all clients given new individual keys. Full Copyright Statement Copyright (C) The Internet Society (2001). All Rights Reserved. This document and translations of it may be copied and furnished to others, and derivative works that comment on or otherwise explain it or assist in its implementation may be prepared, copied, published and distributed, in whole or in part, without restriction of any kind, provided that the above copyright notice and this paragraph are included on all such copies and derivative works. However, this document itself may not be modified in any way, such as by removing the copyright notice or references to the Internet Society or other Internet organizations, except as needed for the purpose of developing Internet standards in which case the procedures for copyrights defined in the Internet Standards process must be followed, or as required to translate it into languages other than English. The limited permissions granted above are perpetual and will not be revoked by the Internet Society or its successors or assigns. This document and the information contained herein is provided on an "AS IS" basis and THE INTERNET SOCIETY AND THE INTERNET ENGINEERING TASK FORCE DISCLAIMS ALL WARRANTIES, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO ANY WARRANTY THAT THE USE OF THE INFORMATION HEREIN WILL NOT INFRINGE ANY RIGHTS OR ANY IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Acknowledgement Funding for the RFC Editor function is currently provided by the Internet Society.

Use only the provided text for your answers. What are some current challenges with our DHCP system as it stands? Authentication for DHCP Messages Status of this Memo This document specifies an Internet standards track protocol for the Internet community, and requests discussion and suggestions for improvements. Please refer to the current edition of the "Internet Official Protocol Standards" (STD 1) for the standardization state and status of this protocol. Distribution of this memo is unlimited. Copyright Notice Copyright (C) The Internet Society (2001). All Rights Reserved. Abstract This document defines a new Dynamic Host Configuration Protocol (DHCP) option through which authorization tickets can be easily generated and newly attached hosts with proper authorization can be automatically configured from an authenticated DHCP server. DHCP provides a framework for passing configuration information to hosts on a TCP/IP network. In some situations, network administrators may wish to constrain the allocation of addresses to authorized hosts. Additionally, some network administrators may wish to provide for authentication of the source and contents of DHCP messages. 1. Introduction DHCP [1] transports protocol stack configuration parameters from centrally administered servers to TCP/IP hosts. Among those parameters are an IP address. DHCP servers can be configured to dynamically allocate addresses from a pool of addresses, eliminating a manual step in configuration of TCP/IP hosts. Some network administrators may wish to provide authentication of the source and contents of DHCP messages. For example, clients may be subject to denial of service attacks through the use of bogus DHCP servers, or may simply be misconfigured due to unintentionally instantiated DHCP servers. Network administrators may wish to constrain the allocation of addresses to authorized hosts to avoid denial of service attacks in "hostile" environments where the network Droms & Arbaugh Standards Track [Page 1] RFC 3118 Authentication for DHCP Messages June 2001 medium is not physically secured, such as wireless networks or college residence halls. This document defines a technique that can provide both entity authentication and message authentication. The current protocol combines the original Schiller-Huitema-Droms authentication mechanism defined in a previous work in progress with the "delayed authentication" proposal developed by Bill Arbaugh. 1.1 DHCP threat model The threat to DHCP is inherently an insider threat (assuming a properly configured network where BOOTP ports are blocked on the enterprise’s perimeter gateways.) Regardless of the gateway configuration, however, the potential attacks by insiders and outsiders are the same. The attack specific to a DHCP client is the possibility of the establishment of a "rogue" server with the intent of providing incorrect configuration information to the client. The motivation for doing so may be to establish a "man in the middle" attack or it may be for a "denial of service" attack. There is another threat to DHCP clients from mistakenly or accidentally configured DHCP servers that answer DHCP client requests with unintentionally incorrect configuration parameters. The threat specific to a DHCP server is an invalid client masquerading as a valid client. The motivation for this may be for "theft of service", or to circumvent auditing for any number of nefarious purposes. The threat common to both the client and the server is the resource "denial of service" (DoS) attack. These attacks typically involve the exhaustion of valid addresses, or the exhaustion of CPU or network bandwidth, and are present anytime there is a shared resource. In current practice, redundancy mitigates DoS attacks the best. 1.2 Design goals These are the goals that were used in the development of the authentication protocol, listed in order of importance: 1. Address the threats presented in Section 1.1. 2. Avoid changing the current protocol. Droms & Arbaugh Standards Track [Page 2] RFC 3118 Authentication for DHCP Messages June 2001 3. Limit state required by the server. 4. Limit complexity (complexity breeds design and implementation errors). 1.3 Requirements Terminology The key words "MUST", "MUST NOT", "REQUIRED", "SHALL", "SHALL NOT", "SHOULD", "SHOULD NOT", "RECOMMENDED", "MAY" and "OPTIONAL" in this document are to be interpreted as described in RFC 2119 [5]. 1.4 DHCP Terminology This document uses the following terms: o "DHCP client" A DHCP client or "client" is an Internet host using DHCP to obtain configuration parameters such as a network address. o "DHCP server" A DHCP server or "server" is an Internet host that returns configuration parameters to DHCP clients. The code for the authentication option is 90, and the length field contains the length of the protocol, RDM, algorithm, Replay Detection fields and authentication information fields in octets.The protocol field defines the particular technique for authentication used in the option. New protocols are defined as described in Section 6. The algorithm field defines the specific algorithm within the technique identified by the protocol field. The Replay Detection field is per the RDM, and the authentication information field is per the protocol in use. The Replay Detection Method (RDM) field determines the type of replay detection used in the Replay Detection field. If the RDM field contains 0x00, the replay detection field MUST be set to the value of a monotonically increasing counter. Using a counter value such as the current time of day (e.g., an NTP-format timestamp [4]) can reduce the danger of replay attacks. This method MUST be supported by all protocols. 3. Interaction with Relay Agents Because a DHCP relay agent may alter the values of the ’giaddr’ and ’hops’ fields in the DHCP message, the contents of those two fields MUST be set to zero for the computation of any hash function over the message header. Additionally, a relay agent may append the DHCP relay agent information option 82 [7] as the last option in a message to servers. If a server finds option 82 included in a received message, the server MUST compute any hash function as if the option were NOT included in the message without changing the order of options. Whenever the server sends back option 82 to a relay agent, the server MUST not include the option in the computation of any hash function over the message. will be defined as separate protocols. 5. Delayed authentication If the protocol field is 1, the message is using the "delayed authentication" mechanism. In delayed authentication, the client requests authentication in its DHCPDISCOVER message and the server replies with a DHCPOFFER message that includes authentication information. This authentication information contains a nonce value generated by the source as a message authentication code (MAC) to provide message authentication and entity authentication. This document defines the use of a particular technique based on the HMAC protocol [3] using the MD5 hash [2]. 5.1 Management Issues The "delayed authentication" protocol does not attempt to address situations where a client may roam from one administrative domain to another, i.e., interdomain roaming. This protocol is focused on solving the intradomain problem where the out-of-band exchange of a shared secret is feasible. Replay Detection - as defined by the RDM field K - a secret value shared between the source and destination of the message; each secret has a unique identifier (secret ID) secret ID - the unique identifier for the secret value used to generate the MAC for this message HMAC-MD5 - the MAC generating function [3, 2]. The sender computes the MAC using the HMAC generation algorithm [3] and the MD5 hash function [2]. The entire DHCP message (except as noted below), including the DHCP message header and the options field, is used as input to the HMAC-MD5 computation function. The ’secret ID’ field MUST be set to the identifier of the secret used to generate the MAC. DISCUSSION: Algorithm 1 specifies the use of HMAC-MD5. Use of a different technique, such as HMAC-SHA, will be specified as a separate protocol. Delayed authentication requires a shared secret key for each client on each DHCP server with which that client may wish to use the DHCP protocol. Each secret key has a unique identifier that can be used by a receiver to determine which secret was used to generate the MAC in the DHCP message. Therefore, delayed authentication may not scale well in an architecture in which a DHCP client connects to multiple administrative domains. 5.3 Message validation To validate an incoming message, the receiver first checks that the value in the replay detection field is acceptable according to the replay detection method specified by the RDM field. Next, the receiver computes the MAC as described in [3]. The receiver MUST set the ’MAC’ field of the authentication option to all 0s for computation of the MAC, and because a DHCP relay agent may alter the values of the ’giaddr’ and ’hops’ fields in the DHCP message, the contents of those two fields MUST also be set to zero for the computation of the MAC. If the MAC computed by the receiver does not match the MAC contained in the authentication option, the receiver MUST discard the DHCP message. Section 3 provides additional information on handling messages that include option 82 (Relay Agents). 5.4 Key utilization Each DHCP client has a key, K. The client uses its key to encode any messages it sends to the server and to authenticate and verify any messages it receives from the server. The client’s key SHOULD be initially distributed to the client through some out-of-band mechanism, and SHOULD be stored locally on the client for use in all authenticated DHCP messages. Once the client has been given its key, it SHOULD use that key for all transactions even if the client’s configuration changes; e.g., if the client is assigned a new network address. Each DHCP server MUST know, or be able to obtain in a secure manner, the keys for all authorized clients. If all clients use the same key, clients can perform both entity and message authentication for all messages received from servers. However, the sharing of keys is strongly discouraged as it allows for unauthorized clients to masquerade as authorized clients by obtaining a copy of the shared key. To authenticate the identity of individual clients, each client MUST be configured with a unique key. Appendix A describes a technique for key management. 5.5 Client considerations This section describes the behavior of a DHCP client using delayed authentication. 5.5.1 INIT state When in INIT state, the client uses delayed authentication as follows: 1. The client MUST include the authentication request option in its DHCPDISCOVER message along with a client identifier option [6] to identify itself uniquely to the server. 2. The client MUST perform the validation test described in section 5.3 on any DHCPOFFER messages that include authentication information. If one or more DHCPOFFER messages pass the validation test, the client chooses one of the offered configurations. Client behavior if no DHCPOFFER messages include authentication information or pass the validation test is controlled by local policy in the client. According to client policy, the client MAY choose to respond to a DHCPOFFER message that has not been authenticated. The decision to set local policy to accept unauthenticated messages should be made with care. Accepting an unauthenticated DHCPOFFER message can make the client vulnerable to spoofing and other attacks. If local users are not explicitly informed that the client has accepted an unauthenticated DHCPOFFER message, the users may incorrectly assume that the client has received an authenticated address and is not subject to DHCP attacks through unauthenticated messages. A client MUST be configurable to decline unauthenticated messages, and SHOULD be configured by default to decline unauthenticated messages. A client MAY choose to differentiate between DHCPOFFER messages with no authentication information and DHCPOFFER messages that do not pass the validation test; for example, a client might accept the former and discard the latter. If a client does accept an unauthenticated message, the client SHOULD inform any local users and SHOULD log the event. 3. The client replies with a DHCPREQUEST message that MUST include authentication information encoded with the same secret used by the server in the selected DHCPOFFER message. 4. If the client authenticated the DHCPOFFER it accepted, the client MUST validate the DHCPACK message from the server. The client MUST discard the DHCPACK if the message fails to pass validation and MAY log the validation failure. If the DHCPACK fails to pass validation, the client MUST revert to INIT state and returns to step 1. The client MAY choose to remember which server replied with a DHCPACK message that failed to pass validation and discard subsequent messages from that server. If the client accepted a DHCPOFFER message that did not include authentication information or did not pass the validation test, the client MAY accept an unauthenticated DHCPACK message from the server. 5.5.2 INIT-REBOOT state When in INIT-REBOOT state, the client MUST use the secret it used in its DHCPREQUEST message to obtain its current configuration to generate authentication information for the DHCPREQUEST message. The client MAY choose to accept unauthenticated DHCPACK/DHCPNAK messages if no authenticated messages were received. The client MUST treat the receipt (or lack thereof) of any DHCPACK/DHCPNAK messages as specified in section 3.2 of [1]. 5.5.3 RENEWING state When in RENEWING state, the client uses the secret it used in its initial DHCPREQUEST message to obtain its current configuration to generate authentication information for the DHCPREQUEST message. If client receives no DHCPACK messages or none of the DHCPACK messages pass validation, the client behaves as if it had not received a DHCPACK message in section 4.4.5 of the DHCP specification [1]. 5.5.4 REBINDING state When in REBINDING state, the client uses the secret it used in its initial DHCPREQUEST message to obtain its current configuration to generate authentication information for the DHCPREQUEST message. If client receives no DHCPACK messages or none of the DHCPACK messages pass validation, the client behaves as if it had not received a DHCPACK message in section 4.4.5 of the DHCP specification [1]. 5.5.5 DHCPINFORM message Since the client already has some configuration information, the client may also have established a shared secret value, K, with a server. Therefore, the client SHOULD use the authentication request as in a DHCPDISCOVER message when a shared secret value exists. The client MUST treat any received DHCPACK messages as it does DHCPOFFER messages, see section 5.5.1. 5.5.6 DHCPRELEASE message Since the client is already in the BOUND state, the client will have a security association already established with the server. Therefore, the client MUST include authentication information with the DHCPRELEASE message. 5.6 Server considerations This section describes the behavior of a server in response to client messages using delayed authentication. 5.6.1 General considerations Each server maintains a list of secrets and identifiers for those secrets that it shares with clients and potential clients. This information must be maintained in such a way that the server can: * Identify an appropriate secret and the identifier for that secret for use with a client that the server may not have previously communicated with * Retrieve the secret and identifier used by a client to which the server has provided previous configuration information Each server MUST save the counter from the previous authenticated message. A server MUST discard any incoming message which fails the replay detection check as defined by the RDM avoid replay attacks. DISCUSSION: The authenticated DHCPREQUEST message from a client in INIT-REBOOT state can only be validated by servers that used the same secret in their DHCPOFFER messages. Other servers will discard the DHCPREQUEST messages. Thus, only servers that used the secret selected by the client will be able to determine that their offered configuration information was not selected and the offered network address can be returned to the server’s pool of available addresses. The servers that cannot validate the DHCPREQUEST message will eventually return their offered network addresses to their pool of available addresses as described in section 3.1 of the DHCP specification [1]. 5.6.2 After receiving a DHCPDISCOVER message The server selects a secret for the client and includes authentication information in the DHCPOFFER message as specified in section 5, above. The server MUST record the identifier of the secret selected for the client and use that same secret for validating subsequent messages with the client. 5.6.3 After receiving a DHCPREQUEST message The server uses the secret identified in the message and validates the message as specified in section 5.3. If the message fails to pass validation or the server does not know the secret identified by the ’secret ID’ field, the server MUST discard the message and MAY choose to log the validation failure. If the message passes the validation procedure, the server responds as described in the DHCP specification. The server MUST include authentication information generated as specified in section 5.2. 5.6.4 After receiving a DHCPINFORM message The server MAY choose to accept unauthenticated DHCPINFORM messages, or only accept authenticated DHCPINFORM messages based on a site policy. When a client includes the authentication request in a DHCPINFORM message, the server MUST respond with an authenticated DHCPACK message. If the server does not have a shared secret value established with the sender of the DHCPINFORM message, then the server MAY respond with an unauthenticated DHCPACK message, or a DHCPNAK if the server does not accept unauthenticated clients based on the site policy, or the server MAY choose not to respond to the DHCPINFORM message. 6. IANA Considerations Section 2 defines a new DHCP option called the Authentication Option, whose option code is 90. This document specifies three new name spaces associated with the Authentication Option, which are to be created and maintained by IANA: Protocol, Algorithm and RDM. Initial values assigned from the Protocol name space are 0 (for the configuration token Protocol in section 4) and 1 (for the delayed authentication Protocol in section 5). Additional values from the Protocol name space will be assigned through IETF Consensus, as defined in RFC 2434 [8]. The Algorithm name space is specific to individual Protocols. That is, each Protocol has its own Algorithm name space. The guidelines for assigning Algorithm name space values for a particular protocol should be specified along with the definition of a new Protocol. For the configuration token Protocol, the Algorithm field MUST be 0. For the delayed authentication Protocol, the Algorithm value 1 is assigned to the HMAC-MD5 generating function as defined in section 5. Additional values from the Algorithm name space for Algorithm 1 will be assigned through IETF Consensus, as defined in RFC 2434. The initial value of 0 from the RDM name space is assigned to the use of a monotonically increasing value as defined in section 2. Additional values from the RDM name space will be assigned through IETF Consensus, as defined in RFC 2434. 7. References [1] Droms, R., "Dynamic Host Configuration Protocol", RFC 2131, March 1997. [2] Rivest, R., "The MD5 Message-Digest Algorithm", RFC 1321, April 1992.[3] Krawczyk H., Bellare, M. and R. Canetti, "HMAC: Keyed-Hashing for Message Authentication", RFC 2104, February 1997. [4] Mills, D., "Network Time Protocol (Version 3)", RFC 1305, March 1992. [5] Bradner, S., "Key words for use in RFCs to Indicate Requirement Levels", RFC 2219, March 1997. [6] Alexander, S. and R. Droms, "DHCP Options and BOOTP Vendor Extensions", RFC 2132, March 1997. [7] Patrick, M., "DHCP Relay Agent Information Option", RFC 3046, January 2001. [8] Narten, T. and H. Alvestrand, "Guidelines for Writing and IANA Considerations Section in RFCs", BCP 26, RFC 2434, October 1998. 8. Acknowledgments Jeff Schiller and Christian Huitema developed the original version of this authentication protocol in a terminal room BOF at the Dallas IETF meeting, December 1995. One of the editors (Droms) transcribed the notes from that discussion, which form the basis for this document. The editors appreciate Jeff’s and Christian’s patience in reviewing this document and its earlier drafts. The "delayed authentication" mechanism used in section 5 is due to Bill Arbaugh. The threat model and requirements in sections 1.1 and 1.2 come from Bill’s negotiation protocol proposal. The attendees of an interim meeting of the DHC WG held in June, 1998, including Peter Ford, Kim Kinnear, Glenn Waters, Rob Stevens, Bill Arbaugh, Baiju Patel, Carl Smith, Thomas Narten, Stewart Kwan, Munil Shah, Olafur Gudmundsson, Robert Watson, Ralph Droms, Mike Dooley, Greg Rabil and Arun Kapur, developed the threat model and reviewed several alternative proposals. The replay detection method field is due to Vipul Gupta. Other input from Bill Sommerfield is gratefully acknowledged. Thanks also to John Wilkins, Ran Atkinson, Shawn Mamros and Thomas Narten for reviewing earlier drafts of this document. 9. Security Considerations This document describes authentication and verification mechanisms for DHCP. 9.1 Protocol vulnerabilities The configuration token authentication mechanism is vulnerable to interception and provides only the most rudimentary protection against inadvertently instantiated DHCP servers. The delayed authentication mechanism described in this document is vulnerable to a denial of service attack through flooding with DHCPDISCOVER messages, which are not authenticated by this protocol. Such an attack may overwhelm the computer on which the DHCP server is running and may exhaust the addresses available for assignment by the DHCP server. Delayed authentication may also be vulnerable to a denial of service attack through flooding with authenticated messages, which may overwhelm the computer on which the DHCP server is running as the authentication keys for the incoming messages are computed. 9.2 Protocol limitations Delayed authentication does not support interdomain authentication. A real digital signature mechanism such as RSA, while currently computationally infeasible, would provide better security. Appendix A - Key Management Technique To avoid centralized management of a list of random keys, suppose K for each client is generated from the pair (client identifier [6], subnet address, e.g., 192.168.1.0), which must be unique to that client. That is, K = MAC(MK, unique-id), where MK is a secret master key and MAC is a keyed one-way function such as HMAC-MD5. Without knowledge of the master key MK, an unauthorized client cannot generate its own key K. The server can quickly validate an incoming message from a new client by regenerating K from the client-id. For known clients, the server can choose to recover the client’s K dynamically from the client-id in the DHCP message, or can choose to precompute and cache all of the Ks a priori. By deriving all keys from a single master key, the DHCP server does not need access to clear text passwords, and can compute and verify the keyed MACs without requiring help from a centralized authentication server. To avoid compromise of this key management system, the master key, MK, MUST NOT be stored by any clients. The client SHOULD only be given its key, K. If MK is compromised, a new MK SHOULD be chosen and all clients given new individual keys. Full Copyright Statement Copyright (C) The Internet Society (2001). All Rights Reserved. This document and translations of it may be copied and furnished to others, and derivative works that comment on or otherwise explain it or assist in its implementation may be prepared, copied, published and distributed, in whole or in part, without restriction of any kind, provided that the above copyright notice and this paragraph are included on all such copies and derivative works. However, this document itself may not be modified in any way, such as by removing the copyright notice or references to the Internet Society or other Internet organizations, except as needed for the purpose of developing Internet standards in which case the procedures for copyrights defined in the Internet Standards process must be followed, or as required to translate it into languages other than English. The limited permissions granted above are perpetual and will not be revoked by the Internet Society or its successors or assigns. This document and the information contained herein is provided on an "AS IS" basis and THE INTERNET SOCIETY AND THE INTERNET ENGINEERING TASK FORCE DISCLAIMS ALL WARRANTIES, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO ANY WARRANTY THAT THE USE OF THE INFORMATION HEREIN WILL NOT INFRINGE ANY RIGHTS OR ANY IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Acknowledgement Funding for the RFC Editor function is currently provided by the Internet Society.

[question] [user request] ===================== [text] [context document] ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

What are the steps to apoptosis? What are the differentiating factors of necrosis and apoptosis? What are the different ways a cell can be affected by necrosis?

The stages of cell death differ depending on how a cell dies. When it comes to cell death, there are two main types to consider: Necrosis Vs. Apoptosis. Each of these involves a distinct process and has a distinct impact on the rest of the body.It holds utmost significance for researchers and they must choose the best Cell Separation technologies to get high-quality results. What is Cell Apoptosis? Apoptosis, or programmed cell death, is a normal growth and development mechanism within an organism. Because the cell participates in its own death, this process is also known as “cellular suicide.” Apoptosis contributes to the balance of cell multiplication. Uncontrolled cell growth will result in tumors and other problems if cells continue to reproduce without apoptosis. What Causes Apoptosis? Apoptosis is also known as programmed cell death because it is usually triggered by self-generated signals within a cell. It is a normal part of the cell cycle that begins with mitosis in cell reproduction. Caspases, enzymes found in all cells that cleave specific proteins to initiate cell death, mediate this process. Apoptosis Steps Apoptosis occurs in a gentle and controlled manner that has no negative impact on surrounding cells. A cell will expel moisture in order to dry out and condense until fragmentation occurs. Because the cell does not release into the extracellular environment, there are no morphological changes. Apoptotic bodies are small vesicles that form to transport the contents of the cell elsewhere. This enables cells to die gently and without causing inflammation. Apoptosis is signaled by chromatin condensation in a cell’s nucleus. This allows scientists to determine whether a cell is dying naturally or unnaturally. What is Cell Necrosis? Necrosis is a type of cell death that occurs when cells are exposed to extreme conditions. Cells may sustain damage to their internal environment when not under normal conditions. Tissues may deteriorate quickly and harshly. As a result, necrosis is commonly defined as unintentional cell death. Causes of Necrotic Cell Death External factors influencing the physiology of cells in the body cause necrosis. The following are some examples of necrotic cell death causes: Bacterial infection – Bacteria are microscopic organisms that can cause infections in the body if they enter through an airway or an open wound. They may be responsible for a variety of illnesses linked to unplanned cell death. Fungal infection – A fungus infection, also known as mycosis, occurs when any fungus infiltrates human tissues. This could result in skin or internal system diseases, as well as unprogrammed cell death. Pancreatitis – Pancreatitis is an inflammation of the pancreas, a gland in the body that helps regulate hormones and digestion. Protein denaturation – Protein denaturation occurs when weak bonds in proteins break down, causing the cells’ ability to function properly to suffer. Apoptosis Vs. Necrosis While both necrosis and apoptosis are mechanisms involved in multicellular organism cell death, they can be distinguished in a variety of ways. Apoptosis is regarded as a naturally occurring process, whereas necrosis is regarded as a pathological process. Pathological processes are often unregulated and are caused by toxins, infections, or traumas. Apoptosis is controlled and timely, making it predictable and beneficial to the host. Read Also: T Cell Isolation:A Comprehensive Guide to the Key Components The distinction between apoptosis and necrosis is also visible in the following factors: Process – Apoptosis is characterized by the shrinking of the cytoplasm, which results in the condensation of the nucleus. Necrosis occurs when the cytoplasm and mitochondria swell, resulting in cell lysis or a rupture in the cell membrane. Membrane Integrity – Blebbing is a defining feature of apoptosis. Blebbing occurs when a cell’s cytoskeleton degrades and the membrane bulges outward. Apoptotic blebs can form when cytoplasmic capsules detach from dying cells. This has no effect on the membrane’s integrity. The integrity of the membrane is loosened and thus significantly reduced, if not completely lost, during necrosis. Organelle Behavior – Organelles can continue to function even after a cell has died due to apoptosis. Organelles swell and disintegrate during necrotic cell death. After necrosis, organelles are no longer functional. Scope of Affected Cells – Apoptosis is a localized process that only destroys individual or single cells. Necrosis can spread to affect adjacent cell groups, causing damage beyond the initial site. Bodily Influence – Apoptosis is involved in controlling cell numbers and is frequently beneficial. Apoptosis, on the other hand, can cause diseases if it becomes abnormal in either direction. Necrosis, on the other hand, is always harmful and, if left untreated, can be fatal. In essence, apoptosis is planned cell death in which the cell actively destroys itself in order to maintain body functionality. Necrosis is an unintentional or unplanned cell death caused by the cell’s external environment, which impedes or interferes with body functions or health. Dangers of Cell Death in a Sample Cell enrichment assays can be hampered by both Necrosis & Apoptosis. The goal of studying a cell population is to collect as many healthy target cells as possible. Damaged cells do not behave the same as healthy cells and thus produce insufficient results. When collecting and storing cell samples, the longer a cell is kept outside of its preferred environment, the more likely it will die from necrosis. Cells can swell and die as a result of external factors. Dead cells can clump and cause more cell death in the surrounding population when using traditional cell separation methods such as magnetic-based cell sorting. It is critical to follow protocols, use gentle cell separation methods, and use additional products for increased downstream accuracy to maintain cell health and purity during cell separation assays. Harnessing Pluriselect’s Innovative Technology: Plurispin and PluriBead The first method for reducing cell death is to use a gentler isolation method. Traditional separation technologies, such as magnetic bead-based sorting, can be harsh on cells and result in less-than-desirable outcomes. Let’s see what Plurispin and PluriBead can do for us. Plurispin The pluriSpin system is a new negative cell isolation technology that can be used to isolate cells directly from whole blood, buffy coat, or cord blood. This new method isolates viable, untouched, and highly purified cells in a single step without the use of magnets or a column. As a result, there is less chance of activating or damaging the cells of interest. PluriBead PluriBead is a unique cell separation technology that does not rely on magnetic components. The steps are straightforward: Your pluriBeads (containing bound target cells) are sieved through a strainer; the pluriBeads containing your target cells remain on top, while the unwanted cells pass through. You have your target cells ready after detaching. Ready to get started? Stop wasting your valuable samples on inefficient processes and see the difference for yourself. Pluriselect’s innovative technology provides an incredibly fast, simple workflow that allows you to confidently move to downstream processing.

[question] What are the steps to apoptosis? What are the differentiating factors of necrosis and apoptosis? What are the different ways a cell can be affected by necrosis? ===================== [text] The stages of cell death differ depending on how a cell dies. When it comes to cell death, there are two main types to consider: Necrosis Vs. Apoptosis. Each of these involves a distinct process and has a distinct impact on the rest of the body.It holds utmost significance for researchers and they must choose the best Cell Separation technologies to get high-quality results. What is Cell Apoptosis? Apoptosis, or programmed cell death, is a normal growth and development mechanism within an organism. Because the cell participates in its own death, this process is also known as “cellular suicide.” Apoptosis contributes to the balance of cell multiplication. Uncontrolled cell growth will result in tumors and other problems if cells continue to reproduce without apoptosis. What Causes Apoptosis? Apoptosis is also known as programmed cell death because it is usually triggered by self-generated signals within a cell. It is a normal part of the cell cycle that begins with mitosis in cell reproduction. Caspases, enzymes found in all cells that cleave specific proteins to initiate cell death, mediate this process. Apoptosis Steps Apoptosis occurs in a gentle and controlled manner that has no negative impact on surrounding cells. A cell will expel moisture in order to dry out and condense until fragmentation occurs. Because the cell does not release into the extracellular environment, there are no morphological changes. Apoptotic bodies are small vesicles that form to transport the contents of the cell elsewhere. This enables cells to die gently and without causing inflammation. Apoptosis is signaled by chromatin condensation in a cell’s nucleus. This allows scientists to determine whether a cell is dying naturally or unnaturally. What is Cell Necrosis? Necrosis is a type of cell death that occurs when cells are exposed to extreme conditions. Cells may sustain damage to their internal environment when not under normal conditions. Tissues may deteriorate quickly and harshly. As a result, necrosis is commonly defined as unintentional cell death. Causes of Necrotic Cell Death External factors influencing the physiology of cells in the body cause necrosis. The following are some examples of necrotic cell death causes: Bacterial infection – Bacteria are microscopic organisms that can cause infections in the body if they enter through an airway or an open wound. They may be responsible for a variety of illnesses linked to unplanned cell death. Fungal infection – A fungus infection, also known as mycosis, occurs when any fungus infiltrates human tissues. This could result in skin or internal system diseases, as well as unprogrammed cell death. Pancreatitis – Pancreatitis is an inflammation of the pancreas, a gland in the body that helps regulate hormones and digestion. Protein denaturation – Protein denaturation occurs when weak bonds in proteins break down, causing the cells’ ability to function properly to suffer. Apoptosis Vs. Necrosis While both necrosis and apoptosis are mechanisms involved in multicellular organism cell death, they can be distinguished in a variety of ways. Apoptosis is regarded as a naturally occurring process, whereas necrosis is regarded as a pathological process. Pathological processes are often unregulated and are caused by toxins, infections, or traumas. Apoptosis is controlled and timely, making it predictable and beneficial to the host. Read Also: T Cell Isolation:A Comprehensive Guide to the Key Components The distinction between apoptosis and necrosis is also visible in the following factors: Process – Apoptosis is characterized by the shrinking of the cytoplasm, which results in the condensation of the nucleus. Necrosis occurs when the cytoplasm and mitochondria swell, resulting in cell lysis or a rupture in the cell membrane. Membrane Integrity – Blebbing is a defining feature of apoptosis. Blebbing occurs when a cell’s cytoskeleton degrades and the membrane bulges outward. Apoptotic blebs can form when cytoplasmic capsules detach from dying cells. This has no effect on the membrane’s integrity. The integrity of the membrane is loosened and thus significantly reduced, if not completely lost, during necrosis. Organelle Behavior – Organelles can continue to function even after a cell has died due to apoptosis. Organelles swell and disintegrate during necrotic cell death. After necrosis, organelles are no longer functional. Scope of Affected Cells – Apoptosis is a localized process that only destroys individual or single cells. Necrosis can spread to affect adjacent cell groups, causing damage beyond the initial site. Bodily Influence – Apoptosis is involved in controlling cell numbers and is frequently beneficial. Apoptosis, on the other hand, can cause diseases if it becomes abnormal in either direction. Necrosis, on the other hand, is always harmful and, if left untreated, can be fatal. In essence, apoptosis is planned cell death in which the cell actively destroys itself in order to maintain body functionality. Necrosis is an unintentional or unplanned cell death caused by the cell’s external environment, which impedes or interferes with body functions or health. Dangers of Cell Death in a Sample Cell enrichment assays can be hampered by both Necrosis & Apoptosis. The goal of studying a cell population is to collect as many healthy target cells as possible. Damaged cells do not behave the same as healthy cells and thus produce insufficient results. When collecting and storing cell samples, the longer a cell is kept outside of its preferred environment, the more likely it will die from necrosis. Cells can swell and die as a result of external factors. Dead cells can clump and cause more cell death in the surrounding population when using traditional cell separation methods such as magnetic-based cell sorting. It is critical to follow protocols, use gentle cell separation methods, and use additional products for increased downstream accuracy to maintain cell health and purity during cell separation assays. Harnessing Pluriselect’s Innovative Technology: Plurispin and PluriBead The first method for reducing cell death is to use a gentler isolation method. Traditional separation technologies, such as magnetic bead-based sorting, can be harsh on cells and result in less-than-desirable outcomes. Let’s see what Plurispin and PluriBead can do for us. Plurispin The pluriSpin system is a new negative cell isolation technology that can be used to isolate cells directly from whole blood, buffy coat, or cord blood. This new method isolates viable, untouched, and highly purified cells in a single step without the use of magnets or a column. As a result, there is less chance of activating or damaging the cells of interest. PluriBead PluriBead is a unique cell separation technology that does not rely on magnetic components. The steps are straightforward: Your pluriBeads (containing bound target cells) are sieved through a strainer; the pluriBeads containing your target cells remain on top, while the unwanted cells pass through. You have your target cells ready after detaching. Ready to get started? Stop wasting your valuable samples on inefficient processes and see the difference for yourself. Pluriselect’s innovative technology provides an incredibly fast, simple workflow that allows you to confidently move to downstream processing. https://uberstrainer.com/necrosis-vs-apoptosis-necrotic-cell-death-processes-apoptosis-steps/?srsltid=AfmBOorXdBv0i9nIoJj0a0EJSaMNsEfUera9WQT93AqxIR9fd5FupZMu ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

Write the answer in one paragraph, using full sentences. Use only the document provided. Use language that is easy to understand.

What is the clinical consensus on whether THC affects the brain during adolescence?

AHA SCIENTIFIC STATEMENT Use of Marijuana: Effect on Brain Health: A Scientific Statement From the American Heart Association The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Fernando D. Testai, MD, PhD, Chair; Philip B. Gorelick, MD, MPH, Vice Chair; Hugo J. Aparicio, MD, MPH; Francesca M. Filbey, PhD; Raul Gonzalez, PhD; Rebecca F. Gottesman, MD, PhD; Miriam Melis, PhD; Mariann R. Piano, RN, PhD; Tiziana Rubino, PhD; Sarah Y. Song, MD; on behalf of the American Heart Association Stroke Brain Health Science Subcommittee of the Stroke Council; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Lifestyle and Cardiometabolic Health; and Council on Peripheral Vascular Disease ABSTRACT: Marijuana is perceived as a harmless drug, and its recreational use has gained popularity among young individuals. The concentration of active ingredients in recreational formulations has gradually increased over time, and high-potency illicit cannabinomimetics have become available. Thus, the consumption of cannabis in the general population is rising. Data from preclinical models demonstrate that cannabinoid receptors are expressed in high density in areas involved in cognition and behavior, particularly during periods of active neurodevelopment and maturation. In addition, growing evidence highlights the role of endogenous cannabinoid pathways in the regulation of neurotransmitter release, synaptic plasticity, and neurodevelopment. In animal models, exogenous cannabinoids disrupt these important processes and lead to cognitive and behavioral abnormalities. These data correlate with the higher risk of cognitive impairment reported in some observational studies done in humans. It is unclear whether the effect of cannabis on cognition reverts after abstinence. However, this evidence, along with the increased risk of stroke reported in marijuana users, raises concerns about its potential long-term effects on cognitive function. This scientific statement reviews the safety of cannabis use from the perspective of brain health, describes mechanistically how cannabis may cause cognitive dysfunction, and advocates for a more informed health care worker and consumer about the potential for cannabis to adversely affect the brain. Key Words: AHA Scientific Statements ◼ brain ◼ cannabis ◼ cognition ◼ marijuana ◼ stroke M M arijuana, or cannabis, was considered an illicit drug for decades. However, in many parts of the world, cannabis has been legalized for medical use or decriminalized for recreational or medicinal applications. This shift in attitude has resulted in a rapid increase in its use. It has been estimated that ≈183 million people in the world used marijuana in 20141 and that 22 million met criteria for cannabis use disorder in 2016.2 In addition, according to the 2002 to 2019 National Survey on Drug Use and Health, the proportion of the US population >12 years of age who used marijuana in the past year increased gradually from 11% in 2002 to 18% in 2019.3 The use of marijuana has gained popularity, particularly among adolescents and young adults, with ≈36% of 12th graders and 43% of college students reporting having used it in the past year.4 In parallel, evidence suggests that the potency of cannabis products in the United States, measured by the concentration of the primary psychoactive constituent of marijuana, Δ9-tetrahydrocannabinol (THC), has gradually increased from ≈4% in 1995 to 15% in 2018.5 Cannabinoid receptors are expressed in high density in areas of the brain involved in executive function and The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. © 2022 American Heart Association, Inc. e176 April 2022 Stroke. 2022;53:e176–e187. DOI: 10.1161/STR.0000000000000396  memory such as the hippocampus, amygdala, and prefrontal cortex (PFC), particularly during periods of active brain development.6 Acute intoxication with cannabinoids can impair memory and behavioral inhibition.7 Cannabinoids also regulate anxiety and can produce psychosis- like effects.6 Evidence shows that age at exposure may influence the effect of cannabinoids on cognitive function. For example, the prenatal, perinatal, and adolescent periods may be particularly sensitive to these compounds.8 Data obtained in preclinical models have shown that cannabis and its associated signaling pathways regulate neurotransmission and play an active role in key cerebral processes, including neuroinflammation, neurogenesis, neural migration, synaptic pruning, and white matter development.6,9 Furthermore, experimental data show that cannabinoids can regulate the functioning of different cytochrome-P450 isoforms and uridine 5′-diphospho-glucuronosyltransferases. Thus, there is a potential risk for drug-to-drug interactions with medications commonly used by the elderly such as warfarin, antiarrhythmic agents, sedatives, and anticonvulsants.10 These factors have raised concerns about the potential effect of cannabis on cognitive vitality. The goal of this scientific statement is to critically appraise the safety of cannabis use from the perspective of brain health. CANNABIS AND ENDOCANNABINOIDS Anandamide and 2-arachidonoyl-glycerol are endogenous bioactive lipids that activate 2 G-protein–coupled receptors designated as cannabinoid receptor type 1 (CB1) and 2 (CB2). These lipids, called endocannabinoids, are not stored in vesicles but are synthesized on demand. The system formed by the cannabinoid receptors CB1 and CB2, endogenous ligands, and enzymes involved in their production and degradation is known as the endocannabinoid system (ECS). A detailed description of the composition and regulation of the ECS is beyond the scope of this publication; this topic has been reviewed extensively elsewhere.9,11,12 Phytocannabinoids are exogenous cannabinoids extracted from flowering plants from the cannabis genus, including Cannabis sativa, Cannabis indica, and Cannabis ruderalis. Whether these are species or subspecies is a matter of debate. More than 100 phytocannabinoids have been extracted from these plants, with THC and cannabidiol (CBD) being the most abundant. The relative concentration of THC and CBD in these strains is variable. In general, cannabis cultivars can be classified according to the cannabinoid produced as chemotype I (THC rich), II (THC/CBD balanced), III (CBD rich), IV (cannabigerol rich), or V (cannabinoid free).13 THC is a psychoactive alkaloid that signals through CB1 and CB2 receptors. Cannabinoid receptor type 1 is expressed abundantly in peripheral and central neural cells. In the periphery, CB1 localizes to sympathetic nerve terminals and sensory neurons. In the central nervous system, it is expressed mainly in presynaptic membranes of excitatory and inhibitory neurons, where it regulates the vesicular release of dopamine, GABA, and glutamate. In comparison, CB2 is expressed mainly in immune cells, including microglia.9 CBD is a nonpsychoactive cannabinoid that has antioxidant and anti-inflammatory properties. It is thought that CBD exerts some of the beneficial effects that phytocannabinoids have in Dravet syndrome and Lennox- Gastaut syndrome. Furthermore, studies done in preclinical models suggest that CBD is beneficial in Alzheimer disease, cerebral ischemia, multiple sclerosis, and other neurologic disorders.9,14 The therapeutic potential of CBD is being investigated in different clinical trials. Compared with THC, CBD signals through different pathways but does not activate CB1 and CB2. At low concentration, CBD blocks the orphan G-protein–coupled receptor-55, the equilibrative nucleoside transporter 1, and the transient receptor potential of melastatin type 8 channel. It also activates the serotonin (5-hydroxytryptamine) 1A receptor, the transient receptor potential of ankyrin type 1 channel, and α3 and α1 glycine receptors. At high concentration, CBD activates the nuclear peroxisome proliferator-activated receptor γ and the transient receptor potential of vanilloid types 1 and 2.12,14 Several cannabinoids have received approval in different countries for the treatment of specific medical conditions. In addition, high-potency synthetic cannabimimetics such as Spice are available in the illegal market (Table 1).15–17 NEUROBIOLOGICAL ACTIONS OF CANNABIS IN ANIMAL MODELS Molecular and cellular mechanisms underlying the effects of cannabis on the developing brain are inferred mainly from preclinical studies that permit controlling for social and environmental factors that could influence outcomes of interest. In addition, animal models allow the investigation of a range of human age-related behavioral factors (eg, novelty and sensation seeking, impulsivity, risk-taking behaviors) and key stages of neurodevelopment that are conserved across many mammalian species. However, many individual (eg, species, strain, age) and experimental (eg, design, drug, dose, delivery, regimen) variables, along with objective end points (eg, behavioral paradigm, experimental technique), have contributed to equivocal findings across studies. Nonetheless, experimental animal models of prenatal and adolescent cannabis exposure have proved fundamental in disclosing the underlying neurobiological mechanisms that might explain several clinical neuropsychiatric outcomes outlined here. Stroke. 2022;53:e176–e187. DOI: 10.1161/STR.0000000000000396 April 2022 e177  Table 1. Synthetic and Semisynthetic Cannabinoids Cannabinoid type Active ingredient Indication Medical15,16 Cesamet Nabilone (synthetic THC analog) Treatment of refractory cancer chemotherapy– associated nausea and vomiting*† Marinol (pill) Dronabinol (synthetic THC) Anorexia with weight loss in patients with AIDS or cancer*† Syndros (solution) Dronabinol (synthetic THC) Treatment of refractory cancer chemotherapy– associated nausea and vomiting*† Epidiolex Purified CBD Seizures associated with Lennox- Gastaut syndrome and Dravet syndrome in patients >1 y of age* Seizures associated with tuberous sclerosis complex in patients >1 y of age* Sativex Nabiximols (extract of THC, CBD, and other minor cannabinoids, terpenoids, and flavonoids) Adjunctive therapy for symptomatic treatment of refractory spasticity in adult patients with multiple sclerosis indication† Adjunctive treatment for symptomatic neuropathy in adult patients with multiple sclerosis indication† Adjunctive treatment for patients with advanced cancer with refractory severe pain indication† Illicit17 K2, Spice, Kronic, Kaos Originally synthesized to study the endocannabinoid system Bind cannabinoid receptors with high affinity and can cause hallucinations, agitation, psychosis, short-term memory loss, seizures, coagulopathy, and myocardial infarction CBD indicates cannabidiol; and THC, Δ9-tetrahydrocannabinol. *Approved by the US Food and Drug Administration. †Approved by the Health Products and Food Branch of Health Canada. Animal models have been used to examine the role of the ECS in the modulation of synaptic plasticity, a process that allows the brain to change and adapt to new information.18 The ECS modulates synaptic plasticity by affecting the strength of interneuronal connections and, ultimately, the functioning of neuronal networks. From the mechanistic standpoint, THC activates cannabinoid receptors in the brain, thus interfering with physiological actions of endocannabinoids. Spatial and time resolution of endocannabinoid production is pivotal for correct processing of different brain functions such as higher-order cognition, memory, reward, mood, and stress sensitiv ity.8,19,20 Consequently, THC, activating nonspecifically CB1 receptors in the brain, disrupts the fine-tuning of synaptic activity exerted by endocannabinoids, eventually impairing connectivity of neuronal networks and brain functionality. Although incompletely understood, the way in which THC disrupts memory and learning may be through its differential effect on neurotransmitter release and binding to CB1 receptors.19 For example, THC activates CB1 receptors located on GABAergic interneurons, which represent nearly three-quarters of the brain CB1 receptors, and astrocytes, resulting in the release of hippocampal glutamate. Concomitantly, THC affects the transmission of other neurotransmitters involved in the modulation of memory such as acetylcholine, adenosine, and serotonin.19,20 Furthermore, THC activation of CB1 receptors present on mitochondria leads to decreased cellular respiration and ATP supply.19 ATP is fundamental in maintaining and regulating neurotransmission, and its reduction might contribute to THC- induced cognitive deficits. Repeated exposure to cannabis, especially during the adolescent developmental period, may be especially harmful to brain health and cause structural, molecular, and functional alterations of brain circuits, particularly in the PFC and hippocampus.8,21,22 Long-term THC exposure induces CB1 receptor downregulation and desensitization that appear more intense and widespread after adolescent exposure as opposed to adulthood exposure. 22 Data obtained in experimental models showed that these effects could have implications for neurodevelopmental processes in which the ECS plays a role. Accordingly, long-term THC exposure during adolescence may disrupt dynamic changes occurring in glutamatergic and GABAergic systems, leading to excessive synaptic pruning (ie, loss of synaptic contacts), long-term dysfunction in prefrontal excitatory/inhibitory balance, and desynchronization of PFC neuronal networks, which also dysregulate the mesolimbic dopaminergic pathway (Figure).23 These changes may represent the molecular underpinnings of cognitive deficits and altered emotional reactivity and social behavior observed long after adolescent long-term THC exposure.22 Long-term changes in brain functionality induced by THC exposure during adolescence might also arise from epigenetic modifications with a marked reprogramming of the transcriptome, affecting mainly genes related to synaptic plasticity processes. 8,19 These effects have not been reported after adult THC exposure.19 In addition to the effects on neuron cellular and sub- cellular components, recent evidence suggests that alterations in glial cells have a key role in the actions of THC.24 Long-term THC exposure activates microglia and astrocytes to produce inflammatory cytokines. For example, long-term administration of THC during adolescence increased the microglial expression of the proinflammatory mediators tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2 by 60%, 130%, and 80%, respectively, and reduced the expression of the anti-inflammatory cytokine interleukin-10 by 30% in the PFC. The resulting neuroinflammatory response was associated with memory impairment during adulthood.25 Dose constitutes an additional important variable to consider. Most studies describe detrimental effects of e178 April 2022 Stroke. 2022;53:e176–e187. DOI: 10.1161/STR.0000000000000396  Figure. Effect of Δ9-tetrahydrocannabinol (THC) on different neurobiological processes. The effect of THC on the brain constitutes a continuum throughout the lifetime of an individual. However, 2 windows of brain vulnerability have been identified in preclinical models. The colored boxes represent the different processes that have been demonstrated to be affected on exposure to THC during these sensitive developmental periods. PFC indicates prefrontal cortex. THC in models of heavy cannabis use in middle adolescence. However, even lower doses may produce these same effects when administered earlier in adolescence.22 EFFECT OF PRENATAL EXPOSURE TO CANNABINOID AGONISTS A recent study examined associations between prenatal cannabis exposure (PCE) and various indicators of mental and neurocognitive health in a sample of 11489 youth.26 Self-report of maternal cannabis use during pregnancy was associated with various adverse outcomes among youth at 9 to 10 years of age, including poorer performance on tests of neurocognitive functioning and total intracranial volumes, even after controlling for potential confounders. Several reviews describe PCE sequelae in preclinical models.8,24,27–30 Here, we focus on mechanistic insights inferred from animal studies recapitulating the neuropsychiatric features of clinical outcomes.31 The detrimental effect of PCE on cognitive processing and emotional regulation of the progeny has been ascribed to changes in intrinsic and synaptic properties and plasticity of cortical (eg, PFC), limbic (eg, amygdala, hippocampus), and midbrain (eg, ventral tegmentum) regions. Changes in the balance of excitatory and inhibitory input strength, along with alterations in how principal neurons and interneurons receive, integrate, and convey information, have been observed in these neuroanatomic areas (Figure).8,24,27–30 Aberrant glutamatergic function is a common hallmark, as indexed by changes in the expression and function of ionotropic and metabotropic receptors and in dynamic regulation of glutamate levels by glutamate transporters at both synaptic cleft and extrasynaptic spaces. These changes depend largely on the alterations of endocannabinoid signaling pathways caused by exogenous cannabinoids during development and throughout ontogenesis (eg, neural proliferation, survival, directional axonal growth).8,24,27–30 Defects in ECS function also may account for the interneuronopathy observed in many brain regions of PCE offspring, a phenomenon often more prominent in female than in male animals.8,27–29 In the PFC, this persistent inhibitory circuit deficit also is associated with a delayed switch of GABA from its excitatory role early in development to a classic inhibitory function exerted throughout the central nervous system later in life.8,29 This is particularly relevant because the GABA switch represents a critical milestone during neurodevelopment. Any alteration in the normal and predictable temporal sequence of these periods such as delays, stalls, or accelerations imposed by PCE may lead to perturbations of offspring cognitive processing and emotional behavior.8,29 It was observed that marijuana use leads to dysregulation of monoaminergic pathways and stress response  systems.8,27–29 PCE hampers the maturation of mono- amines, which also exert trophic actions on target neurons and afferent terminals. This phenomenon may depend on epigenetic modifications and may be implicated in aberrant reward signaling. Furthermore, PCE is associated with an endophenotype in the offspring, which displays protracted dysregulation of stress responsivity that is not explained by glucocorticoid levels. A susceptibility to acute and chronic stress is tied to many psychiatric disorders, ranging from depressed mood and psychosis to substance use disorders and anxiety. A deeper understanding of how PCE interferes with endocannabinoid signaling during neurodevelopment would allow us to explore potential interventions aimed at restoring or reprogramming the hierarchical progression of developmental milestones. EFFECTS OF MARIJUANA USE ON HUMAN COGNITION Acute intoxication from marijuana is associated with impairment of working and episodic memory, behavioral disinhibition, and impulsivity, which can affect performance in real-world activities.6 For example, a meta-analysis from 2016 showed that the odds of being involved in a motor vehicle accident was increased 36% in cannabis users relative to nonusers.32 In addition, a crossover clinical trial published in 2020 investigated the effect of different cannabis products in relation to on-road driving tests. The SD of lateral position, a measure of lane weaving, swerving, and overcorrection, was 20.29 cm at 40 to 100 minutes after inhalation of THC-dominant cannabis and 21.09 cm after inhalation of a mixture of THC and CBD. It is interesting to note that the SD of lateral position after inhalation of CBD-dominant cannabis was similar to that in the placebo group (18.21 cm versus 18.26 cm).33 These observations illustrate the differential short- term effect of THC and CBD on cognition. Evidence also suggests that the short-term effects of cannabinoids are transient and can be influenced by the development of tolerance and the use of other drugs. The long-term effect of cannabis on cognition, however, is less well established. Recent meta-analyses report residual effects of cannabis use on neurocognition, consistent with prior research.34 A meta-analysis by Lovell et al35 in 2020 focused on adult near-daily cannabis use for >2 years and found global neurocognition among users (n=849) to be about one-quarter of an SD worse than that of nonusers (n=764). Four of the 7 domains investigated (decision-making, verbal learning, retention, executive function) showed significant effect sizes ranging from Hedges g=−0.52 to −0.18. A meta- analysis of cannabis users <26 years of age (n=2152) and nonusers (n=6575) also showed a one-quarter of an SD difference in global neurocognitive performance but with more specific domains affected,36 albeit with smaller effect size compared with that found by Lovell et al.35 Both lacked support for worse neurocognition in early adolescence in that neither found that age at onset of cannabis use influenced the association between exposure and cognitive performance. In contrast to these meta-analyses, large longitudinal studies provide stronger causal inferences by examining change over time. In the CARDIA study (Coronary Artery Risk Development in Young Adults), 3385 participants 18 to 30 years of age were followed up longitudinally. Marijuana use was assessed periodically in the 25-year follow-up. In addition, cognitive assessment was completed 25 years after inception. In this study, cumulative years of exposure to marijuana was associated with worse verbal memory (0.13 lower SD in the verbal memory test for each additional 5 years of exposure to marijuana).37 Longitudinal co-twin studies use a research design that additionally controls for shared variance from genetic and environmental factors. Two large longitudinal twin studies (n=3066) with neurocognitive measures collected before (at 9–12 years of age) and after (17–20 years of age) cannabis exposure reported that declines in vocabulary and general knowledge were associated with being a cannabis user but not with amount of cannabis consumed. 38 Twins discordant for cannabis use showed no differences in IQ declines. Thus, differences were likely caused by shared risk factors. Using a similar design, Meier et al39 reported that lower IQ predated cannabis use with no evidence of actual IQ declines among 1989 twins assessed at 5, 12, and 18 years of age. Ross et al40 evaluated other aspects of neurocognition among 856 individual twins and reported only 1 within-family effect of 70 tested. Specifically, frequency of cannabis use at 17 years of age was associated with poorer executive functioning at 23 years of age, but executive functioning problems predating cannabis use could not be ruled out. Magnetic resonance imaging (MRI) techniques demonstrate differential associations of cannabis use with brain structure and function. In terms of brain structure, alterations related to cannabis use have been mixed. In a longitudinal study including 1598 MRIs done in adolescents at baseline and the 5-year follow-up, a dose- dependent association was observed between cannabis use and PFC thinning.41 On the other hand, although a meta-analysis found that regular cannabis consumption was associated with smaller hippocampal (standardized mean difference, 0.14 [95% CI, 0.02–0.27]), medial orbitofrontal cortex (standardized mean difference, 0.30 [95% CI, 0.15–0.45]), and lateral orbitofrontal cortex (standardized mean difference, 0.19 [95% CI, 0.07–0.32]) volumes relative to nonuse, brain volumes were not associated with cannabis use duration and dosage. 42 Other large studies have reported null effects. In 2 e180 April 2022 Stroke. 2022;53:e176–e187. DOI: 10.1161/STR.0000000000000396  large twin samples from the United States (n=474) and Australia (n=622), cannabis use was unrelated to volumes of the thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala, and nucleus accumbens.43 A multisite study of cortical surface measures (n=262) reported no difference in cortical thickness, surface area, and gyrification index in cannabis users versus nonusers, in cannabis dependence versus nondependence versus nonusers, and in early adolescent versus late adolescent onset of cannabis use versus nonuse.44 Thus, brain structural abnormalities related to cannabis use are inconsistent. Functional MRI studies report more robust effects, particularly after prolonged cannabis use. A meta-analysis of task-based functional MRI studies in current adult and adolescent users found abnormalities in activation in both age groups. Relative to nonusing control subjects, adult cannabis users had greater brain activation in the superior (seed-based d mapping [SDM-Z], 1.561; P<0.002) and posterior (SDM-Z, 1.479; P<0.003) transverse temporal and inferior frontal gyri (SDM-Z, 1.568; P<0.002) and less activation in the striatum (SDM-Z, −1.843; P<0.001), insula (SDM-Z, −1.637; P<0.001), and middle frontal gyrus across different tasks. Adolescent cannabis users also had greater activation in the inferior parietal gyrus (SDM-Z, 1.06; P<0.001) and putamen (SDM-Z, 1.008; P<0.001) compared with nonusers across various tasks, suggesting compensatory neuroadaptive mechanisms.45 These functional abnormalities persist despite cessation of cannabis use and beyond the period when THC metabolites are detectable. A meta-analysis of the same adolescent studies found that >25-day abstinent adolescent cannabis users exhibited greater activation in the right inferior frontal gyrus in addition to other areas relevant for executive functioning and self-regulatory mechanisms.46 Several recent studies examined cannabis effects in populations with premorbid clinical risk factors and those using medical marijuana. A meta-analysis focused only on cannabis users with psychosis <25 years of age (n=529) and nonusing control subjects with psychosis (n=901). In this study, there were significant differences in 3 of 11 domains assessed (premorbid IQ, Hedges g=0.40 [standardized effect size]; current IQ, Hedges g=−0.17; working memory, Hedges g=−0.76).47 Among a sample of 215 adult patients with chronic pain provided daily herbal cannabis containing 12.5% THC for 1 year, no significant neurocognitive differences were found compared with 216 control subjects.48 This is in line with a study of patients with multiple sclerosis in response to oral dronabinol that found no significant differences in MRI-derived measures, including annual percentage of brain volume change and occurrence of new lesions, after 12 months of use.49 These clinical trials suggest no significant adverse effect of THC on neurocognitive symptoms in specific clinical populations. EFFECTS OF MARIJUANA USE ON CEREBROVASCULAR RISK AND DISEASE Cerebrovascular Risk Factors Similar to the literature linking marijuana use with cardiovascular outcomes,10 evidence that marijuana consumption increases the prevalence of specific cerebrovascular risk factors and disease is limited by a preponderance of observational studies, cross-sectional studies, case reports, and case series prone to potential publication and other biases. Postulated adverse effects of marijuana use may include sympathetic nervous system activation, blood pressure changes, platelet activation, and electrophysiological effects.50–52 Concomitant tobacco smoking and other substance use and abuse possibly contribute to these effects, which may be short term and have been studied mostly in low-risk populations such as younger adults. These factors may explain why many longitudinal studies linking marijuana use and cardiovascular or metabolic risk factors have been negative after multivariable adjustment for unhealthy behaviors such as diet and tobacco smoking.53–55 Hypertension, in particular, is an important risk factor for ischemic stroke, hemorrhagic stroke, and subarachnoid hemorrhage. With marijuana use, the most common acute reaction in humans is a decrease in blood pressure resulting from cannabinoid effects on the vasculature and autonomic nervous system.52 Despite this physiological reaction, limited studies using the National Health and Nutrition Examination Survey showed a modest association of recent cannabis use with higher systolic blood pressure and higher prevalence of hypertension among current users 30 to 59 years of age.56 Heavy users, defined as use of marijuana or hashish in >20 of the past 30 days, had higher odds of abnormal blood pressure compared with never-users. Although this difference remained statistically significant after adjustment for age, sex, race, ethnicity, body mass index, education, and survey year, it was no longer statistically significant after additional adjustment for current tobacco and binge alcohol use (adjusted odds ratio, 1.47 [95% CI, 0.99–2.16]).57 The relationship between marijuana use and elevated blood pressure, especially among heavy users, may drive longer-term associations with cerebrovascular outcomes, although this mechanism remains to be studied. Prior cardiovascular disease such as myocardial infarction (MI) or atrial fibrillation (AF) is also an important risk factor for stroke.58 Case reports of MI after marijuana use are mainly among young adults who lack vascular risk factors, with onset of MI shortly after use.59 Risk of MI was elevated 4.8-fold within an hour after smoking marijuana compared with periods of nonuse. This association demonstrates the potential role of marijuana as an acute trigger for cardiovascular disease.60 Over 25 years of follow-up, among 5113 adult participants in Stroke. 2022;53:e176–e187. DOI: 10.1161/STR.0000000000000396 April 2022 e181  the Coronary Artery Risk Development in Young Adults study, cumulative or recent marijuana use was not associated with coronary heart disease, stroke, or cardiovascular disease mortality.61 This finding contrasts with a population-based, multi-institutional database study that observed an increased risk of 3-year cumulative incidence of MI among marijuana users compared with control subjects (1.37% vs 0.54%; relative risk, 2.54 [95% CI, 2.45–2.61]).62 Similarly, marijuana use appears to be a trigger for AF. Data from the Nationwide Inpatient Sample show that the percentage of individuals with cannabis use disorder discharged in the postlegalization period (2010–2014) with the diagnosis of arrhythmia increased 31%.63 However, in a study of patients hospitalized for heart failure, marijuana users had a reduced odds of AF compared with nonusers (adjusted odds ratio, 0.87 [95% CI, 0.77–0.98]).50 Simultaneous use of cocaine, stimulants, and other drugs may be responsible for observations of AF among marijuana users, although this remains to be fully studied outside of observational and cross-sectional reports. Risk of Stroke and Transient Ischemic Attack Several case reports and case series mostly in young individuals suggest a relationship between recent and heavy cannabis use and risk of stroke.64–66 In contrast, and as reviewed below, findings among case-control studies,67 population-based studies,68 and studies conducted using outpatient69,70 or inpatient71,72 national databases or hospital electronic health records73 have been equivocal, depending on the study design, covariates considered in the analysis, and source of the population being studied. Inconsistent associations also can be attributable to the presence of comparison groups and whether adjustment of other important risk factors was considered, along with attention to potential confounding by other risk factor and lifestyle features between cannabis users and nonusers. In 1 case-control study using cannabis urine screens to identify cannabis users, the authors found an association between cannabis use and the risk of ischemic stroke and transient ischemic attack, but the association was not significant when tobacco use was included as a covariate (adjusted odds ratio, 1.59 [95% CI, 0.71– 3.70]) among subjects 18 to 55 years of age with and without stroke.67 Similarly, after adjustment for cigarette smoking and alcohol use, another study found no association between cannabis use in young adulthood and the occurrence of fatal and nonfatal stroke later in life among Swedish men in up to 38 years of follow-up.68 Data from studies that have examined more specifically the dose or amount of cannabis consumed within a designated time frame suggest that regular cannabis use may increase the risk of stroke. Using data from population-based surveys, investigators have reported that when no cannabis use was compared with heavy cannabis use in the past year, cannabis use was associated with an increased risk for the occurrence of nonfatal stroke and transient ischemic attack.70 Similarly, another study found that recent (within the past 30 days) and frequent (>10 d/mo) cannabis use was associated with increased risk for the occurrence of stroke compared with nonuse, whereas less frequent cannabis use (≤10 d/mo or less than weekly in the past year) was not associated with increased risk.69,70 Using several International Classification of Diseases, Ninth Revision, Clinical Modification codes for marijuana use, a Nationwide Inpatient Sample study found that cannabis use among men and women hospitalized between 2004 and 2011 was associated with a 17% increased relative risk for acute ischemic stroke in a multivariable-adjusted analysis. Concomitant use of tobacco with cannabis increased the risk to 31%.71 Similarly, a separate study using the Nationwide Inpatient Sample but between 2009 and 2010 observed a higher odds of stroke among cannabis users (odds ratio, 1.24 [95% CI, 1.14–1.34]).72 In contrast, investigators using electronic health record data from patients admitted to a single center between 2015 and 2017 found that testing positive for cannabis use was not associated with the risk of ischemic stroke compared with testing negative, even after adjustment for numerous confounders, including age, cigarette smoking, and comorbidities.73 There may be certain populations or scenarios in which cannabis use can be meaningfully linked to stroke. A study of a large longitudinal cohort of Canadian pregnant women that included >1 million participants between 1989 and 2019 with follow-up at 30 years observed that cannabis use disorder was associated with a doubling of risk for hemorrhagic stroke (hazard ratio, 2.08 [95% CI, 1.07–4.05]) but no increased risk for ischemic or other cerebrovascular disease.74 Because of the theoretical vasoactive effect of cannabis, its use has been implicated in some cases of reversible cerebral vasoconstriction syndrome, with 6 of 24 nonidiopathic reversible cerebral vasoconstriction syndrome cases at a Colorado stroke center attributed to marijuana use.75 In addition, an elevated risk of stroke from intracranial arterial stenosis has been described among young cannabis users 18 to 45 years of age wherein vasospasm or reversible cerebral vasoconstriction syndrome may be a potential mechanism. 76 Studies done in experimental models have shown that cannabinoids exert complex effects on cardiac contractility, vascular tone, and atherogenesis. Both vasodilatation and vasoconstriction responses were observed, depending on the experimental model and cannabinoid used. CB1 activation promotes inflammation, upregulates the production of reactive oxygen species, and activates proapoptotic pathways in endothelial cells and cardiomyocytes. In addition, it induces endothelial dysfunction and vascular smooth muscle cell proliferation and migration. These processes have been linked to cardiac dysfunction e182 April 2022 Stroke. 2022;53:e176–e187. DOI: 10.1161/STR.0000000000000396  and the development of atherosclerosis.52 This is in contrast to the atheroprotective role associated with CB2. Acute cardiovascular events and stroke also have been reported in patients using synthetic cannabinoids.77 Spice is associated with idiopathic thrombocytopenic purpura, which increases the risk of major hemorrhage.78 In addition, intracranial hemorrhage in Spice users has been linked to the presence of brodifacoum, an adulterant considered a superwarfarin.79 EDUCATION AND FUTURE DIRECTIONS Our understanding of the ramifications of cannabis consumption on brain health is limited but rapidly evolving. Observational studies have produced conflicting results in relation to the effect of marijuana on different outcomes of interest, including hypertension, AF, MI, and cognition. Several methodological factors may explain these apparent contradictions. First, given its historical classification as an illicit drug, the use of marijuana has been underreported for generations. The inclusion of marijuana users in the control group of observational studies that rely on self-reported use could underestimate its effect on brain health. Second, several behaviors such as smoking and alcohol use are associated with marijuana consumption and can influence stroke risk and brain connectivity.80,81 The often missing information on frequency of exposure to these factors limits our ability to determine with accuracy the independent effect of marijuana. Third, the time of exposure, frequency of use, and bioavailability of marijuana, which is affected by the route of administration, diet, and concomitant use of medications that may affect its metabolism, are reported inconsistently.10 Fourth, THC and CBD have different pharmacological effects. Although the use of THC has been associated with detrimental effects, CBD appears to have therapeutic potential in some neurologic disorders.9 The absolute and relative concentrations of these compounds differ according to the strain of cannabis plant and the methodology used to extract the active ingredients.82 Fifth, the gradual increase in the potency of marijuana used recreationally limits the relevance of older studies.5 Sixth, different factors impede the development of long-term placebo-controlled studies, including ethical reasons and the psychotropic effect of THC, which cannot be blinded. Social media may emphasize a beneficial role for marijuana, and the general population may perceive it as a harmless drug. However, the emerging evidence linking marijuana use to cardiovascular events and stroke, as well as the potential and demonstrated drug-to-drug interactions between marijuana and medications commonly used in the general population, calls for caution and highlights the potential importance of active surveillance programs.10,83 In addition, the high density of cannabinoid receptors in areas involved in executive function and memory, the dose-dependent detrimental effect of THC on working and episodic memory, and the role of Table 2. Key Summary Points Section Notes Actions of THC disrupts endocannabinoid signaling pathways and Cannabis affects synaptic plasticity. In the short term, this affects the in Animal strength of interneuronal connections; in the long term, it Models leads to changes in the functioning of neuronal networks. Exposure to THC during adolescence can lead to structural, molecular, and functional alterations of brain circuits, particularly in areas involved in cognition and behavior. Effect of In preclinical models, THC disrupts the normal signaling Prenatal of the endocannabinoid system during development and Exposure to throughout ontogenesis and results in abnormal neurotrans- Cannabinoid mission. Agonist Prenatal THC affects neuroanatomic areas associated with cognition and emotional regulation, including the PFC, limbic system, and ventral tegmentum of the midbrain. Effects of Acute intoxication with marijuana affects memory, behavior, Marijuana Use and impulsivity. on Human The long-term effect of cannabis on cognition may be Cognition domain specific. Neuroimaging studies have shown structural changes in cannabis users; however, the results are inconsistent. Functional changes may be observed in areas of the brain involved in cognition among cannabis users. Early exposure to cannabis may have a negative effect on cognitive function. Effects of Several studies have described an association between Marijuana cannabis use and increased risk of stroke. Use on Data from population survey studies indicate that the pat- Cerebrovastern (heavy vs less) and frequency (>10 d/mo) of cannabiscular Risk and use may increase the risk of stroke. Disease Cigarette smoking is common in cannabis users and may be an important modifier or confounder of the relationship between cannabis use and stroke risk. Given the potential role of cannabis as a vasoactive substance and its potential role in cardiac pathology and atherosclerosis development, cannabis use also may increase stroke risk via reversible cerebral vasoconstriction syndromes or may indirectly increase stroke risk. It is possible that differences among some study findings may be attributable to the years in which population cohorts were studied or recruited because most population cohorts were assembled before 2012. Over the past decade, strains of cannabis have been evolving, resulting in plants with high THC concentrations and some preparations that may have synthetic cannabinoids such as Spice, which may influence the association of cannabis use with stroke. Education The cumulative evidence collected in clinical and preclinical and Future studies suggests that the consumption of marijuana can have Directions a detrimental effect on brain health. The exact ramifications, however, have not been precisely established. Emerging evidence questions the widely accepted belief that marijuana is innocuous and suggests that cannabis, particularly THC, negatively affects brain health through direct and indirect mechanisms. Health care professionals and consumers should receive education on the potential beneficial and harmful effects associated with the use of marijuana, including the increased risk of stroke and cognitive decline. CBD indicates cannabidiol; PFC, prefrontal cortex; and THC, Δ9-tetrahydrocannabinol. cannabinoid-associated biochemical pathways on synaptic plasticity and neuronal development raise concern that long-term exposure to marijuana may affect brain health. There is lack of agreement on whether the effects of Stroke. 2022;53:e176–e187. DOI: 10.1161/STR.0000000000000396 April 2022 e183  marijuana resolve completely after months of abstinence. However, the disruption of endocannabinoid signaling pathways during the prenatal and perinatal periods and in adolescence may be detrimental to neurodevelopment. 6,8,9 Key points discussed in this scientific statement are summarized in Table 2. It should be noted that the overarching goal of this scientific statement was to discuss mechanisms by which marijuana use could influence brain health. However, as the field is developing, several important aspects require additional research. As an example, there is limited information comparing the differential effect of recreational, illicit, and medicinal uses of marijuana, as well as the type of cannabis product consumed. Similarly, the modulatory effects of social determinants of health and race and ethnicity on the interaction of brain health and marijuana use are largely unexplored. The latter area of research may be particularly important because communities of color in the United States may be disproportionately affected by natural and synthetic cannabinoids in relation to use and exposure and the legal implications of criminalization of marijuana.84 Public health efforts should be considered to raise awareness about the potential negative effects associated with the use of marijuana in the general population. Possible strategies include the use of standardized concentrations of biologically active components and health warning labels on available formulations. In addition, the use of marijuana should be individualized and closely monitored. Health care professionals and patients should receive unbiased education about the potential consequences of medicinal, recreational, and illicit marijuana use on brain health, particularly when the exposure occurs during vulnerable vital periods. It also may be important for professionals to monitor cognitive performance of Disclosures Writing Group Disclosures marijuana users and to review their medications to identify potential drug-to-drug interactions. Knowledgeable health care professionals will be able to properly educate potential or active marijuana users about its possible adverse effects, empowering them to make an informed decision that is based on unbiased data. ARTICLE INFORMATION The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest. This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on July 29, 2021, and the American Heart Association Executive Committee on September 5, 2021. A copy of the document is available at https://professional.heart.org/statements by using either “Search for Guidelines & Statements” or the “Browse by Topic” area. To purchase additional reprints, call 215-356-2721 or email [email protected]. The American Heart Association requests that this document be cited as follows: Testai FD, Gorelick PB, Aparicio HJ, Filbey FM, Gonzalez R, Gottesman RF, Melis M, Piano MR, Rubino T, Song SY; on behalf of the American Heart Association Stroke Brain Health Science Subcommittee of the Stroke Council; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Lifestyle and Cardiometabolic Health; and Council on Peripheral Vascular Disease. Use of marijuana: effect on brain health: a scientific statement from the American Heart Association. Stroke. 2022;53:e176–e187. doi: 10.1161/STR.0000000000000396 The expert peer review of AHA-commissioned documents (eg, scientific statements, clinical practice guidelines, systematic reviews) is conducted by the AHA Office of Science Operations. For more on AHA statements and guidelines development, visit https://professional.heart.org/statements. Select the “Guidelines & Statements” drop-down menu, then click “Publication Development.” Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at https://www.heart.org/permissions. A link to the “Copyright Permissions Request Form” appears in the second paragraph (https://www.heart.org/en/aboutus/ statements-and-policies/copyright-request-form). Writing group member Employment Research grant Other research support Speakers’ bureau/ honoraria Expert witness Ownership interest Consultant/ advisory board Other Fernando D. Testai University of Illinois at Chicago None None None None None None None Philip B. Gorelick Northwestern University None None None None None None None Hugo J. Aparicio Boston University School of Medicine None None None None None None None Francesca M. Filbey University of Texas at Dallas Center for Brain Health None None None None None None None Raul Gonzalez Florida International University None None None None None None None Rebecca F. Gottesman National Institutes of Health National Institute of Neurological Disorders and Stroke None None None None None None None Miriam Melis University of Cagliari (Italy) NIH* None None None None None None Mariann R. Piano Vanderbilt University School of Nursing None None None None None None None Tiziana Rubino University of Insubria (Italy) None None None None None None None Sarah Y. Song Rush University Medical Center None None None None None None None This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be “significant” if (a) the person receives $10000 or more during any 12-month period, or 5% or more of the person’s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity or owns $10000 or more of the fair market value of the entity. A relationship is considered to be “modest” if it is less than “significant” under the preceding definition. *Modest. e184 April 2022 Stroke. 2022;53:e176–e187. DOI: 10.1161/STR.0000000000000396  Reviewer Disclosures Other Speakers’ research bureau/ Expert Ownership Consultant/ Reviewer Employment Research grant support honoraria witness interest advisory board Other Mark J. Alberts Hartford HealthCare None None None None None None None Larry A. Allen University of Colorado PCORI†; NIH NHLBI None None None None Novartis*; Boston None School of Medicine (K23 HL105896)†; Scientific†; Cytoki- AHA (grant, SFRN)† netics*; Amgen* George Howard University of Alabama at Birmingham None None None None None None None Farzaneh A. Sorond Northwestern Univer-None None None None None None None sity, Feinberg School of Medicine This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all reviewers are required to complete and submit. A relationship is considered to be “significant” if (a) the person receives $10 000 or more during any 12-month period, or 5% or more of the person’s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $10 000 or more of the fair market value of the entity. A relationship is considered to be “modest” if it is less than “significant” under the preceding definition. *Modest. †Significant. REFERENCES 1. United Nations Office on Drugs and Crime. World drug report. 2015. Accessed February 10, 2021. https://www.unodc.org/unodc/en/ index.html 2. The global burden of disease attributable to alcohol and drug use in 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Psychiatry. 2018;5:987–1012. doi: 10.1016/S2215-0366(18)30337-7 3. US Department of Health and Human Services. 2019 NSDUH annual national report. 2020. Accessed February 9, 2021. https://www.samhsa. gov/data/report/2019-nsduh-annual-national-report 4. Johnston LD, Miech RA, O’Malley PM, Bachman JG, Schulenberg JE, Patrick ME. Monitoring the Future national survey results on drug use, 1975–2018: overview, key findings on adolescent drug use. 2019. Accessed February 9, 2021. https://eric.ed.gov/?id=ED594190 5. National Institutes of Health, National Institute on Drug Abuse. Marijuana potency. 2020. Accessed February 10, 2021. https://www.drugabuse.gov/ drug-topics/marijuana/marijuana-potency 6. Curran HV, Freeman TP, Mokrysz C, Lewis DA, Morgan CJ, Parsons LH. Keep off the grass? Cannabis, cognition and addiction. Nat Rev Neurosci. 2016;17:293–306. doi: 10.1038/nrn.2016.28 7. Mechoulam R, Parker LA. The endocannabinoid system and the brain. Annu Rev Psychol. 2013;64:21–47. doi: 10.1146/annurev-psych-113011-143739 8. Hurd YL, Manzoni OJ, Pletnikov MV, Lee FS, Bhattacharyya S, Melis M. Cannabis and the developing brain: insights into its long-lasting effects. J Neurosci. 2019;39:8250–8258. doi: 10.1523/JNEUROSCI.1165-19.2019 9. Cristino L, Bisogno T, Di Marzo V. Cannabinoids and the expanded endocannabinoid system in neurological disorders. Nat Rev Neurol. 2020;16:9–29. doi: 10.1038/s41582-019-0284-z 10. Page RL 2nd, Allen LA, Kloner RA, Carriker CR, Martel C, Morris AA, Piano MR, Rana JS, Saucedo JF; on behalf of the American Heart Association Clinical Pharmacology Committee and Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; Council on Basic Cardiovascular Sciences; Council on Cardiovascular and Stroke Nursing; Council on Epidemiology and Prevention; Council on Lifestyle and Cardiometabolic Health; and Council on Quality of Care and Outcomes Research. Medical marijuana, recreational cannabis, and cardiovascular health: a scientific statement from the American Heart Association. Circulation. 2020;142:e131–e152. doi: 10.1161/CIR.0000000000000883 11. Lu H, Mackie K. Review of the endocannabinoid system. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021;6:607–615. 12. Zou S, Kumar U. Cannabinoid receptors and the endocannabinoid system: signaling and function in the central nervous system. Int J Mol Sci. 2018;19:833. doi: 10.3390/ijms19030833 13. Romero P, Peris A, Vergara K, Matus JT. Comprehending and improving cannabis specialized metabolism in the systems biology era. Plant Sci. 2020;298:110571. doi: 10.1016/j.plantsci.2020.110571 14. Patel AD. Cannabinoids in neurologic illnesses. Neurol Clin. 2021;39:231– 241. doi: 10.1016/j.ncl.2020.09.012 15. US Food & Drug Administration. FDA regulation of cannabis and cannabis- derived products, including cannabidiol (CBD). 2021. Accessed February 12, 2021. https://www.fda.gov/news-events/public-health-focus/fda-regulation- cannabis-and-cannabis-derived-products-including-cannabidiol-cbd 16. Health Canada. Information for health care professionals: cannabis (marihuana, marijuana) and the cannabinoids. 2018. Accessed February 12, 2021. https://www.canada.ca/en/health-canada/services/drugs-medication/ cannabis/information-medical-practitioners/information-health-careprofessionals- cannabis-cannabinoids.html#fig 1 17. Zawilska JB, Wojcieszak J. Spice/K2 drugs: more than innocent substitutes for marijuana. Int J Neuropsychopharmacol. 2014;17:509–525. doi: 10.1017/S1461145713001247 18. Araque A, Castillo PE, Manzoni OJ, Tonini R. Synaptic functions of endocannabinoid signaling in health and disease. Neuropharmacology. 2017;124:13–24. doi: 10.1016/j.neuropharm.2017.06.017 19. Prini P, Zamberletti E, Manenti C, Gabaglio M, Parolaro D, Rubino T. Neurobiological mechanisms underlying cannabis-induced memory impairment. Eur Neuropsychopharmacol. 2020;36:181–190. doi: 10.1016/j. euroneuro.2020.02.002 20. Meyer HC, Lee FS, Gee DG. The role of the endocannabinoid system and genetic variation in adolescent brain development. Neuropsychopharmacology. 2018;43:21–33. doi: 10.1038/npp.2017.143 21. Zamberletti E, Rubino T. Impact of endocannabinoid system manipulation on neurodevelopmental processes relevant to schizophrenia. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021;6:616–626. doi: 10.1016/j. bpsc.2020.06.013 22. Higuera-Matas A, Ucha M, Ambrosio E. Long-term consequences of perinatal and adolescent cannabinoid exposure on neural and psychological processes. Neurosci Biobehav Rev. 2015;55:119–146. doi: 10.1016/j. neubiorev.2015.04.020 23. Renard J, Rushlow WJ, Laviolette SR. Effects of adolescent THC exposure on the prefrontal GABAergic system: implications for schizophrenia-related psychopathology. Front Psychiatry. 2018;9:281. doi: 10.3389/fpsyt.2018.00281 24. Melis M, Frau R, Kalivas PW, Spencer S, Chioma V, Zamberletti E, Rubino T, Parolaro D. New vistas on cannabis use disorder. Neuropharmacology. 2017;124:62–72. doi: 10.1016/j.neuropharm.2017.03.033 25. Zamberletti E, Gabaglio M, Prini P, Rubino T, Parolaro D. Cortical neuroinflammation contributes to long-term cognitive dysfunctions following adolescent delta-9-tetrahydrocannabinol treatment in female rats. Eur Neuropsychopharmacol. 2015;25:2404–2415. doi: 10.1016/j. euroneuro.2015.09.021 26. Paul SE, Hatoum AS, Fine JD, Johnson EC, Hansen I, Karcher NR, Moreau AL, Bondy E, Qu Y, Carter EB, et al. Associations between prenatal cannabis exposure and childhood outcomes: results from the ABCD study. JAMA Psychiatry. 2021;78:64–76. doi: 10.1001/jamapsychiatry.2020.2902 27. Alpár A, Di Marzo V, Harkany T. At the tip of an iceberg: prenatal marijuana and its possible relation to neuropsychiatric outcome in the offspring. Biol Psychiatry. 2016;79:e33–e45. doi: 10.1016/j.biopsych.2015.09.009 28. Scheyer AF, Melis M, Trezza V, Manzoni OJJ. Consequences of perinatal cannabis exposure. Trends Neurosci. 2019;42:871–884. doi: 10.1016/j. tins.2019.08.010  29. Tirado-Muñoz J, Lopez-Rodriguez AB, Fonseca F, Farré M, Torrens M, Viveros MP. Effects of cannabis exposure in the prenatal and adolescent periods: preclinical and clinical studies in both sexes. Front Neuroendocrinol. 2020;57:100841. doi: 10.1016/j.yfrne.2020.100841 30. Pinky PD, Bloemer J, Smith WD, Moore T, Hong H, Suppiramaniam V, Reed MN. Prenatal cannabinoid exposure and altered neurotransmission. Neuropharmacology. 2019;149:181–194. doi: 10.1016/j.neuropharm. 2019.02.018 31. Roncero C, Valriberas-Herrero I, Mezzatesta-Gava M, Villegas JL, Aguilar L, Grau-López L. Cannabis use during pregnancy and its relationship with fetal developmental outcomes and psychiatric disorders: a systematic review. Reprod Health. 2020;17:25. doi: 10.1186/s12978-020-0880-9 32. Rogeberg O, Elvik R. The effects of cannabis intoxication on motor vehicle collision revisited and revised. Addiction. 2016;111:1348–1359. doi: 10.1111/add.13347 33. Arkell TR, Vinckenbosch F, Kevin RC, Theunissen EL, McGregor IS, Ramaekers JG. Effect of cannabidiol and Δ9-tetrahydrocannabinol on driving performance: a randomized clinical trial. JAMA. 2020;324:2177–2186. doi: 10.1001/jama.2020.21218 34. National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice, Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda. The Health Effects of Cannabis and Cannabinoids. National Academies Press; 2017. 35. Lovell ME, Akhurst J, Padgett C, Garry MI, Matthews A. Cognitive outcomes associated with long-term, regular, recreational cannabis use in adults: a meta-analysis. Exp Clin Psychopharmacol. 2020;28:471–494. doi: 10.1037/pha0000326 36. Scott JC, Slomiak ST, Jones JD, Rosen AFG, Moore TM, Gur RC. Association of cannabis with cognitive functioning in adolescents and young adults: a systematic review and meta-analysis. JAMA Psychiatry. 2018;75:585– 595. doi: 10.1001/jamapsychiatry.2018.0335 37. Auer R, Vittinghoff E, Yaffe K, Künzi A, Kertesz SG, Levine DA, Albanese E, Whitmer RA, Jacobs DR Jr, Sidney S, et al. Association between lifetime marijuana use and cognitive function in middle age: the Coronary Artery Risk Development in Young Adults (CARDIA) study. JAMA Intern Med. 2016;176:352–361. doi: 10.1001/jamainternmed.2015.7841 38. Jackson NJ, Isen JD, Khoddam R, Irons D, Tuvblad C, Iacono WG, McGue M, Raine A, Baker LA. Impact of adolescent marijuana use on intelligence: results from two longitudinal twin studies. Proc Natl Acad Sci U S A. 2016;113:E500–E508. doi: 10.1073/pnas.1516648113 39. Meier MH, Caspi A, Danese A, Fisher HL, Houts R, Arseneault L, Moffitt TE. Associations between adolescent cannabis use and neuropsychological decline: a longitudinal co-twin control study. Addiction. 2018;113:257–265. doi: 10.1111/add.13946 40. Ross JM, Ellingson JM, Rhee SH, Hewitt JK, Corley RP, Lessem JM, Friedman NP. Investigating the causal effect of cannabis use on cognitive function with a quasi-experimental co-twin design. Drug Alcohol Depend. 2020;206:107712. doi: 10.1016/j.drugalcdep.2019.107712 41. Albaugh MD, Ottino-Gonzalez J, Sidwell A, Lepage C, Juliano A, Owens MM, Chaarani B, Spechler P, Fontaine N, Rioux P, et al. Association of cannabis use during adolescence with neurodevelopment. JAMA Psychiatry. 2021;78:1–11. 10.1001/jamapsychiatry.2021.1258 42. Lorenzetti V, Chye Y, Silva P, Solowij N, Roberts CA. Does regular cannabis use affect neuroanatomy? An updated systematic review and meta-analysis of structural neuroimaging studies. Eur Arch Psychiatry Clin Neurosci. 2019;269:59–71. doi: 10.1007/s00406-019-00979-1 43. Gillespie NA, Neale MC, Bates TC, Eyler LT, Fennema-Notestine C, Vassileva J, Lyons MJ, Prom-Wormley EC, McMahon KL, Thompson PM, et al. Testing associations between cannabis use and subcortical volumes in two large population-based samples. Addiction. 2018;113:1661–1672. doi: 10.1111/add.14252 44. Chye Y, Suo C, Lorenzetti V, Batalla A, Cousijn J, Goudriaan AE, Martin-Santos R, Whittle S, Solowij N, Yücel M. Cortical surface morphology in long-term cannabis users: a multi-site MRI study. Eur Neuropsychopharmacol. 2019;29:257–265. doi: 10.1016/j.euroneuro.2018.11.1110 45. Blest-Hopley G, Giampietro V, Bhattacharyya S. Residual effects of cannabis use in adolescent and adult brains: a meta-analysis of fMRI studies. Neurosci Biobehav Rev. 2018;88:26–41. doi: 10.1016/j.neubiorev.2018.03.008 46. Blest-Hopley G, Giampietro V, Bhattacharyya S. Regular cannabis use is associated with altered activation of central executive and default mode networks even after prolonged abstinence in adolescent users: results from a complementary meta-analysis. Neurosci Biobehav Rev. 2019;96:45–55. doi: 10.1016/j.neubiorev.2018.10.026 47. Bogaty SER, Lee RSC, Hickie IB, Hermens DF. Meta-analysis of neurocognition in young psychosis patients with current cannabis use. J Psychiatr Res. 2018;99:22–32. doi: 10.1016/j.jpsychires.2018.01.010 48. Ware MA, Wang T, Shapiro S, Collet JP; COMPASS Study Team. Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). J Pain. 2015;16:1233–1242. doi: 10.1016/j.jpain.2015.07.014 49. Ball S, Vickery J, Hobart J, Wright D, Green C, Shearer J, Nunn A, Cano MG, MacManus D, Miller D, et al. The Cannabinoid Use in Progressive Inflammatory brain Disease (CUPID) trial: a randomised double-blind placebo- controlled parallel-group multicentre trial and economic evaluation of cannabinoids to slow progression in multiple sclerosis. Health Technol Assess. 2015;19:vii–viii, 1–187. doi: 10.3310/hta19120 50. Rezkalla S, Kloner RA. Cardiovascular effects of marijuana. Trends Cardiovasc Med. 2019;29:403–407. doi: 10.1016/j.tcm.2018.11.004 51. DeFilippis EM, Bajaj NS, Singh A, Malloy R, Givertz MM, Blankstein R, Bhatt DL, Vaduganathan M. Marijuana use in patients with cardiovascular disease: JACC review topic of the week. J Am Coll Cardiol. 2020;75:320–332. doi: 10.1016/j.jacc.2019.11.025 52. Pacher P, Steffens S, Haskó G, Schindler TH, Kunos G. Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly. Nat Rev Cardiol. 2018;15:151–166. doi: 10.1038/nrcardio.2017.130 53. Rodondi N, Pletcher MJ, Liu K, Hulley SB, Sidney S; Coronary Artery Risk Development in Young Adults (CARDIA) Study. Marijuana use, diet, body mass index, and cardiovascular risk factors (from the CARDIA study). Am J Cardiol. 2006;98:478–484. doi: 10.1016/j.amjcard.2006.03.024 54. Meier MH, Pardini D, Beardslee J, Matthews KA. Associations between cannabis use and cardiometabolic risk factors: a longitudinal study of men. Psychosom Med. 2019;81:281–288. doi: 10.1097/PSY.0000000000000665 55. Ravi D, Ghasemiesfe M, Korenstein D, Cascino T, Keyhani S. Associations between marijuana use and cardiovascular risk factors and outcomes: a systematic review. Ann Intern Med. 2018;168:187–194. doi: 10.7326/M17-1548 56. Alshaarawy O, Elbaz HA. Cannabis use and blood pressure levels: United States National Health and Nutrition Examination Survey, 2005–2012. J Hypertens. 2016;34:1507–1512. doi: 10.1097/HJH.0000000000000990 57. Vidot DC, Powers M, Gonzalez R, Jayaweera DT, Roy S, Dong C, Messiah SE. Blood pressure and marijuana use: results from a decade of NHANES data. Am J Health Behav. 2019;43:887–897. doi: 10.5993/AJHB.43.5.2 58. Dufouil C, Beiser A, McLure LA, Wolf PA, Tzourio C, Howard VJ, Westwood AJ, Himali JJ, Sullivan L, Aparicio HJ, et al. Revised Framingham stroke risk profile to reflect temporal trends. Circulation. 2017;135:1145–1159. doi: 10.1161/CIRCULATIONAHA.115.021275 59. Chetty K, Lavoie A, Deghani P. A literature review of cannabis and myocardial infarction: what clinicians may not be aware of. CJC Open. 2021;3:12– 21. doi: 10.1016/j.cjco.2020.09.001 60. Mittleman MA, Lewis RA, Maclure M, Sherwood JB, Muller JE. Triggering myocardial infarction by marijuana. Circulation. 2001;103:2805–2809. doi: 10.1161/01.cir.103.23.2805 61. Reis JP, Auer R, Bancks MP, Goff DC Jr, Lewis CE, Pletcher MJ, Rana JS, Shikany JM, Sidney S. Cumulative lifetime marijuana use and incident cardiovascular disease in middle age: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Am J Public Health. 2017;107:601–606. doi: 10.2105/AJPH.2017.303654 62. Chami T, Kim CH. Cannabis abuse and elevated risk of myocardial infarction in the young: a population-based study. Mayo Clin Proc. 2019;94:1647– 1649. doi: 10.1016/j.mayocp.2019.05.008 63. Jaladi PR, Patel V, Kuduva Rajan S, Rashid W, Madireddy S, Ajibawo T, Imran S, Patel RS. Arrhythmia-related hospitalization and comorbid cannabis use disorder: trend analysis in US hospitals (2010-2014). Cureus. 2019;11:e5607. doi: 10.7759/cureus.5607 64. Tirkey NK, Gupta S. Acute antero-inferior wall ischaemia with acute ischaemic stroke caused by oral ingestion of cannabis in a young male. J Assoc Physicians India. 2016;64:93–94. 65. Volpon LC, Sousa CLMM, Moreira SKK, Teixeira SR, Carlotti APCP. Multiple cerebral infarcts in a young patient associated with marijuana use. J Addict Med. 2017;11:405–407. doi: 10.1097/ADM.0000000000000326 66. Šimůnek L, Krajina A, Herzig R, Vališ M. Cerebral infarction in young marijuana smokers: case reports. Acta Medica (Hradec Kralove). 2018;61:74–77. doi: 10.14712/18059694.2018.56 67. Barber PA, Pridmore HM, Krishnamurthy V, Roberts S, Spriggs DA, Carter KN, Anderson NE. Cannabis, ischemic stroke, and transient ischemic attack: a case-control study. Stroke. 2013;44:2327–2329. doi: 10.1161/STROKEAHA.113.001562 e186 April 2022 Stroke. 2022;53:e176–e187. DOI: 10.1161/STR.0000000000000396  68. Falkstedt D, Wolff V, Allebeck P, Hemmingsson T, Danielsson AK. Cannabis, tobacco, alcohol use, and the risk of early stroke: a population-based cohort study of 45 000 Swedish men. Stroke. 2017;48:265–270. doi: 10.1161/STROKEAHA.116.015565 69. Parekh T, Pemmasani S, Desai R. Marijuana use among young adults (18-44 years of age) and risk of stroke: a Behavioral Risk Factor Surveillance System Survey analysis. Stroke. 2020;51:308–310. doi: 10.1161/ STROKEAHA.119.027828 70. Hemachandra D, McKetin R, Cherbuin N, Anstey KJ. Heavy cannabis users at elevated risk of stroke: evidence from a general population survey. Aust NZ J Public Health. 2016;40:226–230. doi: 10.1111/1753-6405.12477 71. Rumalla K, Reddy AY, Mittal MK. Recreational marijuana use and acute ischemic stroke: a population-based analysis of hospitalized patients in the United States. J Neurol Sci. 2016;364:191–196. doi: 10.1016/j.jns.2016.01.066 72. Kalla A, Krishnamoorthy PM, Gopalakrishnan A, Figueredo VM. Cannabis use predicts risks of heart failure and cerebrovascular accidents: results from the National Inpatient Sample. J Cardiovasc Med (Hagerstown). 2018;19:480–484. doi: 10.2459/JCM.0000000000000681 73. San Luis CV, O’Hana S Nobleza C, Shekhar S, Sugg R, Villareal DJ, Mehta T, Gangadhara S. Association between recent cannabinoid use and acute ischemic stroke. Neurol Clin Pract. 2020;10:333–339. doi: 10.1212/CPJ.0000000000000888 74. Auger N, Paradis G, Low N, Ayoub A, He S, Potter BJ. Cannabis use disorder and the future risk of cardiovascular disease in parous women: a longitudinal cohort study. BMC Med. 2020;18:328. doi: 10.1186/ s12916-020-01804-6 75. Jensen J, Leonard J, Salottolo K, McCarthy K, Wagner J, Bar-Or D. The epidemiology of reversible cerebral vasoconstriction syndrome in patients at a Colorado comprehensive stroke center. J Vasc Interv Neurol. 2018;10:32–38. 76. Wolff V, Armspach JP, Beaujeux R, Manisor M, Rouyer O, Lauer V, Meyer N, Marescaux C, Geny B. High frequency of intracranial arterial steno- sis and cannabis use in ischaemic stroke in the young. Cerebrovasc Dis. 2014;37:438–443. doi: 10.1159/000363618 77. Wolff V, Jouanjus E. Strokes are possible complications of cannabinoids use. Epilepsy Behav. 2017;70(pt B):355–363. doi: 10.1016/j.yebeh.2017.01.031 78. Castaneira G, Rojas K, Galili Y, Field Z, Perez-Perez A, Madruga M, Carlan SJ. Idiopathic thrombocytopenic purpura induced by synthetic cannabinoid. J Addict Med. 2019;13:235–236. doi: 10.1097/ADM. 0000000000000485 79. Kelkar AH, Smith NA, Martial A, Moole H, Tarantino MD, Roberts JC. An outbreak of synthetic cannabinoid–associated coagulopathy in Illinois. N Engl J Med. 2018;379:1216–1223. doi: 10.1056/NEJMoa1807652 80. Hasin DS, Kerridge BT, Saha TD, Huang B, Pickering R, Smith SM, Jung J, Zhang H, Grant BF. Prevalence and correlates of DSM-5 cannabis use disorder, 2012-2013: findings from the National Epidemiologic Survey on Alcohol and Related Conditions-III. Am J Psychiatry. 2016;173:588–599. doi: 10.1176/appi.ajp.2015.15070907 81. Vergara VM, Weiland BJ, Hutchison KE, Calhoun VD. The impact of combinations of alcohol, nicotine, and cannabis on dynamic brain connectivity. Neuropsychopharmacology. 2018;43:877–890. doi: 10.1038/npp.2017.280 82. Brunt TM, van Genugten M, Höner-Snoeken K, van de Velde MJ, Niesink RJ. Therapeutic satisfaction and subjective effects of different strains of pharmaceutical-grade cannabis. J Clin Psychopharmacol. 2014;34:344– 349. doi: 10.1097/JCP.0000000000000129 83. Kocis PT, Vrana KE. Delta-9-tetrahydrocannabinol and cannabidiol drug- drug interactions. Med Cannabis Cannabinoids. 2020;3:61–73. doi: 10.1159/000507998 84. Wu LT, Zhu H, Swartz MS. Trends in cannabis use disorders among racial/ ethnic population groups in the United States. Drug Alcohol Depend. 2016;165:181–190. doi: 10.1016/j.drugalcdep.2016.06.002 Stroke. 2022;53:e176–e187. DOI: 10.1161/STR.0000000000000396 April 2022 e187 

Write the answer in one paragraph, using full sentences. Use only the document provided. Use language that is easy to understand. What is the clinical consensus on whether THC affects the brain during adolescence? AHA SCIENTIFIC STATEMENT Use of Marijuana: Effect on Brain Health: A Scientific Statement From the American Heart Association The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Fernando D. Testai, MD, PhD, Chair; Philip B. Gorelick, MD, MPH, Vice Chair; Hugo J. Aparicio, MD, MPH; Francesca M. Filbey, PhD; Raul Gonzalez, PhD; Rebecca F. Gottesman, MD, PhD; Miriam Melis, PhD; Mariann R. Piano, RN, PhD; Tiziana Rubino, PhD; Sarah Y. Song, MD; on behalf of the American Heart Association Stroke Brain Health Science Subcommittee of the Stroke Council; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Lifestyle and Cardiometabolic Health; and Council on Peripheral Vascular Disease ABSTRACT: Marijuana is perceived as a harmless drug, and its recreational use has gained popularity among young individuals. The concentration of active ingredients in recreational formulations has gradually increased over time, and high-potency illicit cannabinomimetics have become available. Thus, the consumption of cannabis in the general population is rising. Data from preclinical models demonstrate that cannabinoid receptors are expressed in high density in areas involved in cognition and behavior, particularly during periods of active neurodevelopment and maturation. In addition, growing evidence highlights the role of endogenous cannabinoid pathways in the regulation of neurotransmitter release, synaptic plasticity, and neurodevelopment. In animal models, exogenous cannabinoids disrupt these important processes and lead to cognitive and behavioral abnormalities. These data correlate with the higher risk of cognitive impairment reported in some observational studies done in humans. It is unclear whether the effect of cannabis on cognition reverts after abstinence. However, this evidence, along with the increased risk of stroke reported in marijuana users, raises concerns about its potential long-term effects on cognitive function. This scientific statement reviews the safety of cannabis use from the perspective of brain health, describes mechanistically how cannabis may cause cognitive dysfunction, and advocates for a more informed health care worker and consumer about the potential for cannabis to adversely affect the brain. Key Words: AHA Scientific Statements ◼ brain ◼ cannabis ◼ cognition ◼ marijuana ◼ stroke M M arijuana, or cannabis, was considered an illicit drug for decades. However, in many parts of the world, cannabis has been legalized for medical use or decriminalized for recreational or medicinal applications. This shift in attitude has resulted in a rapid increase in its use. It has been estimated that ≈183 million people in the world used marijuana in 20141 and that 22 million met criteria for cannabis use disorder in 2016.2 In addition, according to the 2002 to 2019 National Survey on Drug Use and Health, the proportion of the US population >12 years of age who used marijuana in the past year increased gradually from 11% in 2002 to 18% in 2019.3 The use of marijuana has gained popularity, particularly among adolescents and young adults, with ≈36% of 12th graders and 43% of college students reporting having used it in the past year.4 In parallel, evidence suggests that the potency of cannabis products in the United States, measured by the concentration of the primary psychoactive constituent of marijuana, Δ9-tetrahydrocannabinol (THC), has gradually increased from ≈4% in 1995 to 15% in 2018.5 Cannabinoid receptors are expressed in high density in areas of the brain involved in executive function and The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. © 2022 American Heart Association, Inc. e176 April 2022 Stroke. 2022;53:e176–e187. DOI: 10.1161/STR.0000000000000396  memory such as the hippocampus, amygdala, and prefrontal cortex (PFC), particularly during periods of active brain development.6 Acute intoxication with cannabinoids can impair memory and behavioral inhibition.7 Cannabinoids also regulate anxiety and can produce psychosis- like effects.6 Evidence shows that age at exposure may influence the effect of cannabinoids on cognitive function. For example, the prenatal, perinatal, and adolescent periods may be particularly sensitive to these compounds.8 Data obtained in preclinical models have shown that cannabis and its associated signaling pathways regulate neurotransmission and play an active role in key cerebral processes, including neuroinflammation, neurogenesis, neural migration, synaptic pruning, and white matter development.6,9 Furthermore, experimental data show that cannabinoids can regulate the functioning of different cytochrome-P450 isoforms and uridine 5′-diphospho-glucuronosyltransferases. Thus, there is a potential risk for drug-to-drug interactions with medications commonly used by the elderly such as warfarin, antiarrhythmic agents, sedatives, and anticonvulsants.10 These factors have raised concerns about the potential effect of cannabis on cognitive vitality. The goal of this scientific statement is to critically appraise the safety of cannabis use from the perspective of brain health. CANNABIS AND ENDOCANNABINOIDS Anandamide and 2-arachidonoyl-glycerol are endogenous bioactive lipids that activate 2 G-protein–coupled receptors designated as cannabinoid receptor type 1 (CB1) and 2 (CB2). These lipids, called endocannabinoids, are not stored in vesicles but are synthesized on demand. The system formed by the cannabinoid receptors CB1 and CB2, endogenous ligands, and enzymes involved in their production and degradation is known as the endocannabinoid system (ECS). A detailed description of the composition and regulation of the ECS is beyond the scope of this publication; this topic has been reviewed extensively elsewhere.9,11,12 Phytocannabinoids are exogenous cannabinoids extracted from flowering plants from the cannabis genus, including Cannabis sativa, Cannabis indica, and Cannabis ruderalis. Whether these are species or subspecies is a matter of debate. More than 100 phytocannabinoids have been extracted from these plants, with THC and cannabidiol (CBD) being the most abundant. The relative concentration of THC and CBD in these strains is variable. In general, cannabis cultivars can be classified according to the cannabinoid produced as chemotype I (THC rich), II (THC/CBD balanced), III (CBD rich), IV (cannabigerol rich), or V (cannabinoid free).13 THC is a psychoactive alkaloid that signals through CB1 and CB2 receptors. Cannabinoid receptor type 1 is expressed abundantly in peripheral and central neural cells. In the periphery, CB1 localizes to sympathetic nerve terminals and sensory neurons. In the central nervous system, it is expressed mainly in presynaptic membranes of excitatory and inhibitory neurons, where it regulates the vesicular release of dopamine, GABA, and glutamate. In comparison, CB2 is expressed mainly in immune cells, including microglia.9 CBD is a nonpsychoactive cannabinoid that has antioxidant and anti-inflammatory properties. It is thought that CBD exerts some of the beneficial effects that phytocannabinoids have in Dravet syndrome and Lennox- Gastaut syndrome. Furthermore, studies done in preclinical models suggest that CBD is beneficial in Alzheimer disease, cerebral ischemia, multiple sclerosis, and other neurologic disorders.9,14 The therapeutic potential of CBD is being investigated in different clinical trials. Compared with THC, CBD signals through different pathways but does not activate CB1 and CB2. At low concentration, CBD blocks the orphan G-protein–coupled receptor-55, the equilibrative nucleoside transporter 1, and the transient receptor potential of melastatin type 8 channel. It also activates the serotonin (5-hydroxytryptamine) 1A receptor, the transient receptor potential of ankyrin type 1 channel, and α3 and α1 glycine receptors. At high concentration, CBD activates the nuclear peroxisome proliferator-activated receptor γ and the transient receptor potential of vanilloid types 1 and 2.12,14 Several cannabinoids have received approval in different countries for the treatment of specific medical conditions. In addition, high-potency synthetic cannabimimetics such as Spice are available in the illegal market (Table 1).15–17 NEUROBIOLOGICAL ACTIONS OF CANNABIS IN ANIMAL MODELS Molecular and cellular mechanisms underlying the effects of cannabis on the developing brain are inferred mainly from preclinical studies that permit controlling for social and environmental factors that could influence outcomes of interest. In addition, animal models allow the investigation of a range of human age-related behavioral factors (eg, novelty and sensation seeking, impulsivity, risk-taking behaviors) and key stages of neurodevelopment that are conserved across many mammalian species. However, many individual (eg, species, strain, age) and experimental (eg, design, drug, dose, delivery, regimen) variables, along with objective end points (eg, behavioral paradigm, experimental technique), have contributed to equivocal findings across studies. Nonetheless, experimental animal models of prenatal and adolescent cannabis exposure have proved fundamental in disclosing the underlying neurobiological mechanisms that might explain several clinical neuropsychiatric outcomes outlined here. Stroke. 2022;53:e176–e187. DOI: 10.1161/STR.0000000000000396 April 2022 e177  Table 1. Synthetic and Semisynthetic Cannabinoids Cannabinoid type Active ingredient Indication Medical15,16 Cesamet Nabilone (synthetic THC analog) Treatment of refractory cancer chemotherapy– associated nausea and vomiting*† Marinol (pill) Dronabinol (synthetic THC) Anorexia with weight loss in patients with AIDS or cancer*† Syndros (solution) Dronabinol (synthetic THC) Treatment of refractory cancer chemotherapy– associated nausea and vomiting*† Epidiolex Purified CBD Seizures associated with Lennox- Gastaut syndrome and Dravet syndrome in patients >1 y of age* Seizures associated with tuberous sclerosis complex in patients >1 y of age* Sativex Nabiximols (extract of THC, CBD, and other minor cannabinoids, terpenoids, and flavonoids) Adjunctive therapy for symptomatic treatment of refractory spasticity in adult patients with multiple sclerosis indication† Adjunctive treatment for symptomatic neuropathy in adult patients with multiple sclerosis indication† Adjunctive treatment for patients with advanced cancer with refractory severe pain indication† Illicit17 K2, Spice, Kronic, Kaos Originally synthesized to study the endocannabinoid system Bind cannabinoid receptors with high affinity and can cause hallucinations, agitation, psychosis, short-term memory loss, seizures, coagulopathy, and myocardial infarction CBD indicates cannabidiol; and THC, Δ9-tetrahydrocannabinol. *Approved by the US Food and Drug Administration. †Approved by the Health Products and Food Branch of Health Canada. Animal models have been used to examine the role of the ECS in the modulation of synaptic plasticity, a process that allows the brain to change and adapt to new information.18 The ECS modulates synaptic plasticity by affecting the strength of interneuronal connections and, ultimately, the functioning of neuronal networks. From the mechanistic standpoint, THC activates cannabinoid receptors in the brain, thus interfering with physiological actions of endocannabinoids. Spatial and time resolution of endocannabinoid production is pivotal for correct processing of different brain functions such as higher-order cognition, memory, reward, mood, and stress sensitiv ity.8,19,20 Consequently, THC, activating nonspecifically CB1 receptors in the brain, disrupts the fine-tuning of synaptic activity exerted by endocannabinoids, eventually impairing connectivity of neuronal networks and brain functionality. Although incompletely understood, the way in which THC disrupts memory and learning may be through its differential effect on neurotransmitter release and binding to CB1 receptors.19 For example, THC activates CB1 receptors located on GABAergic interneurons, which represent nearly three-quarters of the brain CB1 receptors, and astrocytes, resulting in the release of hippocampal glutamate. Concomitantly, THC affects the transmission of other neurotransmitters involved in the modulation of memory such as acetylcholine, adenosine, and serotonin.19,20 Furthermore, THC activation of CB1 receptors present on mitochondria leads to decreased cellular respiration and ATP supply.19 ATP is fundamental in maintaining and regulating neurotransmission, and its reduction might contribute to THC- induced cognitive deficits. Repeated exposure to cannabis, especially during the adolescent developmental period, may be especially harmful to brain health and cause structural, molecular, and functional alterations of brain circuits, particularly in the PFC and hippocampus.8,21,22 Long-term THC exposure induces CB1 receptor downregulation and desensitization that appear more intense and widespread after adolescent exposure as opposed to adulthood exposure. 22 Data obtained in experimental models showed that these effects could have implications for neurodevelopmental processes in which the ECS plays a role. Accordingly, long-term THC exposure during adolescence may disrupt dynamic changes occurring in glutamatergic and GABAergic systems, leading to excessive synaptic pruning (ie, loss of synaptic contacts), long-term dysfunction in prefrontal excitatory/inhibitory balance, and desynchronization of PFC neuronal networks, which also dysregulate the mesolimbic dopaminergic pathway (Figure).23 These changes may represent the molecular underpinnings of cognitive deficits and altered emotional reactivity and social behavior observed long after adolescent long-term THC exposure.22 Long-term changes in brain functionality induced by THC exposure during adolescence might also arise from epigenetic modifications with a marked reprogramming of the transcriptome, affecting mainly genes related to synaptic plasticity processes. 8,19 These effects have not been reported after adult THC exposure.19 In addition to the effects on neuron cellular and sub- cellular components, recent evidence suggests that alterations in glial cells have a key role in the actions of THC.24 Long-term THC exposure activates microglia and astrocytes to produce inflammatory cytokines. For example, long-term administration of THC during adolescence increased the microglial expression of the proinflammatory mediators tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2 by 60%, 130%, and 80%, respectively, and reduced the expression of the anti-inflammatory cytokine interleukin-10 by 30% in the PFC. The resulting neuroinflammatory response was associated with memory impairment during adulthood.25 Dose constitutes an additional important variable to consider. Most studies describe detrimental effects of e178 April 2022 Stroke. 2022;53:e176–e187. DOI: 10.1161/STR.0000000000000396  Figure. Effect of Δ9-tetrahydrocannabinol (THC) on different neurobiological processes. The effect of THC on the brain constitutes a continuum throughout the lifetime of an individual. However, 2 windows of brain vulnerability have been identified in preclinical models. The colored boxes represent the different processes that have been demonstrated to be affected on exposure to THC during these sensitive developmental periods. PFC indicates prefrontal cortex. THC in models of heavy cannabis use in middle adolescence. However, even lower doses may produce these same effects when administered earlier in adolescence.22 EFFECT OF PRENATAL EXPOSURE TO CANNABINOID AGONISTS A recent study examined associations between prenatal cannabis exposure (PCE) and various indicators of mental and neurocognitive health in a sample of 11489 youth.26 Self-report of maternal cannabis use during pregnancy was associated with various adverse outcomes among youth at 9 to 10 years of age, including poorer performance on tests of neurocognitive functioning and total intracranial volumes, even after controlling for potential confounders. Several reviews describe PCE sequelae in preclinical models.8,24,27–30 Here, we focus on mechanistic insights inferred from animal studies recapitulating the neuropsychiatric features of clinical outcomes.31 The detrimental effect of PCE on cognitive processing and emotional regulation of the progeny has been ascribed to changes in intrinsic and synaptic properties and plasticity of cortical (eg, PFC), limbic (eg, amygdala, hippocampus), and midbrain (eg, ventral tegmentum) regions. Changes in the balance of excitatory and inhibitory input strength, along with alterations in how principal neurons and interneurons receive, integrate, and convey information, have been observed in these neuroanatomic areas (Figure).8,24,27–30 Aberrant glutamatergic function is a common hallmark, as indexed by changes in the expression and function of ionotropic and metabotropic receptors and in dynamic regulation of glutamate levels by glutamate transporters at both synaptic cleft and extrasynaptic spaces. These changes depend largely on the alterations of endocannabinoid signaling pathways caused by exogenous cannabinoids during development and throughout ontogenesis (eg, neural proliferation, survival, directional axonal growth).8,24,27–30 Defects in ECS function also may account for the interneuronopathy observed in many brain regions of PCE offspring, a phenomenon often more prominent in female than in male animals.8,27–29 In the PFC, this persistent inhibitory circuit deficit also is associated with a delayed switch of GABA from its excitatory role early in development to a classic inhibitory function exerted throughout the central nervous system later in life.8,29 This is particularly relevant because the GABA switch represents a critical milestone during neurodevelopment. Any alteration in the normal and predictable temporal sequence of these periods such as delays, stalls, or accelerations imposed by PCE may lead to perturbations of offspring cognitive processing and emotional behavior.8,29 It was observed that marijuana use leads to dysregulation of monoaminergic pathways and stress response  systems.8,27–29 PCE hampers the maturation of mono- amines, which also exert trophic actions on target neurons and afferent terminals. This phenomenon may depend on epigenetic modifications and may be implicated in aberrant reward signaling. Furthermore, PCE is associated with an endophenotype in the offspring, which displays protracted dysregulation of stress responsivity that is not explained by glucocorticoid levels. A susceptibility to acute and chronic stress is tied to many psychiatric disorders, ranging from depressed mood and psychosis to substance use disorders and anxiety. A deeper understanding of how PCE interferes with endocannabinoid signaling during neurodevelopment would allow us to explore potential interventions aimed at restoring or reprogramming the hierarchical progression of developmental milestones. EFFECTS OF MARIJUANA USE ON HUMAN COGNITION Acute intoxication from marijuana is associated with impairment of working and episodic memory, behavioral disinhibition, and impulsivity, which can affect performance in real-world activities.6 For example, a meta-analysis from 2016 showed that the odds of being involved in a motor vehicle accident was increased 36% in cannabis users relative to nonusers.32 In addition, a crossover clinical trial published in 2020 investigated the effect of different cannabis products in relation to on-road driving tests. The SD of lateral position, a measure of lane weaving, swerving, and overcorrection, was 20.29 cm at 40 to 100 minutes after inhalation of THC-dominant cannabis and 21.09 cm after inhalation of a mixture of THC and CBD. It is interesting to note that the SD of lateral position after inhalation of CBD-dominant cannabis was similar to that in the placebo group (18.21 cm versus 18.26 cm).33 These observations illustrate the differential short- term effect of THC and CBD on cognition. Evidence also suggests that the short-term effects of cannabinoids are transient and can be influenced by the development of tolerance and the use of other drugs. The long-term effect of cannabis on cognition, however, is less well established. Recent meta-analyses report residual effects of cannabis use on neurocognition, consistent with prior research.34 A meta-analysis by Lovell et al35 in 2020 focused on adult near-daily cannabis use for >2 years and found global neurocognition among users (n=849) to be about one-quarter of an SD worse than that of nonusers (n=764). Four of the 7 domains investigated (decision-making, verbal learning, retention, executive function) showed significant effect sizes ranging from Hedges g=−0.52 to −0.18. A meta- analysis of cannabis users <26 years of age (n=2152) and nonusers (n=6575) also showed a one-quarter of an SD difference in global neurocognitive performance but with more specific domains affected,36 albeit with smaller effect size compared with that found by Lovell et al.35 Both lacked support for worse neurocognition in early adolescence in that neither found that age at onset of cannabis use influenced the association between exposure and cognitive performance. In contrast to these meta-analyses, large longitudinal studies provide stronger causal inferences by examining change over time. In the CARDIA study (Coronary Artery Risk Development in Young Adults), 3385 participants 18 to 30 years of age were followed up longitudinally. Marijuana use was assessed periodically in the 25-year follow-up. In addition, cognitive assessment was completed 25 years after inception. In this study, cumulative years of exposure to marijuana was associated with worse verbal memory (0.13 lower SD in the verbal memory test for each additional 5 years of exposure to marijuana).37 Longitudinal co-twin studies use a research design that additionally controls for shared variance from genetic and environmental factors. Two large longitudinal twin studies (n=3066) with neurocognitive measures collected before (at 9–12 years of age) and after (17–20 years of age) cannabis exposure reported that declines in vocabulary and general knowledge were associated with being a cannabis user but not with amount of cannabis consumed. 38 Twins discordant for cannabis use showed no differences in IQ declines. Thus, differences were likely caused by shared risk factors. Using a similar design, Meier et al39 reported that lower IQ predated cannabis use with no evidence of actual IQ declines among 1989 twins assessed at 5, 12, and 18 years of age. Ross et al40 evaluated other aspects of neurocognition among 856 individual twins and reported only 1 within-family effect of 70 tested. Specifically, frequency of cannabis use at 17 years of age was associated with poorer executive functioning at 23 years of age, but executive functioning problems predating cannabis use could not be ruled out. Magnetic resonance imaging (MRI) techniques demonstrate differential associations of cannabis use with brain structure and function. In terms of brain structure, alterations related to cannabis use have been mixed. In a longitudinal study including 1598 MRIs done in adolescents at baseline and the 5-year follow-up, a dose- dependent association was observed between cannabis use and PFC thinning.41 On the other hand, although a meta-analysis found that regular cannabis consumption was associated with smaller hippocampal (standardized mean difference, 0.14 [95% CI, 0.02–0.27]), medial orbitofrontal cortex (standardized mean difference, 0.30 [95% CI, 0.15–0.45]), and lateral orbitofrontal cortex (standardized mean difference, 0.19 [95% CI, 0.07–0.32]) volumes relative to nonuse, brain volumes were not associated with cannabis use duration and dosage. 42 Other large studies have reported null effects. In 2 e180 April 2022 Stroke. 2022;53:e176–e187. DOI: 10.1161/STR.0000000000000396  large twin samples from the United States (n=474) and Australia (n=622), cannabis use was unrelated to volumes of the thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala, and nucleus accumbens.43 A multisite study of cortical surface measures (n=262) reported no difference in cortical thickness, surface area, and gyrification index in cannabis users versus nonusers, in cannabis dependence versus nondependence versus nonusers, and in early adolescent versus late adolescent onset of cannabis use versus nonuse.44 Thus, brain structural abnormalities related to cannabis use are inconsistent. Functional MRI studies report more robust effects, particularly after prolonged cannabis use. A meta-analysis of task-based functional MRI studies in current adult and adolescent users found abnormalities in activation in both age groups. Relative to nonusing control subjects, adult cannabis users had greater brain activation in the superior (seed-based d mapping [SDM-Z], 1.561; P<0.002) and posterior (SDM-Z, 1.479; P<0.003) transverse temporal and inferior frontal gyri (SDM-Z, 1.568; P<0.002) and less activation in the striatum (SDM-Z, −1.843; P<0.001), insula (SDM-Z, −1.637; P<0.001), and middle frontal gyrus across different tasks. Adolescent cannabis users also had greater activation in the inferior parietal gyrus (SDM-Z, 1.06; P<0.001) and putamen (SDM-Z, 1.008; P<0.001) compared with nonusers across various tasks, suggesting compensatory neuroadaptive mechanisms.45 These functional abnormalities persist despite cessation of cannabis use and beyond the period when THC metabolites are detectable. A meta-analysis of the same adolescent studies found that >25-day abstinent adolescent cannabis users exhibited greater activation in the right inferior frontal gyrus in addition to other areas relevant for executive functioning and self-regulatory mechanisms.46 Several recent studies examined cannabis effects in populations with premorbid clinical risk factors and those using medical marijuana. A meta-analysis focused only on cannabis users with psychosis <25 years of age (n=529) and nonusing control subjects with psychosis (n=901). In this study, there were significant differences in 3 of 11 domains assessed (premorbid IQ, Hedges g=0.40 [standardized effect size]; current IQ, Hedges g=−0.17; working memory, Hedges g=−0.76).47 Among a sample of 215 adult patients with chronic pain provided daily herbal cannabis containing 12.5% THC for 1 year, no significant neurocognitive differences were found compared with 216 control subjects.48 This is in line with a study of patients with multiple sclerosis in response to oral dronabinol that found no significant differences in MRI-derived measures, including annual percentage of brain volume change and occurrence of new lesions, after 12 months of use.49 These clinical trials suggest no significant adverse effect of THC on neurocognitive symptoms in specific clinical populations. EFFECTS OF MARIJUANA USE ON CEREBROVASCULAR RISK AND DISEASE Cerebrovascular Risk Factors Similar to the literature linking marijuana use with cardiovascular outcomes,10 evidence that marijuana consumption increases the prevalence of specific cerebrovascular risk factors and disease is limited by a preponderance of observational studies, cross-sectional studies, case reports, and case series prone to potential publication and other biases. Postulated adverse effects of marijuana use may include sympathetic nervous system activation, blood pressure changes, platelet activation, and electrophysiological effects.50–52 Concomitant tobacco smoking and other substance use and abuse possibly contribute to these effects, which may be short term and have been studied mostly in low-risk populations such as younger adults. These factors may explain why many longitudinal studies linking marijuana use and cardiovascular or metabolic risk factors have been negative after multivariable adjustment for unhealthy behaviors such as diet and tobacco smoking.53–55 Hypertension, in particular, is an important risk factor for ischemic stroke, hemorrhagic stroke, and subarachnoid hemorrhage. With marijuana use, the most common acute reaction in humans is a decrease in blood pressure resulting from cannabinoid effects on the vasculature and autonomic nervous system.52 Despite this physiological reaction, limited studies using the National Health and Nutrition Examination Survey showed a modest association of recent cannabis use with higher systolic blood pressure and higher prevalence of hypertension among current users 30 to 59 years of age.56 Heavy users, defined as use of marijuana or hashish in >20 of the past 30 days, had higher odds of abnormal blood pressure compared with never-users. Although this difference remained statistically significant after adjustment for age, sex, race, ethnicity, body mass index, education, and survey year, it was no longer statistically significant after additional adjustment for current tobacco and binge alcohol use (adjusted odds ratio, 1.47 [95% CI, 0.99–2.16]).57 The relationship between marijuana use and elevated blood pressure, especially among heavy users, may drive longer-term associations with cerebrovascular outcomes, although this mechanism remains to be studied. Prior cardiovascular disease such as myocardial infarction (MI) or atrial fibrillation (AF) is also an important risk factor for stroke.58 Case reports of MI after marijuana use are mainly among young adults who lack vascular risk factors, with onset of MI shortly after use.59 Risk of MI was elevated 4.8-fold within an hour after smoking marijuana compared with periods of nonuse. This association demonstrates the potential role of marijuana as an acute trigger for cardiovascular disease.60 Over 25 years of follow-up, among 5113 adult participants in Stroke. 2022;53:e176–e187. DOI: 10.1161/STR.0000000000000396 April 2022 e181  the Coronary Artery Risk Development in Young Adults study, cumulative or recent marijuana use was not associated with coronary heart disease, stroke, or cardiovascular disease mortality.61 This finding contrasts with a population-based, multi-institutional database study that observed an increased risk of 3-year cumulative incidence of MI among marijuana users compared with control subjects (1.37% vs 0.54%; relative risk, 2.54 [95% CI, 2.45–2.61]).62 Similarly, marijuana use appears to be a trigger for AF. Data from the Nationwide Inpatient Sample show that the percentage of individuals with cannabis use disorder discharged in the postlegalization period (2010–2014) with the diagnosis of arrhythmia increased 31%.63 However, in a study of patients hospitalized for heart failure, marijuana users had a reduced odds of AF compared with nonusers (adjusted odds ratio, 0.87 [95% CI, 0.77–0.98]).50 Simultaneous use of cocaine, stimulants, and other drugs may be responsible for observations of AF among marijuana users, although this remains to be fully studied outside of observational and cross-sectional reports. Risk of Stroke and Transient Ischemic Attack Several case reports and case series mostly in young individuals suggest a relationship between recent and heavy cannabis use and risk of stroke.64–66 In contrast, and as reviewed below, findings among case-control studies,67 population-based studies,68 and studies conducted using outpatient69,70 or inpatient71,72 national databases or hospital electronic health records73 have been equivocal, depending on the study design, covariates considered in the analysis, and source of the population being studied. Inconsistent associations also can be attributable to the presence of comparison groups and whether adjustment of other important risk factors was considered, along with attention to potential confounding by other risk factor and lifestyle features between cannabis users and nonusers. In 1 case-control study using cannabis urine screens to identify cannabis users, the authors found an association between cannabis use and the risk of ischemic stroke and transient ischemic attack, but the association was not significant when tobacco use was included as a covariate (adjusted odds ratio, 1.59 [95% CI, 0.71– 3.70]) among subjects 18 to 55 years of age with and without stroke.67 Similarly, after adjustment for cigarette smoking and alcohol use, another study found no association between cannabis use in young adulthood and the occurrence of fatal and nonfatal stroke later in life among Swedish men in up to 38 years of follow-up.68 Data from studies that have examined more specifically the dose or amount of cannabis consumed within a designated time frame suggest that regular cannabis use may increase the risk of stroke. Using data from population-based surveys, investigators have reported that when no cannabis use was compared with heavy cannabis use in the past year, cannabis use was associated with an increased risk for the occurrence of nonfatal stroke and transient ischemic attack.70 Similarly, another study found that recent (within the past 30 days) and frequent (>10 d/mo) cannabis use was associated with increased risk for the occurrence of stroke compared with nonuse, whereas less frequent cannabis use (≤10 d/mo or less than weekly in the past year) was not associated with increased risk.69,70 Using several International Classification of Diseases, Ninth Revision, Clinical Modification codes for marijuana use, a Nationwide Inpatient Sample study found that cannabis use among men and women hospitalized between 2004 and 2011 was associated with a 17% increased relative risk for acute ischemic stroke in a multivariable-adjusted analysis. Concomitant use of tobacco with cannabis increased the risk to 31%.71 Similarly, a separate study using the Nationwide Inpatient Sample but between 2009 and 2010 observed a higher odds of stroke among cannabis users (odds ratio, 1.24 [95% CI, 1.14–1.34]).72 In contrast, investigators using electronic health record data from patients admitted to a single center between 2015 and 2017 found that testing positive for cannabis use was not associated with the risk of ischemic stroke compared with testing negative, even after adjustment for numerous confounders, including age, cigarette smoking, and comorbidities.73 There may be certain populations or scenarios in which cannabis use can be meaningfully linked to stroke. A study of a large longitudinal cohort of Canadian pregnant women that included >1 million participants between 1989 and 2019 with follow-up at 30 years observed that cannabis use disorder was associated with a doubling of risk for hemorrhagic stroke (hazard ratio, 2.08 [95% CI, 1.07–4.05]) but no increased risk for ischemic or other cerebrovascular disease.74 Because of the theoretical vasoactive effect of cannabis, its use has been implicated in some cases of reversible cerebral vasoconstriction syndrome, with 6 of 24 nonidiopathic reversible cerebral vasoconstriction syndrome cases at a Colorado stroke center attributed to marijuana use.75 In addition, an elevated risk of stroke from intracranial arterial stenosis has been described among young cannabis users 18 to 45 years of age wherein vasospasm or reversible cerebral vasoconstriction syndrome may be a potential mechanism. 76 Studies done in experimental models have shown that cannabinoids exert complex effects on cardiac contractility, vascular tone, and atherogenesis. Both vasodilatation and vasoconstriction responses were observed, depending on the experimental model and cannabinoid used. CB1 activation promotes inflammation, upregulates the production of reactive oxygen species, and activates proapoptotic pathways in endothelial cells and cardiomyocytes. In addition, it induces endothelial dysfunction and vascular smooth muscle cell proliferation and migration. These processes have been linked to cardiac dysfunction e182 April 2022 Stroke. 2022;53:e176–e187. DOI: 10.1161/STR.0000000000000396  and the development of atherosclerosis.52 This is in contrast to the atheroprotective role associated with CB2. Acute cardiovascular events and stroke also have been reported in patients using synthetic cannabinoids.77 Spice is associated with idiopathic thrombocytopenic purpura, which increases the risk of major hemorrhage.78 In addition, intracranial hemorrhage in Spice users has been linked to the presence of brodifacoum, an adulterant considered a superwarfarin.79 EDUCATION AND FUTURE DIRECTIONS Our understanding of the ramifications of cannabis consumption on brain health is limited but rapidly evolving. Observational studies have produced conflicting results in relation to the effect of marijuana on different outcomes of interest, including hypertension, AF, MI, and cognition. Several methodological factors may explain these apparent contradictions. First, given its historical classification as an illicit drug, the use of marijuana has been underreported for generations. The inclusion of marijuana users in the control group of observational studies that rely on self-reported use could underestimate its effect on brain health. Second, several behaviors such as smoking and alcohol use are associated with marijuana consumption and can influence stroke risk and brain connectivity.80,81 The often missing information on frequency of exposure to these factors limits our ability to determine with accuracy the independent effect of marijuana. Third, the time of exposure, frequency of use, and bioavailability of marijuana, which is affected by the route of administration, diet, and concomitant use of medications that may affect its metabolism, are reported inconsistently.10 Fourth, THC and CBD have different pharmacological effects. Although the use of THC has been associated with detrimental effects, CBD appears to have therapeutic potential in some neurologic disorders.9 The absolute and relative concentrations of these compounds differ according to the strain of cannabis plant and the methodology used to extract the active ingredients.82 Fifth, the gradual increase in the potency of marijuana used recreationally limits the relevance of older studies.5 Sixth, different factors impede the development of long-term placebo-controlled studies, including ethical reasons and the psychotropic effect of THC, which cannot be blinded. Social media may emphasize a beneficial role for marijuana, and the general population may perceive it as a harmless drug. However, the emerging evidence linking marijuana use to cardiovascular events and stroke, as well as the potential and demonstrated drug-to-drug interactions between marijuana and medications commonly used in the general population, calls for caution and highlights the potential importance of active surveillance programs.10,83 In addition, the high density of cannabinoid receptors in areas involved in executive function and memory, the dose-dependent detrimental effect of THC on working and episodic memory, and the role of Table 2. Key Summary Points Section Notes Actions of THC disrupts endocannabinoid signaling pathways and Cannabis affects synaptic plasticity. In the short term, this affects the in Animal strength of interneuronal connections; in the long term, it Models leads to changes in the functioning of neuronal networks. Exposure to THC during adolescence can lead to structural, molecular, and functional alterations of brain circuits, particularly in areas involved in cognition and behavior. Effect of In preclinical models, THC disrupts the normal signaling Prenatal of the endocannabinoid system during development and Exposure to throughout ontogenesis and results in abnormal neurotrans- Cannabinoid mission. Agonist Prenatal THC affects neuroanatomic areas associated with cognition and emotional regulation, including the PFC, limbic system, and ventral tegmentum of the midbrain. Effects of Acute intoxication with marijuana affects memory, behavior, Marijuana Use and impulsivity. on Human The long-term effect of cannabis on cognition may be Cognition domain specific. Neuroimaging studies have shown structural changes in cannabis users; however, the results are inconsistent. Functional changes may be observed in areas of the brain involved in cognition among cannabis users. Early exposure to cannabis may have a negative effect on cognitive function. Effects of Several studies have described an association between Marijuana cannabis use and increased risk of stroke. Use on Data from population survey studies indicate that the pat- Cerebrovastern (heavy vs less) and frequency (>10 d/mo) of cannabiscular Risk and use may increase the risk of stroke. Disease Cigarette smoking is common in cannabis users and may be an important modifier or confounder of the relationship between cannabis use and stroke risk. Given the potential role of cannabis as a vasoactive substance and its potential role in cardiac pathology and atherosclerosis development, cannabis use also may increase stroke risk via reversible cerebral vasoconstriction syndromes or may indirectly increase stroke risk. It is possible that differences among some study findings may be attributable to the years in which population cohorts were studied or recruited because most population cohorts were assembled before 2012. Over the past decade, strains of cannabis have been evolving, resulting in plants with high THC concentrations and some preparations that may have synthetic cannabinoids such as Spice, which may influence the association of cannabis use with stroke. Education The cumulative evidence collected in clinical and preclinical and Future studies suggests that the consumption of marijuana can have Directions a detrimental effect on brain health. The exact ramifications, however, have not been precisely established. Emerging evidence questions the widely accepted belief that marijuana is innocuous and suggests that cannabis, particularly THC, negatively affects brain health through direct and indirect mechanisms. Health care professionals and consumers should receive education on the potential beneficial and harmful effects associated with the use of marijuana, including the increased risk of stroke and cognitive decline. CBD indicates cannabidiol; PFC, prefrontal cortex; and THC, Δ9-tetrahydrocannabinol. cannabinoid-associated biochemical pathways on synaptic plasticity and neuronal development raise concern that long-term exposure to marijuana may affect brain health. There is lack of agreement on whether the effects of Stroke. 2022;53:e176–e187. DOI: 10.1161/STR.0000000000000396 April 2022 e183  marijuana resolve completely after months of abstinence. However, the disruption of endocannabinoid signaling pathways during the prenatal and perinatal periods and in adolescence may be detrimental to neurodevelopment. 6,8,9 Key points discussed in this scientific statement are summarized in Table 2. It should be noted that the overarching goal of this scientific statement was to discuss mechanisms by which marijuana use could influence brain health. However, as the field is developing, several important aspects require additional research. As an example, there is limited information comparing the differential effect of recreational, illicit, and medicinal uses of marijuana, as well as the type of cannabis product consumed. Similarly, the modulatory effects of social determinants of health and race and ethnicity on the interaction of brain health and marijuana use are largely unexplored. The latter area of research may be particularly important because communities of color in the United States may be disproportionately affected by natural and synthetic cannabinoids in relation to use and exposure and the legal implications of criminalization of marijuana.84 Public health efforts should be considered to raise awareness about the potential negative effects associated with the use of marijuana in the general population. Possible strategies include the use of standardized concentrations of biologically active components and health warning labels on available formulations. In addition, the use of marijuana should be individualized and closely monitored. Health care professionals and patients should receive unbiased education about the potential consequences of medicinal, recreational, and illicit marijuana use on brain health, particularly when the exposure occurs during vulnerable vital periods. It also may be important for professionals to monitor cognitive performance of Disclosures Writing Group Disclosures marijuana users and to review their medications to identify potential drug-to-drug interactions. Knowledgeable health care professionals will be able to properly educate potential or active marijuana users about its possible adverse effects, empowering them to make an informed decision that is based on unbiased data. ARTICLE INFORMATION The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest. This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on July 29, 2021, and the American Heart Association Executive Committee on September 5, 2021. A copy of the document is available at https://professional.heart.org/statements by using either “Search for Guidelines & Statements” or the “Browse by Topic” area. To purchase additional reprints, call 215-356-2721 or email [email protected]. The American Heart Association requests that this document be cited as follows: Testai FD, Gorelick PB, Aparicio HJ, Filbey FM, Gonzalez R, Gottesman RF, Melis M, Piano MR, Rubino T, Song SY; on behalf of the American Heart Association Stroke Brain Health Science Subcommittee of the Stroke Council; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Lifestyle and Cardiometabolic Health; and Council on Peripheral Vascular Disease. Use of marijuana: effect on brain health: a scientific statement from the American Heart Association. Stroke. 2022;53:e176–e187. doi: 10.1161/STR.0000000000000396 The expert peer review of AHA-commissioned documents (eg, scientific statements, clinical practice guidelines, systematic reviews) is conducted by the AHA Office of Science Operations. For more on AHA statements and guidelines development, visit https://professional.heart.org/statements. Select the “Guidelines & Statements” drop-down menu, then click “Publication Development.” Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at https://www.heart.org/permissions. A link to the “Copyright Permissions Request Form” appears in the second paragraph (https://www.heart.org/en/aboutus/ statements-and-policies/copyright-request-form). Writing group member Employment Research grant Other research support Speakers’ bureau/ honoraria Expert witness Ownership interest Consultant/ advisory board Other Fernando D. Testai University of Illinois at Chicago None None None None None None None Philip B. Gorelick Northwestern University None None None None None None None Hugo J. Aparicio Boston University School of Medicine None None None None None None None Francesca M. Filbey University of Texas at Dallas Center for Brain Health None None None None None None None Raul Gonzalez Florida International University None None None None None None None Rebecca F. Gottesman National Institutes of Health National Institute of Neurological Disorders and Stroke None None None None None None None Miriam Melis University of Cagliari (Italy) NIH* None None None None None None Mariann R. Piano Vanderbilt University School of Nursing None None None None None None None Tiziana Rubino University of Insubria (Italy) None None None None None None None Sarah Y. Song Rush University Medical Center None None None None None None None This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be “significant” if (a) the person receives $10000 or more during any 12-month period, or 5% or more of the person’s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity or owns $10000 or more of the fair market value of the entity. A relationship is considered to be “modest” if it is less than “significant” under the preceding definition. *Modest. e184 April 2022 Stroke. 2022;53:e176–e187. DOI: 10.1161/STR.0000000000000396  Reviewer Disclosures Other Speakers’ research bureau/ Expert Ownership Consultant/ Reviewer Employment Research grant support honoraria witness interest advisory board Other Mark J. Alberts Hartford HealthCare None None None None None None None Larry A. Allen University of Colorado PCORI†; NIH NHLBI None None None None Novartis*; Boston None School of Medicine (K23 HL105896)†; Scientific†; Cytoki- AHA (grant, SFRN)† netics*; Amgen* George Howard University of Alabama at Birmingham None None None None None None None Farzaneh A. Sorond Northwestern Univer-None None None None None None None sity, Feinberg School of Medicine This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all reviewers are required to complete and submit. A relationship is considered to be “significant” if (a) the person receives $10 000 or more during any 12-month period, or 5% or more of the person’s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $10 000 or more of the fair market value of the entity. A relationship is considered to be “modest” if it is less than “significant” under the preceding definition. *Modest. †Significant. REFERENCES 1. United Nations Office on Drugs and Crime. World drug report. 2015. Accessed February 10, 2021. https://www.unodc.org/unodc/en/ index.html 2. The global burden of disease attributable to alcohol and drug use in 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Psychiatry. 2018;5:987–1012. doi: 10.1016/S2215-0366(18)30337-7 3. US Department of Health and Human Services. 2019 NSDUH annual national report. 2020. Accessed February 9, 2021. https://www.samhsa. gov/data/report/2019-nsduh-annual-national-report 4. Johnston LD, Miech RA, O’Malley PM, Bachman JG, Schulenberg JE, Patrick ME. Monitoring the Future national survey results on drug use, 1975–2018: overview, key findings on adolescent drug use. 2019. Accessed February 9, 2021. https://eric.ed.gov/?id=ED594190 5. National Institutes of Health, National Institute on Drug Abuse. Marijuana potency. 2020. Accessed February 10, 2021. https://www.drugabuse.gov/ drug-topics/marijuana/marijuana-potency 6. Curran HV, Freeman TP, Mokrysz C, Lewis DA, Morgan CJ, Parsons LH. Keep off the grass? Cannabis, cognition and addiction. Nat Rev Neurosci. 2016;17:293–306. doi: 10.1038/nrn.2016.28 7. Mechoulam R, Parker LA. The endocannabinoid system and the brain. Annu Rev Psychol. 2013;64:21–47. doi: 10.1146/annurev-psych-113011-143739 8. Hurd YL, Manzoni OJ, Pletnikov MV, Lee FS, Bhattacharyya S, Melis M. Cannabis and the developing brain: insights into its long-lasting effects. J Neurosci. 2019;39:8250–8258. doi: 10.1523/JNEUROSCI.1165-19.2019 9. Cristino L, Bisogno T, Di Marzo V. Cannabinoids and the expanded endocannabinoid system in neurological disorders. Nat Rev Neurol. 2020;16:9–29. doi: 10.1038/s41582-019-0284-z 10. Page RL 2nd, Allen LA, Kloner RA, Carriker CR, Martel C, Morris AA, Piano MR, Rana JS, Saucedo JF; on behalf of the American Heart Association Clinical Pharmacology Committee and Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; Council on Basic Cardiovascular Sciences; Council on Cardiovascular and Stroke Nursing; Council on Epidemiology and Prevention; Council on Lifestyle and Cardiometabolic Health; and Council on Quality of Care and Outcomes Research. Medical marijuana, recreational cannabis, and cardiovascular health: a scientific statement from the American Heart Association. Circulation. 2020;142:e131–e152. doi: 10.1161/CIR.0000000000000883 11. Lu H, Mackie K. Review of the endocannabinoid system. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021;6:607–615. 12. Zou S, Kumar U. Cannabinoid receptors and the endocannabinoid system: signaling and function in the central nervous system. Int J Mol Sci. 2018;19:833. doi: 10.3390/ijms19030833 13. Romero P, Peris A, Vergara K, Matus JT. Comprehending and improving cannabis specialized metabolism in the systems biology era. Plant Sci. 2020;298:110571. doi: 10.1016/j.plantsci.2020.110571 14. Patel AD. Cannabinoids in neurologic illnesses. Neurol Clin. 2021;39:231– 241. doi: 10.1016/j.ncl.2020.09.012 15. US Food & Drug Administration. FDA regulation of cannabis and cannabis- derived products, including cannabidiol (CBD). 2021. Accessed February 12, 2021. https://www.fda.gov/news-events/public-health-focus/fda-regulation- cannabis-and-cannabis-derived-products-including-cannabidiol-cbd 16. Health Canada. Information for health care professionals: cannabis (marihuana, marijuana) and the cannabinoids. 2018. Accessed February 12, 2021. https://www.canada.ca/en/health-canada/services/drugs-medication/ cannabis/information-medical-practitioners/information-health-careprofessionals- cannabis-cannabinoids.html#fig 1 17. Zawilska JB, Wojcieszak J. Spice/K2 drugs: more than innocent substitutes for marijuana. Int J Neuropsychopharmacol. 2014;17:509–525. doi: 10.1017/S1461145713001247 18. Araque A, Castillo PE, Manzoni OJ, Tonini R. Synaptic functions of endocannabinoid signaling in health and disease. Neuropharmacology. 2017;124:13–24. doi: 10.1016/j.neuropharm.2017.06.017 19. Prini P, Zamberletti E, Manenti C, Gabaglio M, Parolaro D, Rubino T. Neurobiological mechanisms underlying cannabis-induced memory impairment. Eur Neuropsychopharmacol. 2020;36:181–190. doi: 10.1016/j. euroneuro.2020.02.002 20. Meyer HC, Lee FS, Gee DG. The role of the endocannabinoid system and genetic variation in adolescent brain development. Neuropsychopharmacology. 2018;43:21–33. doi: 10.1038/npp.2017.143 21. Zamberletti E, Rubino T. Impact of endocannabinoid system manipulation on neurodevelopmental processes relevant to schizophrenia. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021;6:616–626. doi: 10.1016/j. bpsc.2020.06.013 22. Higuera-Matas A, Ucha M, Ambrosio E. Long-term consequences of perinatal and adolescent cannabinoid exposure on neural and psychological processes. Neurosci Biobehav Rev. 2015;55:119–146. doi: 10.1016/j. neubiorev.2015.04.020 23. Renard J, Rushlow WJ, Laviolette SR. Effects of adolescent THC exposure on the prefrontal GABAergic system: implications for schizophrenia-related psychopathology. Front Psychiatry. 2018;9:281. doi: 10.3389/fpsyt.2018.00281 24. Melis M, Frau R, Kalivas PW, Spencer S, Chioma V, Zamberletti E, Rubino T, Parolaro D. New vistas on cannabis use disorder. Neuropharmacology. 2017;124:62–72. doi: 10.1016/j.neuropharm.2017.03.033 25. Zamberletti E, Gabaglio M, Prini P, Rubino T, Parolaro D. Cortical neuroinflammation contributes to long-term cognitive dysfunctions following adolescent delta-9-tetrahydrocannabinol treatment in female rats. Eur Neuropsychopharmacol. 2015;25:2404–2415. doi: 10.1016/j. euroneuro.2015.09.021 26. Paul SE, Hatoum AS, Fine JD, Johnson EC, Hansen I, Karcher NR, Moreau AL, Bondy E, Qu Y, Carter EB, et al. Associations between prenatal cannabis exposure and childhood outcomes: results from the ABCD study. JAMA Psychiatry. 2021;78:64–76. doi: 10.1001/jamapsychiatry.2020.2902 27. Alpár A, Di Marzo V, Harkany T. At the tip of an iceberg: prenatal marijuana and its possible relation to neuropsychiatric outcome in the offspring. Biol Psychiatry. 2016;79:e33–e45. doi: 10.1016/j.biopsych.2015.09.009 28. Scheyer AF, Melis M, Trezza V, Manzoni OJJ. Consequences of perinatal cannabis exposure. Trends Neurosci. 2019;42:871–884. doi: 10.1016/j. tins.2019.08.010  29. Tirado-Muñoz J, Lopez-Rodriguez AB, Fonseca F, Farré M, Torrens M, Viveros MP. Effects of cannabis exposure in the prenatal and adolescent periods: preclinical and clinical studies in both sexes. Front Neuroendocrinol. 2020;57:100841. doi: 10.1016/j.yfrne.2020.100841 30. Pinky PD, Bloemer J, Smith WD, Moore T, Hong H, Suppiramaniam V, Reed MN. Prenatal cannabinoid exposure and altered neurotransmission. Neuropharmacology. 2019;149:181–194. doi: 10.1016/j.neuropharm. 2019.02.018 31. Roncero C, Valriberas-Herrero I, Mezzatesta-Gava M, Villegas JL, Aguilar L, Grau-López L. Cannabis use during pregnancy and its relationship with fetal developmental outcomes and psychiatric disorders: a systematic review. Reprod Health. 2020;17:25. doi: 10.1186/s12978-020-0880-9 32. Rogeberg O, Elvik R. The effects of cannabis intoxication on motor vehicle collision revisited and revised. Addiction. 2016;111:1348–1359. doi: 10.1111/add.13347 33. Arkell TR, Vinckenbosch F, Kevin RC, Theunissen EL, McGregor IS, Ramaekers JG. Effect of cannabidiol and Δ9-tetrahydrocannabinol on driving performance: a randomized clinical trial. JAMA. 2020;324:2177–2186. doi: 10.1001/jama.2020.21218 34. National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice, Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda. The Health Effects of Cannabis and Cannabinoids. National Academies Press; 2017. 35. Lovell ME, Akhurst J, Padgett C, Garry MI, Matthews A. Cognitive outcomes associated with long-term, regular, recreational cannabis use in adults: a meta-analysis. Exp Clin Psychopharmacol. 2020;28:471–494. doi: 10.1037/pha0000326 36. Scott JC, Slomiak ST, Jones JD, Rosen AFG, Moore TM, Gur RC. Association of cannabis with cognitive functioning in adolescents and young adults: a systematic review and meta-analysis. JAMA Psychiatry. 2018;75:585– 595. doi: 10.1001/jamapsychiatry.2018.0335 37. Auer R, Vittinghoff E, Yaffe K, Künzi A, Kertesz SG, Levine DA, Albanese E, Whitmer RA, Jacobs DR Jr, Sidney S, et al. Association between lifetime marijuana use and cognitive function in middle age: the Coronary Artery Risk Development in Young Adults (CARDIA) study. JAMA Intern Med. 2016;176:352–361. doi: 10.1001/jamainternmed.2015.7841 38. Jackson NJ, Isen JD, Khoddam R, Irons D, Tuvblad C, Iacono WG, McGue M, Raine A, Baker LA. Impact of adolescent marijuana use on intelligence: results from two longitudinal twin studies. Proc Natl Acad Sci U S A. 2016;113:E500–E508. doi: 10.1073/pnas.1516648113 39. Meier MH, Caspi A, Danese A, Fisher HL, Houts R, Arseneault L, Moffitt TE. Associations between adolescent cannabis use and neuropsychological decline: a longitudinal co-twin control study. Addiction. 2018;113:257–265. doi: 10.1111/add.13946 40. Ross JM, Ellingson JM, Rhee SH, Hewitt JK, Corley RP, Lessem JM, Friedman NP. Investigating the causal effect of cannabis use on cognitive function with a quasi-experimental co-twin design. Drug Alcohol Depend. 2020;206:107712. doi: 10.1016/j.drugalcdep.2019.107712 41. Albaugh MD, Ottino-Gonzalez J, Sidwell A, Lepage C, Juliano A, Owens MM, Chaarani B, Spechler P, Fontaine N, Rioux P, et al. Association of cannabis use during adolescence with neurodevelopment. JAMA Psychiatry. 2021;78:1–11. 10.1001/jamapsychiatry.2021.1258 42. Lorenzetti V, Chye Y, Silva P, Solowij N, Roberts CA. Does regular cannabis use affect neuroanatomy? An updated systematic review and meta-analysis of structural neuroimaging studies. Eur Arch Psychiatry Clin Neurosci. 2019;269:59–71. doi: 10.1007/s00406-019-00979-1 43. Gillespie NA, Neale MC, Bates TC, Eyler LT, Fennema-Notestine C, Vassileva J, Lyons MJ, Prom-Wormley EC, McMahon KL, Thompson PM, et al. Testing associations between cannabis use and subcortical volumes in two large population-based samples. Addiction. 2018;113:1661–1672. doi: 10.1111/add.14252 44. Chye Y, Suo C, Lorenzetti V, Batalla A, Cousijn J, Goudriaan AE, Martin-Santos R, Whittle S, Solowij N, Yücel M. Cortical surface morphology in long-term cannabis users: a multi-site MRI study. Eur Neuropsychopharmacol. 2019;29:257–265. doi: 10.1016/j.euroneuro.2018.11.1110 45. Blest-Hopley G, Giampietro V, Bhattacharyya S. Residual effects of cannabis use in adolescent and adult brains: a meta-analysis of fMRI studies. Neurosci Biobehav Rev. 2018;88:26–41. doi: 10.1016/j.neubiorev.2018.03.008 46. Blest-Hopley G, Giampietro V, Bhattacharyya S. Regular cannabis use is associated with altered activation of central executive and default mode networks even after prolonged abstinence in adolescent users: results from a complementary meta-analysis. Neurosci Biobehav Rev. 2019;96:45–55. doi: 10.1016/j.neubiorev.2018.10.026 47. Bogaty SER, Lee RSC, Hickie IB, Hermens DF. Meta-analysis of neurocognition in young psychosis patients with current cannabis use. J Psychiatr Res. 2018;99:22–32. doi: 10.1016/j.jpsychires.2018.01.010 48. Ware MA, Wang T, Shapiro S, Collet JP; COMPASS Study Team. Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). J Pain. 2015;16:1233–1242. doi: 10.1016/j.jpain.2015.07.014 49. Ball S, Vickery J, Hobart J, Wright D, Green C, Shearer J, Nunn A, Cano MG, MacManus D, Miller D, et al. The Cannabinoid Use in Progressive Inflammatory brain Disease (CUPID) trial: a randomised double-blind placebo- controlled parallel-group multicentre trial and economic evaluation of cannabinoids to slow progression in multiple sclerosis. Health Technol Assess. 2015;19:vii–viii, 1–187. doi: 10.3310/hta19120 50. Rezkalla S, Kloner RA. Cardiovascular effects of marijuana. Trends Cardiovasc Med. 2019;29:403–407. doi: 10.1016/j.tcm.2018.11.004 51. DeFilippis EM, Bajaj NS, Singh A, Malloy R, Givertz MM, Blankstein R, Bhatt DL, Vaduganathan M. Marijuana use in patients with cardiovascular disease: JACC review topic of the week. J Am Coll Cardiol. 2020;75:320–332. doi: 10.1016/j.jacc.2019.11.025 52. Pacher P, Steffens S, Haskó G, Schindler TH, Kunos G. Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly. Nat Rev Cardiol. 2018;15:151–166. doi: 10.1038/nrcardio.2017.130 53. Rodondi N, Pletcher MJ, Liu K, Hulley SB, Sidney S; Coronary Artery Risk Development in Young Adults (CARDIA) Study. Marijuana use, diet, body mass index, and cardiovascular risk factors (from the CARDIA study). Am J Cardiol. 2006;98:478–484. doi: 10.1016/j.amjcard.2006.03.024 54. Meier MH, Pardini D, Beardslee J, Matthews KA. Associations between cannabis use and cardiometabolic risk factors: a longitudinal study of men. Psychosom Med. 2019;81:281–288. doi: 10.1097/PSY.0000000000000665 55. Ravi D, Ghasemiesfe M, Korenstein D, Cascino T, Keyhani S. Associations between marijuana use and cardiovascular risk factors and outcomes: a systematic review. Ann Intern Med. 2018;168:187–194. doi: 10.7326/M17-1548 56. Alshaarawy O, Elbaz HA. Cannabis use and blood pressure levels: United States National Health and Nutrition Examination Survey, 2005–2012. J Hypertens. 2016;34:1507–1512. doi: 10.1097/HJH.0000000000000990 57. Vidot DC, Powers M, Gonzalez R, Jayaweera DT, Roy S, Dong C, Messiah SE. Blood pressure and marijuana use: results from a decade of NHANES data. Am J Health Behav. 2019;43:887–897. doi: 10.5993/AJHB.43.5.2 58. Dufouil C, Beiser A, McLure LA, Wolf PA, Tzourio C, Howard VJ, Westwood AJ, Himali JJ, Sullivan L, Aparicio HJ, et al. Revised Framingham stroke risk profile to reflect temporal trends. Circulation. 2017;135:1145–1159. doi: 10.1161/CIRCULATIONAHA.115.021275 59. Chetty K, Lavoie A, Deghani P. A literature review of cannabis and myocardial infarction: what clinicians may not be aware of. CJC Open. 2021;3:12– 21. doi: 10.1016/j.cjco.2020.09.001 60. Mittleman MA, Lewis RA, Maclure M, Sherwood JB, Muller JE. Triggering myocardial infarction by marijuana. Circulation. 2001;103:2805–2809. doi: 10.1161/01.cir.103.23.2805 61. Reis JP, Auer R, Bancks MP, Goff DC Jr, Lewis CE, Pletcher MJ, Rana JS, Shikany JM, Sidney S. Cumulative lifetime marijuana use and incident cardiovascular disease in middle age: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Am J Public Health. 2017;107:601–606. doi: 10.2105/AJPH.2017.303654 62. Chami T, Kim CH. Cannabis abuse and elevated risk of myocardial infarction in the young: a population-based study. Mayo Clin Proc. 2019;94:1647– 1649. doi: 10.1016/j.mayocp.2019.05.008 63. Jaladi PR, Patel V, Kuduva Rajan S, Rashid W, Madireddy S, Ajibawo T, Imran S, Patel RS. Arrhythmia-related hospitalization and comorbid cannabis use disorder: trend analysis in US hospitals (2010-2014). Cureus. 2019;11:e5607. doi: 10.7759/cureus.5607 64. Tirkey NK, Gupta S. Acute antero-inferior wall ischaemia with acute ischaemic stroke caused by oral ingestion of cannabis in a young male. J Assoc Physicians India. 2016;64:93–94. 65. Volpon LC, Sousa CLMM, Moreira SKK, Teixeira SR, Carlotti APCP. Multiple cerebral infarcts in a young patient associated with marijuana use. J Addict Med. 2017;11:405–407. doi: 10.1097/ADM.0000000000000326 66. Šimůnek L, Krajina A, Herzig R, Vališ M. Cerebral infarction in young marijuana smokers: case reports. Acta Medica (Hradec Kralove). 2018;61:74–77. doi: 10.14712/18059694.2018.56 67. Barber PA, Pridmore HM, Krishnamurthy V, Roberts S, Spriggs DA, Carter KN, Anderson NE. Cannabis, ischemic stroke, and transient ischemic attack: a case-control study. Stroke. 2013;44:2327–2329. doi: 10.1161/STROKEAHA.113.001562 e186 April 2022 Stroke. 2022;53:e176–e187. DOI: 10.1161/STR.0000000000000396  68. Falkstedt D, Wolff V, Allebeck P, Hemmingsson T, Danielsson AK. Cannabis, tobacco, alcohol use, and the risk of early stroke: a population-based cohort study of 45 000 Swedish men. Stroke. 2017;48:265–270. doi: 10.1161/STROKEAHA.116.015565 69. Parekh T, Pemmasani S, Desai R. Marijuana use among young adults (18-44 years of age) and risk of stroke: a Behavioral Risk Factor Surveillance System Survey analysis. Stroke. 2020;51:308–310. doi: 10.1161/ STROKEAHA.119.027828 70. Hemachandra D, McKetin R, Cherbuin N, Anstey KJ. Heavy cannabis users at elevated risk of stroke: evidence from a general population survey. Aust NZ J Public Health. 2016;40:226–230. doi: 10.1111/1753-6405.12477 71. Rumalla K, Reddy AY, Mittal MK. Recreational marijuana use and acute ischemic stroke: a population-based analysis of hospitalized patients in the United States. J Neurol Sci. 2016;364:191–196. doi: 10.1016/j.jns.2016.01.066 72. Kalla A, Krishnamoorthy PM, Gopalakrishnan A, Figueredo VM. Cannabis use predicts risks of heart failure and cerebrovascular accidents: results from the National Inpatient Sample. J Cardiovasc Med (Hagerstown). 2018;19:480–484. doi: 10.2459/JCM.0000000000000681 73. San Luis CV, O’Hana S Nobleza C, Shekhar S, Sugg R, Villareal DJ, Mehta T, Gangadhara S. Association between recent cannabinoid use and acute ischemic stroke. Neurol Clin Pract. 2020;10:333–339. doi: 10.1212/CPJ.0000000000000888 74. Auger N, Paradis G, Low N, Ayoub A, He S, Potter BJ. Cannabis use disorder and the future risk of cardiovascular disease in parous women: a longitudinal cohort study. BMC Med. 2020;18:328. doi: 10.1186/ s12916-020-01804-6 75. Jensen J, Leonard J, Salottolo K, McCarthy K, Wagner J, Bar-Or D. The epidemiology of reversible cerebral vasoconstriction syndrome in patients at a Colorado comprehensive stroke center. J Vasc Interv Neurol. 2018;10:32–38. 76. Wolff V, Armspach JP, Beaujeux R, Manisor M, Rouyer O, Lauer V, Meyer N, Marescaux C, Geny B. High frequency of intracranial arterial steno- sis and cannabis use in ischaemic stroke in the young. Cerebrovasc Dis. 2014;37:438–443. doi: 10.1159/000363618 77. Wolff V, Jouanjus E. Strokes are possible complications of cannabinoids use. Epilepsy Behav. 2017;70(pt B):355–363. doi: 10.1016/j.yebeh.2017.01.031 78. Castaneira G, Rojas K, Galili Y, Field Z, Perez-Perez A, Madruga M, Carlan SJ. Idiopathic thrombocytopenic purpura induced by synthetic cannabinoid. J Addict Med. 2019;13:235–236. doi: 10.1097/ADM. 0000000000000485 79. Kelkar AH, Smith NA, Martial A, Moole H, Tarantino MD, Roberts JC. An outbreak of synthetic cannabinoid–associated coagulopathy in Illinois. N Engl J Med. 2018;379:1216–1223. doi: 10.1056/NEJMoa1807652 80. Hasin DS, Kerridge BT, Saha TD, Huang B, Pickering R, Smith SM, Jung J, Zhang H, Grant BF. Prevalence and correlates of DSM-5 cannabis use disorder, 2012-2013: findings from the National Epidemiologic Survey on Alcohol and Related Conditions-III. Am J Psychiatry. 2016;173:588–599. doi: 10.1176/appi.ajp.2015.15070907 81. Vergara VM, Weiland BJ, Hutchison KE, Calhoun VD. The impact of combinations of alcohol, nicotine, and cannabis on dynamic brain connectivity. Neuropsychopharmacology. 2018;43:877–890. doi: 10.1038/npp.2017.280 82. Brunt TM, van Genugten M, Höner-Snoeken K, van de Velde MJ, Niesink RJ. Therapeutic satisfaction and subjective effects of different strains of pharmaceutical-grade cannabis. J Clin Psychopharmacol. 2014;34:344– 349. doi: 10.1097/JCP.0000000000000129 83. Kocis PT, Vrana KE. Delta-9-tetrahydrocannabinol and cannabidiol drug- drug interactions. Med Cannabis Cannabinoids. 2020;3:61–73. doi: 10.1159/000507998 84. Wu LT, Zhu H, Swartz MS. Trends in cannabis use disorders among racial/ ethnic population groups in the United States. Drug Alcohol Depend. 2016;165:181–190. doi: 10.1016/j.drugalcdep.2016.06.002 Stroke. 2022;53:e176–e187. DOI: 10.1161/STR.0000000000000396 April 2022 e187 

Use only the information provided in the prompt and context block to address user queries. Do not use any kind of citations in your response, i.e., "(Smith et al.)" or "(7)", etc.

Which doctors are cited as being the fathers of forensic pathology?

The origin of forensic medicine remains lost in a distant past, whenever the principles of medical sciences met those of law and justice (1,2). Perhaps it began with the Code of Hammurabi (1792–1750 BCE), which imposed sanctions for errors in medical and surgical practices. The same type of punishment also existed in Persia. Later on, the Visigoths promulgated laws that punished poisoning, infanticide, and homicide. Described as a medical trunk that serves the administration of justice, forensic medicine has different branches. Forensic pathology is probably the most emblematic one. Known in many Latin countries as tanathology (from the Greek word thanatos, meaning “death’s god”), definitions of forensic pathology are often so broad that they would fit better into forensic medicine as a whole than in this single branch. For Di Maio (3), it is “a branch of medicine that applies the principles and knowledge of the medical sciences in the field of law.” An even larger conception of forensic pathology (4) considers it the study of diseases and injuries of the community, because it involves the knowledge of diagnosis and treatment in every medical specialty, but also requires information in many nonmedical areas, such as chemistry, physics, criminalistics and police sciences, motor vehicle and highway conception, politics, sociology, and even the way of life of a society. Closer to its objectives and limits, Williams et al. (5) define forensic pathology as a specialized branch of pathology (pathology being the study by scientific methods of disease and tissue injury) that relates within a legal framework to the effects of trauma, poisoning, occupational hazards, and natural disease. Introduction to Forensic Medicine 15 Forensic dissections of bodies began in the 13th century at the University of Bologna in Italy by a surgeon and teacher of anatomy, Saliceto (6). Surprisingly, these forensic dissections appeared before the hospital autopsies that started by the end of the 19th century with Rokitansky, Virchow, and the advent of the pathogenesis of diseases and cellular pathology (6). However, some authors (7) consider the French surgeon Ambrosio Paré, who in 1575 began a real scientific period in France, the father of legal medicine. This paternity is divided with Zacchia, the Pope’s physician, who taught in Italy and wrote in 1601 what can be considered the first medicolegal textbook (7). This was of decisive influence on the development of forensic sciences, as were the European codes of the 16th century (6): the Bamberg Code in 1507 and especially the Caroline Code in 1532, which obliged the courts to call specialized doctors to clarify forensic questions. Nevertheless, the 19th century was indeed a reference for modern legal medicine, born formally in many countries, almost at the same time: 1855 in Austria (6), 1872 in Hungary (8), 1886 in Brazil (7), 1887 in Great Britain (9,10), and 1889 in Portugal (when legal medicine was first referred to as being legally organized [11]). This century was really a golden age for forensic medicine (1,11), which knew a quick but supported growth, especially in France, Italy, and Germany (11). Besides, in German countries, forensic matters were always carefully treated, as can be proved by the early beginning of teaching forensic medicine in some universities in 1720 (11). The posterior development of forensic pathology was processed in accordance with the legal systems and sociopolitical conditions of each country. At the end of the 19th century, complementary sciences, such as toxicology and histology, were aggregate to forensic pathology, and from that union resulted the constitution of legal medicine institutes similar to the medicolegal units known today, where every type of expertise related to justice may be executed. Later, in the second half of the 20th century, a new medicolegal problem arose in Europe and wherever roads and cars existed. The traffic accidents and the necessity of civil litigations of the injuries of the victims led to a new medicolegal subspecialty concerning living people: clinical forensic medicine. It started in Belgium and France with Derobert, Roche, Muller, and Rousseau (12). Supported by the Deliberation 75 (7) of the Committee of Ministers of the Council of Europe, an “expertise-type” was created (12,13) to achieve a global evaluation of consequences resulting from injuries caused by accidents to the body of an individual (as a whole being). This process was crucial for the financial indemnity of the injuries by insurance companies. These ideas, adopted in Portugal by Oliveira Sá, a great enthusiast of this new 16 Pinheiro discipline, were developed and “exported” to Spain through the excellent relationship he had with the forensic physicians in the neighbor country, where a huge development took place; however, it was more as a private medical activity than centralized in medicolegal institutions. The popularity of this new forensic area increased quickly because of the growing number of traffic accidents in the world. Once the Iberian Peninsula was “conquered,” the area extended to South and Latin America. The English-speaking countries were the last to develop this new specialty; it has been only within the last several years that the popularity of clinical forensic medicine has exploded in the United States and the United Kingdom.

CONTEXT BLOCK The origin of forensic medicine remains lost in a distant past, whenever the principles of medical sciences met those of law and justice (1,2). Perhaps it began with the Code of Hammurabi (1792–1750 BCE), which imposed sanctions for errors in medical and surgical practices. The same type of punishment also existed in Persia. Later on, the Visigoths promulgated laws that punished poisoning, infanticide, and homicide. Described as a medical trunk that serves the administration of justice, forensic medicine has different branches. Forensic pathology is probably the most emblematic one. Known in many Latin countries as tanathology (from the Greek word thanatos, meaning “death’s god”), definitions of forensic pathology are often so broad that they would fit better into forensic medicine as a whole than in this single branch. For Di Maio (3), it is “a branch of medicine that applies the principles and knowledge of the medical sciences in the field of law.” An even larger conception of forensic pathology (4) considers it the study of diseases and injuries of the community, because it involves the knowledge of diagnosis and treatment in every medical specialty, but also requires information in many nonmedical areas, such as chemistry, physics, criminalistics and police sciences, motor vehicle and highway conception, politics, sociology, and even the way of life of a society. Closer to its objectives and limits, Williams et al. (5) define forensic pathology as a specialized branch of pathology (pathology being the study by scientific methods of disease and tissue injury) that relates within a legal framework to the effects of trauma, poisoning, occupational hazards, and natural disease. Introduction to Forensic Medicine 15 Forensic dissections of bodies began in the 13th century at the University of Bologna in Italy by a surgeon and teacher of anatomy, Saliceto (6). Surprisingly, these forensic dissections appeared before the hospital autopsies that started by the end of the 19th century with Rokitansky, Virchow, and the advent of the pathogenesis of diseases and cellular pathology (6). However, some authors (7) consider the French surgeon Ambrosio Paré, who in 1575 began a real scientific period in France, the father of legal medicine. This paternity is divided with Zacchia, the Pope’s physician, who taught in Italy and wrote in 1601 what can be considered the first medicolegal textbook (7). This was of decisive influence on the development of forensic sciences, as were the European codes of the 16th century (6): the Bamberg Code in 1507 and especially the Caroline Code in 1532, which obliged the courts to call specialized doctors to clarify forensic questions. Nevertheless, the 19th century was indeed a reference for modern legal medicine, born formally in many countries, almost at the same time: 1855 in Austria (6), 1872 in Hungary (8), 1886 in Brazil (7), 1887 in Great Britain (9,10), and 1889 in Portugal (when legal medicine was first referred to as being legally organized [11]). This century was really a golden age for forensic medicine (1,11), which knew a quick but supported growth, especially in France, Italy, and Germany (11). Besides, in German countries, forensic matters were always carefully treated, as can be proved by the early beginning of teaching forensic medicine in some universities in 1720 (11). The posterior development of forensic pathology was processed in accordance with the legal systems and sociopolitical conditions of each country. At the end of the 19th century, complementary sciences, such as toxicology and histology, were aggregate to forensic pathology, and from that union resulted the constitution of legal medicine institutes similar to the medicolegal units known today, where every type of expertise related to justice may be executed. Later, in the second half of the 20th century, a new medicolegal problem arose in Europe and wherever roads and cars existed. The traffic accidents and the necessity of civil litigations of the injuries of the victims led to a new medicolegal subspecialty concerning living people: clinical forensic medicine. It started in Belgium and France with Derobert, Roche, Muller, and Rousseau (12). Supported by the Deliberation 75 (7) of the Committee of Ministers of the Council of Europe, an “expertise-type” was created (12,13) to achieve a global evaluation of consequences resulting from injuries caused by accidents to the body of an individual (as a whole being). This process was crucial for the financial indemnity of the injuries by insurance companies. These ideas, adopted in Portugal by Oliveira Sá, a great enthusiast of this new 16 Pinheiro discipline, were developed and “exported” to Spain through the excellent relationship he had with the forensic physicians in the neighbor country, where a huge development took place; however, it was more as a private medical activity than centralized in medicolegal institutions. The popularity of this new forensic area increased quickly because of the growing number of traffic accidents in the world. Once the Iberian Peninsula was “conquered,” the area extended to South and Latin America. The English-speaking countries were the last to develop this new specialty; it has been only within the last several years that the popularity of clinical forensic medicine has exploded in the United States and the United Kingdom. SYSTEM INSTRUCTION Use only the information provided in the prompt and context block to address user queries. Do not use any kind of citations in your response, i.e., "(Smith et al.)" or "(7)", etc. QUESTION Which doctors are cited as being the fathers of forensic pathology?

"================ <TEXT PASSAGE> ======= [context document] ================ <QUESTION> ======= [user request] ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

What companies are mentioned in the following, and why are they important? Also, how much did each stock increase from last week? Explain the relevance of the Federal Reserve to the economy.

NEW YORK (AP) — U.S. stocks climbed Monday to claw back some of the losses from their worst week in nearly a year and a half. The S&P 500 rallied 1.2%, though it didn’t recoup all of its drop from Friday, let alone from the rest of the four-day losing streak that it broke. The Dow Jones Industrial Average rose 484 points, or 1.2%, and the Nasdaq composite gained 1.2%. Boeing climbed 3.4% after reaching a tentative deal with its largest union on a new contract that, if ratified, will avoid a strike that threatened to shut down aircraft production by the end of the week. Boeing said 33,000 workers represented by the International Association of Machinists and Aerospace Workers would get pay raises of 25% over the four-year contract. Nvidia and other Big Tech companies also returned to their long-held position of leading the market, at least briefly. Nvidia climbed 3.5% and was the strongest force pushing the S&P 500 upward. That cut into its 13.9% tumble last week, as questions continued about whether its stock price went too high in investors’ frenzy around artificial intelligence, even if Nvidia has continued to top analysts’ expectations for growth. After likewise climbing a bit in the morning, Treasury yields later pared their gains. That followed sharp swings in the bond market last week, when a highly anticipated update on the U.S. job market came in weak enough to worsen worries about the slowing U.S. economy. The Federal Reserve has been intentionally pressing the brakes on the economy through high interest rates in order to stifle high inflation. It’s about to start lowering rates later this month, which would ease the pressure on the economy, as it turns its focus toward protecting the job market and avoiding a recession. The question on Wall Street is if the Fed’s shift in focus will prove to be too late. Cuts to interest rates give stock prices a boost, but if an economic downturn does hit, it could more than offset such a benefit by dragging down profits for companies. That’s what happened in 2007, for example, when the Great Recession wrecked the global economy and financial markets. “Today, the absence of glaring household or corporate balance sheet vulnerabilities means Fed easing should be enough to prevent recession, and should provide investors some optimism for the future of the market,” suggests Seema Shah, chief global strategist at Principal Asset Management. On Wall Street, Palantir Technologies jumped 14.1% in its first trading after S&P Dow Jones Indices said it would add the company to its widely followed S&P 500 index. Dell Technologies rose 3.8% after likewise getting a notice of promotion to the index, though and Erie Indemnity lost an early gain to slip 0.6%. Apple’s stock was virutally flat after the company unveiled its latest iPhone model, the 16. It’s the first model to be tailored specifically for artificial intelligence, with expected improvements to its often dim-witted virtual assistant, Siri. Trading in Big Lots was halted after the discount retailer filed for Chapter 11 bankruptcy protection and said it plans to sell its assets and ongoing business operations to private equity firm Nexus Capital Management. All told, the S&P 500 rose 62.63 points to 5,471.05. The Dow gained 484.18 to 40,829.59, and the Nasdaq composite gained 193.77 to 16,884.60. In the bond market, the 10-year Treasury yield edged down to 3.71% from 3.72% late Friday. This upcoming week will feature the latest monthly updates on inflation at the consumer and wholesale levels. Such reports used to be the most anticipated economic data of each month, but market watchers say they’re now taking the back seat to updates on the job market because of the worries about a possible recession. Of course, if the reports show an unexpected spike higher in inflation, that could put the Federal Reserve in its worst-case scenario. Lower interest rates could help boost the economy, but they could also give inflation more fuel. In stock markets abroad, indexes rose in much of Europe after falling in Asia. Japan’s Nikkei 225 slipped 0.5% after the country’s economic growth for the second quarter was revised below expectations. Chinese stocks racked up losses after worse-than-expected inflation data disappointed investors. Indexes fell 1.4% in Hong Kong and 1.1% in Shanghai.

"================ <TEXT PASSAGE> ======= NEW YORK (AP) — U.S. stocks climbed Monday to claw back some of the losses from their worst week in nearly a year and a half. The S&P 500 rallied 1.2%, though it didn’t recoup all of its drop from Friday, let alone from the rest of the four-day losing streak that it broke. The Dow Jones Industrial Average rose 484 points, or 1.2%, and the Nasdaq composite gained 1.2%. Boeing climbed 3.4% after reaching a tentative deal with its largest union on a new contract that, if ratified, will avoid a strike that threatened to shut down aircraft production by the end of the week. Boeing said 33,000 workers represented by the International Association of Machinists and Aerospace Workers would get pay raises of 25% over the four-year contract. Nvidia and other Big Tech companies also returned to their long-held position of leading the market, at least briefly. Nvidia climbed 3.5% and was the strongest force pushing the S&P 500 upward. That cut into its 13.9% tumble last week, as questions continued about whether its stock price went too high in investors’ frenzy around artificial intelligence, even if Nvidia has continued to top analysts’ expectations for growth. After likewise climbing a bit in the morning, Treasury yields later pared their gains. That followed sharp swings in the bond market last week, when a highly anticipated update on the U.S. job market came in weak enough to worsen worries about the slowing U.S. economy. The Federal Reserve has been intentionally pressing the brakes on the economy through high interest rates in order to stifle high inflation. It’s about to start lowering rates later this month, which would ease the pressure on the economy, as it turns its focus toward protecting the job market and avoiding a recession. The question on Wall Street is if the Fed’s shift in focus will prove to be too late. Cuts to interest rates give stock prices a boost, but if an economic downturn does hit, it could more than offset such a benefit by dragging down profits for companies. That’s what happened in 2007, for example, when the Great Recession wrecked the global economy and financial markets. “Today, the absence of glaring household or corporate balance sheet vulnerabilities means Fed easing should be enough to prevent recession, and should provide investors some optimism for the future of the market,” suggests Seema Shah, chief global strategist at Principal Asset Management. On Wall Street, Palantir Technologies jumped 14.1% in its first trading after S&P Dow Jones Indices said it would add the company to its widely followed S&P 500 index. Dell Technologies rose 3.8% after likewise getting a notice of promotion to the index, though and Erie Indemnity lost an early gain to slip 0.6%. Apple’s stock was virutally flat after the company unveiled its latest iPhone model, the 16. It’s the first model to be tailored specifically for artificial intelligence, with expected improvements to its often dim-witted virtual assistant, Siri. Trading in Big Lots was halted after the discount retailer filed for Chapter 11 bankruptcy protection and said it plans to sell its assets and ongoing business operations to private equity firm Nexus Capital Management. All told, the S&P 500 rose 62.63 points to 5,471.05. The Dow gained 484.18 to 40,829.59, and the Nasdaq composite gained 193.77 to 16,884.60. In the bond market, the 10-year Treasury yield edged down to 3.71% from 3.72% late Friday. This upcoming week will feature the latest monthly updates on inflation at the consumer and wholesale levels. Such reports used to be the most anticipated economic data of each month, but market watchers say they’re now taking the back seat to updates on the job market because of the worries about a possible recession. Of course, if the reports show an unexpected spike higher in inflation, that could put the Federal Reserve in its worst-case scenario. Lower interest rates could help boost the economy, but they could also give inflation more fuel. In stock markets abroad, indexes rose in much of Europe after falling in Asia. Japan’s Nikkei 225 slipped 0.5% after the country’s economic growth for the second quarter was revised below expectations. Chinese stocks racked up losses after worse-than-expected inflation data disappointed investors. Indexes fell 1.4% in Hong Kong and 1.1% in Shanghai. https://apnews.com/article/stock-markets-fed-inflation-recession-jobs-32f3ec68b11f87b2194e04c2a29f537c ================ <QUESTION> ======= What companies are mentioned in the following, and why are they important? Also, how much did each stock increase from last week? Explain the relevance of the Federal Reserve to the economy. ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

Use the source provided only.

Who should not get the vaccine, and what other common products should these people be careful of?

Number 124a October 2023 COVID-19 mRNA vaccines Immunization has saved more lives in Canada in the Getting all of the recommended doses of vaccine is last 50 years than any other health measure. your best protection against COVID-19. It is important to keep a record of all immunizations What are COVID-19 mRNA vaccines? received. The COVID-19 mRNA vaccines (Moderna and Pfizer- BioNTech) protect against infection from the severe What are the benefits of the vaccines? acute respiratory syndrome coronavirus 2 (SARS-CoV- Immunization is the best way to protect you against 2) that causes COVID-19. The vaccines cause your COVID-19, which is a serious and sometimes fatal body to produce antibodies that will help protect you disease. The vaccines provide strong protection from getting sick if exposed to the virus. The vaccines against severe COVID-19 illness, including are approved by Health Canada. hospitalization and death. The COVID-19 mRNA vaccines provide better protection than other COVID- Who should get the vaccines? 19 vaccines. When you get immunized, you help The vaccines are recommended for those 6 months of protect others as well, including those who are unable age and older. The vaccines are especially important to get the vaccine. for those at increased risk of infection or severe disease, including: What are the possible reactions after the  People 65 years of age and older vaccines?  Residents of long-term care facilities Vaccines are very safe. It is much safer to get the  People with underlying medical conditions vaccine than to get COVID-19. The vaccines are not live virus vaccines and cannot give you COVID-19.  Pregnant people Common reactions to the vaccines may include  Healthcare workers soreness, redness, swelling and itchiness where the  First responders (police, firefighters, ambulance vaccine was given. For some people, these reactions attendants) may show up 8 or more days after getting the Indigenous peoples may be at increased risk of vaccine. Other reactions may include tiredness, serious illness from COVID-19 due to health inequities headache, fever, chills, muscle or joint soreness, resulting from colonialism. swollen lymph nodes under the armpit, nausea and vomiting. Babies and young children may be irritable, More information, including how to register for the sleepy and have a decreased appetite. These vaccine, can be found on the Government of British reactions are mild and generally last 1 to 2 days. If Columbia’s website: you have concerns about any symptoms you develop www2.gov.bc.ca/gov/content/covid- after receiving the vaccine, speak with your health 19/vaccine/register. care provider or call 8-1-1 for advice. If you had, or may have had, COVID-19 you should Rare cases of inflammation of the heart (myocarditis still get the vaccine. This is because you may not be and pericarditis) have been reported after getting the immune to the virus and/or variants of the virus that COVID-19 mRNA vaccines. These were most often causes COVID-19 and could get infected and sick seen: again.  After a second dose of the vaccine when the time How are the vaccines given? between doses was less than 8 weeks The vaccines are given by injection. People 5 years of  In males 12-29 years of age age and older should get 1 dose. Children 6 months to 4 years of age and people with weakened immune systems may need more than 1 dose depending on their immunization history.  With a higher dose of the Moderna vaccine vaccine or if you have had anaphylaxis with an unknown cause. Acetaminophen (e.g. Tylenol®) or ibuprofen (e.g. Are there additional considerations to getting Advil®) can be taken for fever or soreness. ASA the vaccine? (e.g. Aspirin®) should not be given to anyone Speak with your health care provider if you: under 18 years of age due to the risk of Reye  Were diagnosed with inflammation of the heart syndrome. (myocarditis or pericarditis) by a physician after a *Ibuprofen should not be given to children under 6 previous dose of COVID-19 vaccine without another months of age without first speaking to your health cause being identified care provider.  Have a history of multisystem inflammatory For information on Reye syndrome, see HealthLinkBC syndrome following COVID-19 File #84 Reye syndrome.  Have symptoms of COVID-19 It is important to stay in the clinic for 15 minutes after If you have a new illness preventing you from your getting any vaccine. There is an extremely rare regular activities, you should wait until you have possibility of a life-threatening allergic reaction called recovered. This will help to distinguish side effects of anaphylaxis. This happens in less than 1 in a million the vaccine from worsening of your illness. people who get the vaccine. Symptoms may include hives, difficulty breathing, or swelling of the throat, What is COVID-19? tongue or lips. If this reaction occurs, your health care COVID-19 is an infection of the airways and lungs provider is prepared to treat it. Emergency treatment caused by the SARS-CoV-2 coronavirus. Symptoms of includes administration of epinephrine (adrenaline) COVID-19 can include cough, shortness of breath, and transfer by ambulance to the nearest emergency fever, chills, tiredness and loss of smell or taste. While department. If symptoms develop after you leave the some people with COVID-19 may have no symptoms clinic, call 9-1-1 or your local emergency number. or only mild symptoms, others can require Always report serious or unexpected reactions to your hospitalization and may die. Serious illness is more health care provider. common in those who are older and those with After getting the COVID-19 mRNA vaccine, you might certain chronic health conditions such as diabetes, be contacted to participate in a study monitoring the heart disease or lung disease. For some people, safety of the vaccine. To learn more about the study symptoms of COVID-19 can last for weeks or longer. please visit https://canvas-network.ca. The long-term effects of COVID-19 on a person’s health are unknown. Who should not get the vaccine? You should not get the vaccine if you have a serious How is COVID-19 spread? allergy (anaphylaxis) to polyethylene glycol (PEG) The virus that causes COVID-19 is spread from person which is in both of the COVID-19 mRNA vaccines. PEG to person by coughing, sneezing, talking and singing. can be found in some cosmetics, skin care products, It can also be spread by touching an object or surface laxatives, cough syrups, and bowel preparation with the virus on it and then touching your eyes, nose products for colonoscopy. PEG can be an additive in or mouth. some processed foods and drinks, but no cases of For more information on COVID-19 vaccines, visit anaphylaxis to PEG in foods and drinks have been BCCDC’s COVID-19 vaccine page reported. www.bccdc.ca/health-info/diseases-conditions/covid- Speak with your health care provider if you had 19/covid-19-vaccine. anaphylaxis after a previous dose of a COVID-19 For more HealthLinkBC File topics, visit www.HealthLinkBC.ca/more/resources/healthlink-bc-files or your local public health unit. For non-emergency health information and advice in B.C. visit www.HealthLinkBC.ca or call 8- 1-1 (toll-free). For the deaf and hard of hearing, call 7-1-1. Translation services are available in more than 130 languages on request.

Use the source provided only. Who should not get the vaccine, and what other common products should these people be careful of? Number 124a October 2023 COVID-19 mRNA vaccines Immunization has saved more lives in Canada in the Getting all of the recommended doses of vaccine is last 50 years than any other health measure. your best protection against COVID-19. It is important to keep a record of all immunizations What are COVID-19 mRNA vaccines? received. The COVID-19 mRNA vaccines (Moderna and Pfizer- BioNTech) protect against infection from the severe What are the benefits of the vaccines? acute respiratory syndrome coronavirus 2 (SARS-CoV- Immunization is the best way to protect you against 2) that causes COVID-19. The vaccines cause your COVID-19, which is a serious and sometimes fatal body to produce antibodies that will help protect you disease. The vaccines provide strong protection from getting sick if exposed to the virus. The vaccines against severe COVID-19 illness, including are approved by Health Canada. hospitalization and death. The COVID-19 mRNA vaccines provide better protection than other COVID- Who should get the vaccines? 19 vaccines. When you get immunized, you help The vaccines are recommended for those 6 months of protect others as well, including those who are unable age and older. The vaccines are especially important to get the vaccine. for those at increased risk of infection or severe disease, including: What are the possible reactions after the  People 65 years of age and older vaccines?  Residents of long-term care facilities Vaccines are very safe. It is much safer to get the  People with underlying medical conditions vaccine than to get COVID-19. The vaccines are not live virus vaccines and cannot give you COVID-19.  Pregnant people Common reactions to the vaccines may include  Healthcare workers soreness, redness, swelling and itchiness where the  First responders (police, firefighters, ambulance vaccine was given. For some people, these reactions attendants) may show up 8 or more days after getting the Indigenous peoples may be at increased risk of vaccine. Other reactions may include tiredness, serious illness from COVID-19 due to health inequities headache, fever, chills, muscle or joint soreness, resulting from colonialism. swollen lymph nodes under the armpit, nausea and vomiting. Babies and young children may be irritable, More information, including how to register for the sleepy and have a decreased appetite. These vaccine, can be found on the Government of British reactions are mild and generally last 1 to 2 days. If Columbia’s website: you have concerns about any symptoms you develop www2.gov.bc.ca/gov/content/covid- after receiving the vaccine, speak with your health 19/vaccine/register. care provider or call 8-1-1 for advice. If you had, or may have had, COVID-19 you should Rare cases of inflammation of the heart (myocarditis still get the vaccine. This is because you may not be and pericarditis) have been reported after getting the immune to the virus and/or variants of the virus that COVID-19 mRNA vaccines. These were most often causes COVID-19 and could get infected and sick seen: again.  After a second dose of the vaccine when the time How are the vaccines given? between doses was less than 8 weeks The vaccines are given by injection. People 5 years of  In males 12-29 years of age age and older should get 1 dose. Children 6 months to 4 years of age and people with weakened immune systems may need more than 1 dose depending on their immunization history.  With a higher dose of the Moderna vaccine vaccine or if you have had anaphylaxis with an unknown cause. Acetaminophen (e.g. Tylenol®) or ibuprofen (e.g. Are there additional considerations to getting Advil®) can be taken for fever or soreness. ASA the vaccine? (e.g. Aspirin®) should not be given to anyone Speak with your health care provider if you: under 18 years of age due to the risk of Reye  Were diagnosed with inflammation of the heart syndrome. (myocarditis or pericarditis) by a physician after a *Ibuprofen should not be given to children under 6 previous dose of COVID-19 vaccine without another months of age without first speaking to your health cause being identified care provider.  Have a history of multisystem inflammatory For information on Reye syndrome, see HealthLinkBC syndrome following COVID-19 File #84 Reye syndrome.  Have symptoms of COVID-19 It is important to stay in the clinic for 15 minutes after If you have a new illness preventing you from your getting any vaccine. There is an extremely rare regular activities, you should wait until you have possibility of a life-threatening allergic reaction called recovered. This will help to distinguish side effects of anaphylaxis. This happens in less than 1 in a million the vaccine from worsening of your illness. people who get the vaccine. Symptoms may include hives, difficulty breathing, or swelling of the throat, What is COVID-19? tongue or lips. If this reaction occurs, your health care COVID-19 is an infection of the airways and lungs provider is prepared to treat it. Emergency treatment caused by the SARS-CoV-2 coronavirus. Symptoms of includes administration of epinephrine (adrenaline) COVID-19 can include cough, shortness of breath, and transfer by ambulance to the nearest emergency fever, chills, tiredness and loss of smell or taste. While department. If symptoms develop after you leave the some people with COVID-19 may have no symptoms clinic, call 9-1-1 or your local emergency number. or only mild symptoms, others can require Always report serious or unexpected reactions to your hospitalization and may die. Serious illness is more health care provider. common in those who are older and those with After getting the COVID-19 mRNA vaccine, you might certain chronic health conditions such as diabetes, be contacted to participate in a study monitoring the heart disease or lung disease. For some people, safety of the vaccine. To learn more about the study symptoms of COVID-19 can last for weeks or longer. please visit https://canvas-network.ca. The long-term effects of COVID-19 on a person’s health are unknown. Who should not get the vaccine? You should not get the vaccine if you have a serious How is COVID-19 spread? allergy (anaphylaxis) to polyethylene glycol (PEG) The virus that causes COVID-19 is spread from person which is in both of the COVID-19 mRNA vaccines. PEG to person by coughing, sneezing, talking and singing. can be found in some cosmetics, skin care products, It can also be spread by touching an object or surface laxatives, cough syrups, and bowel preparation with the virus on it and then touching your eyes, nose products for colonoscopy. PEG can be an additive in or mouth. some processed foods and drinks, but no cases of For more information on COVID-19 vaccines, visit anaphylaxis to PEG in foods and drinks have been BCCDC’s COVID-19 vaccine page reported. www.bccdc.ca/health-info/diseases-conditions/covid- Speak with your health care provider if you had 19/covid-19-vaccine. anaphylaxis after a previous dose of a COVID-19 For more HealthLinkBC File topics, visit www.HealthLinkBC.ca/more/resources/healthlink-bc-files or your local public health unit. For non-emergency health information and advice in B.C. visit www.HealthLinkBC.ca or call 8- 1-1 (toll-free). For the deaf and hard of hearing, call 7-1-1. Translation services are available in more than 130 languages on request.

You must answer based solely on the information provided, no outside information is allowed.

What caused the boat to sink?

December 24, the day Peterson said he was fishing, was gray, damp, and cold with a bit of wind. Few people were at the Berkeley Marina. When questioned by police, Peterson would not say what he was hoping to catch, but the fishing searches performed from his computer earlier in the month had included searches relating to sturgeon and striped bass. Angelo Cuanang, a published author on fishing in the San Francisco Bay who was accepted by the court as an expert fisherman, testified that Brooks Island was the wrong place to seek sturgeon, which congregated in a different part of the bay that time of year. Sturgeon also preferred live bait to lures, and Peterson’s rod was too weak to catch them. Anchoring was essential to reel in sturgeon; the homemade cement anchor in his boat would have been inadequate. Finally, it was illegal to troll for sturgeon, as Peterson claimed to have done. Peterson’s lures and the time of year he was fishing were also wrong for catching striped bass. The prosecution’s theory was as follows: Peterson killed Laci sometime on the night of December 23 or morning of December 24. On the morning of the 24th, Peterson let their dog McKenzie out with his leash on to make it appear something had happened while Laci was walking him. He wrapped Laci’s body in a tarp in the bed of his truck, covered her with the patio umbrellas, drove to the warehouse, and then moved her body into his boat. He drove to the Berkeley Marina, motored out to an area near Brooks Island, and slipped her body, attached to homemade concrete weights like the homemade anchor Peterson had made, into the bay. Peterson then returned to Modesto, dropped off the boat at the warehouse, put the boat cover out back under a leaky gas blower so that any scent would be obscured, washed his clothes, and proceeded with the ruse that Laci was missing, hoping her body would never be discovered. The defense argued the police had not diligently pursued whether a person or persons other than Peterson were more likely responsible for Laci’s disappearance and murder. The defense presented evidence that a burglary had occurred on the Petersons’ street the week of her disappearance and argued that the police failed adequately to follow up on whether that burglary had any connection to Laci’s disappearance. It also presented evidence that a stranger had gone to several houses on December 23 asking for money and, one neighbor thought, casing houses for burglaries, and so might have had something to do with her disappearance. Testimony was presented thatthe same neighbor, walking with a police officer on Christmas Day to look for the stranger, had seen a pair of sandals lying in the road 150 feet from the Petersons’ home; the neighbor wondered at the time if they might have any connection to Laci’s disappearance, but the officer just left them there. To support the possibility of a third party’s involvement, the defense challenged the prosecution’s theory that Conner died December 23 or 24, presenting its own expert who testified based on ultrasounds and other evidence that Conner lived until after Christmas.The defense also sought to challenge other aspects of the prosecution’s case. To rebut the dog-trailing evidence, the defense called Ronald Seitz, a second dog handler who also had his dog try to find Laci’s scent at the Berkeley Marina on December 28. The dog, T.J., was given Laci’s slipper as a scent object, but discovered no scent trail. To rebut the inference that Peterson had a financial incentive to kill Laci, the defense presented a financial expert who testified that TradeCorp U.S.A. and the Petersons were both reasonably financially healthy. To portray the prosecution’s theory as physically impossible, the defense also sought to introduce video of a demonstration with a weighted 150-pound dummy in a boat on the bay in which a defense firm employee, trying to dump the dummy out, sank the boat. As will be discussed below, the trial court excluded the video. The defense offered explanations for the circumstances of Peterson’s behavior in April. His use of his mother’s name to purchase a car was at her suggestion, to avoid having it impounded. He had large amounts of cash because she gave it to him to reimburse him for money erroneously withdrawn from his bank account rather than hers. Finally, he had his brother’s driver’s license because the club where he was going to golf that day gave discounts for local residents such as his brother. The jury found Peterson guilty of murder in the first degree for killing Laci and murder in the second degree for killing Conner. (See Pen. Code, §§ 187, 189.) It found true the sole charged special circumstance, for multiple murder. Peterson had no criminal record nor any history of violent acts. At the penalty phase, the prosecution relied exclusively on the circumstances of the crime and victim impact evidence. Four members of Laci’s immediate family — her mother, Sharon; her stepfather, Ron Grantski; her brother, Brent; and her sister, Amy — testified. They described who Laci was as a person, shared photographs, memories, and vignettes from her life, and conveyed the grief and loss they each felt after the deaths of Laci and her unborn child. Through friends, family, neighbors, teachers, coworkers, employers, and other witnesses, the defense offered evidence that Peterson had been a kind and positive member of the community. Peterson grew up in a loving family, displayed a patient and gentle disposition, and was a solid student. As part of his high school community service requirement, Peterson worked at a home for the elderly and tutored homeless children. He started his own business and worked a variety of other jobs while in college. According to the defense, Peterson was always calm with Laci. Indeed, witnesses testified Peterson was calm at all times — at work, on the golf course, and in his dealings with all those around him. Friends and family testified to the impact the trial had had on Peterson’s relatives and indicated they believed, if sentenced to life in prison, Peterson could make a positive impact on the lives of others. In closing argument, defense counsel described Peterson’s life as one worth saving and argued that lingering doubt about Peterson’s guilt should also weigh in favor of a life verdict.

You must answer based solely on the information provided, no outside information is allowed. What caused the boat to sink? December 24, the day Peterson said he was fishing, was gray, damp, and cold with a bit of wind. Few people were at the Berkeley Marina. When questioned by police, Peterson would not say what he was hoping to catch, but the fishing searches performed from his computer earlier in the month had included searches relating to sturgeon and striped bass. Angelo Cuanang, a published author on fishing in the San Francisco Bay who was accepted by the court as an expert fisherman, testified that Brooks Island was the wrong place to seek sturgeon, which congregated in a different part of the bay that time of year. Sturgeon also preferred live bait to lures, and Peterson’s rod was too weak to catch them. Anchoring was essential to reel in sturgeon; the homemade cement anchor in his boat would have been inadequate. Finally, it was illegal to troll for sturgeon, as Peterson claimed to have done. Peterson’s lures and the time of year he was fishing were also wrong for catching striped bass. The prosecution’s theory was as follows: Peterson killed Laci sometime on the night of December 23 or morning of December 24. On the morning of the 24th, Peterson let their dog McKenzie out with his leash on to make it appear something had happened while Laci was walking him. He wrapped Laci’s body in a tarp in the bed of his truck, covered her with the patio umbrellas, drove to the warehouse, and then moved her body into his boat. He drove to the Berkeley Marina, motored out to an area near Brooks Island, and slipped her body, attached to homemade concrete weights like the homemade anchor Peterson had made, into the bay. Peterson then returned to Modesto, dropped off the boat at the warehouse, put the boat cover out back under a leaky gas blower so that any scent would be obscured, washed his clothes, and proceeded with the ruse that Laci was missing, hoping her body would never be discovered. The defense argued the police had not diligently pursued whether a person or persons other than Peterson were more likely responsible for Laci’s disappearance and murder. The defense presented evidence that a burglary had occurred on the Petersons’ street the week of her disappearance and argued that the police failed adequately to follow up on whether that burglary had any connection to Laci’s disappearance. It also presented evidence that a stranger had gone to several houses on December 23 asking for money and, one neighbor thought, casing houses for burglaries, and so might have had something to do with her disappearance. Testimony was presented thatthe same neighbor, walking with a police officer on Christmas Day to look for the stranger, had seen a pair of sandals lying in the road 150 feet from the Petersons’ home; the neighbor wondered at the time if they might have any connection to Laci’s disappearance, but the officer just left them there. To support the possibility of a third party’s involvement, the defense challenged the prosecution’s theory that Conner died December 23 or 24, presenting its own expert who testified based on ultrasounds and other evidence that Conner lived until after Christmas.The defense also sought to challenge other aspects of the prosecution’s case. To rebut the dog-trailing evidence, the defense called Ronald Seitz, a second dog handler who also had his dog try to find Laci’s scent at the Berkeley Marina on December 28. The dog, T.J., was given Laci’s slipper as a scent object, but discovered no scent trail. To rebut the inference that Peterson had a financial incentive to kill Laci, the defense presented a financial expert who testified that TradeCorp U.S.A. and the Petersons were both reasonably financially healthy. To portray the prosecution’s theory as physically impossible, the defense also sought to introduce video of a demonstration with a weighted 150-pound dummy in a boat on the bay in which a defense firm employee, trying to dump the dummy out, sank the boat. As will be discussed below, the trial court excluded the video. The defense offered explanations for the circumstances of Peterson’s behavior in April. His use of his mother’s name to purchase a car was at her suggestion, to avoid having it impounded. He had large amounts of cash because she gave it to him to reimburse him for money erroneously withdrawn from his bank account rather than hers. Finally, he had his brother’s driver’s license because the club where he was going to golf that day gave discounts for local residents such as his brother. The jury found Peterson guilty of murder in the first degree for killing Laci and murder in the second degree for killing Conner. (See Pen. Code, §§ 187, 189.) It found true the sole charged special circumstance, for multiple murder. Peterson had no criminal record nor any history of violent acts. At the penalty phase, the prosecution relied exclusively on the circumstances of the crime and victim impact evidence. Four members of Laci’s immediate family — her mother, Sharon; her stepfather, Ron Grantski; her brother, Brent; and her sister, Amy — testified. They described who Laci was as a person, shared photographs, memories, and vignettes from her life, and conveyed the grief and loss they each felt after the deaths of Laci and her unborn child. Through friends, family, neighbors, teachers, coworkers, employers, and other witnesses, the defense offered evidence that Peterson had been a kind and positive member of the community. Peterson grew up in a loving family, displayed a patient and gentle disposition, and was a solid student. As part of his high school community service requirement, Peterson worked at a home for the elderly and tutored homeless children. He started his own business and worked a variety of other jobs while in college. According to the defense, Peterson was always calm with Laci. Indeed, witnesses testified Peterson was calm at all times — at work, on the golf course, and in his dealings with all those around him. Friends and family testified to the impact the trial had had on Peterson’s relatives and indicated they believed, if sentenced to life in prison, Peterson could make a positive impact on the lives of others. In closing argument, defense counsel described Peterson’s life as one worth saving and argued that lingering doubt about Peterson’s guilt should also weigh in favor of a life verdict.

[question] [user request] ===================== [text] [context document] ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

Give me a bullet point list of all the categories of personal information that can be legally collected in the state of California. Then, in 200 words or less, explain why this information is taken and why it is sometimes sold.

NOTICE AT COLLECTION We may collect the following categories of personal information (as defined in the California Consumer Privacy Act (CCPA) and the California Customer Records statute), including sensitive personal information (as defined in the CCPA): Identifiers, such as name, email address, username and password, postal address, telephone number, signature, government-issued identifier, license plate number, IP address, and other similar identifiers. Characteristics of protected classifications and demographic information, such as gender, age, race, disability status, sexual orientation, gender identity, military/veteran status, marital status, national origin, and medical information. Commercial information, including information about your interests and consuming history or tendencies, such as products or services considered; transaction information when you request information, contact Guest Services, or purchase, return, request or exchange a product or service, including payment card information or other financial information; information provided in response to surveys or other research conducted on our behalf; and information you provide in public forums. Internet or other electronic network activity information, including information regarding your interactions with us online and information we obtain from third parties about use of our applications on third-party platforms or devices. Geolocation data, including precise or approximate location information provided by a mobile device or other device or product interacting with or detected by our sites, applications, or physical properties, where we are permitted by law to process this information. Audio, electronic, visual, or similar information, including telephone call recordings, other voice recordings, and still or video images captured by cameras or readers on or around our physical properties. Inferences based on the above. We collect this information so that we can best serve you, including to fulfill your requests and to share offers or information that we think you may be interested in. As further described in the “Use of Your Information by The Walt Disney Family of Companies” section in our Privacy Policy, we generally collect and use the above-listed categories of personal information to provide and manage our sites, applications, products, and services, and for other business or commercial purposes, such as advertising, marketing, and to improve our products and services. Certain data collection on our sites and applications by third parties for purposes of interest-based advertising and social media tools may be a “sale” or “sharing” under California privacy law. As defined by California law, we “sold” or “shared” certain data elements within the following categories of personal information: identifiers, demographic information, commercial information, Internet or other electronic network activity information, approximate geolocation, and inferences drawn from the above. If you would like to opt out of the sale or sharing of your personal information, you may click the “Do Not Sell or Share My Personal Information” link in our website footers or in our application settings. Please note that your opt-out choice is specific to the digital property and to the device and browser you are using. You may additionally choose to provide the information requested in this opt-out form, which may enable us to take action on your opt-out request more broadly than for a specific digital property. We retain each category of personal information that we collect for as long as necessary to fulfill the purposes described in our Privacy Policy, including to satisfy legal or reporting requirements. What this means in practice will vary for different types of information, but the criteria assessed in the data retention analysis take into account ongoing business or legal needs for the information, for example in relation to tax, health and safety, and potential or actual disputes or investigations. More information, including a description of your legal rights, can be found in the “California Privacy Rights” section below. ADDITIONAL PRIVACY MANDATORY DISCLOSURES We also make the following disclosures for purposes of compliance with California privacy law: We collected the following categories of personal information in the last 12 months: identifiers, characteristics of protected classifications and demographic information, commercial information, Internet or other electronic network activity information, geolocation data, audio, electronic, visual or similar information, and inferences drawn from the above. The sources of personal information from whom we collected are: directly from our guests, third-party sites or platforms that you link with your registration account, analytics tools, social networks, advertising networks, and third-party services that update or supplement information we hold about you. The business or commercial purposes of collecting personal information are as summarized in our “Notice at Collection” section, and as described in more detail in our Privacy Policy under “Use of Your Information by The Walt Disney Family of Companies.” We disclosed certain data elements within the following categories of personal information for a business purpose in the last 12 months: identifiers, characteristics of protected classifications and demographic information, commercial information, Internet or other electronic network activity information, geolocation data, audio, electronic, visual or similar information, and inferences drawn from the above. We disclosed each category to business partners, service providers, government entities, and other third parties as described in the “Sharing Your Personal Information with Other Entities” section of the Privacy Policy. As defined by applicable law, we “sold” or “shared” certain data elements within the following categories of personal information in the last 12 months: identifiers, demographic information, commercial information, Internet or other electronic network activity information, approximate geolocation, and inferences drawn from the above. We “sold” or “shared” each category to or with entities who provide advertising, marketing, or audience measurement; other online third-party branded tools or functionality (such as maps or video players); and social networks. The business or commercial purposes of “selling” or “sharing” personal information is to assist us with advertising, marketing, audience measurement, and other functionality on our digital properties. We do not “sell” or “share” the personal information of known minors under 16 years of age. We do not use or disclose sensitive personal information for purposes other than those specified in Section 7027(m) of the CCPA regulations.

[question] Give me a bullet point list of all the categories of personal information that can be legally collected in the state of California. Then, in 200 words or less, explain why this information is taken and why it is sometimes sold. ===================== [text] NOTICE AT COLLECTION We may collect the following categories of personal information (as defined in the California Consumer Privacy Act (CCPA) and the California Customer Records statute), including sensitive personal information (as defined in the CCPA): Identifiers, such as name, email address, username and password, postal address, telephone number, signature, government-issued identifier, license plate number, IP address, and other similar identifiers. Characteristics of protected classifications and demographic information, such as gender, age, race, disability status, sexual orientation, gender identity, military/veteran status, marital status, national origin, and medical information. Commercial information, including information about your interests and consuming history or tendencies, such as products or services considered; transaction information when you request information, contact Guest Services, or purchase, return, request or exchange a product or service, including payment card information or other financial information; information provided in response to surveys or other research conducted on our behalf; and information you provide in public forums. Internet or other electronic network activity information, including information regarding your interactions with us online and information we obtain from third parties about use of our applications on third-party platforms or devices. Geolocation data, including precise or approximate location information provided by a mobile device or other device or product interacting with or detected by our sites, applications, or physical properties, where we are permitted by law to process this information. Audio, electronic, visual, or similar information, including telephone call recordings, other voice recordings, and still or video images captured by cameras or readers on or around our physical properties. Inferences based on the above. We collect this information so that we can best serve you, including to fulfill your requests and to share offers or information that we think you may be interested in. As further described in the “Use of Your Information by The Walt Disney Family of Companies” section in our Privacy Policy, we generally collect and use the above-listed categories of personal information to provide and manage our sites, applications, products, and services, and for other business or commercial purposes, such as advertising, marketing, and to improve our products and services. Certain data collection on our sites and applications by third parties for purposes of interest-based advertising and social media tools may be a “sale” or “sharing” under California privacy law. As defined by California law, we “sold” or “shared” certain data elements within the following categories of personal information: identifiers, demographic information, commercial information, Internet or other electronic network activity information, approximate geolocation, and inferences drawn from the above. If you would like to opt out of the sale or sharing of your personal information, you may click the “Do Not Sell or Share My Personal Information” link in our website footers or in our application settings. Please note that your opt-out choice is specific to the digital property and to the device and browser you are using. You may additionally choose to provide the information requested in this opt-out form, which may enable us to take action on your opt-out request more broadly than for a specific digital property. We retain each category of personal information that we collect for as long as necessary to fulfill the purposes described in our Privacy Policy, including to satisfy legal or reporting requirements. What this means in practice will vary for different types of information, but the criteria assessed in the data retention analysis take into account ongoing business or legal needs for the information, for example in relation to tax, health and safety, and potential or actual disputes or investigations. More information, including a description of your legal rights, can be found in the “California Privacy Rights” section below. ADDITIONAL PRIVACY MANDATORY DISCLOSURES We also make the following disclosures for purposes of compliance with California privacy law: We collected the following categories of personal information in the last 12 months: identifiers, characteristics of protected classifications and demographic information, commercial information, Internet or other electronic network activity information, geolocation data, audio, electronic, visual or similar information, and inferences drawn from the above. The sources of personal information from whom we collected are: directly from our guests, third-party sites or platforms that you link with your registration account, analytics tools, social networks, advertising networks, and third-party services that update or supplement information we hold about you. The business or commercial purposes of collecting personal information are as summarized in our “Notice at Collection” section, and as described in more detail in our Privacy Policy under “Use of Your Information by The Walt Disney Family of Companies.” We disclosed certain data elements within the following categories of personal information for a business purpose in the last 12 months: identifiers, characteristics of protected classifications and demographic information, commercial information, Internet or other electronic network activity information, geolocation data, audio, electronic, visual or similar information, and inferences drawn from the above. We disclosed each category to business partners, service providers, government entities, and other third parties as described in the “Sharing Your Personal Information with Other Entities” section of the Privacy Policy. As defined by applicable law, we “sold” or “shared” certain data elements within the following categories of personal information in the last 12 months: identifiers, demographic information, commercial information, Internet or other electronic network activity information, approximate geolocation, and inferences drawn from the above. We “sold” or “shared” each category to or with entities who provide advertising, marketing, or audience measurement; other online third-party branded tools or functionality (such as maps or video players); and social networks. The business or commercial purposes of “selling” or “sharing” personal information is to assist us with advertising, marketing, audience measurement, and other functionality on our digital properties. We do not “sell” or “share” the personal information of known minors under 16 years of age. We do not use or disclose sensitive personal information for purposes other than those specified in Section 7027(m) of the CCPA regulations. https://privacy.thewaltdisneycompany.com/en/current-privacy-policy/your-us-state-privacy-rights/ ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

Please only respond to questions using the provided text as a reference.

What resilience factors led to the smallest declines in new business activity during the COVID-19 pandemic?

Since its emergence in 2019, the worldwide spread of the novel coronavirus SARS-CoV-2 (COVID-19) has created a vast economic crisis as government lockdowns place considerable strain on businesses of all kinds – particularly those that rely on face- to-face contact, such as retail restaurants, and personal services. Given the importance of these businesses to local economic development and urban vitality, this paper makes use of the point-level Chicago Business License dataset to examine the impact of the COVID-19 pandemic on new business activity in the City of Chicago. The results indicate that on average, from March to September 2020, total monthly new business starts have declined by 33.4% compared to the monthly average of new starts in the City from 2016 to 2019. Food service and retail businesses have been hardest hit during this period, while chains of all types have seen larger average declines in new startup activity than independent businesses. These patterns also demonstrate interesting intra-urban spatial heterogeneity; ZIP codes with the largest resilience to pandemic-related drops in new business activity tend to have more dense, diverse, and walkable built environments, lower levels of social vulnerability, lower percentages of young residents, and higher percentages of Black and Asian (non-Hispanic) residents. These findings provide some useful evidence in support of the “15-minute city” and ethnic enclave resilience hypotheses. Interestingly, observed COVID-19 case rates also appear to have a positive relationship with new business resilience for new chain and food service establishments. This is likely due to the fact that neighborhoods with relatively high levels of new food service business activity also have relatively higher proportions of food service employees, who are more at risk for contracting COVID-19 as “essential” workers. Since the emergence of the novel SARS-CoV-2 (COVID-19) virus in late 2019, its global spread has led to a variety of negative economic consequences, from restrictions on business operations and government lockdowns to reduced consumer confidence, discretionary mobility, and stock market fluctuations (McKinsey & Company 2020). According to some estimates, real global Gross Domestic Product (GDP) dropped by 10% between 2019Q4 and 2020Q2 (McKinsey & Company 2020), while US GDP experienced its largest quarterly drop in history (9.1% in Quarter 2 of 2020), far outstripping the impact of any previous recessions (measured since data collection began in 1947) (Bauer et al. 2020, Routley 2020). Concurrently, the US unemployment rate reached its highest-ever recorded value in April 2020 at 14.7% (FRED 2020), while the S&P 500 lost 33% of its value in just one month (Capelle-Blancard, Desroziers 2020). Accordingly, US national data show that small business revenues across all industrial sectors dropped by 40% in April and had not yet recovered to pre-pandemic (January 2020) levels by August, remaining at a 20% deficit; revenue in “leisure and hospitality” small businesses, which includes the arts, entertainment, recreation, accommodation, and food service sectors, have fared even worse, bottoming out at a roughly 70% deficit and only recovering to around 40% of pre-pandemic levels (Chetty et al. 2020, Bauer et al. 2020). At the same time, as Figure 1 shows, applications for new businesses “with planned wages” dropped significantly in 2020Q1 and 2020Q2 compared to recent years, before significantly rebounding in 2020Q3 and 202Q4 (US Census Bureau 2020). While this amounts to a higher net number of applications in the first four quarters of 2020 compared to the 2016-2019 average, it is not yet clear whether this is due primarily to an administrative backlog created by the pandemic, the entrepreneurial activity of the newly unemployed, or re-adjustments in the market due to increased demand for particular kinds of goods and services (Bauer et al. 2020). Further understanding the specific effects of the pandemic on entrepreneurial activity is particularly important because new business creation is the primary engine for diversity, economic growth, and innovation in the economy as a whole (Frenken et al. 2007, Neumark et al. 2006, Wennekers, Thurik 1999), and declines in startup activity can have substantial negative long-term economic consequences (Sedl´aˇcek 2020, Guorio et al. 2016). There is also significant spatial heterogeneity in startup activity that plays an important role in cluster formation, regional economic development, and even the development trajectory of individual neighbourhoods within regions (Mack, Credit 2016, Malmberg, Maskell 2002, Florida 2002, Klepper 2009a,b, Porter 2000, Rutten, Boekema 2007). Understanding the fine-grained spatial and industrial effects of the pandemic on new businesses in more detail can help researchers and local governments to understand how to develop more economically resilient regions, which can provide insulation from future economic shocks. Data on new business applications are available on a weekly basis at the state level from the US Census Bureau’s Business Formation Statistics (2020). However, other datasets used to evaluate new business activity at finer spatial scales are not updated quickly enough to allow researchers to examine the fine-grained spatial and industrial/sectoral effects of the pandemic on new business activity. These include public datasets like the ZIP Code Business Patterns, as well as private datasets such as InfoUSA or the National Establishment Time Series (NETS). To overcome this problem, this paper utilizes a novel large dataset of business establishments (at the point level) derived from the open source Chicago Business License dataset, which is updated weekly and contains a comprehensive set of information on all new business license applications in the City of Chicago (2020) to assess two primary questions: first, to what extent has there been a decline in new business establishment1 starts during the pandemic (March to September, 2020) when compared to recent pre-pandemic trends (averages from 2016 to 2019)? Specifically, we are interested in whether there are distinct temporal trends by business sector or type (e.g., retail, food service, personal care and fitness, etc.) or between multi-establishment (or “chain”) (≥ 4 establishment) businesses and “independent” (< 4 establishment) businesses. Second, given the temporal analysis, what is the spatial expression of these trends? Are there particular areas of the city that are more resilient to declines in new business startups, and, if so, what are the characteristics of these areas? To analyse this formally, we aggregate changes in pandemic-related (i.e., March to September 2020) business activity to the ZIP code level in order to explore the relationship between pandemic-related decline and characteristics of social vulnerability, the built environment, demographics, and cumulative COVID-19 activity. The results of the analysis indicate that 1) on average, from March to September 2020 (through which complete data was available at the time of writing), total monthly new business starts have declined by 33.4% compared to the monthly average of new starts in the City from January 2016 to December 2019. 2) In general, food service and retail businesses have been hardest hit during this period (although all categories have experienced declines), while chains of all types have seen larger average declines in new startup activity (an average monthly drop of 61.9% from March to September compared to pre-pandemic averages) than independent businesses (a 29.2% drop). 3) These patterns demonstrate interesting intra-urban spatial heterogeneity; overall, a regression analysis suggests that the ZIP codes with the smallest pandemic-related declines in new business activity (i.e., those most resilient to the effects of the pandemic) tend to have more dense, diverse, and walkable built environments (defined in more detail below), lower levels of social vulnerability, lower percentages of young (age 18-39) residents, and higher percentages of Black and Asian (non-Hispanic) residents. Interestingly, observed COVID-19 case rates appear to have a positive relationship with new business resilience (after controlling for a variety of covariates), particularly for new chain and food service establishments. This could be a case of reverse causality, where areas with relatively high levels of new food service business activity also have relatively higher proportions of food service employees, who are more at risk for contracting COVID-19 as “essential” workers. New business creation provides a number of benefits to both local and macro-level economies that make it particularly important in the contemporary era of “flexible specialization” (Harvey 1989, Piore, Sabel 1984). The theoretical pathways from new business creation to economic benefits are diagrammed in Figure 2. Most directly, new (generally small) businesses create jobs that contribute to local economic growth (Birch 1987, Kirchhoff, Phillips 1988, Neumark et al. 2006). While on net these jobs may not always exceed the number of jobs lost from the older businesses they replace (Mack, Credit 2017), this process of business “churn” increases the probability of creating high-growth firms (so-called “gazelles”) that tend to produce the majority of new jobs (Henrekson, Johansson 2010, Nightingale, Coad 2014) and also provides for the “creative destruction” that fosters evolution and innovation in the economy2 by replacing jobs and businesses in older declining industries with new jobs in more innovative industries (Schumpeter 1934, 1947, 1950, Brown et al. 2006, Fogel et al. 2008). Another way that entrepreneurship fosters innovation and productivity improvement is through the creation of a more competitive economic environment that produces a selection process through which only the most viable and/or innovative businesses survive (Wennekers, Thurik 1999, Carree, Thurik 2003). Interestingly, this more competitive environment can drive a positive feedback loop through which increased competitiveness drives demand for better products, which creates incentives for additional innovation and new business creation (Teece 2007, Asheim 1996, Florida 1995, Porter 2000, Rutten, Boekema 2007, Malmberg, Maskell 2002). Fully fledged clusters, such as Silicon Valley, can develop a unique entrepreneurial culture of “competition and community” (Saxenian 1994) and attract additional educational, political, and financial investments that foster a holistic “entrepreneurial ecosystem” (Mack, Mayer 2015, Stam 2015) that captures the indigenous benefits of innovation, leading to economic success for individual businesses and associated local economic benefits, as well as providing a more supportive environment for further new business creation (Delgado et al. 2010). New businesses also contribute to innovation because they are often created as a direct result of knowledge spillovers, i.e., a new business is formed specifically to take advantage of some newly generated knowledge or idea (Acs, Audretsch 2003, Acs et al. 2009). These are often in the form of spinoffs from large existing companies, which some argue constitute the bulk of cluster forming activity (Buenstorf, Klepper 2009, Klepper, Sleeper 2005, Klepper 2009a,b). Finally, new businesses directly contribute to economic diversity. Increased diversity within related industries (i.e., “related variety”) provides another engine for innovation as the pool of new ideas and possible interactions and exchanges increases with the diversity of firms (Jacobs 1967, Boschma, Lambooy 1999, Boschma, Frenken 2006, Saviotti, Pyka 2004, Frenken et al. 2007). On the other hand, diversity through “unrelated variety” provides important portfolio benefits to local economies by distributing economic risk across a variety of different industries, making the economic system more resilient to unexpected shocks that may occur, no matter what sector they are concentrated in (Montgomery 1994, Frenken et al. 2007). In this paper, we are particularly interested in new business creation for small, independently owned businesses in customer-facing sectors such as retail and food service, for several reasons. These businesses are significant contributors to land use diversity, street life, and overall urban vitality (Jacobs 1961, Gehl 2010). At the same time, small retail shops help to contribute to a unique “sense of place” in a given locality that is the direct product of local creative efforts and sensibilities (Jacobs 1961, Relph 1976, Robertson 1999, Kunstler 1994, Walljasper 2007, Alexander 1977, Montgomery 1998). The owners of these kinds of businesses themselves are also often more connected to the specific dynamics, demands, and politics of the local community, and tend to contribute to local import substitution (increasing the local multiplier effect) by spending profits to purchase requisite subsidiary goods and services locally, rather than exporting profits to another region, as is the case with larger chain businesses (Jacobs 1967, Talen, Jeong 2019a,b).

Please only respond to questions using the provided text as a reference. What resilience factors led to the smallest declines in new business activity during the COVID-19 pandemic? Since its emergence in 2019, the worldwide spread of the novel coronavirus SARS-CoV-2 (COVID-19) has created a vast economic crisis as government lockdowns place considerable strain on businesses of all kinds – particularly those that rely on face- to-face contact, such as retail restaurants, and personal services. Given the importance of these businesses to local economic development and urban vitality, this paper makes use of the point-level Chicago Business License dataset to examine the impact of the COVID-19 pandemic on new business activity in the City of Chicago. The results indicate that on average, from March to September 2020, total monthly new business starts have declined by 33.4% compared to the monthly average of new starts in the City from 2016 to 2019. Food service and retail businesses have been hardest hit during this period, while chains of all types have seen larger average declines in new startup activity than independent businesses. These patterns also demonstrate interesting intra-urban spatial heterogeneity; ZIP codes with the largest resilience to pandemic-related drops in new business activity tend to have more dense, diverse, and walkable built environments, lower levels of social vulnerability, lower percentages of young residents, and higher percentages of Black and Asian (non-Hispanic) residents. These findings provide some useful evidence in support of the “15-minute city” and ethnic enclave resilience hypotheses. Interestingly, observed COVID-19 case rates also appear to have a positive relationship with new business resilience for new chain and food service establishments. This is likely due to the fact that neighborhoods with relatively high levels of new food service business activity also have relatively higher proportions of food service employees, who are more at risk for contracting COVID-19 as “essential” workers. Since the emergence of the novel SARS-CoV-2 (COVID-19) virus in late 2019, its global spread has led to a variety of negative economic consequences, from restrictions on business operations and government lockdowns to reduced consumer confidence, discretionary mobility, and stock market fluctuations (McKinsey & Company 2020). According to some estimates, real global Gross Domestic Product (GDP) dropped by 10% between 2019Q4 and 2020Q2 (McKinsey & Company 2020), while US GDP experienced its largest quarterly drop in history (9.1% in Quarter 2 of 2020), far outstripping the impact of any previous recessions (measured since data collection began in 1947) (Bauer et al. 2020, Routley 2020). Concurrently, the US unemployment rate reached its highest-ever recorded value in April 2020 at 14.7% (FRED 2020), while the S&P 500 lost 33% of its value in just one month (Capelle-Blancard, Desroziers 2020). Accordingly, US national data show that small business revenues across all industrial sectors dropped by 40% in April and had not yet recovered to pre-pandemic (January 2020) levels by August, remaining at a 20% deficit; revenue in “leisure and hospitality” small businesses, which includes the arts, entertainment, recreation, accommodation, and food service sectors, have fared even worse, bottoming out at a roughly 70% deficit and only recovering to around 40% of pre-pandemic levels (Chetty et al. 2020, Bauer et al. 2020). At the same time, as Figure 1 shows, applications for new businesses “with planned wages” dropped significantly in 2020Q1 and 2020Q2 compared to recent years, before significantly rebounding in 2020Q3 and 202Q4 (US Census Bureau 2020). While this amounts to a higher net number of applications in the first four quarters of 2020 compared to the 2016-2019 average, it is not yet clear whether this is due primarily to an administrative backlog created by the pandemic, the entrepreneurial activity of the newly unemployed, or re-adjustments in the market due to increased demand for particular kinds of goods and services (Bauer et al. 2020). Further understanding the specific effects of the pandemic on entrepreneurial activity is particularly important because new business creation is the primary engine for diversity, economic growth, and innovation in the economy as a whole (Frenken et al. 2007, Neumark et al. 2006, Wennekers, Thurik 1999), and declines in startup activity can have substantial negative long-term economic consequences (Sedl´aˇcek 2020, Guorio et al. 2016). There is also significant spatial heterogeneity in startup activity that plays an important role in cluster formation, regional economic development, and even the development trajectory of individual neighbourhoods within regions (Mack, Credit 2016, Malmberg, Maskell 2002, Florida 2002, Klepper 2009a,b, Porter 2000, Rutten, Boekema 2007). Understanding the fine-grained spatial and industrial effects of the pandemic on new businesses in more detail can help researchers and local governments to understand how to develop more economically resilient regions, which can provide insulation from future economic shocks. Data on new business applications are available on a weekly basis at the state level from the US Census Bureau’s Business Formation Statistics (2020). However, other datasets used to evaluate new business activity at finer spatial scales are not updated quickly enough to allow researchers to examine the fine-grained spatial and industrial/sectoral effects of the pandemic on new business activity. These include public datasets like the ZIP Code Business Patterns, as well as private datasets such as InfoUSA or the National Establishment Time Series (NETS). To overcome this problem, this paper utilizes a novel large dataset of business establishments (at the point level) derived from the open source Chicago Business License dataset, which is updated weekly and contains a comprehensive set of information on all new business license applications in the City of Chicago (2020) to assess two primary questions: first, to what extent has there been a decline in new business establishment1 starts during the pandemic (March to September, 2020) when compared to recent pre-pandemic trends (averages from 2016 to 2019)? Specifically, we are interested in whether there are distinct temporal trends by business sector or type (e.g., retail, food service, personal care and fitness, etc.) or between multi-establishment (or “chain”) (≥ 4 establishment) businesses and “independent” (< 4 establishment) businesses. Second, given the temporal analysis, what is the spatial expression of these trends? Are there particular areas of the city that are more resilient to declines in new business startups, and, if so, what are the characteristics of these areas? To analyse this formally, we aggregate changes in pandemic-related (i.e., March to September 2020) business activity to the ZIP code level in order to explore the relationship between pandemic-related decline and characteristics of social vulnerability, the built environment, demographics, and cumulative COVID-19 activity. The results of the analysis indicate that 1) on average, from March to September 2020 (through which complete data was available at the time of writing), total monthly new business starts have declined by 33.4% compared to the monthly average of new starts in the City from January 2016 to December 2019. 2) In general, food service and retail businesses have been hardest hit during this period (although all categories have experienced declines), while chains of all types have seen larger average declines in new startup activity (an average monthly drop of 61.9% from March to September compared to pre-pandemic averages) than independent businesses (a 29.2% drop). 3) These patterns demonstrate interesting intra-urban spatial heterogeneity; overall, a regression analysis suggests that the ZIP codes with the smallest pandemic-related declines in new business activity (i.e., those most resilient to the effects of the pandemic) tend to have more dense, diverse, and walkable built environments (defined in more detail below), lower levels of social vulnerability, lower percentages of young (age 18-39) residents, and higher percentages of Black and Asian (non-Hispanic) residents. Interestingly, observed COVID-19 case rates appear to have a positive relationship with new business resilience (after controlling for a variety of covariates), particularly for new chain and food service establishments. This could be a case of reverse causality, where areas with relatively high levels of new food service business activity also have relatively higher proportions of food service employees, who are more at risk for contracting COVID-19 as “essential” workers. New business creation provides a number of benefits to both local and macro-level economies that make it particularly important in the contemporary era of “flexible specialization” (Harvey 1989, Piore, Sabel 1984). The theoretical pathways from new business creation to economic benefits are diagrammed in Figure 2. Most directly, new (generally small) businesses create jobs that contribute to local economic growth (Birch 1987, Kirchhoff, Phillips 1988, Neumark et al. 2006). While on net these jobs may not always exceed the number of jobs lost from the older businesses they replace (Mack, Credit 2017), this process of business “churn” increases the probability of creating high-growth firms (so-called “gazelles”) that tend to produce the majority of new jobs (Henrekson, Johansson 2010, Nightingale, Coad 2014) and also provides for the “creative destruction” that fosters evolution and innovation in the economy2 by replacing jobs and businesses in older declining industries with new jobs in more innovative industries (Schumpeter 1934, 1947, 1950, Brown et al. 2006, Fogel et al. 2008). Another way that entrepreneurship fosters innovation and productivity improvement is through the creation of a more competitive economic environment that produces a selection process through which only the most viable and/or innovative businesses survive (Wennekers, Thurik 1999, Carree, Thurik 2003). Interestingly, this more competitive environment can drive a positive feedback loop through which increased competitiveness drives demand for better products, which creates incentives for additional innovation and new business creation (Teece 2007, Asheim 1996, Florida 1995, Porter 2000, Rutten, Boekema 2007, Malmberg, Maskell 2002). Fully fledged clusters, such as Silicon Valley, can develop a unique entrepreneurial culture of “competition and community” (Saxenian 1994) and attract additional educational, political, and financial investments that foster a holistic “entrepreneurial ecosystem” (Mack, Mayer 2015, Stam 2015) that captures the indigenous benefits of innovation, leading to economic success for individual businesses and associated local economic benefits, as well as providing a more supportive environment for further new business creation (Delgado et al. 2010). New businesses also contribute to innovation because they are often created as a direct result of knowledge spillovers, i.e., a new business is formed specifically to take advantage of some newly generated knowledge or idea (Acs, Audretsch 2003, Acs et al. 2009). These are often in the form of spinoffs from large existing companies, which some argue constitute the bulk of cluster forming activity (Buenstorf, Klepper 2009, Klepper, Sleeper 2005, Klepper 2009a,b). Finally, new businesses directly contribute to economic diversity. Increased diversity within related industries (i.e., “related variety”) provides another engine for innovation as the pool of new ideas and possible interactions and exchanges increases with the diversity of firms (Jacobs 1967, Boschma, Lambooy 1999, Boschma, Frenken 2006, Saviotti, Pyka 2004, Frenken et al. 2007). On the other hand, diversity through “unrelated variety” provides important portfolio benefits to local economies by distributing economic risk across a variety of different industries, making the economic system more resilient to unexpected shocks that may occur, no matter what sector they are concentrated in (Montgomery 1994, Frenken et al. 2007). In this paper, we are particularly interested in new business creation for small, independently owned businesses in customer-facing sectors such as retail and food service, for several reasons. These businesses are significant contributors to land use diversity, street life, and overall urban vitality (Jacobs 1961, Gehl 2010). At the same time, small retail shops help to contribute to a unique “sense of place” in a given locality that is the direct product of local creative efforts and sensibilities (Jacobs 1961, Relph 1976, Robertson 1999, Kunstler 1994, Walljasper 2007, Alexander 1977, Montgomery 1998). The owners of these kinds of businesses themselves are also often more connected to the specific dynamics, demands, and politics of the local community, and tend to contribute to local import substitution (increasing the local multiplier effect) by spending profits to purchase requisite subsidiary goods and services locally, rather than exporting profits to another region, as is the case with larger chain businesses (Jacobs 1967, Talen, Jeong 2019a,b).

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. [user request] [context document]

I see that on the new flagship Nvidia models, there is always the designation RTX. What does this mean and why is it important? Explain in under 300 words.

“Ray tracing is the future, and it always will be!” has been the tongue-in-cheek phrase used by graphics developers for decades when asked whether real-time ray tracing will ever be feasible. Everyone seems to agree on the first part: ray tracing is the future. That’s because ray tracing is the only technology we know of that enables the rendering of truly photorealistic images. It’s no coincidence that every offline renderer used in the movie industry, where compromises on image quality are unacceptable, is based on ray tracing. Rasterization has made immense strides over the years, and it is still evolving even today. But it is also fundamentally limited in the type of effects it can compute. Truly taking graphics to the next level requires new underlying technology. This is where ray tracing comes in, and this is why real-time ray tracing has long been the dream of gamers and game developers. So will ray tracing always remain a dream of the future, and never arrive in the present? At GDC 2018, NVIDIA unveiled RTX, a high-performance implementation that will power all ray tracing APIs supported by NVIDIA on Volta and future GPUs. At the same event, Microsoft announced the integration of ray tracing as a first-class citizen into their industry standard DirectX API. Putting these two technologies together forms such a powerful combination that we can confidently answer the above question: the future is here! This is not a hyperbole: leading game studios are developing upcoming titles using RTX through DirectX — today. Ray tracing in games is no longer a pipe dream. It’s happening, and it will usher in a new era of real-time graphics. he API that Microsoft announced, DirectX Raytracing (DXR), is a natural extension of DirectX 12. It fully integrates ray tracing into DirectX, and makes it a companion (as opposed to a replacement) to rasterization and compute. API Overview The DXR API focuses on delivering high performance by giving the application signficant low-level control, as with earlier versions of DirectX 12. Several design decisions reflect this: All ray tracing related GPU work is dispatched via command lists and queues that the application schedules. Ray tracing therefore integrates tightly with other work such as rasterization or compute, and can be enqueued efficiently by a multithreaded application. Ray tracing shaders are dispatched as grids of work items, similar to compute shaders. This lets the implementation utilize the massive parallel processing throughput of GPUs and perform low-level scheduling of work items as appropriate for the given hardware. The application retains the responsibility of explicitly synchronizing GPU work and resources where necessary, as it does with rasterization and compute. This allows developers to optimize for the maximum amount of overlap between ray tracing, rasterization, compute work, and memory transfers. Ray tracing and other dispatch types share all resources such as textures, buffers, and constants. No conversion, duplication, or mapping is required to access a resource from ray tracing shaders. Resources that hold ray tracing specific data, such as acceleration structures and shader tables (see below), are entirely managed by the application. No memory allocations or transfers happen implicitly “under the hood”. Shader compilation is explicit and therefore under full application control. Shaders can be compiled individually or in batch. Compilation can be parallelized across multiple CPU threads if desired. At a high level, DXR introduces three new concepts to DirectX that the application must manage: Ray Tracing Pipeline State Objects contain the compiled shader code that gets executed during a ray tracing dispatch. Acceleration Structures contain the data structures used to accelerate ray tracing itself, i.e. the search for intersections between rays and scene geometry. Shader Tables define the relationship between ray tracing shaders, their resources (textures, constants, etc), and scene geometry. Let’s take a closer look at these. The traditional raster graphics pipeline defines a number of shader types: vertex shader, geometry shader, pixel shader, etc. Analog to that model, a ray tracing pipeline consists of five new shader types which are executed at different stages: The ray generation shader is the first thing invoked in a ray tracing dispatch. Ray generation shaders are comparable to compute shaders, with the added capability of calling the new HLSL function TraceRay(). This function casts a single ray into the scene to search for intersections, triggering other shaders in the process. A ray generation shader may call TraceRay() as many times as it likes. Intersection and any hit shaders are invoked whenever TraceRay() finds a potential intersection between the ray and the scene. The intersection shader determines whether the ray intersects an individual geometric primitive — for example a sphere, a subdivision surface, or really any primitive type you can code up! The most common type is, of course, triangles, for which the API offers special support through a built-in, highly tuned intersection shader. Once an intersection is found, the any hit shader may be used to process it further or potentially discard it. Any hit shaders commonly implement alpha testing by performing a texture lookup and deciding based on the texel’s value whether or not to discard an intersection. Once TraceRay() has completed the search for ray-scene intersections, either a closest hit or a miss shader is invoked, depending on the outcome of the search. The closest hit shader is typically where most shading operations take place: material evaluation, texture lookups, and so on. The miss shader can be used to implement environment lookups, for example. Both closest hit and miss shaders can recursively trace rays by calling TraceRay() themselves. The pipeline constructed from these shaders defines a single-ray programming model. Semantically, each GPU thread handles one ray at a time and cannot communicate with other threads or see other rays currently being processed. This keeps things simple for developers writing shaders, while allowing room for vendor-specific optimizations under the hood of the API. The main way for the different shader types to communicate with each other is the ray payload. The payload is simply a user-defined struct that’s passed as an inout parameter to TraceRay(). Any hit, closest hit, and miss shaders can read and write the payload, and therefore pass back the result of their computations to the caller of TraceRay().

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. I see that on the new flagship Nvidia models, there is always the designation RTX. What does this mean and why is it important? Explain in under 300 words. “Ray tracing is the future, and it always will be!” has been the tongue-in-cheek phrase used by graphics developers for decades when asked whether real-time ray tracing will ever be feasible. Everyone seems to agree on the first part: ray tracing is the future. That’s because ray tracing is the only technology we know of that enables the rendering of truly photorealistic images. It’s no coincidence that every offline renderer used in the movie industry, where compromises on image quality are unacceptable, is based on ray tracing. Rasterization has made immense strides over the years, and it is still evolving even today. But it is also fundamentally limited in the type of effects it can compute. Truly taking graphics to the next level requires new underlying technology. This is where ray tracing comes in, and this is why real-time ray tracing has long been the dream of gamers and game developers. So will ray tracing always remain a dream of the future, and never arrive in the present? At GDC 2018, NVIDIA unveiled RTX, a high-performance implementation that will power all ray tracing APIs supported by NVIDIA on Volta and future GPUs. At the same event, Microsoft announced the integration of ray tracing as a first-class citizen into their industry standard DirectX API. Putting these two technologies together forms such a powerful combination that we can confidently answer the above question: the future is here! This is not a hyperbole: leading game studios are developing upcoming titles using RTX through DirectX — today. Ray tracing in games is no longer a pipe dream. It’s happening, and it will usher in a new era of real-time graphics. he API that Microsoft announced, DirectX Raytracing (DXR), is a natural extension of DirectX 12. It fully integrates ray tracing into DirectX, and makes it a companion (as opposed to a replacement) to rasterization and compute. API Overview The DXR API focuses on delivering high performance by giving the application signficant low-level control, as with earlier versions of DirectX 12. Several design decisions reflect this: All ray tracing related GPU work is dispatched via command lists and queues that the application schedules. Ray tracing therefore integrates tightly with other work such as rasterization or compute, and can be enqueued efficiently by a multithreaded application. Ray tracing shaders are dispatched as grids of work items, similar to compute shaders. This lets the implementation utilize the massive parallel processing throughput of GPUs and perform low-level scheduling of work items as appropriate for the given hardware. The application retains the responsibility of explicitly synchronizing GPU work and resources where necessary, as it does with rasterization and compute. This allows developers to optimize for the maximum amount of overlap between ray tracing, rasterization, compute work, and memory transfers. Ray tracing and other dispatch types share all resources such as textures, buffers, and constants. No conversion, duplication, or mapping is required to access a resource from ray tracing shaders. Resources that hold ray tracing specific data, such as acceleration structures and shader tables (see below), are entirely managed by the application. No memory allocations or transfers happen implicitly “under the hood”. Shader compilation is explicit and therefore under full application control. Shaders can be compiled individually or in batch. Compilation can be parallelized across multiple CPU threads if desired. At a high level, DXR introduces three new concepts to DirectX that the application must manage: Ray Tracing Pipeline State Objects contain the compiled shader code that gets executed during a ray tracing dispatch. Acceleration Structures contain the data structures used to accelerate ray tracing itself, i.e. the search for intersections between rays and scene geometry. Shader Tables define the relationship between ray tracing shaders, their resources (textures, constants, etc), and scene geometry. Let’s take a closer look at these. The traditional raster graphics pipeline defines a number of shader types: vertex shader, geometry shader, pixel shader, etc. Analog to that model, a ray tracing pipeline consists of five new shader types which are executed at different stages: The ray generation shader is the first thing invoked in a ray tracing dispatch. Ray generation shaders are comparable to compute shaders, with the added capability of calling the new HLSL function TraceRay(). This function casts a single ray into the scene to search for intersections, triggering other shaders in the process. A ray generation shader may call TraceRay() as many times as it likes. Intersection and any hit shaders are invoked whenever TraceRay() finds a potential intersection between the ray and the scene. The intersection shader determines whether the ray intersects an individual geometric primitive — for example a sphere, a subdivision surface, or really any primitive type you can code up! The most common type is, of course, triangles, for which the API offers special support through a built-in, highly tuned intersection shader. Once an intersection is found, the any hit shader may be used to process it further or potentially discard it. Any hit shaders commonly implement alpha testing by performing a texture lookup and deciding based on the texel’s value whether or not to discard an intersection. Once TraceRay() has completed the search for ray-scene intersections, either a closest hit or a miss shader is invoked, depending on the outcome of the search. The closest hit shader is typically where most shading operations take place: material evaluation, texture lookups, and so on. The miss shader can be used to implement environment lookups, for example. Both closest hit and miss shaders can recursively trace rays by calling TraceRay() themselves. The pipeline constructed from these shaders defines a single-ray programming model. Semantically, each GPU thread handles one ray at a time and cannot communicate with other threads or see other rays currently being processed. This keeps things simple for developers writing shaders, while allowing room for vendor-specific optimizations under the hood of the API. The main way for the different shader types to communicate with each other is the ray payload. The payload is simply a user-defined struct that’s passed as an inout parameter to TraceRay(). Any hit, closest hit, and miss shaders can read and write the payload, and therefore pass back the result of their computations to the caller of TraceRay(). https://developer.nvidia.com/blog/introduction-nvidia-rtx-directx-ray-tracing/

You must respond solely based on the provided context, so do not rely on external knowledge or sources. Answer in 100 words or less.

I don't agree terms of my digital copy. Without referencing the context, what does Disney say is the process of returning a digital movie code purchased in a combination disc + code package.

4. Paid Transactions Identity of Seller Sales are made by Disney DTC or the seller identified at the time of sale, if different. If you have questions about your order, please contact the seller at the address provided and they will assist you. Some digital storefronts on the Disney Services are operated by third parties and, in that case, different or additional sale terms may apply, which you should read when they are presented to you. Digital Content and Virtual Items We may make applications, games, software or other digital content available on the Disney Services for you to license for a one-time fee. When purchasing a license to access such material from a Disney Service, charges will be disclosed to you on the Disney Service before you complete the license purchase. Your purchase of a virtual item or in-game currency is a payment for a limited, non-assignable license to access and use such content or functionality in the Disney Services with no right to reproduce, distribute, communicate to the public, make available to the public or transform any Disney Service via any online media, in any media format or channel now known or hereafter devised (except as may be expressly described or contemplated within the Disney Service). Virtual items (including characters and character names) or in-game currency purchased or available to you in the Disney Services can only be used in connection with the Disney Services where you obtained them or where they were developed by you as a result of game play. These items are not redeemable or subject to refund and cannot be traded outside of the Disney Services for money or other items for value. We may modify or discontinue virtual items or ingame currency at any time. Digital Movie Codes Digital codes originally packaged in a combination disc + code package (a package that includes a DVD, Blu-Ray, and/or 4K/UHD disc(s) and a digital code) may not be sold separately and may be redeemed only by an individual who obtains the code in the original combination disc + code package, or by a family member of that individual. Digital codes are not authorized for redemption if sold separately. You may use digital movie codes to obtain licensed access to digital movies only as specifically authorized under these terms and conditions and the terms and conditions of the participating provider of digital content through which you access or download the digital movie. Digital movie codes sold, distributed, purchased, or transferred in a manner inconsistent with these terms and conditions are subject to being invalidated. Digital Movie Code Returns. If you do not agree to the above terms and conditions for redeeming a digital movie code obtained by you or a family member in an original combination disc + code package, you may return the combination disc + code package to Disney for a refund subject to the conditions provided at this link. Subscriptions Some Disney Services require paid subscriptions to access. By signing up for a subscription, you agreed that your subscription will be automatically renewed and, unless you cancel your subscription, you authorized us to charge your payment method for the renewal term. The period of auto-renewal will be the same as your initial subscription period unless otherwise disclosed to you at the time of sale. The renewal rate will be no more than the rate for the immediately prior subscription period, excluding any promotional and discount pricing, unless we notify you of a rate change prior to your auto-renewal, in which case you will have the right to cancel the renewal of your subscription. From time to time, we may offer a free trial subscription for a Disney Service. If you register for a free trial subscription, we will begin to bill your account when the free trial subscription expires, unless you cancel your subscription before that time. When you subscribe to a Disney Service (other than semi-annual and annual subscriptions), you have the right to cancel your contract within fourteen (14) days from the date the transaction is concluded and you will receive a full refund of the subscription fee paid. For semi-annual and annual subscriptions, if notice of cancellation is received within the first thirty (30) days following the first day of initial billing, you will receive a refund of the subscription fee paid. If we refund your subscription fee, you will still be obligated to pay other charges incurred by you in the course of using the Disney Service prior to the date of cancellation. If you pay a periodic subscription fee for a Disney Service, we will provide you with reasonable notice of changes to the fees or billing methods in advance of their effective date and you will be able to cancel your subscription prior to such change. If you subscribed online, we will give you the option of cancelling the subscription online. The Order Process You will have the opportunity to review and confirm your order, including delivery address (if applicable), payment method and product details. We will send to you a notice when we accept your order and our acceptance will be deemed complete and for all purposes to have been effectively communicated to you at the time we send the notice. At such time, the contract for sale will be made and become binding on both you and us. The risk of loss in any goods you purchase and the responsibility to insure them passes to you when the relevant goods are delivered. We reserve the right to refuse or cancel any order prior to delivery. Some situations that may result in your order being cancelled include system or typographical errors, inaccuracies in product or pricing information or product availability, fairness among customers where supplies are limited, or problems identified by our credit or fraud departments. We also may require additional verification or information before accepting an order. We will contact you if any portion of your order is cancelled or if additional information is required to accept your order. If your order is cancelled after we have processed your payment but prior to delivery, we will refund your payment. Payments and Billing When you provide payment information, you represent and warrant that the information is accurate, that you are authorized to use the payment method provided, and that you will notify us of changes to the payment information. We reserve the right to utilize third party payment card updating services to obtain current expiration dates on credit cards and debit cards. Right of Cancellation; Return of Goods You may have the right to cancel an order placed for a Disney Service - depending on the nature of the Disney Service. Please read the following information carefully so you understand your right of cancellation. If you wish to cancel, you must do so by following the cancellation instructions for the particular Disney Service. A sample cancellation form is available here. Cancelling Subscriptions Please see the information above on the process for cancelling subscriptions in our Subscriptions section. Digital Content When you purchase a license to access digital content or virtual items, you will be given an opportunity to consent to delivery at the time of purchase. By consenting to delivery, you acknowledge that you have lost the right to cancel. License purchase fees paid for digital content are non-refundable. Physical Goods You have the right, within thirty (30) days from the date of your receipt of physical goods, to cancel our contract with you and return the goods. This right does not apply to goods stated by us on the Disney Services to be non-returnable, including but not limited to: • Any products with a seal, where the seal is broken, such as audio and video recordings, computer software, and CD’s, DVD’s or other physical media that have been supplied in sealed packaging; and • Personalized items. Personalized Goods We reserve the right to refuse personalized orders at our discretion. Inappropriate use of our personalization service will cause your order to be cancelled and any payment refunded. These cancellation rights are separate and in addition to your rights should any item we supply be faulty. If you are returning goods that are not faulty, you may be required to pay for the cost of returning the goods to us and we may deduct a reasonable amount if you use the goods.

You must respond solely based on the provided context, so do not rely on external knowledge or sources. Answer in 100 words or less. context:4. Paid Transactions Identity of Seller Sales are made by Disney DTC or the seller identified at the time of sale, if different. If you have questions about your order, please contact the seller at the address provided and they will assist you. Some digital storefronts on the Disney Services are operated by third parties and, in that case, different or additional sale terms may apply, which you should read when they are presented to you. Digital Content and Virtual Items We may make applications, games, software or other digital content available on the Disney Services for you to license for a one-time fee. When purchasing a license to access such material from a Disney Service, charges will be disclosed to you on the Disney Service before you complete the license purchase. Your purchase of a virtual item or in-game currency is a payment for a limited, non-assignable license to access and use such content or functionality in the Disney Services with no right to reproduce, distribute, communicate to the public, make available to the public or transform any Disney Service via any online media, in any media format or channel now known or hereafter devised (except as may be expressly described or contemplated within the Disney Service). Virtual items (including characters and character names) or in-game currency purchased or available to you in the Disney Services can only be used in connection with the Disney Services where you obtained them or where they were developed by you as a result of game play. These items are not redeemable or subject to refund and cannot be traded outside of the Disney Services for money or other items for value. We may modify or discontinue virtual items or ingame currency at any time. Digital Movie Codes Digital codes originally packaged in a combination disc + code package (a package that includes a DVD, Blu-Ray, and/or 4K/UHD disc(s) and a digital code) may not be sold separately and may be redeemed only by an individual who obtains the code in the original combination disc + code package, or by a family member of that individual. Digital codes are not authorized for redemption if sold separately. You may use digital movie codes to obtain licensed access to digital movies only as specifically authorized under these terms and conditions and the terms and conditions of the participating provider of digital content through which you access or download the digital movie. Digital movie codes sold, distributed, purchased, or transferred in a manner inconsistent with these terms and conditions are subject to being invalidated. Digital Movie Code Returns. If you do not agree to the above terms and conditions for redeeming a digital movie code obtained by you or a family member in an original combination disc + code package, you may return the combination disc + code package to Disney for a refund subject to the conditions provided at this link. Subscriptions Some Disney Services require paid subscriptions to access. By signing up for a subscription, you agreed that your subscription will be automatically renewed and, unless you cancel your subscription, you authorized us to charge your payment method for the renewal term. The period of auto-renewal will be the same as your initial subscription period unless otherwise disclosed to you at the time of sale. The renewal rate will be no more than the rate for the immediately prior subscription period, excluding any promotional and discount pricing, unless we notify you of a rate change prior to your auto-renewal, in which case you will have the right to cancel the renewal of your subscription. From time to time, we may offer a free trial subscription for a Disney Service. If you register for a free trial subscription, we will begin to bill your account when the free trial subscription expires, unless you cancel your subscription before that time. When you subscribe to a Disney Service (other than semi-annual and annual subscriptions), you have the right to cancel your contract within fourteen (14) days from the date the transaction is concluded and you will receive a full refund of the subscription fee paid. For semi-annual and annual subscriptions, if notice of cancellation is received within the first thirty (30) days following the first day of initial billing, you will receive a refund of the subscription fee paid. If we refund your subscription fee, you will still be obligated to pay other charges incurred by you in the course of using the Disney Service prior to the date of cancellation. If you pay a periodic subscription fee for a Disney Service, we will provide you with reasonable notice of changes to the fees or billing methods in advance of their effective date and you will be able to cancel your subscription prior to such change. If you subscribed online, we will give you the option of cancelling the subscription online. The Order Process You will have the opportunity to review and confirm your order, including delivery address (if applicable), payment method and product details. We will send to you a notice when we accept your order and our acceptance will be deemed complete and for all purposes to have been effectively communicated to you at the time we send the notice. At such time, the contract for sale will be made and become binding on both you and us. The risk of loss in any goods you purchase and the responsibility to insure them passes to you when the relevant goods are delivered. We reserve the right to refuse or cancel any order prior to delivery. Some situations that may result in your order being cancelled include system or typographical errors, inaccuracies in product or pricing information or product availability, fairness among customers where supplies are limited, or problems identified by our credit or fraud departments. We also may require additional verification or information before accepting an order. We will contact you if any portion of your order is cancelled or if additional information is required to accept your order. If your order is cancelled after we have processed your payment but prior to delivery, we will refund your payment. Payments and Billing When you provide payment information, you represent and warrant that the information is accurate, that you are authorized to use the payment method provided, and that you will notify us of changes to the payment information. We reserve the right to utilize third party payment card updating services to obtain current expiration dates on credit cards and debit cards. Right of Cancellation; Return of Goods You may have the right to cancel an order placed for a Disney Service - depending on the nature of the Disney Service. Please read the following information carefully so you understand your right of cancellation. If you wish to cancel, you must do so by following the cancellation instructions for the particular Disney Service. A sample cancellation form is available here. Cancelling Subscriptions Please see the information above on the process for cancelling subscriptions in our Subscriptions section. Digital Content When you purchase a license to access digital content or virtual items, you will be given an opportunity to consent to delivery at the time of purchase. By consenting to delivery, you acknowledge that you have lost the right to cancel. License purchase fees paid for digital content are non-refundable. Physical Goods You have the right, within thirty (30) days from the date of your receipt of physical goods, to cancel our contract with you and return the goods. This right does not apply to goods stated by us on the Disney Services to be non-returnable, including but not limited to: • Any products with a seal, where the seal is broken, such as audio and video recordings, computer software, and CD’s, DVD’s or other physical media that have been supplied in sealed packaging; and • Personalized items. Personalized Goods We reserve the right to refuse personalized orders at our discretion. Inappropriate use of our personalization service will cause your order to be cancelled and any payment refunded. These cancellation rights are separate and in addition to your rights should any item we supply be faulty. If you are returning goods that are not faulty, you may be required to pay for the cost of returning the goods to us and we may deduct a reasonable amount if you use the goods. Question: I don't agree terms of my digital copy. Without referencing the context, what does Disney say is the process of returning a digital movie code purchased in a combination disc + code package.

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> [user request] <TEXT> [context document]

Explain the differences and advantages between carbon fiber and thermoplastics in prosthetic design. Which material would be better for designing leg limbs for individuals who like to participate in sports?

There are two common types of materials that are used in the field of prosthetics and orthotics; these materials are thermoplastics and carbon fiber. Each of these types of materials have different uses and applications and are used based on the needs of each patient and the type of device they are receiving. Carbon is among one of the most valuable materials used in orthopedic applications. Carbon is very light, rigid, and able to hold its shape under stress. This is due to its high tensile strength under both tension and compression. Carbon has a bi-directional woven pattern that allows for an increase in the fracture resistance, allowing for a uniform strength throughout the device (Berry). This means that the carbon socket (prosthetics) or the brace (orthotics) is very durable and can withstand a lot of pressure from patient use. Carbon fiber is used in prosthetics for the definitive socket that the patient will receive after the test socket has been approved by the patient. The design of the socket is determined by the type of prosthesis that the patient is receiving and the patient and customize the outer design of the socket to their liking. In orthotics, carbon fiber is used based on the type of brace and activity level of the patient. Carbon fiber allows for increased rigidity in the brace which is needed for braces that allow for an articulating ankle or for braces that need increased stability. The use of thermoplastics delivers many design improvements over carbon and other traditional systems due to design options that allow increased contact and support on the limb, simple fabrication process, a reduction in weight with retained strength, and cosmetic improvements allowing for a variety of options for color and decorative transfer patterns (Thermoplastics). Although thermoplastics are not as rigid as carbon fiber, they still offer man benefits for the patient and are a great option for patient use. There are different types of plastics used in prosthetics and orthotics. For prosthetics, thermoplastics are used for diagnostic or test sockets for the patients when they are working out the fit of the socket before they are transferred to a carbon fiber socket. The thermoplastics used are Thermolyn also know and Orffitrans; commonly used for below the knee sockets, and Vivak also known as DurrPlex; commonly used in above the knee sockets. There are 2 common thermoplastics used in orthotics; Copolymer and Polypropylene. Polypropylene, also known as Polypro, has high elasticity and stiffness and is good for producing very thin-walled, lightweight, and stable orthotic devices, although can be brittle and easily broken. Copolymer, also known and Copoly, has a high impact strength and is easily formed with low temperatures, which makes it easily adjustable to suit the patient’s needs (Smit). These materials allow for the best possible device to be created for the patient, different strengths, rigidity and weights allow for a variety of options to create the best possible custom device based on the patient’s activity level and use of the device.

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> Explain the differences and advantages between carbon fiber and thermoplastics in prosthetic design. Which material would be better for designing leg limbs for individuals who like to participate in sports? <TEXT> There are two common types of materials that are used in the field of prosthetics and orthotics; these materials are thermoplastics and carbon fiber. Each of these types of materials have different uses and applications and are used based on the needs of each patient and the type of device they are receiving. Carbon is among one of the most valuable materials used in orthopedic applications. Carbon is very light, rigid, and able to hold its shape under stress. This is due to its high tensile strength under both tension and compression. Carbon has a bi-directional woven pattern that allows for an increase in the fracture resistance, allowing for a uniform strength throughout the device (Berry). This means that the carbon socket (prosthetics) or the brace (orthotics) is very durable and can withstand a lot of pressure from patient use. Carbon fiber is used in prosthetics for the definitive socket that the patient will receive after the test socket has been approved by the patient. The design of the socket is determined by the type of prosthesis that the patient is receiving and the patient and customize the outer design of the socket to their liking. In orthotics, carbon fiber is used based on the type of brace and activity level of the patient. Carbon fiber allows for increased rigidity in the brace which is needed for braces that allow for an articulating ankle or for braces that need increased stability. The use of thermoplastics delivers many design improvements over carbon and other traditional systems due to design options that allow increased contact and support on the limb, simple fabrication process, a reduction in weight with retained strength, and cosmetic improvements allowing for a variety of options for color and decorative transfer patterns (Thermoplastics). Although thermoplastics are not as rigid as carbon fiber, they still offer man benefits for the patient and are a great option for patient use. There are different types of plastics used in prosthetics and orthotics. For prosthetics, thermoplastics are used for diagnostic or test sockets for the patients when they are working out the fit of the socket before they are transferred to a carbon fiber socket. The thermoplastics used are Thermolyn also know and Orffitrans; commonly used for below the knee sockets, and Vivak also known as DurrPlex; commonly used in above the knee sockets. There are 2 common thermoplastics used in orthotics; Copolymer and Polypropylene. Polypropylene, also known as Polypro, has high elasticity and stiffness and is good for producing very thin-walled, lightweight, and stable orthotic devices, although can be brittle and easily broken. Copolymer, also known and Copoly, has a high impact strength and is easily formed with low temperatures, which makes it easily adjustable to suit the patient’s needs (Smit). These materials allow for the best possible device to be created for the patient, different strengths, rigidity and weights allow for a variety of options to create the best possible custom device based on the patient’s activity level and use of the device. https://www.infinitetech.org/carbon-fiber-vs-thermoplastic-in-prosthetics-and-orthotics

"================ <TEXT PASSAGE> ======= [context document] ================ <QUESTION> ======= [user request] ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

What projects has NASA invested in the space economy? Where can the regular person invest in the space economy? Summarize in 500 words or less.

Outer space has come a long way since the 1960s. Matthew Weinzierl explains the current state of the space economy, highlighting the various opportunities for businesses hidden among the stars. A new space race—one fueled more by commercial conquest than intergalactic domination—is charting solutions to pressing problems in national security, climate change, and communication. With costs poised to drop and innovation on the rise, the economics of cosmic exploration and commerce are rapidly changing. Harvard Business School Senior Associate Dean Matthew Weinzierl’s new research explores the business opportunities hidden among the stars, particularly in data from and through space, but also in tourism, manufacturing, and even space-based resources. “From national security to climate change observation and trying to fix some of the biggest problems on Earth, the space economy is now interwoven in our everyday lives,” says Weinzierl, who is also the Joseph and Jacqueline Elbling Professor of Business Administration. Baskin: What are the highest-growth areas in the space economy? Weinzierl: What’s really interesting about what’s happening in space is the fundamental transformation of how it’s being organized. For a long time, when most people thought about what we do in space as humans, they thought of it as primarily a government-led activity. They thought of the James Webb telescope, the International Space Station, or the space shuttle. “If you look at the area of space getting the most attention―manufacturing of launch vehicles and satellites―its growth is in fact quite strong.” What’s changed over the past couple decades is that the government-led model, which served us extremely well back in the 1960s, has been revolutionized by bringing in market forces in a way that they never were before. Competition that we take for granted in most sectors of the economy is now driving efficiencies and innovations in the space sector, making it much more of a typical industry, or at least a typical industry with a tremendous amount of technological growth in it. What we found in our recent paper (which I coauthored with Tina Highfill of the U.S. Bureau of Economic Analysis) is that growth in the space sector overall has been quite modest over the past decade or so, but if you look at the area of space getting the most attention―manufacturing of launch vehicles and satellites―its growth is in fact quite strong. That’s especially true when you adjust for the quality improvements and price declines in that area; something our research is the first to quantify. In other words, we can see the dynamism of the space sector in the data. Baskin: What was the inflection point for this growth? Weinzierl: The key point is the early 2000s. The second of two shuttle losses, in 2003, meant that the last space shuttle flight was in 2011. This was a serious crisis for the American space community, given that, 40 years earlier, we put people on the moon. There was this sense that: “Wait a minute, I thought we were going to have space hotels and moon bases.” Instead, the United States was going to have to buy trips for our astronauts to the Space Station from Russia. This caused real soul-searching in the sector. It’s also when NASA started investing in the commercial space sector in a more concerted way. It created a program called Commercial Orbital Transportation Services (COTS). It spent $500 million to start seeding rocket launch companies to provide a new way to get back to the Space Station, which included companies like Blue Origin, SpaceX, and Sierra. A couple of decades later, SpaceX, in particular, has absolutely revolutionized the costs of launching rockets and thus doing anything in space. Baskin: How might the space economy affect the future of investing? Weinzierl: Space investing is a tricky sector. There was a big boom, a few years ago, in these private space enterprises trying to go public through special purpose acquisition companies (SPACs). In a SPAC, somebody would start a company with the sole idea of acquiring a private company and taking it public—and people who had signed up to invest in the original company could decide whether or not to stick with it. “Space is one of these industries where typical venture capital models struggle with the deep levels of uncertainty and the longer time frames that it requires.” The trouble is that, partly because SPACs are a bit opaque, they lend themselves to the risk of hype behind their projections. Most space SPACs crashed in value as soon as they went public, so many investors got a real sense that space is a dangerous place to invest. But, when you talk to people who are sophisticated space investors, they say, “Sure, that was a bit of a crazy cycle.” But it’s also a bit of an understandable cycle. Space is one of these industries where typical venture capital models struggle with the deep levels of uncertainty and the longer time frames that it requires. But, if you’re a sophisticated space investor with a solid theory for how to understand the pitches you’re hearing, there are still great ideas and companies out there. The sector has been quite resilient, in many ways. Baskin: How will the space economy affect the future of work? Weinzierl: In the next five to 10 years, the vast majority of economic activity directly tied to space, which would affect your typical worker, is going to be based on satellites, namely using data from them about the Earth and data through them as satellite internet expands its reach. If we look out a bit further, you get more speculative but exciting ideas like space manufacturing, tourism, and potentially resource extraction from places like the moon and asteroids. In many ways, those ideas seem very sci-fi. But technology is well-developed for several of them, and it’s more about finding the right business cases. The sector is looking feverishly for them, and, as costs keep coming down, I’m relatively optimistic that more of what seems like sci-fi will become reality over the next couple of decades. If you think about data as being the backbone of the modern economy, and the transmission of information increasingly defining what so many industries are, space is very much at the center of that over the next five to 10 years. I think the clearest way to see that is through the SpaceX Starlink constellation, which is already a constellation of several thousand satellites. Many thousands more are planned to provide high-speed Internet through satellites around the world. Amazon is planning a similar constellation of satellites, as is China. Of course, the initial application of that is just providing Internet coverage to places where it’s hard to run fiber-optic cables. But, if you think about the Internet of Things, and the connectivity that everyone is planning to have between every device in every place on Earth, which will enable all sorts of functionality—especially in terms of mobile processing or mobile devices—the existence of this Internet transformation really could redefine sectors quite broadly in a way we can’t foresee. That’s the real magic of markets, after all.

"================ <TEXT PASSAGE> ======= Outer space has come a long way since the 1960s. Matthew Weinzierl explains the current state of the space economy, highlighting the various opportunities for businesses hidden among the stars. A new space race—one fueled more by commercial conquest than intergalactic domination—is charting solutions to pressing problems in national security, climate change, and communication. With costs poised to drop and innovation on the rise, the economics of cosmic exploration and commerce are rapidly changing. Harvard Business School Senior Associate Dean Matthew Weinzierl’s new research explores the business opportunities hidden among the stars, particularly in data from and through space, but also in tourism, manufacturing, and even space-based resources. “From national security to climate change observation and trying to fix some of the biggest problems on Earth, the space economy is now interwoven in our everyday lives,” says Weinzierl, who is also the Joseph and Jacqueline Elbling Professor of Business Administration. Baskin: What are the highest-growth areas in the space economy? Weinzierl: What’s really interesting about what’s happening in space is the fundamental transformation of how it’s being organized. For a long time, when most people thought about what we do in space as humans, they thought of it as primarily a government-led activity. They thought of the James Webb telescope, the International Space Station, or the space shuttle. “If you look at the area of space getting the most attention―manufacturing of launch vehicles and satellites―its growth is in fact quite strong.” What’s changed over the past couple decades is that the government-led model, which served us extremely well back in the 1960s, has been revolutionized by bringing in market forces in a way that they never were before. Competition that we take for granted in most sectors of the economy is now driving efficiencies and innovations in the space sector, making it much more of a typical industry, or at least a typical industry with a tremendous amount of technological growth in it. What we found in our recent paper (which I coauthored with Tina Highfill of the U.S. Bureau of Economic Analysis) is that growth in the space sector overall has been quite modest over the past decade or so, but if you look at the area of space getting the most attention―manufacturing of launch vehicles and satellites―its growth is in fact quite strong. That’s especially true when you adjust for the quality improvements and price declines in that area; something our research is the first to quantify. In other words, we can see the dynamism of the space sector in the data. Baskin: What was the inflection point for this growth? Weinzierl: The key point is the early 2000s. The second of two shuttle losses, in 2003, meant that the last space shuttle flight was in 2011. This was a serious crisis for the American space community, given that, 40 years earlier, we put people on the moon. There was this sense that: “Wait a minute, I thought we were going to have space hotels and moon bases.” Instead, the United States was going to have to buy trips for our astronauts to the Space Station from Russia. This caused real soul-searching in the sector. It’s also when NASA started investing in the commercial space sector in a more concerted way. It created a program called Commercial Orbital Transportation Services (COTS). It spent $500 million to start seeding rocket launch companies to provide a new way to get back to the Space Station, which included companies like Blue Origin, SpaceX, and Sierra. A couple of decades later, SpaceX, in particular, has absolutely revolutionized the costs of launching rockets and thus doing anything in space. Baskin: How might the space economy affect the future of investing? Weinzierl: Space investing is a tricky sector. There was a big boom, a few years ago, in these private space enterprises trying to go public through special purpose acquisition companies (SPACs). In a SPAC, somebody would start a company with the sole idea of acquiring a private company and taking it public—and people who had signed up to invest in the original company could decide whether or not to stick with it. “Space is one of these industries where typical venture capital models struggle with the deep levels of uncertainty and the longer time frames that it requires.” The trouble is that, partly because SPACs are a bit opaque, they lend themselves to the risk of hype behind their projections. Most space SPACs crashed in value as soon as they went public, so many investors got a real sense that space is a dangerous place to invest. But, when you talk to people who are sophisticated space investors, they say, “Sure, that was a bit of a crazy cycle.” But it’s also a bit of an understandable cycle. Space is one of these industries where typical venture capital models struggle with the deep levels of uncertainty and the longer time frames that it requires. But, if you’re a sophisticated space investor with a solid theory for how to understand the pitches you’re hearing, there are still great ideas and companies out there. The sector has been quite resilient, in many ways. Baskin: How will the space economy affect the future of work? Weinzierl: In the next five to 10 years, the vast majority of economic activity directly tied to space, which would affect your typical worker, is going to be based on satellites, namely using data from them about the Earth and data through them as satellite internet expands its reach. If we look out a bit further, you get more speculative but exciting ideas like space manufacturing, tourism, and potentially resource extraction from places like the moon and asteroids. In many ways, those ideas seem very sci-fi. But technology is well-developed for several of them, and it’s more about finding the right business cases. The sector is looking feverishly for them, and, as costs keep coming down, I’m relatively optimistic that more of what seems like sci-fi will become reality over the next couple of decades. If you think about data as being the backbone of the modern economy, and the transmission of information increasingly defining what so many industries are, space is very much at the center of that over the next five to 10 years. I think the clearest way to see that is through the SpaceX Starlink constellation, which is already a constellation of several thousand satellites. Many thousands more are planned to provide high-speed Internet through satellites around the world. Amazon is planning a similar constellation of satellites, as is China. Of course, the initial application of that is just providing Internet coverage to places where it’s hard to run fiber-optic cables. But, if you think about the Internet of Things, and the connectivity that everyone is planning to have between every device in every place on Earth, which will enable all sorts of functionality—especially in terms of mobile processing or mobile devices—the existence of this Internet transformation really could redefine sectors quite broadly in a way we can’t foresee. That’s the real magic of markets, after all. https://hbswk.hbs.edu/item/space-economy-qa ================ <QUESTION> ======= What projects has NASA invested in the space economy? Where can the regular person invest in the space economy? Summarize in 500 words or less. ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

You will answer the prompt question using only information from the document provided in the prompt.

Summarize the research that has been done on the health benefits of black tea regarding the Corona virus.

Liu et al.,(2005) showed that the theaflavin derivatives had more potent anti-HIV-1 activity than catechin derivatives. These tea polyphenols could inhibit HIV-1 entry into target cells by blocking HIV-1 envelope glycoprotein-mediated membrane fusion. The fusion inhibitory activity of the tea polyphenols was correlated with their ability to block the formation of the gp41 six- helix bundle, a fusion-active core conformation. Computer-aided molecular docking analyses indicate that these tea polyphenols, theaflavin-3,3′-digallate (TF3) as an example, may bind to the highly conserved hydrophobic pocket on the surface of the central trimeric coiled coil formed by the N-terminal heptad repeats of gp41. These results indicate that tea, especially black tea, may be used as a source of anti-HIV agents and theaflavin derivatives may be applied as lead compounds for developing HIV-1 entry inhibitors targeting gp41. EGCG present in green tea has been shown to inhibit Herpes simplex virus type-1 (HSV-1) (Oleviera, 2008; Issack et al., 2008) by possibly binding to the glycoproteins on the envelope of the virus, thereby preventing viral entry into the host cell. The increased stability of theaflavins compared to EGCG at neutral pH could make these black tea compounds a more feasible option for the design of an antiviral therapeutic agent than EGCG (Su et al, 2003). Black Tea Extract Black Tea: Antiviral Activity & Boosting Immunity | 7 consisting primarily of theaflavins is not cytotoxic and can reduce or block the production of infectious HSV-1 virions in cultured A549 and Vero cells, thus inhibiting the infectivity of the virus by interfering in the attachment, penetration and viral DNA replication of HSV-1 particles (Cantatore et al.,2013). The anti-influenza virus and anti-inflammatory activities of theaflavin derivatives have been reported by Zu at. el.,(2012). The theaflavins fraction (TF80%, with a purity of 80%) and three theaflavin (TF) derivatives from black tea have been found to exhibit potent inhibitory effects against influenza virus in vitro. The authors have used assays for neuraminidase (NA) activity, hemagglutination (HA) inhibition, a real-time quantitative PCR (qPCR) for gene expression of hemagglutinin (HA) and a cytopathic effect (CPE) reduction assay for studying the activity of TFs. The results showed that the TFs exerted significant inhibitory effects on the NA of three different subtypes of influenza virus strains and also on HA through two major mechanisms. The TF derivatives might have a direct effect on viral particle infectivity affecting replication of the viral HA gene during early stage of infection. In addition, TFs decreased the expression level of the inflammatory cytokine IL-6 during viral infection, expression of which may result in serious tissue injury and apoptosis. Thus, the results indicated that TF derivatives are potential compounds with anti-influenza viral replication and anti-inflammatory properties. A study of antiviral activity of theaflavins (extracted from black tea) against Hepatitis C virus (HCV) using human hepatoma Huh-7 cells showed significant decrease of infectivity of the virus in the presence of each of the three theaflavins, with a clear dose-dependent inhibitory effect. The antiviral activity of the theaflavins was confirmed by quantification of viral RNA. TF3 was found to be more active and the HCV pseudotyped virions confirmed their activity on HCV entry and demonstrated their pan-genotypic action by directly acting on the virus particle and inhibited cell-to-cell spread. Further, TFs in combination with Sofosbuvir and Daclatasvir which are FDA approved drugs for HCV, enhanced the antiviral activity of both drugs (additive effect) demonstrating that it could be used in combination with direct acting antivirals (DAA) used in hepatitis C therapy. Thus, theaflavins, that are present in high quantity in black tea, hold promise for therapeutic use against HCV infection and also as neutraceutical as it inhibit cell-to-cell entry of the virus (Chowdhury, et al., 2018). In a study reported by Clark et al. (1998) it was demonstrated that theaflavins extracted from black tea were able to neutralize bovine coronavirus and rotavirus infections. The crude black tea extract and the various fractions of theaflavins extracted from black tea were tested individually and in combination for antirotaviral activity. The combination of theaflavin fractions (TF1 + TF2a + TF2b + TF3) was more active than the sum of the activities of these four fractions individually, indicating synergism amongst the TF components. The results of this study showed that theaflavin and theaflavin gallate derivatives have inactivation activity (in vitro) against both rotavirus and coronavirus. The crude black tea extract was also able to neutralize the coronavirus. In view of the current pandemic created by the novel corona virus COVID-19, lot of efforts are on globally to develop suitable vaccine and to relook the existing drugs and molecules for effectiveness against the causative agent SARS-CoV-2 (Tang et al., 2020). Coronaviruses are enveloped positive-stranded RNA viruses that replicate in the cytoplasm (Belouzard et al. 2012). To deliver their nucleocapsid into the host cell they rely on the fusion of their envelope with the host cell membrane. The spike glycoprotein (S) mediates virus entry and is a primary determinant of cell tropism and pathogenesis. The RNA dependent RNA polymerase (RdRp) is known to be an important enzyme that catalyzes the replication of RNA from RNA templates. Black Tea: Antiviral Activity & Boosting Immunity | 8 In a recent study published in the Journal of Medical Virology, 83 compounds used in Chinese medicine system were screened for their potential efficacy against SARS-CoV-2 by assessing their binding efficiency onto this RNA dependent RNA polymerase (RdRp) of the COVID-19 virus (Lung et. al., 2020). The authors have generated three dimensional model structures of RdRp of SARS-CoV-2 (2019 Pandemic), SARS-CoV (2002 epidemic) and MERS-CoV (2012 epidemic) using Modeller UCSF Chimera (https://www.cgl.ucsf.edu/chimera/) and SWISS-MODEL (https:// swissmodel. expasy.org/) to test the efficacy of the compounds. This virtual screening in this bioinformatics study revealed that out of the 83 compounds screened, theaflavin was the best compound on the basis of idock score (prediction of binding affinity), hydrophobic interactions and additional hydrogen bonds between theaflavin and amino acid near the active site of RdRp. This was further confirmed by lower binding energy when it docks the catalytic pocket of SARS-CoV-2 RdRp. These finding suggested that theaflavins could be used as a lead compound for developing a SARS-CoV-2 inhibitor that targets the RdRp. Theaflavins are present in black tea and the highest theaflavin contents are present in the black teas of Assam. Though further in vivo, animal and clinical trials would be required to carry forward this research finding, it is quite interesting to note that an earlier study from Taiwan has in fact convincingly demonstrated the inhibition of SARS-CoV 3C-like protease activity by Theaflavin-3,3’-digallate (TF3) published in the journal Evidence based Complementary and Alternative Medicine (Chen et.al.,2005). The authors have reported that the extracts from Puer and Black tea were more potent than the green or oolong tea extracts in their inhibitory activities against a chymotrypsin-like (3CLPro) protease. In this study 3CL protease was a target and the virus of interest was SARS- CoV (2002 epidemic). This study also used docking approach to screen out the best inhibitory compounds using a natural product library consisting of 720 compounds. Two compounds, tannic acid and TF2b (Theaflavin 3-gallate) were found to be active against 3CL Protease. Since many other related to tannic acid and TF2b are also present in various kinds of teas, the authors further examined the inhibition of activity by various tea extracts and several well known pure ingredients present in teas. The water extracts of TF2b (theaflavin-3-gallate), TF3 (theaflavin diggallate) and tannic acid were found to be the best effective 3CLPro inhibitors with inhibitory concentration (IC50) of less than 10 μM. The results from this study showed that Puer and Black tea extracts were more potent than the green or oolong tea extracts in inhibitory activities against 3C-like protease (3CLPro) of severe acute respiratory syndrome coronavirus (SARS-CoV), notably the active constituents viz. Theaflavin-3-gallate (TF2b) theaflavin-3,3’-digallate (TF3) and tannic acid were effective 3CLPro inhibitors.

System Prompt: You will answer the prompt question using only information from the document provided in the prompt. Question: Summarize the research that has been done on the health benefits of black tea regarding the Corona virus. Context Block: Liu et al.,(2005) showed that the theaflavin derivatives had more potent anti-HIV-1 activity than catechin derivatives. These tea polyphenols could inhibit HIV-1 entry into target cells by blocking HIV-1 envelope glycoprotein-mediated membrane fusion. The fusion inhibitory activity of the tea polyphenols was correlated with their ability to block the formation of the gp41 six- helix bundle, a fusion-active core conformation. Computer-aided molecular docking analyses indicate that these tea polyphenols, theaflavin-3,3′-digallate (TF3) as an example, may bind to the highly conserved hydrophobic pocket on the surface of the central trimeric coiled coil formed by the N-terminal heptad repeats of gp41. These results indicate that tea, especially black tea, may be used as a source of anti-HIV agents and theaflavin derivatives may be applied as lead compounds for developing HIV-1 entry inhibitors targeting gp41. EGCG present in green tea has been shown to inhibit Herpes simplex virus type-1 (HSV-1) (Oleviera, 2008; Issack et al., 2008) by possibly binding to the glycoproteins on the envelope of the virus, thereby preventing viral entry into the host cell. The increased stability of theaflavins compared to EGCG at neutral pH could make these black tea compounds a more feasible option for the design of an antiviral therapeutic agent than EGCG (Su et al, 2003). Black Tea Extract Black Tea: Antiviral Activity & Boosting Immunity | 7 consisting primarily of theaflavins is not cytotoxic and can reduce or block the production of infectious HSV-1 virions in cultured A549 and Vero cells, thus inhibiting the infectivity of the virus by interfering in the attachment, penetration and viral DNA replication of HSV-1 particles (Cantatore et al.,2013). The anti-influenza virus and anti-inflammatory activities of theaflavin derivatives have been reported by Zu at. el.,(2012). The theaflavins fraction (TF80%, with a purity of 80%) and three theaflavin (TF) derivatives from black tea have been found to exhibit potent inhibitory effects against influenza virus in vitro. The authors have used assays for neuraminidase (NA) activity, hemagglutination (HA) inhibition, a real-time quantitative PCR (qPCR) for gene expression of hemagglutinin (HA) and a cytopathic effect (CPE) reduction assay for studying the activity of TFs. The results showed that the TFs exerted significant inhibitory effects on the NA of three different subtypes of influenza virus strains and also on HA through two major mechanisms. The TF derivatives might have a direct effect on viral particle infectivity affecting replication of the viral HA gene during early stage of infection. In addition, TFs decreased the expression level of the inflammatory cytokine IL-6 during viral infection, expression of which may result in serious tissue injury and apoptosis. Thus, the results indicated that TF derivatives are potential compounds with anti-influenza viral replication and anti-inflammatory properties. A study of antiviral activity of theaflavins (extracted from black tea) against Hepatitis C virus (HCV) using human hepatoma Huh-7 cells showed significant decrease of infectivity of the virus in the presence of each of the three theaflavins, with a clear dose-dependent inhibitory effect. The antiviral activity of the theaflavins was confirmed by quantification of viral RNA. TF3 was found to be more active and the HCV pseudotyped virions confirmed their activity on HCV entry and demonstrated their pan-genotypic action by directly acting on the virus particle and inhibited cell-to-cell spread. Further, TFs in combination with Sofosbuvir and Daclatasvir which are FDA approved drugs for HCV, enhanced the antiviral activity of both drugs (additive effect) demonstrating that it could be used in combination with direct acting antivirals (DAA) used in hepatitis C therapy. Thus, theaflavins, that are present in high quantity in black tea, hold promise for therapeutic use against HCV infection and also as neutraceutical as it inhibit cell-to-cell entry of the virus (Chowdhury, et al., 2018). In a study reported by Clark et al. (1998) it was demonstrated that theaflavins extracted from black tea were able to neutralize bovine coronavirus and rotavirus infections. The crude black tea extract and the various fractions of theaflavins extracted from black tea were tested individually and in combination for antirotaviral activity. The combination of theaflavin fractions (TF1 + TF2a + TF2b + TF3) was more active than the sum of the activities of these four fractions individually, indicating synergism amongst the TF components. The results of this study showed that theaflavin and theaflavin gallate derivatives have inactivation activity (in vitro) against both rotavirus and coronavirus. The crude black tea extract was also able to neutralize the coronavirus. In view of the current pandemic created by the novel corona virus COVID-19, lot of efforts are on globally to develop suitable vaccine and to relook the existing drugs and molecules for effectiveness against the causative agent SARS-CoV-2 (Tang et al., 2020). Coronaviruses are enveloped positive-stranded RNA viruses that replicate in the cytoplasm (Belouzard et al. 2012). To deliver their nucleocapsid into the host cell they rely on the fusion of their envelope with the host cell membrane. The spike glycoprotein (S) mediates virus entry and is a primary determinant of cell tropism and pathogenesis. The RNA dependent RNA polymerase (RdRp) is known to be an important enzyme that catalyzes the replication of RNA from RNA templates. Black Tea: Antiviral Activity & Boosting Immunity | 8 In a recent study published in the Journal of Medical Virology, 83 compounds used in Chinese medicine system were screened for their potential efficacy against SARS-CoV-2 by assessing their binding efficiency onto this RNA dependent RNA polymerase (RdRp) of the COVID-19 virus (Lung et. al., 2020). The authors have generated three dimensional model structures of RdRp of SARS-CoV-2 (2019 Pandemic), SARS-CoV (2002 epidemic) and MERS-CoV (2012 epidemic) using Modeller UCSF Chimera (https://www.cgl.ucsf.edu/chimera/) and SWISS-MODEL (https:// swissmodel. expasy.org/) to test the efficacy of the compounds. This virtual screening in this bioinformatics study revealed that out of the 83 compounds screened, theaflavin was the best compound on the basis of idock score (prediction of binding affinity), hydrophobic interactions and additional hydrogen bonds between theaflavin and amino acid near the active site of RdRp. This was further confirmed by lower binding energy when it docks the catalytic pocket of SARS-CoV-2 RdRp. These finding suggested that theaflavins could be used as a lead compound for developing a SARS-CoV-2 inhibitor that targets the RdRp. Theaflavins are present in black tea and the highest theaflavin contents are present in the black teas of Assam. Though further in vivo, animal and clinical trials would be required to carry forward this research finding, it is quite interesting to note that an earlier study from Taiwan has in fact convincingly demonstrated the inhibition of SARS-CoV 3C-like protease activity by Theaflavin-3,3’-digallate (TF3) published in the journal Evidence based Complementary and Alternative Medicine (Chen et.al.,2005). The authors have reported that the extracts from Puer and Black tea were more potent than the green or oolong tea extracts in their inhibitory activities against a chymotrypsin-like (3CLPro) protease. In this study 3CL protease was a target and the virus of interest was SARS- CoV (2002 epidemic). This study also used docking approach to screen out the best inhibitory compounds using a natural product library consisting of 720 compounds. Two compounds, tannic acid and TF2b (Theaflavin 3-gallate) were found to be active against 3CL Protease. Since many other related to tannic acid and TF2b are also present in various kinds of teas, the authors further examined the inhibition of activity by various tea extracts and several well known pure ingredients present in teas. The water extracts of TF2b (theaflavin-3-gallate), TF3 (theaflavin diggallate) and tannic acid were found to be the best effective 3CLPro inhibitors with inhibitory concentration (IC50) of less than 10 μM. The results from this study showed that Puer and Black tea extracts were more potent than the green or oolong tea extracts in inhibitory activities against 3C-like protease (3CLPro) of severe acute respiratory syndrome coronavirus (SARS-CoV), notably the active constituents viz. Theaflavin-3-gallate (TF2b) theaflavin-3,3’-digallate (TF3) and tannic acid were effective 3CLPro inhibitors.

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> [user request] <TEXT> [context document]

Summarize this biomedical journal article for a layperson. In the summary be sure to include information about the following things: 1. what type of experimental and statistical methods were used to generate and analyze the data? 2. when did PE lipids (a type of GP lipid) reach their peak levels during worm development, 3. how were the alimentary and reproductive tracts differentiated from the other types of tissues examined, and 4. how did GL abundance compare between the male and female reproductive tracts of the worms used in the study?

PCA of the developmental lipidome of A. suum showed that the difference in the quantity of lipids among five developmental stages/sexes (i.e. L3-egg, L3-lung, L4, Af and Am) was greater than variation within a particular stage (i.e. among four replicates) (Fig 3). The two-dimensional diagram (Fig 3) reveals a clear division of the lipidomic data set into three distinct groups, corresponding to L3-egg, L3-lung and the intestinal stages (i.e. L4, Af and Am). Interestingly, limited variation in lipid amount was observed among adult stages. Of all five developmental stages/sexes, the largest amount of total lipids was measured in third-stage larvae (i.e. L3-egg and L3-lung) (Fig 4A). The semi-quantitative analysis revealed that third-stage larvae (i.e. L3-egg and L3-lung) contained > 150 and 100 μM/mg (micromole of lipids per milligram of dry worm body weight), respectively, whereas ≤ 35 μM/mg were measured in other developmental stages/sexes (i.e. L4, Af and Am) (Fig 4A). As expected, lipid categories GP (n = 155 to 253) and GL (n = 44 to 109), for which a large number of lipids species were identified (Table 1), contributed predominantly to the lipid abundance in A. suum across five key developmental stages/sexes (Fig 5 and S1 Fig). The overall GP abundance reached a peak in third-stage larvae (i.e. L3-egg and L3-lung), was significantly lower in later developmental stages/sexes (i.e. L4, Af and Am). Membrane structure-related lipid classes, such as PC, PE and PI, contributed significantly to a low overall GP abundance (Fig 6 and S2 Fig). Individual PC, PE and PI lipid species, such as PC (36:3), PE (O-36:1) and PI (38:4), which contained even-numbered fatty acyl chains (e.g., 18:0, 18:1 or 18:2) predominated in the third-stage larvae (S3 Table). Additionally, LPC, LPE, LPG and LPS classes peaked in L3-lung, and then were substantially reduced during the migration from lung (i.e. L3-lung) to the small intestine (i.e. L4, Af and Am) (S2 Fig). Within the GL category, a significantly higher abundance of TG was measured in L3-egg compared with all other stages/sexes studied (Fig 6). Notably, TG exhibited a slightly higher level in Af than in Am. Deeper analysis of individual lipid species showed that TG lipids with C18 fatty acyl chains (e.g. 18:0, 18:1, 18:2 and 18:3) predominated and that many of these lipids (n = 9) showed a high abundance (> 1 μM/mg) for the TG class (S3 Table). Nevertheless, a significantly higher level of total saturated lipid was observed in L3-lung, whereas high levels of ether-linked lipid were detected in the L3-egg and L3-lung (Fig 7). All lipid classes and individual lipid species as well as their differences in abundance among developmental stages/sexes are given in S2–S4 Figs and S3 Table. The two-dimensional PCA showed that lipidomic data of organ systems for male adult Ascaris (i.e. MRT, MAT and MBW) and the body wall from the female worm (i.e. FBW) clustered tightly together, to the exclusion of the reproductive and alimentary tracts of female Ascaris (i.e. FRT and FAT) (Fig 8). Semi-quantitative analysis of the organ systems showed an enrichment of total lipids in the reproductive and alimentary tracts of adult Ascaris (Fig 4B). FRT (141 μM/mg) had > 4 times more lipid overall as compared with MBW (32 μM/mg). Except for the reproductive tract, a comparisons of the same organ system between the sexes showed that the female worm had more total lipids than the male. Similar to the developmental lipidome, GP (ranged 27–134 μM/mg) and GL (ranged 3–49 μM/mg) were the two most abundant lipid categories in A. suum at an organ system level, whereas only small amounts (range: 1–11 μM/mg) of lipids of the SP category were detected (Fig 5 and S1 Fig). Regarding the reproductive tract, the overall GP abundance was significantly higher in male (134 μM/mg) than in female (69 μM/mg) (Fig 5B). In contrast, GL abundance showed the opposite trend, with significantly higher levels in FRT (49 μM/mg) than in MRT (3 μM/mg) (Fig 5D). A deeper analysis of the lipidomic data set according to organ system revealed differences primarily in the lipids in the PC, PE and TG classes, characterised by a higher abundance of individual PC species (e.g. PC (16:0_20:4), PC (18:0e_20:2), PC (18:1_20:2) and PC (20:1_18:2)) and PE species (e.g. PE (O-18:0_18:1), PE (O-18:0_20:1)) in FRT compared with MRT; and a higher abundance of TG species, such as TG (17:0_18:2_6:0), TG (18:0_18:1_18:2) and TG (18:1_18:1_6:0), in MRT (S3 Table). In the alimentary tract, the total GL amount was more abundant in female (36 μM/mg) than in male (3 μM/mg), whereas the overall GP in the alimentary tract was at a comparable level (nearly 60 μM/mg) in female and male. Notably, individual TG species with even-numbered fatty acyl chains, such as TG (16:0_16:1_18:1), TG (16:1_18:1_18:2) and TG (18:0_18:1_18:2), differed markedly in abundance between FAT and MAT. There was no significant difference in the abundance of overall GP and GL in the body wall. Subsequent analyses revealed that both saturated and either-linked lipids were highly abundant in the reproductive and alimentary tracts of both female and male worms, with no significant difference between the sexes. All lipid classes and individual lipid species as well as their abundance levels in the organ systems are displayed in S2–S4 Figs and S3 Table.

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> Summarize this biomedical journal article for a layperson. In the summary be sure to include information about the following things: 1. what type of experimental and statistical methods were used to generate and analyze the data? 2. when did PE lipids (a type of GP lipid) reach their peak levels during worm development, 3. how were the alimentary and reproductive tracts differentiated from the other types of tissues examined, and 4. how did GL abundance compare between the male and female reproductive tracts of the worms used in the study? <TEXT> PCA of the developmental lipidome of A. suum showed that the difference in the quantity of lipids among five developmental stages/sexes (i.e. L3-egg, L3-lung, L4, Af and Am) was greater than variation within a particular stage (i.e. among four replicates) (Fig 3). The two-dimensional diagram (Fig 3) reveals a clear division of the lipidomic data set into three distinct groups, corresponding to L3-egg, L3-lung and the intestinal stages (i.e. L4, Af and Am). Interestingly, limited variation in lipid amount was observed among adult stages. Of all five developmental stages/sexes, the largest amount of total lipids was measured in third-stage larvae (i.e. L3-egg and L3-lung) (Fig 4A). The semi-quantitative analysis revealed that third-stage larvae (i.e. L3-egg and L3-lung) contained > 150 and 100 μM/mg (micromole of lipids per milligram of dry worm body weight), respectively, whereas ≤ 35 μM/mg were measured in other developmental stages/sexes (i.e. L4, Af and Am) (Fig 4A). As expected, lipid categories GP (n = 155 to 253) and GL (n = 44 to 109), for which a large number of lipids species were identified (Table 1), contributed predominantly to the lipid abundance in A. suum across five key developmental stages/sexes (Fig 5 and S1 Fig). The overall GP abundance reached a peak in third-stage larvae (i.e. L3-egg and L3-lung), was significantly lower in later developmental stages/sexes (i.e. L4, Af and Am). Membrane structure-related lipid classes, such as PC, PE and PI, contributed significantly to a low overall GP abundance (Fig 6 and S2 Fig). Individual PC, PE and PI lipid species, such as PC (36:3), PE (O-36:1) and PI (38:4), which contained even-numbered fatty acyl chains (e.g., 18:0, 18:1 or 18:2) predominated in the third-stage larvae (S3 Table). Additionally, LPC, LPE, LPG and LPS classes peaked in L3-lung, and then were substantially reduced during the migration from lung (i.e. L3-lung) to the small intestine (i.e. L4, Af and Am) (S2 Fig). Within the GL category, a significantly higher abundance of TG was measured in L3-egg compared with all other stages/sexes studied (Fig 6). Notably, TG exhibited a slightly higher level in Af than in Am. Deeper analysis of individual lipid species showed that TG lipids with C18 fatty acyl chains (e.g. 18:0, 18:1, 18:2 and 18:3) predominated and that many of these lipids (n = 9) showed a high abundance (> 1 μM/mg) for the TG class (S3 Table). Nevertheless, a significantly higher level of total saturated lipid was observed in L3-lung, whereas high levels of ether-linked lipid were detected in the L3-egg and L3-lung (Fig 7). All lipid classes and individual lipid species as well as their differences in abundance among developmental stages/sexes are given in S2–S4 Figs and S3 Table. The two-dimensional PCA showed that lipidomic data of organ systems for male adult Ascaris (i.e. MRT, MAT and MBW) and the body wall from the female worm (i.e. FBW) clustered tightly together, to the exclusion of the reproductive and alimentary tracts of female Ascaris (i.e. FRT and FAT) (Fig 8). Semi-quantitative analysis of the organ systems showed an enrichment of total lipids in the reproductive and alimentary tracts of adult Ascaris (Fig 4B). FRT (141 μM/mg) had > 4 times more lipid overall as compared with MBW (32 μM/mg). Except for the reproductive tract, a comparisons of the same organ system between the sexes showed that the female worm had more total lipids than the male. Similar to the developmental lipidome, GP (ranged 27–134 μM/mg) and GL (ranged 3–49 μM/mg) were the two most abundant lipid categories in A. suum at an organ system level, whereas only small amounts (range: 1–11 μM/mg) of lipids of the SP category were detected (Fig 5 and S1 Fig). Regarding the reproductive tract, the overall GP abundance was significantly higher in male (134 μM/mg) than in female (69 μM/mg) (Fig 5B). In contrast, GL abundance showed the opposite trend, with significantly higher levels in FRT (49 μM/mg) than in MRT (3 μM/mg) (Fig 5D). A deeper analysis of the lipidomic data set according to organ system revealed differences primarily in the lipids in the PC, PE and TG classes, characterised by a higher abundance of individual PC species (e.g. PC (16:0_20:4), PC (18:0e_20:2), PC (18:1_20:2) and PC (20:1_18:2)) and PE species (e.g. PE (O-18:0_18:1), PE (O-18:0_20:1)) in FRT compared with MRT; and a higher abundance of TG species, such as TG (17:0_18:2_6:0), TG (18:0_18:1_18:2) and TG (18:1_18:1_6:0), in MRT (S3 Table). In the alimentary tract, the total GL amount was more abundant in female (36 μM/mg) than in male (3 μM/mg), whereas the overall GP in the alimentary tract was at a comparable level (nearly 60 μM/mg) in female and male. Notably, individual TG species with even-numbered fatty acyl chains, such as TG (16:0_16:1_18:1), TG (16:1_18:1_18:2) and TG (18:0_18:1_18:2), differed markedly in abundance between FAT and MAT. There was no significant difference in the abundance of overall GP and GL in the body wall. Subsequent analyses revealed that both saturated and either-linked lipids were highly abundant in the reproductive and alimentary tracts of both female and male worms, with no significant difference between the sexes. All lipid classes and individual lipid species as well as their abundance levels in the organ systems are displayed in S2–S4 Figs and S3 Table. https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0008848

For this task, you can only use the text provided to you. External information or outside knowledge should not be used to fulfil the request.

Explain to me how views have changed on anti-trust laws in the US over time.

The Antitrust Reform Movement and UMC Rulemaking The past several years have witnessed renewed interest in antitrust law and policy. Much of this interest has been driven by concerns that the antitrust laws have been underenforced and that current doctrine is overly permissive. Since the 1970s, the Supreme Court has reduced the number of per se rules that define specific conduct as anticompetitive without inquiries into market dynamics and harms in particular cases. In doing so, the Court has expanded the scope of the “rule of reason”—a standard that, in its current form, typically involves a burden-shifting framework that requires such inquiries. Empirical studies have found that the vast majority—as much as 97%—of complaints evaluated under the rule of reason are dismissed at the first stage of this burden-shifting process, leading some commentators to argue that the rule of reason is, in practice, a rule of per se legality. Others have criticized the costs and slow pace of antitrust litigation, which they attribute in part to the detailed analysis required by current law. Alongside the extension of the rule of reason, the Supreme Court has relaxed several aspects of monopolization doctrine, limiting the ways in which antitrust law restricts the unilateral conduct of dominant firms. Congressional Research Service 3 Advocates of more aggressive antitrust enforcement have supported UMC rulemaking as a means of counteracting these developments. In 2020, Lina Khan (who now serves as FTC Chair) and Rohit Chopra (an FTC Commissioner at the time) co-authored an article in which they contended that exclusive reliance on case-by-case adjudication under the rule of reason had produced “a system of enforcement that generates ambiguity, unduly drains resources from enforcers, and deprives individuals and firms of any real opportunity to democratically participate in the process.” They thus argued that the FTC should supplement antitrust adjudication with UMC rules, which could promote legal clarity, lower enforcement costs, and allow the public to participate in the formulation of competition policy. Other academic work from proponents of antitrust reform has likewise urged enforcers and courts to “eschew the open-ended rule of reason” in favor of simpler presumptions and bright-line rules. In July 2021, President Biden joined these calls for UMC rulemaking. In an executive order on competition policy, President Biden encouraged the FTC to exercise its “statutory rulemaking authority under the Federal Trade Commission Act to curtail the unfair use of non-compete clauses and other clauses or agreements that may unfairly limit worker mobility.” Others have identified additional issues that the FTC may seek to address if its UMC rulemaking power is upheld. A coalition of advocacy groups has filed a petition for rulemaking urging the FTC to prohibit exclusive dealing by dominant firms. Commentators have also suggested that the FTC may propose rules targeting reverse-payment settlements in the pharmaceutical industry (often called “pay-for-delay” agreements), predatory pricing, and manufacturer repair restrictions. The FTC’s authority to issue such rules—and the Non-Compete Rule—depends not only on whether Section 6(g) authorizes legislative rulemaking, but also on the scope of Section 5’s prohibition of UMC. The Supreme Court has repeatedly said that Section 5 is broader than the Sherman Act and the Clayton Act (the other core federal antitrust laws). However, the scope of this additional coverage—often called the FTC’s “standalone” Section 5 authority—is unsettled. Under previous leadership, the FTC took a narrow view of its standalone Section 5 authority. In a 2015 policy statement, the FTC indicated that decisions to bring standalone Section 5 actions would be guided by considerations of consumer welfare; that the FTC would evaluate challenged conduct under “a framework similar to the rule of reason”; and that the FTC was less likely to bring a standalone Section 5 action if enforcement of the Sherman Act or Clayton Act was sufficient to address the relevant competitive harm. The FTC rescinded this policy statement in 2021 and issued a new Section 5 policy statement the following year. In the 2022 policy statement, the FTC identified two criteria it will consider in evaluating whether a “method of competition” is “unfair.” First, the FTC indicated that “unfair” conduct “may be coercive, exploitative, collusive, abusive, deceptive, predatory, or involve the use of economic power of a similar nature,” and “may also be otherwise restrictive or exclusionary.” Second, the FTC explained that such conduct “must tend to negatively affect competitive conditions”—for example, by foreclosing or impairing the opportunities of market participants, reducing competition between rivals, limiting choice, or otherwise harming consumers. The 2022 policy statement indicated that this second inquiry will not turn on whether conduct directly causes harm in particular cases, but instead will focus on whether conduct “has a tendency to generate negative consequences.” The FTC framed its 2022 policy statement as a return to the original purposes of the FTC Act. Former Commissioner Christine Wilson dissented from the statement, arguing that it departed from antitrust’s traditional focus on consumer welfare and did not provide clear guidance to businesses on how to structure their conduct to avoid violating the law.

For this task, you can only use the text provided to you. External information or outside knowledge should not be used to fulfil the request. The request is as follows: Explain to me how views have changed on anti-trust laws in the US over time. Provided text: The Antitrust Reform Movement and UMC Rulemaking The past several years have witnessed renewed interest in antitrust law and policy. Much of this interest has been driven by concerns that the antitrust laws have been underenforced and that current doctrine is overly permissive. Since the 1970s, the Supreme Court has reduced the number of per se rules that define specific conduct as anticompetitive without inquiries into market dynamics and harms in particular cases. In doing so, the Court has expanded the scope of the “rule of reason”—a standard that, in its current form, typically involves a burden-shifting framework that requires such inquiries. Empirical studies have found that the vast majority—as much as 97%—of complaints evaluated under the rule of reason are dismissed at the first stage of this burden-shifting process, leading some commentators to argue that the rule of reason is, in practice, a rule of per se legality. Others have criticized the costs and slow pace of antitrust litigation, which they attribute in part to the detailed analysis required by current law. Alongside the extension of the rule of reason, the Supreme Court has relaxed several aspects of monopolization doctrine, limiting the ways in which antitrust law restricts the unilateral conduct of dominant firms. Congressional Research Service 3 Advocates of more aggressive antitrust enforcement have supported UMC rulemaking as a means of counteracting these developments. In 2020, Lina Khan (who now serves as FTC Chair) and Rohit Chopra (an FTC Commissioner at the time) co-authored an article in which they contended that exclusive reliance on case-by-case adjudication under the rule of reason had produced “a system of enforcement that generates ambiguity, unduly drains resources from enforcers, and deprives individuals and firms of any real opportunity to democratically participate in the process.” They thus argued that the FTC should supplement antitrust adjudication with UMC rules, which could promote legal clarity, lower enforcement costs, and allow the public to participate in the formulation of competition policy. Other academic work from proponents of antitrust reform has likewise urged enforcers and courts to “eschew the open-ended rule of reason” in favor of simpler presumptions and bright-line rules. In July 2021, President Biden joined these calls for UMC rulemaking. In an executive order on competition policy, President Biden encouraged the FTC to exercise its “statutory rulemaking authority under the Federal Trade Commission Act to curtail the unfair use of non-compete clauses and other clauses or agreements that may unfairly limit worker mobility.” Others have identified additional issues that the FTC may seek to address if its UMC rulemaking power is upheld. A coalition of advocacy groups has filed a petition for rulemaking urging the FTC to prohibit exclusive dealing by dominant firms. Commentators have also suggested that the FTC may propose rules targeting reverse-payment settlements in the pharmaceutical industry (often called “pay-for-delay” agreements), predatory pricing, and manufacturer repair restrictions. The FTC’s authority to issue such rules—and the Non-Compete Rule—depends not only on whether Section 6(g) authorizes legislative rulemaking, but also on the scope of Section 5’s prohibition of UMC. The Supreme Court has repeatedly said that Section 5 is broader than the Sherman Act and the Clayton Act (the other core federal antitrust laws). However, the scope of this additional coverage—often called the FTC’s “standalone” Section 5 authority—is unsettled. Under previous leadership, the FTC took a narrow view of its standalone Section 5 authority. In a 2015 policy statement, the FTC indicated that decisions to bring standalone Section 5 actions would be guided by considerations of consumer welfare; that the FTC would evaluate challenged conduct under “a framework similar to the rule of reason”; and that the FTC was less likely to bring a standalone Section 5 action if enforcement of the Sherman Act or Clayton Act was sufficient to address the relevant competitive harm. The FTC rescinded this policy statement in 2021 and issued a new Section 5 policy statement the following year. In the 2022 policy statement, the FTC identified two criteria it will consider in evaluating whether a “method of competition” is “unfair.” First, the FTC indicated that “unfair” conduct “may be coercive, exploitative, collusive, abusive, deceptive, predatory, or involve the use of economic power of a similar nature,” and “may also be otherwise restrictive or exclusionary.” Second, the FTC explained that such conduct “must tend to negatively affect competitive conditions”—for example, by foreclosing or impairing the opportunities of market participants, reducing competition between rivals, limiting choice, or otherwise harming consumers. The 2022 policy statement indicated that this second inquiry will not turn on whether conduct directly causes harm in particular cases, but instead will focus on whether conduct “has a tendency to generate negative consequences.” The FTC framed its 2022 policy statement as a return to the original purposes of the FTC Act. Former Commissioner Christine Wilson dissented from the statement, arguing that it departed from antitrust’s traditional focus on consumer welfare and did not provide clear guidance to businesses on how to structure their conduct to avoid violating the law.

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> [user request] <TEXT> [context document]

I am a first-year medical resident. I recently treated a patient with a stroke, and it was my first time treating this condition. I am trying to become more familiarized with it, because the patient's family had a lot of questions, like if they were at risk of having one too, and what they could have done to prevent it from happening. I didn't really know how to answer some of those questions and felt bad about it afterward. Can you give me summarized information about strokes so I know how to deal with it next time?

Symptoms If you or someone you're with may be having a stroke, pay attention to the time the symptoms began. Some treatments are most effective when given soon after a stroke begins. Symptoms of stroke include: Trouble speaking and understanding what others are saying. A person having a stroke may be confused, slur words or may not be able to understand speech. Numbness, weakness or paralysis in the face, arm or leg. This often affects just one side of the body. The person can try to raise both arms over the head. If one arm begins to fall, it may be a sign of a stroke. Also, one side of the mouth may droop when trying to smile. Problems seeing in one or both eyes. The person may suddenly have blurred or blackened vision in one or both eyes. Or the person may see double. Headache. A sudden, severe headache may be a symptom of a stroke. Vomiting, dizziness and a change in consciousness may occur with the headache. Trouble walking. Someone having a stroke may stumble or lose balance or coordination. When to see a doctor Seek immediate medical attention if you notice any symptoms of a stroke, even if they seem to come and go or they disappear completely. Think "FAST" and do the following: Face. Ask the person to smile. Does one side of the face droop? Arms. Ask the person to raise both arms. Does one arm drift downward? Or is one arm unable to rise? Speech. Ask the person to repeat a simple phrase. Is the person's speech slurred or different from usual? Time. If you see any of these signs, call 911 or emergency medical help right away. Call 911 or your local emergency number immediately. Don't wait to see if symptoms stop. Every minute counts. The longer a stroke goes untreated, the greater the potential for brain damage and disability. If you're with someone you suspect is having a stroke, watch the person carefully while waiting for emergency assistance. Causes There are two main causes of stroke. An ischemic stroke is caused by a blocked artery in the brain. A hemorrhagic stroke is caused by leaking or bursting of a blood vessel in the brain. Some people may have only a temporary disruption of blood flow to the brain, known as a transient ischemic attack (TIA). A TIA doesn't cause lasting symptoms. Ischemic stroke This is the most common type of stroke. It happens when the brain's blood vessels become narrowed or blocked. This causes reduced blood flow, known as ischemia. Blocked or narrowed blood vessels can be caused by fatty deposits that build up in blood vessels. Or they can be caused by blood clots or other debris that travel through the bloodstream, most often from the heart. An ischemic stroke occurs when fatty deposits, blood clots or other debris become lodged in the blood vessels in the brain. Some early research shows that COVID-19 infection may increase the risk of ischemic stroke, but more study is needed. Hemorrhagic stroke Hemorrhagic stroke occurs when a blood vessel in the brain leaks or ruptures. Bleeding inside the brain, known as a brain hemorrhage, can result from many conditions that affect the blood vessels. Factors related to hemorrhagic stroke include: High blood pressure that's not under control. Overtreatment with blood thinners, also known as anticoagulants. Bulges at weak spots in the blood vessel walls, known as aneurysms. Head trauma, such as from a car accident. Protein deposits in blood vessel walls that lead to weakness in the vessel wall. This is known as cerebral amyloid angiopathy. Ischemic stroke that leads to a brain hemorrhage. A less common cause of bleeding in the brain is the rupture of an arteriovenous malformation (AVM). An AVM is an irregular tangle of thin-walled blood vessels. Transient ischemic attack A transient ischemic attack (TIA) is a temporary period of symptoms similar to those of a stroke. But a TIA doesn't cause permanent damage. A TIA is caused by a temporary decrease in blood supply to part of the brain. The decrease may last as little as five minutes. A transient ischemic attack is sometimes known as a ministroke. A TIA occurs when a blood clot or fatty deposit reduces or blocks blood flow to part of the nervous system. Seek emergency care even if you think you've had a TIA. It's not possible to tell if you're having a stroke or TIA based only on the symptoms. If you've had a TIA, it means you may have a partially blocked or narrowed artery leading to the brain. Having a TIA increases your risk of having a stroke later. Risk factors Many factors can increase the risk of stroke. Potentially treatable stroke risk factors include: Lifestyle risk factors Being overweight or obese. Physical inactivity. Heavy or binge drinking. Use of illegal drugs such as cocaine and methamphetamine. Medical risk factors High blood pressure. Cigarette smoking or secondhand smoke exposure. High cholesterol. Diabetes. Obstructive sleep apnea. Cardiovascular disease, including heart failure, heart defects, heart infection or irregular heart rhythm, such as atrial fibrillation. Personal or family history of stroke, heart attack or transient ischemic attack. COVID-19 infection. Other factors associated with a higher risk of stroke include: Age — People age 55 or older have a higher risk of stroke than do younger people. Race or ethnicity — African American and Hispanic people have a higher risk of stroke than do people of other races or ethnicities. Sex — Men have a higher risk of stroke than do women. Women are usually older when they have strokes, and they're more likely to die of strokes than are men. Hormones — Taking birth control pills or hormone therapies that include estrogen can increase risk. Complications A stroke can sometimes cause temporary or permanent disabilities. Complications depend on how long the brain lacks blood flow and which part is affected. Complications may include: Loss of muscle movement, known as paralysis. You may become paralyzed on one side of the body. Or you may lose control of certain muscles, such as those on one side of the face or one arm. Trouble talking or swallowing. A stroke might affect the muscles in the mouth and throat. This can make it hard to talk clearly, swallow or eat. You also may have trouble with language, including speaking or understanding speech, reading or writing. Memory loss or trouble thinking. Many people who have had strokes experience some memory loss. Others may have trouble thinking, reasoning, making judgments and understanding concepts. Emotional symptoms. People who have had strokes may have more trouble controlling their emotions. Or they may develop depression. Pain. Pain, numbness or other feelings may occur in the parts of the body affected by stroke. If a stroke causes you to lose feeling in the left arm, you may develop a tingling sensation in that arm. Changes in behavior and self-care. People who have had strokes may become more withdrawn. They also may need help with grooming and daily chores.

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> I am a first-year medical resident. I recently treated a patient with a stroke, and it was my first time treating this condition. I am trying to become more familiarized with it, because the patient's family had a lot of questions, like if they were at risk of having one too, and what they could have done to prevent it from happening. I didn't really know how to answer some of those questions and felt bad about it afterward. Can you give me summarized information about strokes so I know how to deal with it next time? <TEXT> Symptoms If you or someone you're with may be having a stroke, pay attention to the time the symptoms began. Some treatments are most effective when given soon after a stroke begins. Symptoms of stroke include: Trouble speaking and understanding what others are saying. A person having a stroke may be confused, slur words or may not be able to understand speech. Numbness, weakness or paralysis in the face, arm or leg. This often affects just one side of the body. The person can try to raise both arms over the head. If one arm begins to fall, it may be a sign of a stroke. Also, one side of the mouth may droop when trying to smile. Problems seeing in one or both eyes. The person may suddenly have blurred or blackened vision in one or both eyes. Or the person may see double. Headache. A sudden, severe headache may be a symptom of a stroke. Vomiting, dizziness and a change in consciousness may occur with the headache. Trouble walking. Someone having a stroke may stumble or lose balance or coordination. When to see a doctor Seek immediate medical attention if you notice any symptoms of a stroke, even if they seem to come and go or they disappear completely. Think "FAST" and do the following: Face. Ask the person to smile. Does one side of the face droop? Arms. Ask the person to raise both arms. Does one arm drift downward? Or is one arm unable to rise? Speech. Ask the person to repeat a simple phrase. Is the person's speech slurred or different from usual? Time. If you see any of these signs, call 911 or emergency medical help right away. Call 911 or your local emergency number immediately. Don't wait to see if symptoms stop. Every minute counts. The longer a stroke goes untreated, the greater the potential for brain damage and disability. If you're with someone you suspect is having a stroke, watch the person carefully while waiting for emergency assistance. Causes There are two main causes of stroke. An ischemic stroke is caused by a blocked artery in the brain. A hemorrhagic stroke is caused by leaking or bursting of a blood vessel in the brain. Some people may have only a temporary disruption of blood flow to the brain, known as a transient ischemic attack (TIA). A TIA doesn't cause lasting symptoms. Ischemic stroke This is the most common type of stroke. It happens when the brain's blood vessels become narrowed or blocked. This causes reduced blood flow, known as ischemia. Blocked or narrowed blood vessels can be caused by fatty deposits that build up in blood vessels. Or they can be caused by blood clots or other debris that travel through the bloodstream, most often from the heart. An ischemic stroke occurs when fatty deposits, blood clots or other debris become lodged in the blood vessels in the brain. Some early research shows that COVID-19 infection may increase the risk of ischemic stroke, but more study is needed. Hemorrhagic stroke Hemorrhagic stroke occurs when a blood vessel in the brain leaks or ruptures. Bleeding inside the brain, known as a brain hemorrhage, can result from many conditions that affect the blood vessels. Factors related to hemorrhagic stroke include: High blood pressure that's not under control. Overtreatment with blood thinners, also known as anticoagulants. Bulges at weak spots in the blood vessel walls, known as aneurysms. Head trauma, such as from a car accident. Protein deposits in blood vessel walls that lead to weakness in the vessel wall. This is known as cerebral amyloid angiopathy. Ischemic stroke that leads to a brain hemorrhage. A less common cause of bleeding in the brain is the rupture of an arteriovenous malformation (AVM). An AVM is an irregular tangle of thin-walled blood vessels. Transient ischemic attack A transient ischemic attack (TIA) is a temporary period of symptoms similar to those of a stroke. But a TIA doesn't cause permanent damage. A TIA is caused by a temporary decrease in blood supply to part of the brain. The decrease may last as little as five minutes. A transient ischemic attack is sometimes known as a ministroke. A TIA occurs when a blood clot or fatty deposit reduces or blocks blood flow to part of the nervous system. Seek emergency care even if you think you've had a TIA. It's not possible to tell if you're having a stroke or TIA based only on the symptoms. If you've had a TIA, it means you may have a partially blocked or narrowed artery leading to the brain. Having a TIA increases your risk of having a stroke later. Risk factors Many factors can increase the risk of stroke. Potentially treatable stroke risk factors include: Lifestyle risk factors Being overweight or obese. Physical inactivity. Heavy or binge drinking. Use of illegal drugs such as cocaine and methamphetamine. Medical risk factors High blood pressure. Cigarette smoking or secondhand smoke exposure. High cholesterol. Diabetes. Obstructive sleep apnea. Cardiovascular disease, including heart failure, heart defects, heart infection or irregular heart rhythm, such as atrial fibrillation. Personal or family history of stroke, heart attack or transient ischemic attack. COVID-19 infection. Other factors associated with a higher risk of stroke include: Age — People age 55 or older have a higher risk of stroke than do younger people. Race or ethnicity — African American and Hispanic people have a higher risk of stroke than do people of other races or ethnicities. Sex — Men have a higher risk of stroke than do women. Women are usually older when they have strokes, and they're more likely to die of strokes than are men. Hormones — Taking birth control pills or hormone therapies that include estrogen can increase risk. Complications A stroke can sometimes cause temporary or permanent disabilities. Complications depend on how long the brain lacks blood flow and which part is affected. Complications may include: Loss of muscle movement, known as paralysis. You may become paralyzed on one side of the body. Or you may lose control of certain muscles, such as those on one side of the face or one arm. Trouble talking or swallowing. A stroke might affect the muscles in the mouth and throat. This can make it hard to talk clearly, swallow or eat. You also may have trouble with language, including speaking or understanding speech, reading or writing. Memory loss or trouble thinking. Many people who have had strokes experience some memory loss. Others may have trouble thinking, reasoning, making judgments and understanding concepts. Emotional symptoms. People who have had strokes may have more trouble controlling their emotions. Or they may develop depression. Pain. Pain, numbness or other feelings may occur in the parts of the body affected by stroke. If a stroke causes you to lose feeling in the left arm, you may develop a tingling sensation in that arm. Changes in behavior and self-care. People who have had strokes may become more withdrawn. They also may need help with grooming and daily chores. https://www.mayoclinic.org/diseases-conditions/stroke/symptoms-causes/syc-20350113

You can only respond to the prompt using information in the context block and no other sources.

Was Q3 performance better in Asia or the US?

Thank you, Tiffany, and thank you for joining us this afternoon. Let me start by laying out our results for this quarter. Our Q3 total company revenue was $9.1 billion, up 1% year-over-year and 6% over Q2. Our global comparable store sales declined 3% year-over-year driven by a negative 2% comp growth in North America and a negative 14% comp growth in China and partially offset by strong performance in Japan. Our global operating margins contracted by 70 basis points to 16.7% and overall earnings per share for the quarter was $0.93. Our total company results were in line with guidance, but international performance, particularly in China, was challenged. We are not satisfied with the results, but our actions are making an impact, leading business and operational indicators are trending in the right direction ahead of our financial results and our runway for improvement is long. We see green shoots in our US business driven by the three-part action plan outlined last quarter. First, meet and unlock capacity for new demand through a relentless focus on improvements to our US store operations and on elevating the experience we create for our partners and customers. Second, attract new customers and drive transaction growth by launching and integrating more exciting new products with relevant marketing while maintaining our focus on core coffee forward offerings. And third, reach new customers, and demonstrate our value by making sure customers believe the Starbucks experience is worth it every time. First, our largest opportunity, meet and unlock capacity for new demand. A relentless focus on improving operational execution across our nearly 10,000 US company-operated stores is the cornerstone of our near term plan. While it is early days of progress, our plan is working. If you walk away from today's call with one thought, let it be the significant changes and long-term upside potential taking place within our US stores and across our end-to-end supply chain to unlock growth, enhance the customer experience, and drive cost efficiencies. Within our stores, we've seen material positive momentum across core store health and performance metrics with notable improvements in partner scheduling and turnover, critical store issues, and inventory management. Stores ranked in our top two operational performance quartiles reached a new high during the quarter, a 28% upwards shift from Q2, but we have more opportunity. Our focus on operational excellence driven by Reinvention plan has led to a multi-second year-over-year improvement in out-of-the-window times, a nearly 50% reduction in calls received by our Customer Contact Center for my order took too long and Mobile Order & Pay and delivery uptime rates of 99%. These are key indicators of our work to drive growth by addressing customer wait times, product availability, and the customer experience. This quarter, we also introduced phase one of our Siren Craft System, which includes several process and partner driven enhancements to our US store operations. Changes include a new peak time play caller role, strategic investments in partner hours, training, new routines, simple enhancements to technology, and an evolved beverage build process. Early deployment across 1,200 stores demonstrated a material incremental improvement across key performance, throughput efficiency, and reliability metrics. Encouraged by this, we fully deployed Siren Craft System process improvements across our entire portfolio of US company-operated stores this week. Later this quarter, we will begin rolling out a simple refit to our espresso machines which we expect to improve espresso throughput by up to 15% without compromising quality, and with a minor software change in our store production systems, we have a similar ability to improve food throughput. When paired with Siren System equipment announced as part of our Reinvention plan, these new processes become a force multiplier that we expect to drive a true step change improvement. Early assessments demonstrate the capability to drive a 10 to 20 second wait time reduction and a resulting comp opportunity range of 1% to 1.5%. Leveraging our Deep Brew analytics platform, we have identified customer experience outlier stores, approximately 10% of our network, and have developed targeted plans to address and improve them including accelerated Siren System deployment. Similarly, we are accelerating the pace of our new store builds and renovations with 580 net new builds and more than 800 renovations planned in North America for FY 2024. Store development efforts are focused on Tier 2 and Tier 3 cities where we see population growth and forecast both underserved demand and high incrementality. Increasingly, these new store builds and renovations also include Siren System equipment. In line with prior guidance, we remain on track to deploy equipment in less than 10% of company-operated stores by the end of FY 2024 and about 40% by the end of FY 2026. Building on our pilot, Starbucks and Gopuff have agreed to terms for an expanded relationship to open 100 delivery-only kitchens across the US. We're also accelerating the rollout of digital storyboards with target deployment across most US stores in the next two years, a year earlier than originally anticipated. Lastly, we're working in other ways to enhance the café experience. This includes new and expanded seating options that elevate many stores, while upholding a safe and inviting place for partners and customers. A key outcome of our operational efforts has been material and sustained improvements to the partner experience. Driven by precision partner-centric staffing and scheduling efforts, we ended the quarter with a new post-pandemic low partner turnover rate, the best shift completion rate in two years and a 13% improvement in average hours per partner, now the highest on record. These initiatives create more stability in our stores, provide more predictability for our partners and sustain our experience flywheel. Looking beyond our stores, we continue to realize new efficiencies, cost savings, and performance improvements across our end-to-end supply chain thanks to strong support from our suppliers and we see even more headroom. We have a structured process to realize significant continued improvements across our end-to-end supply chain. We are ahead of plan on productivity. We expect our productivity to drive efficiency and unlock capital from areas that don't touch the customer. In turn, these savings will enable us to target investments that drive value for our customers beginning later in Q4, reigniting our North American flywheel for growth. We're early days on this journey, building both our strategic sourcing and revenue management capabilities. Our second priority is to drive demand through relevant product innovation with coffee at our core. We've seen meaningful improvement here as well. This quarter, we drove traffic into our stores through an engaging and innovative pipeline of products supported by integrated marketing campaigns. Cold share was up 1% year-over-year, representing 76% of our beverage mix through the quarter. Our newly formulated Iced Coffee received positive feedback. Our strength in cold espresso innovation continued to drive the platform's growth, up 4% year-over-year. And we launched Starbucks Milano Duetto, whole bean coffee in Milan, ahead of a global launch this October. Beyond coffee, our new Summer-Berry Starbucks Refreshers, beverages with Pearls, drove the highest week- one product launch in our history. Their success buoyed the entire Starbucks Refreshers beverage platform to an all-time high during the quarter. As mentioned in Q2, we continue to build out our 24-month product pipeline while accelerating our pace of innovation. For example, recognizing the growing appeal and opportunity created by the energy category, we launched a new Handcrafted Iced Energy beverages across our US stores in just three months compared to a normal 12 to 18 months. Looking forward, we believe our Q4 product offerings, including the return of Pumpkin Spice combined with supporting marketing activities and offers, provides the right formula to drive customer interest, demand, and deeper engagement with both new and existing customers. Our third and final near-term priority is to reach new customers and demonstrate the value we offer by ensuring the Starbucks experience is worth it every time. Recognizing the premium position of our brand, we've been measured in our use of offers. During this quarter, only 14% of our transactions were driven by offers compared to a competitor average of 29%. Of offer-driven transactions, 10% was star-based offers targeted to Starbucks Rewards Members. Only 4% were driven by price- based offers.

System Instructions: You can only respond to the prompt using information in the context block and no other sources. Question: Was Q3 performance better in Asia or the US? Context block: Thank you, Tiffany, and thank you for joining us this afternoon. Let me start by laying out our results for this quarter. Our Q3 total company revenue was $9.1 billion, up 1% year-over-year and 6% over Q2. Our global comparable store sales declined 3% year-over-year driven by a negative 2% comp growth in North America and a negative 14% comp growth in China and partially offset by strong performance in Japan. Our global operating margins contracted by 70 basis points to 16.7% and overall earnings per share for the quarter was $0.93. Our total company results were in line with guidance, but international performance, particularly in China, was challenged. We are not satisfied with the results, but our actions are making an impact, leading business and operational indicators are trending in the right direction ahead of our financial results and our runway for improvement is long. We see green shoots in our US business driven by the three-part action plan outlined last quarter. First, meet and unlock capacity for new demand through a relentless focus on improvements to our US store operations and on elevating the experience we create for our partners and customers. Second, attract new customers and drive transaction growth by launching and integrating more exciting new products with relevant marketing while maintaining our focus on core coffee forward offerings. And third, reach new customers, and demonstrate our value by making sure customers believe the Starbucks experience is worth it every time. First, our largest opportunity, meet and unlock capacity for new demand. A relentless focus on improving operational execution across our nearly 10,000 US company-operated stores is the cornerstone of our near term plan. While it is early days of progress, our plan is working. If you walk away from today's call with one thought, let it be the significant changes and long-term upside potential taking place within our US stores and across our end-to-end supply chain to unlock growth, enhance the customer experience, and drive cost efficiencies. Within our stores, we've seen material positive momentum across core store health and performance metrics with notable improvements in partner scheduling and turnover, critical store issues, and inventory management. Stores ranked in our top two operational performance quartiles reached a new high during the quarter, a 28% upwards shift from Q2, but we have more opportunity. Our focus on operational excellence driven by Reinvention plan has led to a multi-second year-over-year improvement in out-of-the-window times, a nearly 50% reduction in calls received by our Customer Contact Center for my order took too long and Mobile Order & Pay and delivery uptime rates of 99%. These are key indicators of our work to drive growth by addressing customer wait times, product availability, and the customer experience. This quarter, we also introduced phase one of our Siren Craft System, which includes several process and partner driven enhancements to our US store operations. Changes include a new peak time play caller role, strategic investments in partner hours, training, new routines, simple enhancements to technology, and an evolved beverage build process. Early deployment across 1,200 stores demonstrated a material incremental improvement across key performance, throughput efficiency, and reliability metrics. Encouraged by this, we fully deployed Siren Craft System process improvements across our entire portfolio of US company-operated stores this week. Later this quarter, we will begin rolling out a simple refit to our espresso machines which we expect to improve espresso throughput by up to 15% without compromising quality, and with a minor software change in our store production systems, we have a similar ability to improve food throughput. When paired with Siren System equipment announced as part of our Reinvention plan, these new processes become a force multiplier that we expect to drive a true step change improvement. Early assessments demonstrate the capability to drive a 10 to 20 second wait time reduction and a resulting comp opportunity range of 1% to 1.5%. Leveraging our Deep Brew analytics platform, we have identified customer experience outlier stores, approximately 10% of our network, and have developed targeted plans to address and improve them including accelerated Siren System deployment. Similarly, we are accelerating the pace of our new store builds and renovations with 580 net new builds and more than 800 renovations planned in North America for FY 2024. Store development efforts are focused on Tier 2 and Tier 3 cities where we see population growth and forecast both underserved demand and high incrementality. Increasingly, these new store builds and renovations also include Siren System equipment. In line with prior guidance, we remain on track to deploy equipment in less than 10% of company-operated stores by the end of FY 2024 and about 40% by the end of FY 2026. Building on our pilot, Starbucks and Gopuff have agreed to terms for an expanded relationship to open 100 delivery-only kitchens across the US. We're also accelerating the rollout of digital storyboards with target deployment across most US stores in the next two years, a year earlier than originally anticipated. Lastly, we're working in other ways to enhance the café experience. This includes new and expanded seating options that elevate many stores, while upholding a safe and inviting place for partners and customers. A key outcome of our operational efforts has been material and sustained improvements to the partner experience. Driven by precision partner-centric staffing and scheduling efforts, we ended the quarter with a new post-pandemic low partner turnover rate, the best shift completion rate in two years and a 13% improvement in average hours per partner, now the highest on record. These initiatives create more stability in our stores, provide more predictability for our partners and sustain our experience flywheel. Looking beyond our stores, we continue to realize new efficiencies, cost savings, and performance improvements across our end-to-end supply chain thanks to strong support from our suppliers and we see even more headroom. We have a structured process to realize significant continued improvements across our end-to-end supply chain. We are ahead of plan on productivity. We expect our productivity to drive efficiency and unlock capital from areas that don't touch the customer. In turn, these savings will enable us to target investments that drive value for our customers beginning later in Q4, reigniting our North American flywheel for growth. We're early days on this journey, building both our strategic sourcing and revenue management capabilities. Our second priority is to drive demand through relevant product innovation with coffee at our core. We've seen meaningful improvement here as well. This quarter, we drove traffic into our stores through an engaging and innovative pipeline of products supported by integrated marketing campaigns. Cold share was up 1% year-over-year, representing 76% of our beverage mix through the quarter. Our newly formulated Iced Coffee received positive feedback. Our strength in cold espresso innovation continued to drive the platform's growth, up 4% year-over-year. And we launched Starbucks Milano Duetto, whole bean coffee in Milan, ahead of a global launch this October. Beyond coffee, our new Summer-Berry Starbucks Refreshers, beverages with Pearls, drove the highest week- one product launch in our history. Their success buoyed the entire Starbucks Refreshers beverage platform to an all-time high during the quarter. As mentioned in Q2, we continue to build out our 24-month product pipeline while accelerating our pace of innovation. For example, recognizing the growing appeal and opportunity created by the energy category, we launched a new Handcrafted Iced Energy beverages across our US stores in just three months compared to a normal 12 to 18 months. Looking forward, we believe our Q4 product offerings, including the return of Pumpkin Spice combined with supporting marketing activities and offers, provides the right formula to drive customer interest, demand, and deeper engagement with both new and existing customers. Our third and final near-term priority is to reach new customers and demonstrate the value we offer by ensuring the Starbucks experience is worth it every time. Recognizing the premium position of our brand, we've been measured in our use of offers. During this quarter, only 14% of our transactions were driven by offers compared to a competitor average of 29%. Of offer-driven transactions, 10% was star-based offers targeted to Starbucks Rewards Members. Only 4% were driven by price- based offers.

You are given a reference document. You must only use information found in the reference document to answer the question asked.

How did Goldman Sachs recover from losses caused by the mortgage crisis referenced in this email conversation?

From: Sent: To: Cc: Subject: Cohn, Gary (EO 85830) Sunday, November 18, 2007 6:04 PM Blankfein, Uoyd (EO 85830); van Praag, Lucas (EO PBC09) Winkelried, Jon (EO 85830); Viniar, David; Rogee, John F.W. (EO 85830); Horwitz, Russell (EO 85830) Re: NYT We were just smaller in the toxic products ----- Original Message From: Blank fein, Lloyd To: van Praag, Lucas Cc: Winkelried, Jon; Cohn, Gary; Viniar, David; Rogers, John F.W.; Horwitz, Russell Sent: Sun Nov 18 17:59:01 2007 Subject: RE: NYT Of course we didn't dodge the mortgage mess. We lost money, then made more than we lost because of shorts. Also, it's not over, so who knows how it will turn out Ultimately. -----Original Message----From: van Praag, Lucas Sent: Sunday, November 18, 2007 5:47 PM To: Blankfein, Lloyd Cc: Winkelried, Jon; Cohn, Gary; Viniar, David; Rogers, John F.W.; Horwitz, Russell Subject: NYT Jenny Anderson and Landon Thomas' story about how we dodged the mortgage mess is scheduled to run tomorrow. At this stage, 95% certain to be on the front page. I don't expect it to be materially different to the WSJ story on the same subject that ran last week - although it will have more color and annecdotes. Have given John and Russell a detailed briefing and Russell will update you on the plane, but here are a few points: 1 I have Agreed to brief Jenny thoroughly on it tomorrow and expect the news to run either Tues or Wed. I think it would be good if you had a 5 min phone call with her on the subject and I'll liaise with Russell on timing. We will issue the press release to coincide with publication of her article and will actively work with other media, esp in the UK, to make sure the message is spread and picked up effectively. 2. Tomorrow's story will, of course, have 'balance' (ie stuff we don't like). In this instance, we have spent much time discussing conflicts, and I think we've made some progress as she aknowledges that most of her sources on the subject are financial sponsors which fact, unless edited out, is included and gives context. 3, The article references the extraordinary influence Goldman Sachs has - the most topical being John Thain, but Rubin, Hank, Duncan et al are all in the mix too. She hasn't gone as far as suggesting that there is a credible conspiracy theory (unlike her former colleague at the NY Post). She does, however, make the point that it feels like GS is running everything. 5. We spent a lot of time on culture as a differentiator - she was receptive. 4. She has used several remarks you made at the ML conference on the record - which is If anything changes, I ' l l let you know. I L ---,:;;;eeee-;,;;,;.-_ .. From: Sent: To: Subject: Swenson, Michael Thursday. October 11, 2007 7:06 PM Mullen, Donald RE: Early post on P and L _ = Redacled by the Pennanent Yes we are well positioned -----Original Message----e From: Mullen, Donald Sent: Thursday, October 11, 2001 6:21 To: Swenson, Michael Subject: Re: Early post on P and L Sounds like we will make some serious money ----- Original Message From: Swenson, Michael To: Mullen, Donald Sent: Thu Oct 11 16:24:00 2001 SUbject: RE: Early post on e and L The . . . . . . CDO has a bunch of second lien positions 1n it that have been written down, The collateral balance has fallen below the liabilities triggering an "implied write-down event" which is a credit event in our CDS document. Unlike RMBS structures, COOs do not have a bond write-down feature. On another note, today's RMBS downgrades by Moody's should cause many COOs to fail their triggers. That will result in coupons being shut off on the bonds and hence our CDS protection premie paid out will go to zero. -----Original Message----erom: Mullen, Donald Sent: Thursday, October 11, 2001 5:49 To: Swenson, Michael Subject: Re: Early post on e and L Nice day How did the trigger not work ----- original Message ----From: Swenson, Michael To: Mullen, Donald; Montag, Tom Cc: Sparks, Daniel L; Brafman, Lester R Sent: Thu Oct 11 11:41:02 2001 Subject: Early post on e and L Moody's downgraded 32bb of of 2006 AA, A, BBB and BBB- bonds today. This will eventually filter into downgrades 1n COOs. ABX single-As sold off by a point after the news. ASS Desk P and L will be up between 30 and 35mm today, 12mm of the p and 1 is from our first credit event in COOs where the implied trigger failed on a e deal e 06-1) • Goldman, Sachs & Co, ***** From: Sent: To: Ce, Salem, Deeb Thursday, May 17, 20078:06 AM Swenson, Michael Chin, Edwin Subject, bad news .. , FW, lBMl06A wipes out the m6s and makes a wipeout on the m5 imminent. ,. costs us about 2,5mm 3,5 m6 12.5 m5 marked at $10 marked at $20 good news, , , we own 10mm protection on the m6 marked at $50 "., we make $5mm From: ....t ce, To: Subject: Thlxsday, May 17, 2007 8:00 AM salem, Deeb; Olin, Edwin Poue, Darlush; BrOsterman, Jonathan LBMlO6A -.,- 06:0717May2007 LONG BEACH MORTGAGE LOAN TRUST 2006-A FILES (8-K) Disclosing Other Events May 17 (EDGAR Online)· Item 8.01 Other Events Long Beach Mortgage securities Corp announces that the May 2007 distribution report fOf LBMLT 2OQ6.A will reflect that 616 second-lien mortgage loans with an aggregate urpaid principal balance of $ 49,340.870.90 will be dlarged off on May 25.2007. The total amOllnt to be charged off, $52,797,628.59, includes certain unreimbursed advances of principal and interest made by the servicer, Washington Mutual Bank. Information regarding the characteristics of the loans in LBMLT 2006·A is available from the trustee at its website httos:/Itss.db.oom/invr and at http://wmsubprime.lewtan.CQm. The table below sets forth the numbet' and aggregate unpaid principal balance of the charged otf mortgage loans by distribution date (the month following the due dale of the last monthly payment that should have been received with respect to the klans). The chargeoff assessment date tor the pool was May 1, 2007. Distritution Date November 2006 December 2006 January 2007 February 2007 7,163 March 2007 April 2007 May 2007 Number of Loans in 7,767 7,624 7,468 7,305 6,997 TBO" Pool Aggregate Unpaid $465,292,702.94 S475,682,053.93 S465,992,547.68 S455,518,577.5O $444,362,214.18 $434,469,820.04 charged off for reasons other than 180 days delinquency. Due to the numbef of affected mortgage loans fO( the May 2007 distribution date, there may be a larger than usual reconciliation activity on the remittance report for the June 2007 distribution date to reflect items that have not been closed out as of the scheduled reporting date to the trustee for the May 2007 distribution date. Please Contact: Doug Potolsky at (212) 702- 6961 if you have any questions about this filing. From: Sent: To: Subject: Viniar, David Wednesday, July 25,20079:18 PM Cohn, Gary (EO 85630) RE: Private & Confidential: FICC Financial Package 07125/07 Confidential Sensitivity: Tells you what might be happening to people who don't have the big short. -----Original Message----From: Cohn, Gary (EO 85B30) Sent: Wednesday, July 25, 2007 8:55 PM To: Viniar, David; Blankfein, Lloyd (EO 85B30); Winkelried, Jon (EO 65B30) SUbject: Fw: Private & Confidential: FICC Financial Package 07/25/07 Sensitivity: Confidential Look at the Mortgage numbers up 373 in the index book and wrote down 230 in etO-COO and. 92 in resids Original Message ----From: Tricarico, Geoffrey P. To: ficc-package Sent: Wed Jul 25 19:33:10 2007 Subject: Private & Confidential: FICC Financial Package 07/25/07 REVENUES (Including Estimate) EST $ 126.5

You are given a reference document. You must only use information found in the reference document to answer the question asked. How did Goldman Sachs recover from losses caused by the mortgage crisis referenced in this email conversation? From: Sent: To: Cc: Subject: Cohn, Gary (EO 85830) Sunday, November 18, 2007 6:04 PM Blankfein, Uoyd (EO 85830); van Praag, Lucas (EO PBC09) Winkelried, Jon (EO 85830); Viniar, David; Rogee, John F.W. (EO 85830); Horwitz, Russell (EO 85830) Re: NYT We were just smaller in the toxic products ----- Original Message From: Blank fein, Lloyd To: van Praag, Lucas Cc: Winkelried, Jon; Cohn, Gary; Viniar, David; Rogers, John F.W.; Horwitz, Russell Sent: Sun Nov 18 17:59:01 2007 Subject: RE: NYT Of course we didn't dodge the mortgage mess. We lost money, then made more than we lost because of shorts. Also, it's not over, so who knows how it will turn out Ultimately. -----Original Message----From: van Praag, Lucas Sent: Sunday, November 18, 2007 5:47 PM To: Blankfein, Lloyd Cc: Winkelried, Jon; Cohn, Gary; Viniar, David; Rogers, John F.W.; Horwitz, Russell Subject: NYT Jenny Anderson and Landon Thomas' story about how we dodged the mortgage mess is scheduled to run tomorrow. At this stage, 95% certain to be on the front page. I don't expect it to be materially different to the WSJ story on the same subject that ran last week - although it will have more color and annecdotes. Have given John and Russell a detailed briefing and Russell will update you on the plane, but here are a few points: 1 I have Agreed to brief Jenny thoroughly on it tomorrow and expect the news to run either Tues or Wed. I think it would be good if you had a 5 min phone call with her on the subject and I'll liaise with Russell on timing. We will issue the press release to coincide with publication of her article and will actively work with other media, esp in the UK, to make sure the message is spread and picked up effectively. 2. Tomorrow's story will, of course, have 'balance' (ie stuff we don't like). In this instance, we have spent much time discussing conflicts, and I think we've made some progress as she aknowledges that most of her sources on the subject are financial sponsors which fact, unless edited out, is included and gives context. 3, The article references the extraordinary influence Goldman Sachs has - the most topical being John Thain, but Rubin, Hank, Duncan et al are all in the mix too. She hasn't gone as far as suggesting that there is a credible conspiracy theory (unlike her former colleague at the NY Post). She does, however, make the point that it feels like GS is running everything. 5. We spent a lot of time on culture as a differentiator - she was receptive. 4. She has used several remarks you made at the ML conference on the record - which is If anything changes, I ' l l let you know. I L ---,:;;;eeee-;,;;,;.-_ .. From: Sent: To: Subject: Swenson, Michael Thursday. October 11, 2007 7:06 PM Mullen, Donald RE: Early post on P and L _ = Redacled by the Pennanent Yes we are well positioned -----Original Message----e From: Mullen, Donald Sent: Thursday, October 11, 2001 6:21 To: Swenson, Michael Subject: Re: Early post on P and L Sounds like we will make some serious money ----- Original Message From: Swenson, Michael To: Mullen, Donald Sent: Thu Oct 11 16:24:00 2001 SUbject: RE: Early post on e and L The . . . . . . CDO has a bunch of second lien positions 1n it that have been written down, The collateral balance has fallen below the liabilities triggering an "implied write-down event" which is a credit event in our CDS document. Unlike RMBS structures, COOs do not have a bond write-down feature. On another note, today's RMBS downgrades by Moody's should cause many COOs to fail their triggers. That will result in coupons being shut off on the bonds and hence our CDS protection premie paid out will go to zero. -----Original Message----erom: Mullen, Donald Sent: Thursday, October 11, 2001 5:49 To: Swenson, Michael Subject: Re: Early post on e and L Nice day How did the trigger not work ----- original Message ----From: Swenson, Michael To: Mullen, Donald; Montag, Tom Cc: Sparks, Daniel L; Brafman, Lester R Sent: Thu Oct 11 11:41:02 2001 Subject: Early post on e and L Moody's downgraded 32bb of of 2006 AA, A, BBB and BBB- bonds today. This will eventually filter into downgrades 1n COOs. ABX single-As sold off by a point after the news. ASS Desk P and L will be up between 30 and 35mm today, 12mm of the p and 1 is from our first credit event in COOs where the implied trigger failed on a e deal e 06-1) • Goldman, Sachs & Co, ***** From: Sent: To: Ce, Salem, Deeb Thursday, May 17, 20078:06 AM Swenson, Michael Chin, Edwin Subject, bad news .. , FW, lBMl06A wipes out the m6s and makes a wipeout on the m5 imminent. ,. costs us about 2,5mm 3,5 m6 12.5 m5 marked at $10 marked at $20 good news, , , we own 10mm protection on the m6 marked at $50 "., we make $5mm From: ....t ce, To: Subject: Thlxsday, May 17, 2007 8:00 AM salem, Deeb; Olin, Edwin Poue, Darlush; BrOsterman, Jonathan LBMlO6A -.,- 06:0717May2007 LONG BEACH MORTGAGE LOAN TRUST 2006-A FILES (8-K) Disclosing Other Events May 17 (EDGAR Online)· Item 8.01 Other Events Long Beach Mortgage securities Corp announces that the May 2007 distribution report fOf LBMLT 2OQ6.A will reflect that 616 second-lien mortgage loans with an aggregate urpaid principal balance of $ 49,340.870.90 will be dlarged off on May 25.2007. The total amOllnt to be charged off, $52,797,628.59, includes certain unreimbursed advances of principal and interest made by the servicer, Washington Mutual Bank. Information regarding the characteristics of the loans in LBMLT 2006·A is available from the trustee at its website httos:/Itss.db.oom/invr and at http://wmsubprime.lewtan.CQm. The table below sets forth the numbet' and aggregate unpaid principal balance of the charged otf mortgage loans by distribution date (the month following the due dale of the last monthly payment that should have been received with respect to the klans). The chargeoff assessment date tor the pool was May 1, 2007. Distritution Date November 2006 December 2006 January 2007 February 2007 7,163 March 2007 April 2007 May 2007 Number of Loans in 7,767 7,624 7,468 7,305 6,997 TBO" Pool Aggregate Unpaid $465,292,702.94 S475,682,053.93 S465,992,547.68 S455,518,577.5O $444,362,214.18 $434,469,820.04 charged off for reasons other than 180 days delinquency. Due to the numbef of affected mortgage loans fO( the May 2007 distribution date, there may be a larger than usual reconciliation activity on the remittance report for the June 2007 distribution date to reflect items that have not been closed out as of the scheduled reporting date to the trustee for the May 2007 distribution date. Please Contact: Doug Potolsky at (212) 702- 6961 if you have any questions about this filing. From: Sent: To: Subject: Viniar, David Wednesday, July 25,20079:18 PM Cohn, Gary (EO 85630) RE: Private & Confidential: FICC Financial Package 07125/07 Confidential Sensitivity: Tells you what might be happening to people who don't have the big short. -----Original Message----From: Cohn, Gary (EO 85B30) Sent: Wednesday, July 25, 2007 8:55 PM To: Viniar, David; Blankfein, Lloyd (EO 85B30); Winkelried, Jon (EO 65B30) SUbject: Fw: Private & Confidential: FICC Financial Package 07/25/07 Sensitivity: Confidential Look at the Mortgage numbers up 373 in the index book and wrote down 230 in etO-COO and. 92 in resids Original Message ----From: Tricarico, Geoffrey P. To: ficc-package Sent: Wed Jul 25 19:33:10 2007 Subject: Private & Confidential: FICC Financial Package 07/25/07 REVENUES (Including Estimate) EST $ 126.5

[question] [user request] ===================== [text] [context document] ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

In bullet point form, what is Dobbs and what are some effects that America is having because of it based on this statement from Lopez

Thank you, Chair Sanders, Ranking Member Cassidy, Senator Murray and the members of the Committee for the opportunity to highlight the clear and growing evidence that the Dobbs decision is harming reproductive health and freedom. My name is Destiny Lopez, and I am the acting co-CEO of the Guttmacher Institute, a leading research and policy organization committed to advancing sexual and reproductive health and rights worldwide. For decades following the 1973 Roe v. Wade decision, anti-abortion advocates worked strategically to make abortion harder to get and highly stigmatized. Public support for abortion’s legality has remained high and consistent. But the sheer number of state-level abortion restrictions ensured that abortion became inaccessible for many—even with Roe in place. The Dobbs v. Jackson Women’s Health Organization decision was an inflection point, unleashing chaos and fear across the nation. Our experts are constantly assessing this changing landscape and the increasingly robust body of evidence that illustrates the harms caused and exacerbated by Dobbs. Two years after the decision, here is what we know:i Access to abortion care is severely restricted in many parts of the country. Fourteen states are now enforcing total abortion bans with very limited exceptions, and many more have other new restrictions in place. The total number of brick-and-mortar clinics providing abortion care in the US declined by more than 40 between 2020 and early 2024. Banning abortion does not stop the need for abortion access. Which is why many people seeking abortions post-Dobbs must overcome huge financial and logistical barriers to get care, especially those in states with total or early gestational bans. The number of Americans traveling out of state for abortions doubled from 81,000 in 2020 to more than 170,000 in 2023. States that border states with total abortion bans saw the sharpest increases in out-of-state patients. No one should have to travel to another state to access basic healthcare. And in fact, those who can’t overcome the burdens of travelling for care, which for some might mean crossing multiple state lines, may be forced to stay pregnant against their will. Others may decide to self-manage their abortion. Decades of research have documented that the majority of people obtaining abortions have few financial resources, are people of color, and are already parenting. They are the ones most harshly impacted by bans and restrictions. We also know that providers are resilient and adapting to meet patient needs. While brick-andmortar facilities provide more than three-quarters of all abortions, online clinics are expanding care options by offering medication abortion services via telehealth. Research by the Society for Family Planning shows that virtual-only telehealth abortions accounted for almost one in five abortions from October to December 2023. There are many other important ways Dobbs is interfering with reproductive health care across the nation that I don’t have time to discuss in detail today, from current and future OB-GYNs not wanting to practice in ban states to impacts on maternal health and people facing obstetric emergencies. So what does all this mean? Overturning Roe did not resolve the debates on abortion that have characterized US politics for the past 50 years. Instead, it enabled policies that have significantly worsened the harms faced by individuals who are most marginalized in our health care system. Still, despite these immense hardships and many people being denied care, there were more than one million clinician-provided abortions in 2023—a 10% increase from 2020. This is a testament to the heroic efforts of providers, abortion funds and other support networks, to the resilience and determination of people seeking care, and to the centrality of abortion in peoples’ lives. And it explains why the anti-abortion movement and their political allies are doubling down on even more repressive policies. For instance, this year four states introduced legislation—and one passed a law—criminalizing adults who support adolescents seeking abortion care in another state. Earlier in the year, the Alabama Supreme Court’s decision to classify frozen embryos as “children” wreaked havoc on fertility treatment services while advancing the anti-abortion movement’s long-term goal to enshrine fetal personhood in both law and policy. These attacks on bodily autonomy, coupled with two major abortion cases currently before the Supreme Court, signal that the policy and legal landscape will continue to shift. The full damage caused by Dobbs will not be clear for years to come, but the evidence suggests it will not be easy to repair. That’s why it is imperative that policymakers at all levels of government champion a bold vision of abortion care that goes beyond what Roe promised. Only policies rooted in evidence and human rights will guarantee that all people have meaningful access to high-quality, affordable abortion care where they live and via the method they choose. Thank you.

[question] In bullet point form, what is Dobbs and what are some effects that America is having because of it based on this statement from Lopez ===================== [text] Thank you, Chair Sanders, Ranking Member Cassidy, Senator Murray and the members of the Committee for the opportunity to highlight the clear and growing evidence that the Dobbs decision is harming reproductive health and freedom. My name is Destiny Lopez, and I am the acting co-CEO of the Guttmacher Institute, a leading research and policy organization committed to advancing sexual and reproductive health and rights worldwide. For decades following the 1973 Roe v. Wade decision, anti-abortion advocates worked strategically to make abortion harder to get and highly stigmatized. Public support for abortion’s legality has remained high and consistent. But the sheer number of state-level abortion restrictions ensured that abortion became inaccessible for many—even with Roe in place. The Dobbs v. Jackson Women’s Health Organization decision was an inflection point, unleashing chaos and fear across the nation. Our experts are constantly assessing this changing landscape and the increasingly robust body of evidence that illustrates the harms caused and exacerbated by Dobbs. Two years after the decision, here is what we know:i Access to abortion care is severely restricted in many parts of the country. Fourteen states are now enforcing total abortion bans with very limited exceptions, and many more have other new restrictions in place. The total number of brick-and-mortar clinics providing abortion care in the US declined by more than 40 between 2020 and early 2024. Banning abortion does not stop the need for abortion access. Which is why many people seeking abortions post-Dobbs must overcome huge financial and logistical barriers to get care, especially those in states with total or early gestational bans. The number of Americans traveling out of state for abortions doubled from 81,000 in 2020 to more than 170,000 in 2023. States that border states with total abortion bans saw the sharpest increases in out-of-state patients. No one should have to travel to another state to access basic healthcare. And in fact, those who can’t overcome the burdens of travelling for care, which for some might mean crossing multiple state lines, may be forced to stay pregnant against their will. Others may decide to self-manage their abortion. Decades of research have documented that the majority of people obtaining abortions have few financial resources, are people of color, and are already parenting. They are the ones most harshly impacted by bans and restrictions. We also know that providers are resilient and adapting to meet patient needs. While brick-andmortar facilities provide more than three-quarters of all abortions, online clinics are expanding care options by offering medication abortion services via telehealth. Research by the Society for Family Planning shows that virtual-only telehealth abortions accounted for almost one in five abortions from October to December 2023. There are many other important ways Dobbs is interfering with reproductive health care across the nation that I don’t have time to discuss in detail today, from current and future OB-GYNs not wanting to practice in ban states to impacts on maternal health and people facing obstetric emergencies. So what does all this mean? Overturning Roe did not resolve the debates on abortion that have characterized US politics for the past 50 years. Instead, it enabled policies that have significantly worsened the harms faced by individuals who are most marginalized in our health care system. Still, despite these immense hardships and many people being denied care, there were more than one million clinician-provided abortions in 2023—a 10% increase from 2020. This is a testament to the heroic efforts of providers, abortion funds and other support networks, to the resilience and determination of people seeking care, and to the centrality of abortion in peoples’ lives. And it explains why the anti-abortion movement and their political allies are doubling down on even more repressive policies. For instance, this year four states introduced legislation—and one passed a law—criminalizing adults who support adolescents seeking abortion care in another state. Earlier in the year, the Alabama Supreme Court’s decision to classify frozen embryos as “children” wreaked havoc on fertility treatment services while advancing the anti-abortion movement’s long-term goal to enshrine fetal personhood in both law and policy. These attacks on bodily autonomy, coupled with two major abortion cases currently before the Supreme Court, signal that the policy and legal landscape will continue to shift. The full damage caused by Dobbs will not be clear for years to come, but the evidence suggests it will not be easy to repair. That’s why it is imperative that policymakers at all levels of government champion a bold vision of abortion care that goes beyond what Roe promised. Only policies rooted in evidence and human rights will guarantee that all people have meaningful access to high-quality, affordable abortion care where they live and via the method they choose. Thank you. https://www.help.senate.gov/imo/media/doc/80626e6a-a9e9-50e7-072a-95e7c2a059e3/Lopez%20-%20Testimony.pdf ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

Only use the provided context when answering this task and format your response in bullet points with and follow each with an explanation

What industries will be created or accelerated by robotic ecosystems?

IMPACT ON WORKFORCE While automation will cause significant changes in the composition of employment, it will not cause mass unemployment. Quite the contrary, displaced workers will fill new higher-value-add jobs, and the labor force is likely to increase. The positive impact associated with the retraining of soldiers after World War II8 is quite instructive. The economy assimilated returning soldiers surprisingly well, boosting productivity significantly. Though, as automation accelerates job turnover, the cost of friction in the labor market, which currently stands at more than $630B per annum is expected to grow. These frictions present tremendous opportunity for companies that help firms reduce time-to-hire, provide workers with new skill-sets, and train new employees more efficiently. In the United States today, 5.4 million jobs are unfilled because of skillset mismatches, as shown below. ARK’s research indicates that recruiting and training account for over 2/3 the cost of friction in the labor market. The opportunity for recruiting and retraining has never been better. Some companies already are responding. In 2013, corporate spending on training increased by 15%, to $70 billion and then increased another 10% in 2014.9 Companies such as Cornerstone on Demand (CSOD), Manpower (MAN), Robert Half (RHI), DeVry (DV), Adecco (AHEXY), and LinkedIn (LNKD), which acquired Lynda.com, offer career skill-building programs, and should benefit significantly as automation permeates more industries. The productivity associated with automation will have a profound impact on economic growth. According to ARK’s research, real GDP per worker in the US will double from $113,000 in 2013 to $236,000 in 2035, or at an annual rate of 3.4%. Without automation, productivity would increase at roughly half that rate, or 1.8%, limiting real GDP per worker to $167,000, as shown below. As automation proliferates, the growth of real GDP per worker will accelerate from 2.2% during the next ten years, to roughly 5% between 2025 and 2035. By 2035, real GDP will be 42% higher with automation than without it, as shown below. It will reach roughly $40 trillion, or nearly $12 trillion above the $28 trillion that would otherwise be the case. Clearly, the extra $12 trillion in extra GDP will bring with it many more new jobs. Robotics ecosystems will create new industries and accelerate their growth. Companies already pioneering this movement include Google (GOOG) and Tesla (TSLA) in the autonomous vehicle market, as well as AeroVironment (AVAV), Amazon (AMZN) and Elbit Systems (ESLT) in the drone space. Service robots are in their infancy, but could undergo explosive growth. Early examples include vacuum and lawnmower robots manufactured by iRobot (IRBT), medical robots by Intuitive Surgical (ISRG), and industrial robots by KUKA (KUKAY). Even more embryonic are ReWalk’s10 (RWLK) robot exoskeletons enabling paraplegics to walk.11 Other companies benefitting from these trends manufacture sensors, microcontrollers, cameras, batteries, computerized numerical controls, and materials required for production. Cognex (CGNX), Ambarella (AMBA), Panasonic (PCRFY), Fanuc (FANUY), and Rockwell Automation (ROK) will be prime beneficiaries. Automation will permeate every sector of the economy, with accommodation and food services, agriculture, and retail trade garnering the biggest boosts to productivity. By 2035, GDP per worker will increase by 58% in the accommodation and food services sector, 55% in agriculture, and 53% in retail trade, as depicted below. Spending on automation is poised to soar orders of magnitude above current investment levels. Cumulatively, it will increase by roughly $3.8 trillion through 2035. As artificial intelligence solves increasingly complex problems, the return on investment from “smarter” robots, drones, and automation will drive adoption. Between 2015 and 2035, annual investment in automation could increase at a 16.5% annual growth rate from $11 billion to $242 billion, as illustrated below. During the next decade it should compound at a 33% annual rate. Given the declining cost curves in technology, unit growth rates could be even higher. Several sectors will spend disproportionately on automation to boost productivity. In 2035, manufacturing will account for the largest percentage, 13% of the total, or $31 billion. Spearheaded by companies like Amazon (AMZN), the retail sector will spend roughly $26 billion, or 11% of the total investment. In 2014, Amazon boosted the number of Kiva robots in its global distribution centers from 1,000 to 15,000, a fifteen fold increase in one year, and then doubled its Kiva install base to 30,000 in 2015. Game on! Closely related to retail, the accommodation and food services category is set to spend $24 billion as shown in figure 9.

What industries will be created or accelerated by robotic ecosystems? Only use the provided context when answering this task and format your response in bullet points with and follow each with an explanation. IMPACT ON WORKFORCE While automation will cause significant changes in the composition of employment, it will not cause mass unemployment. Quite the contrary, displaced workers will fill new higher-value-add jobs, and the labor force is likely to increase. The positive impact associated with the retraining of soldiers after World War II8 is quite instructive. The economy assimilated returning soldiers surprisingly well, boosting productivity significantly. Though, as automation accelerates job turnover, the cost of friction in the labor market, which currently stands at more than $630B per annum is expected to grow. These frictions present tremendous opportunity for companies that help firms reduce time-to-hire, provide workers with new skill-sets, and train new employees more efficiently. In the United States today, 5.4 million jobs are unfilled because of skillset mismatches, as shown below. ARK’s research indicates that recruiting and training account for over 2/3 the cost of friction in the labor market. The opportunity for recruiting and retraining has never been better. Some companies already are responding. In 2013, corporate spending on training increased by 15%, to $70 billion and then increased another 10% in 2014.9 Companies such as Cornerstone on Demand (CSOD), Manpower (MAN), Robert Half (RHI), DeVry (DV), Adecco (AHEXY), and LinkedIn (LNKD), which acquired Lynda.com, offer career skill-building programs, and should benefit significantly as automation permeates more industries. The productivity associated with automation will have a profound impact on economic growth. According to ARK’s research, real GDP per worker in the US will double from $113,000 in 2013 to $236,000 in 2035, or at an annual rate of 3.4%. Without automation, productivity would increase at roughly half that rate, or 1.8%, limiting real GDP per worker to $167,000, as shown below. As automation proliferates, the growth of real GDP per worker will accelerate from 2.2% during the next ten years, to roughly 5% between 2025 and 2035. By 2035, real GDP will be 42% higher with automation than without it, as shown below. It will reach roughly $40 trillion, or nearly $12 trillion above the $28 trillion that would otherwise be the case. Clearly, the extra $12 trillion in extra GDP will bring with it many more new jobs. Robotics ecosystems will create new industries and accelerate their growth. Companies already pioneering this movement include Google (GOOG) and Tesla (TSLA) in the autonomous vehicle market, as well as AeroVironment (AVAV), Amazon (AMZN) and Elbit Systems (ESLT) in the drone space. Service robots are in their infancy, but could undergo explosive growth. Early examples include vacuum and lawnmower robots manufactured by iRobot (IRBT), medical robots by Intuitive Surgical (ISRG), and industrial robots by KUKA (KUKAY). Even more embryonic are ReWalk’s10 (RWLK) robot exoskeletons enabling paraplegics to walk.11 Other companies benefitting from these trends manufacture sensors, microcontrollers, cameras, batteries, computerized numerical controls, and materials required for production. Cognex (CGNX), Ambarella (AMBA), Panasonic (PCRFY), Fanuc (FANUY), and Rockwell Automation (ROK) will be prime beneficiaries. Automation will permeate every sector of the economy, with accommodation and food services, agriculture, and retail trade garnering the biggest boosts to productivity. By 2035, GDP per worker will increase by 58% in the accommodation and food services sector, 55% in agriculture, and 53% in retail trade, as depicted below. Spending on automation is poised to soar orders of magnitude above current investment levels. Cumulatively, it will increase by roughly $3.8 trillion through 2035. As artificial intelligence solves increasingly complex problems, the return on investment from “smarter” robots, drones, and automation will drive adoption. Between 2015 and 2035, annual investment in automation could increase at a 16.5% annual growth rate from $11 billion to $242 billion, as illustrated below. During the next decade it should compound at a 33% annual rate. Given the declining cost curves in technology, unit growth rates could be even higher. Several sectors will spend disproportionately on automation to boost productivity. In 2035, manufacturing will account for the largest percentage, 13% of the total, or $31 billion. Spearheaded by companies like Amazon (AMZN), the retail sector will spend roughly $26 billion, or 11% of the total investment. In 2014, Amazon boosted the number of Kiva robots in its global distribution centers from 1,000 to 15,000, a fifteen fold increase in one year, and then doubled its Kiva install base to 30,000 in 2015. Game on! Closely related to retail, the accommodation and food services category is set to spend $24 billion as shown in figure 9.

Give an answer using only the context provided.

What are the names of the Disney theme parks listed in the brochure?

Stay in the Magic… and Play! Customize a Walt Disney World Resort vacation package to suit your style and budget. Start Planning Your Disney Vacation Play Full Video  Design your dream Disney vacation—and create magical memories to last a lifetime. Get Started What’s Exciting and New Enjoy some of the newest experiences at Walt Disney World Resort—and rediscover familiar favorites. Finding Nemo: The Big Blue… Remy’s Ratatouille Adventure Finding Nemo: The Big Blue… and Beyond! Witness a stirring spectacle of puppetry, music and more during this reimagined stage show set in Nemo’s vibrant underwater world. Remy’s Ratatouille Adventure Bring the whole family to zip, dash and scurry through Gusteau’s kitchen as you take in the sights, sounds and even smells from Remy’s world. TRON Lightcycle / Run Leave the real world behind in this high-stakes race across the Grid— the dark, computerized world from TRON. Fantasmic! Watch in awe as Mickey Mouse’s dreams come alive in a nighttime musical with stunning effects, dazzling pyrotechnics and more. 4 Enchanting Theme Parks 4 Enchanting Theme Parks There’s so much magic waiting for you in the Walt Disney World theme parks. Magic Kingdom Park Explore lands of endless enchantment, where your fantasy becomes a reality. Read More Disney’s Animal Kingdom Theme Park Encounter the magic of nature with animal adventures and entertainment. Read More Disney’s Hollywood Studios Let your adventure begin as favorite stories come to life all around you. Read More EPCOT Dare to discover a place where your imagination comes alive and curiosity waits around every corner. Read More Stay Longer and Save More on Rooms Take advantage of a special offer on rooms at select Disney Resort hotels, for stays most nights from March 25 to July 7, 2024. Learn More Stay in the Magic with Disney Resorts Collection Discover the many benefits of staying at our unique Disney Resort hotels. Enjoy More Time in the Parks Disney Resort hotel Guests get extra time to play every day. Read More Start Your Stay with a Water Park Day in 2025 Disney Resort hotel Guests arriving in 2025 can enjoy water park admission on check-in day—included with your stay! Read More Savor a World of Flavor Discover delicious dining options when you stay at a Disney Resort hotel. Read More Immerse Yourself in the Magic Disney Resort hotels offer the same legendary detail, service and storytelling that Guests love in our parks. Read More Make the Most of Your Visit Get Around with Ease It’s fun and easy to get around Walt Disney World Resort when you stay at a Disney Resort hotel. Read More Add More Magic Enjoy special offerings and benefits that take your vacation to the next level. Read More Enjoy Magical Extras with Your Package When you book a roomand-ticket package, you’ll receive Magical Extras— discounts and offerings on dining, entertainment and more. Customize Your Package More Fun for Everyone Disney Water Parks Disney water parks are unlike anything else on Earth—they’re drenched in Disney magic Read More Disney Springs Explore an amazing place featuring an eclectic mix of shops, eateries and entertainment. Read More Delectable Dining Walt Disney World Resort has dining options to delight every taste, style and budget. Read More Enchanting Extras Collection Add even more magic to your visit with a variety of unique experiences, available for a fee. Read More Design Your Disney Vacation Explore Places to Stay Choose from uniquely themed Disney Resort hotels—with options to suit your style and budget. Buy Park Tickets Purchase park tickets—and get ready to experience the theme parks and water parks!

Give an answer using only the context provided. What are the names of the Disney theme parks listed in the brochure? Stay in the Magic… and Play! Customize a Walt Disney World Resort vacation package to suit your style and budget. Start Planning Your Disney Vacation Play Full Video  Design your dream Disney vacation—and create magical memories to last a lifetime. Get Started What’s Exciting and New Enjoy some of the newest experiences at Walt Disney World Resort—and rediscover familiar favorites. Finding Nemo: The Big Blue… Remy’s Ratatouille Adventure Finding Nemo: The Big Blue… and Beyond! Witness a stirring spectacle of puppetry, music and more during this reimagined stage show set in Nemo’s vibrant underwater world. Remy’s Ratatouille Adventure Bring the whole family to zip, dash and scurry through Gusteau’s kitchen as you take in the sights, sounds and even smells from Remy’s world. TRON Lightcycle / Run Leave the real world behind in this high-stakes race across the Grid— the dark, computerized world from TRON. Fantasmic! Watch in awe as Mickey Mouse’s dreams come alive in a nighttime musical with stunning effects, dazzling pyrotechnics and more. 4 Enchanting Theme Parks 4 Enchanting Theme Parks There’s so much magic waiting for you in the Walt Disney World theme parks. Magic Kingdom Park Explore lands of endless enchantment, where your fantasy becomes a reality. Read More Disney’s Animal Kingdom Theme Park Encounter the magic of nature with animal adventures and entertainment. Read More Disney’s Hollywood Studios Let your adventure begin as favorite stories come to life all around you. Read More EPCOT Dare to discover a place where your imagination comes alive and curiosity waits around every corner. Read More Stay Longer and Save More on Rooms Take advantage of a special offer on rooms at select Disney Resort hotels, for stays most nights from March 25 to July 7, 2024. Learn More Stay in the Magic with Disney Resorts Collection Discover the many benefits of staying at our unique Disney Resort hotels. Enjoy More Time in the Parks Disney Resort hotel Guests get extra time to play every day. Read More Start Your Stay with a Water Park Day in 2025 Disney Resort hotel Guests arriving in 2025 can enjoy water park admission on check-in day—included with your stay! Read More Savor a World of Flavor Discover delicious dining options when you stay at a Disney Resort hotel. Read More Immerse Yourself in the Magic Disney Resort hotels offer the same legendary detail, service and storytelling that Guests love in our parks. Read More Make the Most of Your Visit Get Around with Ease It’s fun and easy to get around Walt Disney World Resort when you stay at a Disney Resort hotel. Read More Add More Magic Enjoy special offerings and benefits that take your vacation to the next level. Read More Enjoy Magical Extras with Your Package When you book a roomand-ticket package, you’ll receive Magical Extras— discounts and offerings on dining, entertainment and more. Customize Your Package More Fun for Everyone Disney Water Parks Disney water parks are unlike anything else on Earth—they’re drenched in Disney magic Read More Disney Springs Explore an amazing place featuring an eclectic mix of shops, eateries and entertainment. Read More Delectable Dining Walt Disney World Resort has dining options to delight every taste, style and budget. Read More Enchanting Extras Collection Add even more magic to your visit with a variety of unique experiences, available for a fee. Read More Design Your Disney Vacation Explore Places to Stay Choose from uniquely themed Disney Resort hotels—with options to suit your style and budget. Buy Park Tickets Purchase park tickets—and get ready to experience the theme parks and water parks!

Respond to the prompt using only information provided in the context block. Do not use any external knowledge or information not present in the given text. Your response should focus on providing factual details from the text. Use formal language and avoid any personal opinions or interpretations. If the prompt asks about something not covered in the context, state that the information is not available in the given text.

What specific example does the author use to illustrate the effects of division of labor in a "very trifling manufacture"?

THE greatest improvement in the productive powers of labour, and the greater part of the skill, dexterity, and judgment with which it is any where directed, or applied, seem to have been the effects of the division of labour. The effects of the division of labour, in the general business of society, will be more easily understood, by considering in what manner it operates in some particular manufactures. It is commonly supposed to be carried i furthest in some very trifling ones; not perhaps that it really is carried further in them than in others of more importance: but in those trifling manufactures which are destined to supply the small wants of but a small number of people, the whole number of workmen must necessarily be small; and those employed in every different branch of the work can often be collected into the same [7] workhouse, and placed at once under the view of the spectator. In those great manufactures, on the contrary, which are _- destined to supply the great wants of the great body of the people, every different branch of the work employs so great a number of workmen, that it is impossible to collect them all into the same workhouse. We can seldom b see more, at one time, than those employed in one single branch. Though [ bin such manufactures, b therefore, the work may really be divided into a r much greater number of parts, than in those of a more trifling nature, the division is not near so obvious, and has accordingly been much less observed. 3 To take an example, therefore, from a very trifling manufacture; but one in which the division of labour has been very often taken notice of, the trade of the pin-maker; a workman not educated to this business (which the division of labour has rendered a distinct trade), nor acquainted with the use of the machinery employed in it (to the invention of which the same division of labour has probably given occasion), could scarce, perhaps, with his utmost industry, make one pin in a day, and certainly could not make twenty. 2 But in the way in which this business is now carried on, not only the whole work is a peculiar trade, but it is divided into a number of branches, of which the greater part are likewise peculiar trades. One man draws out the wire, another straights it, a third cuts it, a fourth points it, a fifth grinds it at the top for receiving the head; to make the head requires [8] two or three distinct operations; to put it on, is a peculiar business, to whiten the pins is another; it is even a trade by itself to put them into the paper; and the important business of making a pin is, in this manner, divided into about eighteen distinct operations, 3 which, in some manufactories, are all performed by distinct hands, though in others the same man will sometimes perform two or three of them. I have seen a small manufactory of this kind where ten men only were employed, and where some of them consequently performed two or three distinct operations. But though they were very poor, and therefore but indifferently accommodated with the necessary machinery, they could, when they exerted themselves, make among them about twelve pounds of pins in a day. 4 There are in a pound upwards of four thousand pins of a middling size. Those ten persons, therefore, could make among them upwards of forty-eight thousand pins in a day. Each person, therefore, making a tenth part of forty-eight thousand pins, might be considered as making four thousand eight hundred pins in a day. But if they had all wrought separately and independently, and without any of them having been educated to this peculiar business, they certainly could not each of them have made twenty, perhaps not one pin in a day; that is, certainly, not the two hundred and fortieth, perhaps not the four thousand eight hundredth part of what they are at present capable of performing, in consequence of [9] a proper division and combination of their different operations. 4 In every other art and manufacture, the effects of the division of labour are similar to what they are in this very trifling one; though, in many of them, the labour can neither be so much subdivided, nor reduced to so great a simplicity of operation. The division of labour, however, so far as it can be introduced, occasions, in every art, a proportionable increase of the productive powers of labour. The separation of different trades and employments from one another, seems to have taken place, in consequence of this advantage. This separation too is generally carried furthest in those countries which enjoy the highest degree of industry and improvement; what is the work of one man, in a rude state of society, being generally that of several in an improved one. In every improved society, the farmer is generally nothing but a farmer; the manufacturer, nothing but a manufactures The labour too which is necessary to produce any one complete manufacture, is almost always divided among a great number of hands. How many different trades are employed in each branch of the linen and woollen manufactures, from the growers of the flax and the wool, to the bleachers and smoothers of the linen, or to the dyers and dressers of the cloth[ The nature of agriculture, indeed, does not admit of so many subdivisions of labour, nor of so complete a separation of one business from another, as manufactures.6 It is impossible to separate so entirely, the business of the grazer from that of the corn-farmer, as the trade of the carpenter is commonly separated from that of the smith. The spinner is almost always a distinct person from the weaver; but the ploughman, the harrower, the sower of the seed, and the reaper of the corn, are often the same. 7The occasions for those different sorts of labour returning with the different seasons of the year, it is impossible that one man should be constantly employed in any one of them. This impossibility of m_ing so complete and entire a separation of all the different branches of labour employed in agriculture, is perhaps the reason why the improvement of the productive powers of labour in this art, does not always keep pace with their improvement in manufactures. The most opulent nations, indeed, generally excel all their neighbours in agriculture as well as in manufactures; but they are commonly more distinguished by their superiority in the latter than in the farmers Their lands are in general better cultivated, and having more labour and expence bestowed upon them, produce more, in proportion to the extent and natural fertility of the ground. But this superiority of produce is seldom much more than in proportion to the superiority of labour and expence. In agriculture, the labour of the rich country is not always much more productive than that of the poor; or, at least, it is never so much more productive, as it commonly is in manufactures. The corn of the rich country, therefore, will not always, in the same degree of goodness, come cheaper to [ix] market than that of the poor. The corn of Poland, in the same degree of goodness, is as cheap as that of France, notwithstanding the superior opulence and improvement of the latter country. The corn of France is, in the corn provinces, fully as good, and in most years nearly about the same price with the corn of England, though, in opulence and improvement, France is perhaps inferior to England. The acorn-lands of England, however, are better cultivated than those of France, and the acorn-lands f France are said to be much better cultivated than those of Poland. But though the poor country, notwithstanding the inferiority of its cultivation, can, in some measure, rival the rich in the cheapness and goodness of its corn, it can pretend to no such competition in its manufactures; at least if those manufactures suit the soil, climate, and situation of the rich country. The silks of France are better and cheaper than those of England, because the silk manufacture, _at least under the present high duties upon the importation of raw silk/does not so well suit the climate of England has that of France. n But the hard-ware and the coarse woolens of England are beyond all comparison superior to those of France, and much cheaper too in the same degree of goodness. 9 In Poland there are said to be scarce any manufactures of any kind, a few of those coarser household manufactures excepted, without which no country can well subsist.

Respond to the prompt using only information provided in the context block. Do not use any external knowledge or information not present in the given text. Your response should focus on providing factual details from the text. Use formal language and avoid any personal opinions or interpretations. If the prompt asks about something not covered in the context, state that the information is not available in the given text. What specific example does the author use to illustrate the effects of division of labor in a "very trifling manufacture"? THE greatest improvement in the productive powers of labour, and the greater part of the skill, dexterity, and judgment with which it is any where directed, or applied, seem to have been the effects of the division of labour. The effects of the division of labour, in the general business of society, will be more easily understood, by considering in what manner it operates in some particular manufactures. It is commonly supposed to be carried i furthest in some very trifling ones; not perhaps that it really is carried further in them than in others of more importance: but in those trifling manufactures which are destined to supply the small wants of but a small number of people, the whole number of workmen must necessarily be small; and those employed in every different branch of the work can often be collected into the same [7] workhouse, and placed at once under the view of the spectator. In those great manufactures, on the contrary, which are _- destined to supply the great wants of the great body of the people, every different branch of the work employs so great a number of workmen, that it is impossible to collect them all into the same workhouse. We can seldom b see more, at one time, than those employed in one single branch. Though [ bin such manufactures, b therefore, the work may really be divided into a r much greater number of parts, than in those of a more trifling nature, the division is not near so obvious, and has accordingly been much less observed. 3 To take an example, therefore, from a very trifling manufacture; but one in which the division of labour has been very often taken notice of, the trade of the pin-maker; a workman not educated to this business (which the division of labour has rendered a distinct trade), nor acquainted with the use of the machinery employed in it (to the invention of which the same division of labour has probably given occasion), could scarce, perhaps, with his utmost industry, make one pin in a day, and certainly could not make twenty. 2 But in the way in which this business is now carried on, not only the whole work is a peculiar trade, but it is divided into a number of branches, of which the greater part are likewise peculiar trades. One man draws out the wire, another straights it, a third cuts it, a fourth points it, a fifth grinds it at the top for receiving the head; to make the head requires [8] two or three distinct operations; to put it on, is a peculiar business, to whiten the pins is another; it is even a trade by itself to put them into the paper; and the important business of making a pin is, in this manner, divided into about eighteen distinct operations, 3 which, in some manufactories, are all performed by distinct hands, though in others the same man will sometimes perform two or three of them. I have seen a small manufactory of this kind where ten men only were employed, and where some of them consequently performed two or three distinct operations. But though they were very poor, and therefore but indifferently accommodated with the necessary machinery, they could, when they exerted themselves, make among them about twelve pounds of pins in a day. 4 There are in a pound upwards of four thousand pins of a middling size. Those ten persons, therefore, could make among them upwards of forty-eight thousand pins in a day. Each person, therefore, making a tenth part of forty-eight thousand pins, might be considered as making four thousand eight hundred pins in a day. But if they had all wrought separately and independently, and without any of them having been educated to this peculiar business, they certainly could not each of them have made twenty, perhaps not one pin in a day; that is, certainly, not the two hundred and fortieth, perhaps not the four thousand eight hundredth part of what they are at present capable of performing, in consequence of [9] a proper division and combination of their different operations. 4 In every other art and manufacture, the effects of the division of labour are similar to what they are in this very trifling one; though, in many of them, the labour can neither be so much subdivided, nor reduced to so great a simplicity of operation. The division of labour, however, so far as it can be introduced, occasions, in every art, a proportionable increase of the productive powers of labour. The separation of different trades and employments from one another, seems to have taken place, in consequence of this advantage. This separation too is generally carried furthest in those countries which enjoy the highest degree of industry and improvement; what is the work of one man, in a rude state of society, being generally that of several in an improved one. In every improved society, the farmer is generally nothing but a farmer; the manufacturer, nothing but a manufactures The labour too which is necessary to produce any one complete manufacture, is almost always divided among a great number of hands. How many different trades are employed in each branch of the linen and woollen manufactures, from the growers of the flax and the wool, to the bleachers and smoothers of the linen, or to the dyers and dressers of the cloth[ The nature of agriculture, indeed, does not admit of so many subdivisions of labour, nor of so complete a separation of one business from another, as manufactures.6 It is impossible to separate so entirely, the business of the grazer from that of the corn-farmer, as the trade of the carpenter is commonly separated from that of the smith. The spinner is almost always a distinct person from the weaver; but the ploughman, the harrower, the sower of the seed, and the reaper of the corn, are often the same. 7The occasions for those different sorts of labour returning with the different seasons of the year, it is impossible that one man should be constantly employed in any one of them. This impossibility of m_ing so complete and entire a separation of all the different branches of labour employed in agriculture, is perhaps the reason why the improvement of the productive powers of labour in this art, does not always keep pace with their improvement in manufactures. The most opulent nations, indeed, generally excel all their neighbours in agriculture as well as in manufactures; but they are commonly more distinguished by their superiority in the latter than in the farmers Their lands are in general better cultivated, and having more labour and expence bestowed upon them, produce more, in proportion to the extent and natural fertility of the ground. But this superiority of produce is seldom much more than in proportion to the superiority of labour and expence. In agriculture, the labour of the rich country is not always much more productive than that of the poor; or, at least, it is never so much more productive, as it commonly is in manufactures. The corn of the rich country, therefore, will not always, in the same degree of goodness, come cheaper to [ix] market than that of the poor. The corn of Poland, in the same degree of goodness, is as cheap as that of France, notwithstanding the superior opulence and improvement of the latter country. The corn of France is, in the corn provinces, fully as good, and in most years nearly about the same price with the corn of England, though, in opulence and improvement, France is perhaps inferior to England. The acorn-lands of England, however, are better cultivated than those of France, and the acorn-lands f France are said to be much better cultivated than those of Poland. But though the poor country, notwithstanding the inferiority of its cultivation, can, in some measure, rival the rich in the cheapness and goodness of its corn, it can pretend to no such competition in its manufactures; at least if those manufactures suit the soil, climate, and situation of the rich country. The silks of France are better and cheaper than those of England, because the silk manufacture, _at least under the present high duties upon the importation of raw silk/does not so well suit the climate of England has that of France. n But the hard-ware and the coarse woolens of England are beyond all comparison superior to those of France, and much cheaper too in the same degree of goodness. 9 In Poland there are said to be scarce any manufactures of any kind, a few of those coarser household manufactures excepted, without which no country can well subsist.

"================ <TEXT PASSAGE> ======= [context document] ================ <QUESTION> ======= [user request] ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

Summarize the updated cancer treatments for 2024 in terms a 7th grade student can understand. Include important statistics for all the options that include them.

1. Personalized cancer vaccines Thousands of NHS cancer patients in England could soon access trials of a new vaccine treatment. It's designed to prime the immune system to target cancer cells and reduce recurrence risk. These vaccines are also hoped to produce fewer side effects than conventional chemotherapy. Thirty hospitals have joined the Cancer Vaccine Launch Pad, which matches patients with upcoming trials using the same mRNA technology found in current COVID-19 jabs. Over 200 patients from the UK, Germany, Belgium, Spain and Sweden will receive up to 15 doses of the personalized vaccine, with the study expected to complete by 2027. 2. Test to identify 18 early-stage cancers Researchers in the US have developed a test they say can identify 18 early-stage cancers. Instead of the usual invasive and costly methods, Novelna's test works by analyzing a patient's blood protein. In a screening of 440 people already diagnosed with cancer, the test correctly identified 93% of stage 1 cancers in men and 84% in women. The researchers believe the findings "pave the way for a cost-effective, highly accurate, multi-cancer screening test that can be implemented on a population-wide scale". It's early days, however. With such a small sample screening and a lack of information on co-existing conditions, the test is currently more of "a starting point for developing a new generation of screening tests for the early detection of cancer". 3. Seven-minute cancer treatment jab England's National Health Service (NHS) is to be the first in the world to make use of a cancer treatment injection, which takes just seven minutes to administer, rather than the current time of up to an hour to have the same drug via intravenous infusion. This will not only speed up the treatment process for patients, but also free up time for medical professionals. The drug, Atezolizumab or Tecentriq, treats cancers including lung and breast, and it's expected most of the 3,600 NHS patients in England currently receiving it intravenously will now switch to the jab. 4. Precision oncology Precision oncology is the “best new weapon to defeat cancer”, the chief executive of Genetron Health, Sizhen Wang, says in a blog for the World Economic Forum. This involves studying the genetic makeup and molecular characteristics of cancer tumours in individual patients. The precision oncology approach identifies changes in cells that might be causing the cancer to grow and spread. Personalized treatments can then be developed. The 100,000 Genomes Project, a National Health Service initiative, studied more than 13,000 tumour samples from UK cancer patients, successfully integrating genomic data to more accurately pin-point effective treatment. Because precision oncology treatments are targeted – as opposed to general treatments like chemotherapy – it can mean less harm to healthy cells and fewer side effects as a result. 5. Artificial intelligence fights cancer In India, World Economic Forum partners are using emerging technologies like artificial intelligence (AI) and machine learning to transform cancer care. For example, AI-based risk profiling can help screen for common cancers like breast cancer, leading to early diagnosis. AI technology can also be used to analyze X-rays to identify cancers in places where imaging experts might not be available. These are two of 18 cancer interventions that The Centre for the Fourth Industrial Revolution India, a collaboration with the Forum, hopes to accelerate. 6. Greater prediction capabilities Lung cancer kills more people in the US yearly than the next three deadliest cancers combined. It's notoriously hard to detect the early stages of the disease with X-rays and scans alone. However, MIT scientists have developed an AI learning model to predict a person's likelihood of developing lung cancer up to six years in advance via a low-dose CT scan. Trained using complex imaging data, 'Sybil' can forecast both short- and long-term lung cancer risk, according to a recent study. "We found that while we as humans couldn't quite see where the cancer was, the model could still have some predictive power as to which lung would eventually develop cancer," said co-author Jeremy Wohlwend. 7. Clues in the DNA of cancer At Cambridge University Hospitals in England, the DNA of cancer tumours from 12,000 patients is revealing new clues about the causes of cancer, scientists say. By analyzing genomic data, oncologists are identifying different mutations that have contributed to each person’s cancer. For example, exposure to smoking or UV light, or internal malfunctions in cells. These are like “fingerprints in a crime scene”, the scientists say – and more of them are being found. “We uncovered 58 new mutational signatures and broadened our knowledge of cancer,” says study author Dr Andrea Degasperi, from Cambridge’s Department of Oncology. 8. Liquid and synthetic biopsies Biopsies are the main way doctors diagnose cancer – but the process is invasive and involves removing a section of tissue from the body, sometimes surgically, so it can be examined in a laboratory. Liquid biopsies are an easier and less invasive solution where blood samples can be tested for signs of cancer. Synthetic biopsies are another innovation that can force cancer cells to reveal themselves during the earliest stages of the disease. 9. CAR-T-cell therapy A treatment that makes immune cells hunt down and kill cancer cells was declared a success for leukaemia patients in 2022. Known as CAR-T-cell therapy, it involves removing and genetically altering immune cells, called T cells, from cancer patients. The altered cells then produce proteins called chimeric antigen receptors (CARs), which can recognize and destroy cancer cells. In the journal Nature, scientists at the University of Pennsylvania announced that two of the first people treated with CAR-T-cell therapy were still in remission 12 years on. However, the US Food and Drug Administration is currently investigating whether the process can in fact cause cancer, after 33 cases of secondary cancer were observed in patients receiving CAR-T therapies. The jury is still out as to whether the therapy is to blame but, as a precaution, the drug packaging now carries a warning. 10. Fighting pancreatic cancer Pancreatic cancer is one of the deadliest cancers. It is rarely diagnosed before it starts to spread and has a survival rate of less than 5% over five years. At the University of California San Diego School of Medicine, scientists developed a test that identified 95% of early pancreatic cancers in a study. The research, published in Nature Communications Medicine, explains how biomarkers in extracellular vesicles – particles that regulate communication between cells – were used to detect pancreatic, ovarian and bladder cancer at stages I and II. Scientists are also getting closer to a cure. A new US/UK study has discovered that pancreatic cancer shuts down particular molecules in a key gene. The hope now is that the new knowledge "could lead to the development of more effective treatment options in the future”, Dr Chris Macdonald, head of research at Pancreatic Cancer UK, told The Guardian. 11. A tablet to cut breast cancer risk A drug that could halve the chance of women developing breast cancer is being tested out by England's National Health Service (NHS). It will be made available to almost 300,000 women seen as being at most risk of developing breast cancer, which is the most common type of cancer in the UK. The drug, named anastrozole, cuts the level of oestrogen women produce by blocking the enzyme aromatase. It has already been used for many years as a breast cancer treatment but has now been repurposed as a preventive medicine. “This is the first drug to be repurposed through a world-leading new programme to help us realize the full potential of existing medicines in new uses to save and improve more lives on the NHS," says NHS Chief Executive Amanda Pritchard.

"================ <TEXT PASSAGE> ======= 1. Personalized cancer vaccines Thousands of NHS cancer patients in England could soon access trials of a new vaccine treatment. It's designed to prime the immune system to target cancer cells and reduce recurrence risk. These vaccines are also hoped to produce fewer side effects than conventional chemotherapy. Thirty hospitals have joined the Cancer Vaccine Launch Pad, which matches patients with upcoming trials using the same mRNA technology found in current COVID-19 jabs. Over 200 patients from the UK, Germany, Belgium, Spain and Sweden will receive up to 15 doses of the personalized vaccine, with the study expected to complete by 2027. 2. Test to identify 18 early-stage cancers Researchers in the US have developed a test they say can identify 18 early-stage cancers. Instead of the usual invasive and costly methods, Novelna's test works by analyzing a patient's blood protein. In a screening of 440 people already diagnosed with cancer, the test correctly identified 93% of stage 1 cancers in men and 84% in women. The researchers believe the findings "pave the way for a cost-effective, highly accurate, multi-cancer screening test that can be implemented on a population-wide scale". It's early days, however. With such a small sample screening and a lack of information on co-existing conditions, the test is currently more of "a starting point for developing a new generation of screening tests for the early detection of cancer". 3. Seven-minute cancer treatment jab England's National Health Service (NHS) is to be the first in the world to make use of a cancer treatment injection, which takes just seven minutes to administer, rather than the current time of up to an hour to have the same drug via intravenous infusion. This will not only speed up the treatment process for patients, but also free up time for medical professionals. The drug, Atezolizumab or Tecentriq, treats cancers including lung and breast, and it's expected most of the 3,600 NHS patients in England currently receiving it intravenously will now switch to the jab. 4. Precision oncology Precision oncology is the “best new weapon to defeat cancer”, the chief executive of Genetron Health, Sizhen Wang, says in a blog for the World Economic Forum. This involves studying the genetic makeup and molecular characteristics of cancer tumours in individual patients. The precision oncology approach identifies changes in cells that might be causing the cancer to grow and spread. Personalized treatments can then be developed. The 100,000 Genomes Project, a National Health Service initiative, studied more than 13,000 tumour samples from UK cancer patients, successfully integrating genomic data to more accurately pin-point effective treatment. Because precision oncology treatments are targeted – as opposed to general treatments like chemotherapy – it can mean less harm to healthy cells and fewer side effects as a result. 5. Artificial intelligence fights cancer In India, World Economic Forum partners are using emerging technologies like artificial intelligence (AI) and machine learning to transform cancer care. For example, AI-based risk profiling can help screen for common cancers like breast cancer, leading to early diagnosis. AI technology can also be used to analyze X-rays to identify cancers in places where imaging experts might not be available. These are two of 18 cancer interventions that The Centre for the Fourth Industrial Revolution India, a collaboration with the Forum, hopes to accelerate. 6. Greater prediction capabilities Lung cancer kills more people in the US yearly than the next three deadliest cancers combined. It's notoriously hard to detect the early stages of the disease with X-rays and scans alone. However, MIT scientists have developed an AI learning model to predict a person's likelihood of developing lung cancer up to six years in advance via a low-dose CT scan. Trained using complex imaging data, 'Sybil' can forecast both short- and long-term lung cancer risk, according to a recent study. "We found that while we as humans couldn't quite see where the cancer was, the model could still have some predictive power as to which lung would eventually develop cancer," said co-author Jeremy Wohlwend. 7. Clues in the DNA of cancer At Cambridge University Hospitals in England, the DNA of cancer tumours from 12,000 patients is revealing new clues about the causes of cancer, scientists say. By analyzing genomic data, oncologists are identifying different mutations that have contributed to each person’s cancer. For example, exposure to smoking or UV light, or internal malfunctions in cells. These are like “fingerprints in a crime scene”, the scientists say – and more of them are being found. “We uncovered 58 new mutational signatures and broadened our knowledge of cancer,” says study author Dr Andrea Degasperi, from Cambridge’s Department of Oncology. 8. Liquid and synthetic biopsies Biopsies are the main way doctors diagnose cancer – but the process is invasive and involves removing a section of tissue from the body, sometimes surgically, so it can be examined in a laboratory. Liquid biopsies are an easier and less invasive solution where blood samples can be tested for signs of cancer. Synthetic biopsies are another innovation that can force cancer cells to reveal themselves during the earliest stages of the disease. 9. CAR-T-cell therapy A treatment that makes immune cells hunt down and kill cancer cells was declared a success for leukaemia patients in 2022. Known as CAR-T-cell therapy, it involves removing and genetically altering immune cells, called T cells, from cancer patients. The altered cells then produce proteins called chimeric antigen receptors (CARs), which can recognize and destroy cancer cells. In the journal Nature, scientists at the University of Pennsylvania announced that two of the first people treated with CAR-T-cell therapy were still in remission 12 years on. However, the US Food and Drug Administration is currently investigating whether the process can in fact cause cancer, after 33 cases of secondary cancer were observed in patients receiving CAR-T therapies. The jury is still out as to whether the therapy is to blame but, as a precaution, the drug packaging now carries a warning. 10. Fighting pancreatic cancer Pancreatic cancer is one of the deadliest cancers. It is rarely diagnosed before it starts to spread and has a survival rate of less than 5% over five years. At the University of California San Diego School of Medicine, scientists developed a test that identified 95% of early pancreatic cancers in a study. The research, published in Nature Communications Medicine, explains how biomarkers in extracellular vesicles – particles that regulate communication between cells – were used to detect pancreatic, ovarian and bladder cancer at stages I and II. Scientists are also getting closer to a cure. A new US/UK study has discovered that pancreatic cancer shuts down particular molecules in a key gene. The hope now is that the new knowledge "could lead to the development of more effective treatment options in the future”, Dr Chris Macdonald, head of research at Pancreatic Cancer UK, told The Guardian. 11. A tablet to cut breast cancer risk A drug that could halve the chance of women developing breast cancer is being tested out by England's National Health Service (NHS). It will be made available to almost 300,000 women seen as being at most risk of developing breast cancer, which is the most common type of cancer in the UK. The drug, named anastrozole, cuts the level of oestrogen women produce by blocking the enzyme aromatase. It has already been used for many years as a breast cancer treatment but has now been repurposed as a preventive medicine. “This is the first drug to be repurposed through a world-leading new programme to help us realize the full potential of existing medicines in new uses to save and improve more lives on the NHS," says NHS Chief Executive Amanda Pritchard. https://www.weforum.org/agenda/2024/07/cancer-treatment-and-diagnosis-breakthroughs/ ================ <QUESTION> ======= Summarize the updated cancer treatments for 2024 in terms a 7th grade student can understand. Include important statistics for all the options that include them. ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

System Instructions: [You may only use the provided context to answer. You must not use any outside sources or prior knowledge.]

Question: [Summarize the role of Pros.]

Context: [DIFM Customers Intersecting our DIY customers and our Pros are our DIFM customers. These customers are typically homeowners who use Pros to complete their project or installation. Currently, we offer installation services in a variety of categories, such as flooring, water heaters, bath, garage doors, cabinets, cabinet makeovers, countertops, sheds, furnaces and central air systems, and windows. DIFM customers can purchase these services in our stores, online, or in their homes through in-home consultations. In addition to serving our DIFM customer needs, we believe our focus on the Pros who perform services for these customers helps us drive higher product sales. OUR PRODUCTS AND SERVICES A typical The Home Depot store stocks approximately 30,000 to 40,000 items during the year, including both national brand name and proprietary products. Our online product offerings complement our stores by serving as an extended aisle, and we offer a significantly broader product assortment through our websites and mobile applications, including homedepot.com, our primary website; homedepot.ca and homedepot.com.mx, our websites in Canada and Mexico, respectively; hdsupply.com, our website for our MRO products and related services; our websites for custom window coverings including blinds.com, justblinds.com and americanblinds.com; and thecompanystore.com, our website featuring textiles and décor products. Fiscal 2023 Form 10-K 2 Table of Contents We believe our merchandising organization is a key competitive advantage, delivering product innovation, assortment and value, which reinforces our position as the product authority in home improvement. In fiscal 2023, we continued to invest in merchandising resets in our stores to refine assortments, optimize space productivity, introduce innovative new products to our customers, and improve visual merchandising to drive a better shopping experience. At the same time, we remain focused on offering everyday values in our stores and online. To help our merchandising organization keep pace with changing customer expectations and increasing desire for innovation, localization, and personalization, we are continuing to invest in tools to better leverage our data and drive a deeper level of collaboration with our supplier partners. As a result, we have continued to focus on enhanced merchandising information technology tools to help us: (1) build an interconnected shopping experience that is tailored to our customers’ shopping intent and location; (2) provide the best value in the market; and (3) optimize our product assortments. Our merchandising team leverages technology and works closely with our inventory and supply chain teams, as well as our supplier partners, to manage our assortments, drive innovation, manage the cost environment, and adjust inventory levels to respond to fluctuations in demand. To complement our merchandising efforts, we offer a number of services for our customers, including installation services for our DIY and DIFM customers, as noted above. We also provide tool and equipment rentals at locations across the U.S. and Canada, providing value and convenience for both Pros and consumers. To improve the customer experience and continue to grow this differentiated service offering, we are continuing to invest in more locations (including continuing to pilot rental locations in Mexico), more tools, and better technology. Sourcing and Quality Assurance We maintain a global sourcing program to obtain high-quality and innovative products directly from manufacturers in the U.S. and around the world. During fiscal 2023, in addition to our U.S. sourcing operations, we maintained sourcing offices in Mexico, Canada, China, India, Vietnam and Europe. To ensure that suppliers adhere to our high standards of social and environmental responsibility, we also have a global responsible sourcing program. Under our supplier contracts, our suppliers are obligated to ensure that their products comply with applicable international, federal, state and local laws. These contracts also require compliance with our responsible sourcing standards, which cover a variety of expectations across multiple areas of social compliance, including supply chain transparency, compliance with applicable laws and regulations addressing prohibitions on child and forced labor, health and safety, environmental matters, compensation, and hours of work. To drive accountability with our suppliers, our standard supplier buying agreement includes a factory audit right related to these standards, and we conduct factory audits and compliance visits with non-Canada and non-U.S. suppliers of private branded and direct import products. Our 2023 Responsible Sourcing Report, available on our website at https://corporate.homedepot.com under “Responsibility > Sourcing Responsibly,” provides more information about this program. In addition, we have both quality assurance and engineering resources dedicated to establishing criteria and overseeing compliance with safety, quality and performance standards for our private branded products. Intellectual Property Our business has one of the most recognized brands in North America. As a result, we believe that The Home Depot trademark has significant value and is an important factor in the marketing of our products, e-commerce, stores and business. We have registered or applied for registration of trademarks, service marks, copyrights and internet domain names, both domestically and internationally, for use in our business, including our proprietary brands such as HDX , Husky , Hampton Bay , Home Decorators Collection , Glacier Bay , Vigoro , Everbilt and Lifeproof . The duration of trademark registrations varies from country to country. However, trademarks are generally valid and may be renewed indefinitely as long as they are in use and/or their registrations are properly maintained. We also maintain patent portfolios relating to our business operations, retail services, and products, and we seek to patent or otherwise protect innovations we incorporate into our business. Patents generally have a term of twenty years from the date they are filed. As our patent portfolio has been built over time, the remaining terms of the individual patents across our patent portfolio vary. Although our patents have value, no single patent is essential to our business. We continuously assess our merchandising departments and product lines for opportunities to expand the assortment of products offered within The Home Depot’s portfolio of proprietary and exclusive brands. COMPETITION AND SEASONALITY Our industry is highly competitive, fragmented, and evolving. As a result, we face competition for customers for our products and services from a variety of retailers, suppliers, service providers, and distributors and manufacturers that sell products directly to their respective customer bases. These competitors range from traditional brick-and-mortar, to multichannel, to exclusively online, and they include a number of other home improvement retailers; local, ® ® ® ® ® ® ® ® ® Fiscal 2023 Form 10-K 3 Table of Contents regional and national hardware stores; electrical, plumbing and building materials supply houses; and lumber yards. With respect to some products and services, we also compete with specialty design stores, showrooms, discount stores, paint stores, specialty and mass digital retailers, warehouse clubs, MRO distributors, home décor retailers, and other retailers, as well as with providers of home improvement services and tool and equipment rental. The internet facilitates competitive entry, price transparency, and comparison shopping, increasing the level of competition we face. Both in-store and online, we compete primarily based on customer experience, price, quality, product availability and assortment, and delivery options. We also compete based on store location and appearance, presentation of merchandise, and ease of shopping experience. Our Pros also look for dedicated sales support, competitive credit and pricing options, project planning tools, and product depth and job lot quantities, particularly for their complex purchase needs. Furthermore, with respect to delivery options, customers are seeking faster and/or guaranteed delivery times, low-price or free shipping, and/or convenient pickup options. Our ability to be competitive on delivery and pickup times, options and costs depends on many factors, including the success of our supply chain investments, described more fully under “Our Supply Chain” below. Our business is subject to seasonal influences. Generally, our highest volume of sales occurs in our second fiscal quarter, as we move into the spring season in the regions in which we operate.]

System Instructions: [You may only use the provided context to answer. You must not use any outside sources or prior knowledge.] Question: [Summarize the role of Pros.] Context: [DIFM Customers Intersecting our DIY customers and our Pros are our DIFM customers. These customers are typically homeowners who use Pros to complete their project or installation. Currently, we offer installation services in a variety of categories, such as flooring, water heaters, bath, garage doors, cabinets, cabinet makeovers, countertops, sheds, furnaces and central air systems, and windows. DIFM customers can purchase these services in our stores, online, or in their homes through in-home consultations. In addition to serving our DIFM customer needs, we believe our focus on the Pros who perform services for these customers helps us drive higher product sales. OUR PRODUCTS AND SERVICES A typical The Home Depot store stocks approximately 30,000 to 40,000 items during the year, including both national brand name and proprietary products. Our online product offerings complement our stores by serving as an extended aisle, and we offer a significantly broader product assortment through our websites and mobile applications, including homedepot.com, our primary website; homedepot.ca and homedepot.com.mx, our websites in Canada and Mexico, respectively; hdsupply.com, our website for our MRO products and related services; our websites for custom window coverings including blinds.com, justblinds.com and americanblinds.com; and thecompanystore.com, our website featuring textiles and décor products. Fiscal 2023 Form 10-K 2 Table of Contents We believe our merchandising organization is a key competitive advantage, delivering product innovation, assortment and value, which reinforces our position as the product authority in home improvement. In fiscal 2023, we continued to invest in merchandising resets in our stores to refine assortments, optimize space productivity, introduce innovative new products to our customers, and improve visual merchandising to drive a better shopping experience. At the same time, we remain focused on offering everyday values in our stores and online. To help our merchandising organization keep pace with changing customer expectations and increasing desire for innovation, localization, and personalization, we are continuing to invest in tools to better leverage our data and drive a deeper level of collaboration with our supplier partners. As a result, we have continued to focus on enhanced merchandising information technology tools to help us: (1) build an interconnected shopping experience that is tailored to our customers’ shopping intent and location; (2) provide the best value in the market; and (3) optimize our product assortments. Our merchandising team leverages technology and works closely with our inventory and supply chain teams, as well as our supplier partners, to manage our assortments, drive innovation, manage the cost environment, and adjust inventory levels to respond to fluctuations in demand. To complement our merchandising efforts, we offer a number of services for our customers, including installation services for our DIY and DIFM customers, as noted above. We also provide tool and equipment rentals at locations across the U.S. and Canada, providing value and convenience for both Pros and consumers. To improve the customer experience and continue to grow this differentiated service offering, we are continuing to invest in more locations (including continuing to pilot rental locations in Mexico), more tools, and better technology. Sourcing and Quality Assurance We maintain a global sourcing program to obtain high-quality and innovative products directly from manufacturers in the U.S. and around the world. During fiscal 2023, in addition to our U.S. sourcing operations, we maintained sourcing offices in Mexico, Canada, China, India, Vietnam and Europe. To ensure that suppliers adhere to our high standards of social and environmental responsibility, we also have a global responsible sourcing program. Under our supplier contracts, our suppliers are obligated to ensure that their products comply with applicable international, federal, state and local laws. These contracts also require compliance with our responsible sourcing standards, which cover a variety of expectations across multiple areas of social compliance, including supply chain transparency, compliance with applicable laws and regulations addressing prohibitions on child and forced labor, health and safety, environmental matters, compensation, and hours of work. To drive accountability with our suppliers, our standard supplier buying agreement includes a factory audit right related to these standards, and we conduct factory audits and compliance visits with non-Canada and non-U.S. suppliers of private branded and direct import products. Our 2023 Responsible Sourcing Report, available on our website at https://corporate.homedepot.com under “Responsibility > Sourcing Responsibly,” provides more information about this program. In addition, we have both quality assurance and engineering resources dedicated to establishing criteria and overseeing compliance with safety, quality and performance standards for our private branded products. Intellectual Property Our business has one of the most recognized brands in North America. As a result, we believe that The Home Depot trademark has significant value and is an important factor in the marketing of our products, e-commerce, stores and business. We have registered or applied for registration of trademarks, service marks, copyrights and internet domain names, both domestically and internationally, for use in our business, including our proprietary brands such as HDX , Husky , Hampton Bay , Home Decorators Collection , Glacier Bay , Vigoro , Everbilt and Lifeproof . The duration of trademark registrations varies from country to country. However, trademarks are generally valid and may be renewed indefinitely as long as they are in use and/or their registrations are properly maintained. We also maintain patent portfolios relating to our business operations, retail services, and products, and we seek to patent or otherwise protect innovations we incorporate into our business. Patents generally have a term of twenty years from the date they are filed. As our patent portfolio has been built over time, the remaining terms of the individual patents across our patent portfolio vary. Although our patents have value, no single patent is essential to our business. We continuously assess our merchandising departments and product lines for opportunities to expand the assortment of products offered within The Home Depot’s portfolio of proprietary and exclusive brands. COMPETITION AND SEASONALITY Our industry is highly competitive, fragmented, and evolving. As a result, we face competition for customers for our products and services from a variety of retailers, suppliers, service providers, and distributors and manufacturers that sell products directly to their respective customer bases. These competitors range from traditional brick-and-mortar, to multichannel, to exclusively online, and they include a number of other home improvement retailers; local, ® ® ® ® ® ® ® ® ® Fiscal 2023 Form 10-K 3 Table of Contents regional and national hardware stores; electrical, plumbing and building materials supply houses; and lumber yards. With respect to some products and services, we also compete with specialty design stores, showrooms, discount stores, paint stores, specialty and mass digital retailers, warehouse clubs, MRO distributors, home décor retailers, and other retailers, as well as with providers of home improvement services and tool and equipment rental. The internet facilitates competitive entry, price transparency, and comparison shopping, increasing the level of competition we face. Both in-store and online, we compete primarily based on customer experience, price, quality, product availability and assortment, and delivery options. We also compete based on store location and appearance, presentation of merchandise, and ease of shopping experience. Our Pros also look for dedicated sales support, competitive credit and pricing options, project planning tools, and product depth and job lot quantities, particularly for their complex purchase needs. Furthermore, with respect to delivery options, customers are seeking faster and/or guaranteed delivery times, low-price or free shipping, and/or convenient pickup options. Our ability to be competitive on delivery and pickup times, options and costs depends on many factors, including the success of our supply chain investments, described more fully under “Our Supply Chain” below. Our business is subject to seasonal influences. Generally, our highest volume of sales occurs in our second fiscal quarter, as we move into the spring season in the regions in which we operate.]

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. [user request] [context document]

What is the ID and name of the FMR bulletin, when is a briefing expected from each department, and which departments should provide it? Also, when do operating plans need to be submitted to the Committees on Appropriations? Which cabinet departments are specifically mentioned?

This Committee Report provides additional direction and specificity on the uses of funds provided in this bill. During fiscal year 2025, for the purposes of the Balanced Budget and Emergency Deficit Control Act of 1985, as amended, with respect to appropriations contained in the accompanying bill, the terms ``program, project, and activity'' [PPA] shall mean any item for which a dollar amount is contained in appropriations acts (including joint resolutions providing continuing appropriations) or accompanying reports of the House and Senate Committees on Appropriations, or accompanying conference reports and joint explanatory statements of the committee of conference. The Committee continues longstanding reprogramming requirements and limitations regarding changes to funding for PPAs. The Committee expects agencies to submit any reprogramming requests in compliance with requirements of this act and to provide a thorough explanation of the proposed reallocations, including a detailed justification of increases and reductions. The Committee expects each agency to manage the expenditures of its programs and activities to remain within the amounts appropriated by Congress. The Committee also continues the longstanding requirement that each agency submit an operating plan to the House and Senate Committees on Appropriations not later than 45 days after enactment of this act, in order to establish the baseline for application of reprogramming and transfer authorities provided in this act. The operating plan should include at minimum funding for PPAs as specified above. The Committee reminds agencies funded by this act of their obligation to uphold the Federal trust and treaty responsibilities to Tribes and Federal obligations to the Native Hawaiian Community. This includes upholding treaty and reserved rights, and any other rights and obligations under Federal law; supporting self-determination efforts by Native communities; fulfilling obligations under Presidential Memoranda and Executive Orders; and conducting early and robust government-to-government consultation with Tribes, and meaningful outreach and engagement with Native Hawaiians. The Committee also directs the Secretary of Education, Secretary of Health and Human Services, and Secretary of Labor to release public reports detailing how the Departments are addressing antisemitism, including by implementing the National Strategy to Counter Antisemitism. The Committee directs the Secretary of Education, Secretary of Health and Human Services, and Secretary of Labor to brief the House and Senate Committees on Appropriations no later than 90 days after enactment of this act regarding any strategic plans developed by the Department over the three prior fiscal years outlining the ways that the Department has promoted voter registration, and voter participation. The Committee is encouraged by the General Services Administration's Bulletin FMR C-2024-01, ``Safety Station Program Guidelines in Federal Facilities'' that was issued on December 21, 2023. The Committee encourages all Departments covered in this act to implement these guidelines and establish safety stations in each public building that include automated external defibrillators, opioid reversal agents, and hemorrhagic control programs and requests a briefing from each Department within 90 days of enactment of this act on progress towards implementing these guidelines. The Committee continues to appreciate the close working relationship with the various budget offices of the agencies funded in this bill. Maintaining these relationships is critical for the Committee to perform its duties in both developing these funding requirements and recommendations and providing oversight over the execution of funds.

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. What is the ID and name of the FMR bulletin, when is a briefing expected from each department, and which departments should provide it? Also, when do operating plans need to be submitted to the Committees on Appropriations? Which cabinet departments are specifically mentioned? This Committee Report provides additional direction and specificity on the uses of funds provided in this bill. During fiscal year 2025, for the purposes of the Balanced Budget and Emergency Deficit Control Act of 1985, as amended, with respect to appropriations contained in the accompanying bill, the terms ``program, project, and activity'' [PPA] shall mean any item for which a dollar amount is contained in appropriations acts (including joint resolutions providing continuing appropriations) or accompanying reports of the House and Senate Committees on Appropriations, or accompanying conference reports and joint explanatory statements of the committee of conference. The Committee continues longstanding reprogramming requirements and limitations regarding changes to funding for PPAs. The Committee expects agencies to submit any reprogramming requests in compliance with requirements of this act and to provide a thorough explanation of the proposed reallocations, including a detailed justification of increases and reductions. The Committee expects each agency to manage the expenditures of its programs and activities to remain within the amounts appropriated by Congress. The Committee also continues the longstanding requirement that each agency submit an operating plan to the House and Senate Committees on Appropriations not later than 45 days after enactment of this act, in order to establish the baseline for application of reprogramming and transfer authorities provided in this act. The operating plan should include at minimum funding for PPAs as specified above. The Committee reminds agencies funded by this act of their obligation to uphold the Federal trust and treaty responsibilities to Tribes and Federal obligations to the Native Hawaiian Community. This includes upholding treaty and reserved rights, and any other rights and obligations under Federal law; supporting self-determination efforts by Native communities; fulfilling obligations under Presidential Memoranda and Executive Orders; and conducting early and robust government-to-government consultation with Tribes, and meaningful outreach and engagement with Native Hawaiians. The Committee also directs the Secretary of Education, Secretary of Health and Human Services, and Secretary of Labor to release public reports detailing how the Departments are addressing antisemitism, including by implementing the National Strategy to Counter Antisemitism. The Committee directs the Secretary of Education, Secretary of Health and Human Services, and Secretary of Labor to brief the House and Senate Committees on Appropriations no later than 90 days after enactment of this act regarding any strategic plans developed by the Department over the three prior fiscal years outlining the ways that the Department has promoted voter registration, and voter participation. The Committee is encouraged by the General Services Administration's Bulletin FMR C-2024-01, ``Safety Station Program Guidelines in Federal Facilities'' that was issued on December 21, 2023. The Committee encourages all Departments covered in this act to implement these guidelines and establish safety stations in each public building that include automated external defibrillators, opioid reversal agents, and hemorrhagic control programs and requests a briefing from each Department within 90 days of enactment of this act on progress towards implementing these guidelines. The Committee continues to appreciate the close working relationship with the various budget offices of the agencies funded in this bill. Maintaining these relationships is critical for the Committee to perform its duties in both developing these funding requirements and recommendations and providing oversight over the execution of funds. https://www.congress.gov/congressional-report/118th-congress/senate-report/207/1

Provide your answer in full sentences, referencing the document using quotations.

According to the text, why is the T-Mobile/Sprint merger considered a disaster?

The Real Dish on the T-Mobile/Sprint Merger: A Disastrous Deal From the Start When the Trump-era DOJ allowed T-Mobile and Sprint to merge in July 2019, it promised the best of both worlds: consumers would benefit from T-Mobile’s accelerated 5G deployment and retain a fourth wireless provider. To effect the latter, then-AAG Makan Delrahim devised a divestiture that would reposition satellite-TV provider DISH as Sprint’s replacement. Here was his plan: Sprint would sell its prepaid-wireless assets to DISH. These assets included Sprint’s 9.3 million prepaid subscribers, its Boost brand, its 800 MHz spectrum licenses, and the Sprint stores and cell towers that the new T-Mobile did not want. DISH would then use these cell sites and its pre-existing spectrum, augmented from the divestiture, to build its own wireless network using never-before-deployed technology. While DISH worked on its complex nationwide build, it could serve its customers by paying for them to roam on the new T-Mobile’s infrastructure for seven years. Not even two years later, Delrahim’s plan is already falling apart. The prepaid customers DISH inherited from Sprint disproportionately buy cheap wireless service, which runs on the old CDMA standard used in 3G networks. In the latest turn of events, T-Mobile announced last month that it would discontinue its CDMA service in January 2022, nearly two years ahead of schedule. With T-Mobile’s shutdown, DISH’s customers will have to “get new devices, new SIMs, or upgrade via software.” DISH now has to take on an unexpected upgrade that will cost hundreds of millions of dollars. T-Mobile’s announcement led DISH CEO Charlie Ergen to denounce the unexpected shutdown as “anticompetitive.” DISH has already warned investors that with the shutdown, its trend of bleeding hundreds of thousands of subscribers may soon turn into a hemorrhage. For T-Mobile, this is great news, since many of the subscribers ditching DISH are bound to turn to T-Mobile’s own cheap wireless plan. But for price-sensitive consumers, the forecast is grim: while they could choose between T-Mobile and Sprint before the merger, these dissatisfied customers now effectively face a monopoly provider. It should come as no surprise that DISH is struggling in the wireless market, and price-conscious consumers are bearing the brunt of harm from the merger’s fallout. We knew back in 2011 that T-Mobile and Sprint competed particularly closely in low-cost wireless services. We also knew from DOJ’s longstanding Merger Remedies Policy that remedies should not require an entrant like DISH to depend on an incumbent who is a direct rival; it makes perfect sense that T-Mobile would rebel against helping DISH grow into a firm that can compete against T-Mobile itself. Not only was the DISH divestiture ill-devised, but the T-Mobile/Sprint merger never did pass muster under basic logic. If it was really critical to keep four players in the wireless market—so important that DISH needed to enter—why even let T-Mobile buy Sprint in the first place? Why not just keep the existing fourth player, instead of designing a Rube Goldberg settlement in the hopes that a new player will grow to have the competitive force of Sprint in seven years’ time? These frustrations have fueled heated criticism of the merger. Such critiques are well-placed, as the merger has already produced harm and threatens to wreak more damage. Besides hobbling DISH, T-Mobile will degrade the quality of its service this April by automatically enrolling its subscribers into an aggressive, personalized ad-targeting program. T-Mobile has also signaled to investors that it has become more like its rivals Verizon and AT&T. On an investor call in February, CEO Mike Sievert said, “We’ve competed mostly on price in the past, if we’re honest. Now, we have a premium product.” Translation: the era of aggressive price competition in wireless is over. Looking forward, we can expect T-Mobile, AT&T, and Verizon to nestle into a cozy triopoly that returns immense profits to their shareholders. T-Mobile is already prepared to deliver on this prospect. On March 11, it predicted to investors that its free cash flow will be flush enough to support a $60 billion stock buyback within five years. Stock buybacks benefit the investor class, whose members are disproportionately the wealthiest people in America; recent surveys show that the top 10 percent of households own approximately 80 percent of all stocks. In contrast, nearly all households across the income distribution buy wireless services, and low-income households particularly favor prepaid plans, a segment where T-Mobile and Sprint had competed vigorously pre-merger. With its latest proclamations to investors, T-Mobile celebrates the fact that its merger will transfer billions of wealth from average Americans to the rich, further widening the chasm between the haves and have-nots. For this reason and many others, the T-Mobile/Sprint deal will go down as one of the worst merger-enforcement decisions in decades. “THE T-MOBILE/SPRINT DEAL WILL GO DOWN AS ONE OF THE WORST MERGER-ENFORCEMENT DECISIONS IN DECADES.” In this postmortem, we examine how the deal came to close, and what we might learn from the mistakes made along the way. The Prosecutor: Dealmaker Delrahim Helming DOJ DOJ should never have approved the deal in the first place. The T-Mobile/Sprint merger presented a harmful 4-to-3 combination in the critical and well-defined market of mobile wireless services. Four-to-three mergers deservedly raise eyebrows, and evidence from other countries showed that 4-3 mergers in the wireless market would increase prices. Further, the post-merger market shares blasted through the HHI thresholds in the Horizontal Merger Guidelines, making the transaction presumptively anticompetitive. As such, a settlement should never have been on the table. But after many years of trying to merge, the parties finally found a receptive agency head in Delrahim, the “veteran lobbyist” tapped to be head of the Trump Administration’s Antitrust Division. When presented with the deal, Delrahim was eager to refashion the telecom market and less eager to deliver on his charge of protecting consumer welfare. Delrahim took a series of unorthodox steps. He became a mediator between the parties, helping hold the deal together when tensions between the CEOs ran high. He exchanged text messages with Ergen and advised him on how to secure regulatory approval from the Federal Communications Commission, which also needed to approve the deal. And when the parties closed their transaction in July 2020, Delrahim issued a press release to “congratulate” T-Mobile and Sprint for merging. Not only did his conduct conflict with his role as the nation’s head antitrust enforcer, but the behavioral remedy Delrahim reached in T-Mobile/Sprint contradicted his 2017 statements. Then, with an eye toward signaling his unwillingness to settle in AT&T/Time Warner, he inveighed against behavioral remedies. “[A]t times antitrust enforcers have experimented with allowing illegal mergers to proceed subject to certain behavioral commitments. That approach is fundamentally regulatory, imposing ongoing government oversight on what should preferably be a free market.” He added, “[I]f a merger is illegal, we should only accept a clean and complete solution.” Perhaps Delrahim was conscious of his hypocrisy when he later announced the settlement he had reached in the T-Mobile/Sprint merger, as he was careful to cast it as “structural” and not “behavioral.” But because the crux of the settlement is to have DISH roam on T-Mobile’s network for seven years, the settlement is behavioral at its core. Studying the divestiture against the Trump-era DOJ’s handling of other antitrust cases sheds additional light. Compare Delrahim’s adamant refusal to accept behavioral conditions when the parties proposed them in AT&T/Time Warner—which presented a weaker merits case—with his enthusiasm to strike behavioral conditions in the T-Mobile/Sprint divestiture to DISH—even though this 4-3 merger was presumptively illegal and raised nearly every red flag in the Horizontal Merger Guidelines. Taken together, these two decisions cannot be reconciled on principle. The Court: Judge Marrero Fails as “Fortuneteller” Because the Delrahim-led DOJ was derelict in policing the T-Mobile/Sprint deal, a group of states challenged the merger in federal court. In presenting their case, they pointed out flaws in the DISH settlement—chiefly that the divestiture relied on T-Mobile to help DISH grow to scale in wireless, but T-Mobile would have the ability and incentive to cripple DISH. At trial in the Southern District of New York, Ergen testified that he was confident DISH would receive adequate service from T-Mobile through the roaming agreement, even though new T-Mobile and DISH would compete for wireless subscribers. He offered that DISH had never had a problem with buying services from AT&T, despite AT&T’s DirecTV competing head-to-head with DISH’s satellite-television offering. Ergen, however, conveniently omitted the fact that AT&T, after merging with Time Warner, had blacked out HBO and Cinemax for DISH’s satellite and Sling TV subscribers. The loss of AT&T’s content contributed to DISH’s loss of more than 330,000 subscribers that quarter. Despite this recent experience, Ergen maintained in court that there would be no problem with DISH relying on a direct competitor for a critical input in the mobile-wireless industry it was preparing to enter. Judge Victor Marrero did pick up on this danger during his questioning at trial, but he ultimately believed the DOJ-appointed monitor and wholesale-price formula would be enough to rein in T-Mobile’s incentives. We have now seen that those checks were inadequate. This is no surprise, as economic theory predicts that companies’ profit incentives are strong enough to overcome inevitably incomplete contractual restraints. More generally, Judge Marrero underestimated the strength of the parties’ incentives in his assessment of the merger. Instead of accounting for how the merger would facilitate collusion by creating three symmetrical players, for instance, he decided it would be easier to assess witness credibility. Judge Marrero purported to study the executives’ behavior and glean “telltale” patterns of truthfulness, concluding that the new T-Mobile would continue to compete vigorously against AT&T and Verizon. In so doing, he placed his faith in the self-serving testimony of executives rather than in decades of enforcement experience, economic evidence, and jurisprudence.

{Query} ======= According to the text, why is the T-Mobile/Sprint merger considered a disaster? {Task} ======= Provide your answer in full sentences, referencing the document using quotations. {Document} ======= The Real Dish on the T-Mobile/Sprint Merger: A Disastrous Deal From the Start When the Trump-era DOJ allowed T-Mobile and Sprint to merge in July 2019, it promised the best of both worlds: consumers would benefit from T-Mobile’s accelerated 5G deployment and retain a fourth wireless provider. To effect the latter, then-AAG Makan Delrahim devised a divestiture that would reposition satellite-TV provider DISH as Sprint’s replacement. Here was his plan: Sprint would sell its prepaid-wireless assets to DISH. These assets included Sprint’s 9.3 million prepaid subscribers, its Boost brand, its 800 MHz spectrum licenses, and the Sprint stores and cell towers that the new T-Mobile did not want. DISH would then use these cell sites and its pre-existing spectrum, augmented from the divestiture, to build its own wireless network using never-before-deployed technology. While DISH worked on its complex nationwide build, it could serve its customers by paying for them to roam on the new T-Mobile’s infrastructure for seven years. Not even two years later, Delrahim’s plan is already falling apart. The prepaid customers DISH inherited from Sprint disproportionately buy cheap wireless service, which runs on the old CDMA standard used in 3G networks. In the latest turn of events, T-Mobile announced last month that it would discontinue its CDMA service in January 2022, nearly two years ahead of schedule. With T-Mobile’s shutdown, DISH’s customers will have to “get new devices, new SIMs, or upgrade via software.” DISH now has to take on an unexpected upgrade that will cost hundreds of millions of dollars. T-Mobile’s announcement led DISH CEO Charlie Ergen to denounce the unexpected shutdown as “anticompetitive.” DISH has already warned investors that with the shutdown, its trend of bleeding hundreds of thousands of subscribers may soon turn into a hemorrhage. For T-Mobile, this is great news, since many of the subscribers ditching DISH are bound to turn to T-Mobile’s own cheap wireless plan. But for price-sensitive consumers, the forecast is grim: while they could choose between T-Mobile and Sprint before the merger, these dissatisfied customers now effectively face a monopoly provider. It should come as no surprise that DISH is struggling in the wireless market, and price-conscious consumers are bearing the brunt of harm from the merger’s fallout. We knew back in 2011 that T-Mobile and Sprint competed particularly closely in low-cost wireless services. We also knew from DOJ’s longstanding Merger Remedies Policy that remedies should not require an entrant like DISH to depend on an incumbent who is a direct rival; it makes perfect sense that T-Mobile would rebel against helping DISH grow into a firm that can compete against T-Mobile itself. Not only was the DISH divestiture ill-devised, but the T-Mobile/Sprint merger never did pass muster under basic logic. If it was really critical to keep four players in the wireless market—so important that DISH needed to enter—why even let T-Mobile buy Sprint in the first place? Why not just keep the existing fourth player, instead of designing a Rube Goldberg settlement in the hopes that a new player will grow to have the competitive force of Sprint in seven years’ time? These frustrations have fueled heated criticism of the merger. Such critiques are well-placed, as the merger has already produced harm and threatens to wreak more damage. Besides hobbling DISH, T-Mobile will degrade the quality of its service this April by automatically enrolling its subscribers into an aggressive, personalized ad-targeting program. T-Mobile has also signaled to investors that it has become more like its rivals Verizon and AT&T. On an investor call in February, CEO Mike Sievert said, “We’ve competed mostly on price in the past, if we’re honest. Now, we have a premium product.” Translation: the era of aggressive price competition in wireless is over. Looking forward, we can expect T-Mobile, AT&T, and Verizon to nestle into a cozy triopoly that returns immense profits to their shareholders. T-Mobile is already prepared to deliver on this prospect. On March 11, it predicted to investors that its free cash flow will be flush enough to support a $60 billion stock buyback within five years. Stock buybacks benefit the investor class, whose members are disproportionately the wealthiest people in America; recent surveys show that the top 10 percent of households own approximately 80 percent of all stocks. In contrast, nearly all households across the income distribution buy wireless services, and low-income households particularly favor prepaid plans, a segment where T-Mobile and Sprint had competed vigorously pre-merger. With its latest proclamations to investors, T-Mobile celebrates the fact that its merger will transfer billions of wealth from average Americans to the rich, further widening the chasm between the haves and have-nots. For this reason and many others, the T-Mobile/Sprint deal will go down as one of the worst merger-enforcement decisions in decades. “THE T-MOBILE/SPRINT DEAL WILL GO DOWN AS ONE OF THE WORST MERGER-ENFORCEMENT DECISIONS IN DECADES.” In this postmortem, we examine how the deal came to close, and what we might learn from the mistakes made along the way. The Prosecutor: Dealmaker Delrahim Helming DOJ DOJ should never have approved the deal in the first place. The T-Mobile/Sprint merger presented a harmful 4-to-3 combination in the critical and well-defined market of mobile wireless services. Four-to-three mergers deservedly raise eyebrows, and evidence from other countries showed that 4-3 mergers in the wireless market would increase prices. Further, the post-merger market shares blasted through the HHI thresholds in the Horizontal Merger Guidelines, making the transaction presumptively anticompetitive. As such, a settlement should never have been on the table. But after many years of trying to merge, the parties finally found a receptive agency head in Delrahim, the “veteran lobbyist” tapped to be head of the Trump Administration’s Antitrust Division. When presented with the deal, Delrahim was eager to refashion the telecom market and less eager to deliver on his charge of protecting consumer welfare. Delrahim took a series of unorthodox steps. He became a mediator between the parties, helping hold the deal together when tensions between the CEOs ran high. He exchanged text messages with Ergen and advised him on how to secure regulatory approval from the Federal Communications Commission, which also needed to approve the deal. And when the parties closed their transaction in July 2020, Delrahim issued a press release to “congratulate” T-Mobile and Sprint for merging. Not only did his conduct conflict with his role as the nation’s head antitrust enforcer, but the behavioral remedy Delrahim reached in T-Mobile/Sprint contradicted his 2017 statements. Then, with an eye toward signaling his unwillingness to settle in AT&T/Time Warner, he inveighed against behavioral remedies. “[A]t times antitrust enforcers have experimented with allowing illegal mergers to proceed subject to certain behavioral commitments. That approach is fundamentally regulatory, imposing ongoing government oversight on what should preferably be a free market.” He added, “[I]f a merger is illegal, we should only accept a clean and complete solution.” Perhaps Delrahim was conscious of his hypocrisy when he later announced the settlement he had reached in the T-Mobile/Sprint merger, as he was careful to cast it as “structural” and not “behavioral.” But because the crux of the settlement is to have DISH roam on T-Mobile’s network for seven years, the settlement is behavioral at its core. Studying the divestiture against the Trump-era DOJ’s handling of other antitrust cases sheds additional light. Compare Delrahim’s adamant refusal to accept behavioral conditions when the parties proposed them in AT&T/Time Warner—which presented a weaker merits case—with his enthusiasm to strike behavioral conditions in the T-Mobile/Sprint divestiture to DISH—even though this 4-3 merger was presumptively illegal and raised nearly every red flag in the Horizontal Merger Guidelines. Taken together, these two decisions cannot be reconciled on principle. The Court: Judge Marrero Fails as “Fortuneteller” Because the Delrahim-led DOJ was derelict in policing the T-Mobile/Sprint deal, a group of states challenged the merger in federal court. In presenting their case, they pointed out flaws in the DISH settlement—chiefly that the divestiture relied on T-Mobile to help DISH grow to scale in wireless, but T-Mobile would have the ability and incentive to cripple DISH. At trial in the Southern District of New York, Ergen testified that he was confident DISH would receive adequate service from T-Mobile through the roaming agreement, even though new T-Mobile and DISH would compete for wireless subscribers. He offered that DISH had never had a problem with buying services from AT&T, despite AT&T’s DirecTV competing head-to-head with DISH’s satellite-television offering. Ergen, however, conveniently omitted the fact that AT&T, after merging with Time Warner, had blacked out HBO and Cinemax for DISH’s satellite and Sling TV subscribers. The loss of AT&T’s content contributed to DISH’s loss of more than 330,000 subscribers that quarter. Despite this recent experience, Ergen maintained in court that there would be no problem with DISH relying on a direct competitor for a critical input in the mobile-wireless industry it was preparing to enter. Judge Victor Marrero did pick up on this danger during his questioning at trial, but he ultimately believed the DOJ-appointed monitor and wholesale-price formula would be enough to rein in T-Mobile’s incentives. We have now seen that those checks were inadequate. This is no surprise, as economic theory predicts that companies’ profit incentives are strong enough to overcome inevitably incomplete contractual restraints. More generally, Judge Marrero underestimated the strength of the parties’ incentives in his assessment of the merger. Instead of accounting for how the merger would facilitate collusion by creating three symmetrical players, for instance, he decided it would be easier to assess witness credibility. Judge Marrero purported to study the executives’ behavior and glean “telltale” patterns of truthfulness, concluding that the new T-Mobile would continue to compete vigorously against AT&T and Verizon. In so doing, he placed his faith in the self-serving testimony of executives rather than in decades of enforcement experience, economic evidence, and jurisprudence.

Please only respond using information contained in the context block below. Bullet points must have 4 sentences each.

Explain in detail the disadvantages of global freight-forwarding's legacy system.

Slide 19 - Competitive strength across three axes For the next 8 slides, I am going to take you on a deep dive into the how and the why of WiseTech and CargoWise’s core competitive strengths, differentiators and efficiencies. Firstly, our product’s competitive strength has three distinct axes. As a product-led innovator, we have a long-term strategy of building breakthrough products to revolutionize, not to simply replace. We look to find fundamental flaws, operating problems, inefficient models and incomplete or ineffective processes, and to embed and automate improvements so that we revolutionize the industry’s established model. We have done this very effectively with CargoWise’s international freight forwarding capabilities and the competitive result is clearly visible on slide 26. Similarly, with Global Customs, the Warehouse Suite and soon with the planned release of Container Transport Optimization and ComplianceWise, we are not simply offering a me-too product or a simple upgrade from an aging legacy system, we are providing a dramatically better business model embedded in the CargoWise application suite. In the appendix we outline some of the key business model and product differentiators provided to customers by CargoWise. 15 Secondly, because of the many cost and management efficiencies achieved through CargoWise, we are driving value for our customers across their entire cost base, which I will talk to more in detail on the next slide. Finally, the operating model delivered by CargoWise creates substantial cost efficiencies and global management simplicity. This enables industry consolidation through M&A and the rapid, successful and profitable integration of acquired businesses, whilst also driving competitive advantage and profitable organic growth. Slide 20 - Driving efficiencies across our customers’ entire cost base leading to optimized operations CargoWise delivers cost efficiencies in four distinct layers. About 30% of our customers’ total costs sit within operating expenses from legacy IT systems costs and operational labor costs. The remaining 70% of our customers’ cost base is from the direct costs of air, sea, rail and road transport and from surcharges, fines and penalties related to the management of these transport services. Starting with IT cost efficiency, many freight forwarders still have outdated, in-house legacy IT systems built 20 to 30 years ago. They are inflexible, complex and expensive to maintain, and are supplemented at great cost with hundreds of smaller satellite systems, many of which are also legacy systems with their own costs and risks including cyber security. 16 CargoWise customers replace these myriad legacy systems with a single, global, modern, efficient and fully integrated platform that dramatically reduces IT costs and risks. The second cost efficiency involves tackling the labor cost required to deliver the planning, execution and management of the movement of goods from point of origin to final destination. International freight forwarders are asset light services providers. They have large global workforces in each locale, often with a full management hierarchy, managing the local business and processing the local requirements. Many of these procedures are manually executed, often requiring the rekeying of critical data multiple times into many separate, satellite systems. CargoWise provides a single, comprehensive, global system that streamlines and automates many of these procedures, removing much of the original data entry and avoiding rekeying data multiple times. With CargoWise, it is also simple to visualize, plan, manage and control globally from a single location and to move low value work to lower cost locations. Export offices or shared services centers can perform most of the critical tasks including data entry, leaving the often-higher cost import location a much smaller set of tasks. All this allows our customers to extract much greater value by substantially improving operational yield. The third cost efficiency addresses fines, penalties and unwanted surcharges on the movement of cargo. Aging legacy systems have many costs, complexities and risks and can't keep up with the rapidly changing compliance obligations that govern 17 global trade. Because they’re unable to comply or optimize effectively, many logistics providers build in margins or substantial budgets to cover fines and penalties or attempt to pass incidental surcharges on to their customers. The fourth cost efficiency is freight cost efficiency. Given the global scale of CargoWise, and its integration with electronic schedules, rates, booking, tracking, job costing and account settlement, CargoWise customers are able to acquire and optimize transport services much more efficiently than ever before, improving freight utilization, negotiating better rates with carriers, optimizing packing and movement, and allowing economies of scale, to become more price competitive, and improve unit economics and the value delivered to their customers. By creating substantial cost benefits over time, through these four layers of cost improvements, customers also consume more CargoWise services, which drives ongoing long-term revenue growth for WiseTech.

Please only respond using information contained in the context block below. Bullet points must have 4 sentences each. Slide 19 - Competitive strength across three axes For the next 8 slides, I am going to take you on a deep dive into the how and the why of WiseTech and CargoWise’s core competitive strengths, differentiators and efficiencies. Firstly, our product’s competitive strength has three distinct axes. As a product-led innovator, we have a long-term strategy of building breakthrough products to revolutionize, not to simply replace. We look to find fundamental flaws, operating problems, inefficient models and incomplete or ineffective processes, and to embed and automate improvements so that we revolutionize the industry’s established model. We have done this very effectively with CargoWise’s international freight forwarding capabilities and the competitive result is clearly visible on slide 26. Similarly, with Global Customs, the Warehouse Suite and soon with the planned release of Container Transport Optimization and ComplianceWise, we are not simply offering a me-too product or a simple upgrade from an aging legacy system, we are providing a dramatically better business model embedded in the CargoWise application suite. In the appendix we outline some of the key business model and product differentiators provided to customers by CargoWise. 15 Secondly, because of the many cost and management efficiencies achieved through CargoWise, we are driving value for our customers across their entire cost base, which I will talk to more in detail on the next slide. Finally, the operating model delivered by CargoWise creates substantial cost efficiencies and global management simplicity. This enables industry consolidation through M&A and the rapid, successful and profitable integration of acquired businesses, whilst also driving competitive advantage and profitable organic growth. Slide 20 - Driving efficiencies across our customers’ entire cost base leading to optimized operations CargoWise delivers cost efficiencies in four distinct layers. About 30% of our customers’ total costs sit within operating expenses from legacy IT systems costs and operational labor costs. The remaining 70% of our customers’ cost base is from the direct costs of air, sea, rail and road transport and from surcharges, fines and penalties related to the management of these transport services. Starting with IT cost efficiency, many freight forwarders still have outdated, in-house legacy IT systems built 20 to 30 years ago. They are inflexible, complex and expensive to maintain, and are supplemented at great cost with hundreds of smaller satellite systems, many of which are also legacy systems with their own costs and risks including cyber security. 16 CargoWise customers replace these myriad legacy systems with a single, global, modern, efficient and fully integrated platform that dramatically reduces IT costs and risks. The second cost efficiency involves tackling the labor cost required to deliver the planning, execution and management of the movement of goods from point of origin to final destination. International freight forwarders are asset light services providers. They have large global workforces in each locale, often with a full management hierarchy, managing the local business and processing the local requirements. Many of these procedures are manually executed, often requiring the rekeying of critical data multiple times into many separate, satellite systems. CargoWise provides a single, comprehensive, global system that streamlines and automates many of these procedures, removing much of the original data entry and avoiding rekeying data multiple times. With CargoWise, it is also simple to visualize, plan, manage and control globally from a single location and to move low value work to lower cost locations. Export offices or shared services centers can perform most of the critical tasks including data entry, leaving the often-higher cost import location a much smaller set of tasks. All this allows our customers to extract much greater value by substantially improving operational yield. The third cost efficiency addresses fines, penalties and unwanted surcharges on the movement of cargo. Aging legacy systems have many costs, complexities and risks and can't keep up with the rapidly changing compliance obligations that govern 17 global trade. Because they’re unable to comply or optimize effectively, many logistics providers build in margins or substantial budgets to cover fines and penalties or attempt to pass incidental surcharges on to their customers. The fourth cost efficiency is freight cost efficiency. Given the global scale of CargoWise, and its integration with electronic schedules, rates, booking, tracking, job costing and account settlement, CargoWise customers are able to acquire and optimize transport services much more efficiently than ever before, improving freight utilization, negotiating better rates with carriers, optimizing packing and movement, and allowing economies of scale, to become more price competitive, and improve unit economics and the value delivered to their customers. By creating substantial cost benefits over time, through these four layers of cost improvements, customers also consume more CargoWise services, which drives ongoing long-term revenue growth for WiseTech. Explain in detail the disadvantages of global freight-forwarding's legacy system.

You can only answer the prompt using information found in the context block. You can't use information from external sources or rely heavily on your knowledge. You are not an expert in any field, you are simply extracting information from the context block to answer the prompt. Respond in using 100 words or less.

What is the main argument made by scholars like Moringiello and Odinet against considering NFTs as property?

OVERVIEW OF HOW NFTS HAVE BEEN CHARACTERIZED Property law perspective What rights do owners of NFTs actually own? In this respect, the concept of possession in property law is currently understood to apply only to tangible assets, and hence inapplicable to intangible assets.17 Marinoti explores the possibility of understanding the rights owned in intangibles such as NFTs from a property law perspective.18 He has argued that intangibles such as NFTs can be governed by property law, through reference to the concepts such as ‘possession’ which is often related mainly to tangible property (i.e., things that are usually physical and that you can touch and identify, such as land and equipment, etc.).19 According to Marinoti, the true function of possession is communicative and its purpose is to convey the availability of an object discernible to an audience. He argued further that communities can also give this meaning through conduct and symbolic acts.20 The narrower concept ‘thinghood’, on the other hand, is often subsumed within the discussion on possession. Tinghood is defined by whether there are discernible boundaries around one thing to distinguish it from another. Physical tangibility is said to be only one way in which thinghood delineates boundaries; social practices and norms can similarly indicate boundaries.21 Marinoti also suggested that property law doctrines like conversion and trespass can be extended to apply to digital assets.22 Even concepts such as the relativity of title (ie, wrongful 13 See, eg, Vijayakumaran (n 10) 409. 14 See, eg, Michael D. Murray, ‘NFT Ownership and Copyrights’ (2023) Indiana Law Rev 366. 15 Many popular NFT projects such as CryptoPunks have been released with no explicitly written copyright terms. See, eg, Grimmelman, Yan and Kell (n 9). An instance is that of the popular NFT project CryptoPunks which has been released with no explicitly written copyright terms. 16 Tese are leading NFT marketplaces. See, eg, Bitdeal, ‘Top 7 NFT Marketplaces to look in 2023 and beyond’ (BLOG, 2023) <www.bitdeal.net/top-7-nf-marketplaces-in-2023 -:~:text=Top 7 NFT Marketplaces 2023 1 1. OpenSea,Marketplace... 7 7. Solanart NFT Marketplace > accessed 13 January 2024. 17 See, eg, Marinoti (n 11). 18 Ibid. 19 Ibid 1277. 20 Ibid 1236. 21 Ibid. 22 Ibid 1269. Downloaded from https://academic.oup.com/ijlit/article/32/1/eaae018/7746479 by guest on 17 September 2024 4 • Tan possession can support an interest held by the wrongful possessor which is stronger than that of the world at large, save for the right owner) can arguably apply.23 While protecting wrongful possession may seem unjust, this could help avoid the scenario of having no legal recourse to an endless series of unlawful conversions of ‘NFTs’ after one single wrongful possession.24 To clarify, Marinoti’s reference to property law concepts drew from both real property and personal property laws, although this was not expressly stated. Along the same vein, other scholars such as Trautman and Fairfield have also proposed that the legal system should treat NFTs as digital personal property because NFTs comprise strong property interests through enabling parties to buy, sell, or own digital assets similar to personal property.25 On the other hand, some scholars do not agree that NFTs should be defined as properties. Lee, for example, has analogized NFTs with library catalog cards to illustrate that the value of NFTs is derived from their underlying properties (ie, books) and to highlight that people do not own these properties when they transact in NFTs.26 Further, Moringiello and Odinet rejected the perception of any property rights in NFTs—through comparison of their characteristics with those of negotiable instruments, securities, deeds of real property, bills of lading and other legal tokens—reasoning that NFTs lack the tethering effect that other properties have and that it is meaningless to view them as such, thus NFT holders do not control anything substantive.27

[System Instructions] You can only answer the prompt using information found in the context block. You can't use information from external sources or rely heavily on your knowledge. You are not an expert in any field, you are simply extracting information from the context block to answer the prompt. Respond in using 100 words or less. [Question] What do scholars like Moringiello and Odinet make the main argument against considering NFTs as property? [Context Block] OVERVIEW OF HOW NFTS HAVE BEEN CHARACTERIZED Property law perspective What rights do owners of NFTs actually own? In this respect, the concept of possession in property law is currently understood to apply only to tangible assets, and hence inapplicable to intangible assets.17 Marinoti explores the possibility of understanding the rights owned in intangibles such as NFTs from a property law perspective.18 He has argued that intangibles such as NFTs can be governed by property law, through reference to the concepts such as ‘possession’ which is often related mainly to tangible property (i.e., things that are usually physical and that you can touch and identify, such as land and equipment, etc.).19 According to Marinoti, the true function of possession is communicative and its purpose is to convey the availability of an object discernible to an audience. He argued further that communities can also give this meaning through conduct and symbolic acts.20 The narrower concept ‘thinghood’, on the other hand, is often subsumed within the discussion on possession. Tinghood is defined by whether there are discernible boundaries around one thing to distinguish it from another. Physical tangibility is said to be only one way in which thinghood delineates boundaries; social practices and norms can similarly indicate boundaries.21 Marinoti also suggested that property law doctrines like conversion and trespass can be extended to apply to digital assets.22 Even concepts such as the relativity of title (ie, wrongful 13 See, eg, Vijayakumaran (n 10) 409. 14 See, eg, Michael D. Murray, ‘NFT Ownership and Copyrights’ (2023) Indiana Law Rev 366. 15 Many popular NFT projects such as CryptoPunks have been released with no explicitly written copyright terms. See, eg, Grimmelman, Yan and Kell (n 9). An instance is that of the popular NFT project CryptoPunks which has been released with no explicitly written copyright terms. 16 Tese are leading NFT marketplaces. See, eg, Bitdeal, ‘Top 7 NFT Marketplaces to look in 2023 and beyond’ (BLOG, 2023) <www.bitdeal.net/top-7-nf-marketplaces-in-2023 -:~:text=Top 7 NFT Marketplaces 2023 1 1. OpenSea,Marketplace... 7 7. Solanart NFT Marketplace > accessed 13 January 2024. 17 See, eg, Marinoti (n 11). 18 Ibid. 19 Ibid 1277. 20 Ibid 1236. 21 Ibid. 22 Ibid 1269. Downloaded from https://academic.oup.com/ijlit/article/32/1/eaae018/7746479 by guest on 17 September 2024 4 • Tan possession can support an interest held by the wrongful possessor which is stronger than that of the world at large, save for the right owner) can arguably apply.23 While protecting wrongful possession may seem unjust, this could help avoid the scenario of having no legal recourse to an endless series of unlawful conversions of ‘NFTs’ after one single wrongful possession.24 To clarify, Marinoti’s reference to property law concepts drew from both real property and personal property laws, although this was not expressly stated. Along the same vein, other scholars such as Trautman and Fairfield have also proposed that the legal system should treat NFTs as digital personal property because NFTs comprise strong property interests through enabling parties to buy, sell, or own digital assets similar to personal property.25 On the other hand, some scholars do not agree that NFTs should be defined as properties. Lee, for example, has analogized NFTs with library catalog cards to illustrate that the value of NFTs is derived from their underlying properties (ie, books) and to highlight that people do not own these properties when they transact in NFTs.26 Further, Moringiello and Odinet rejected the perception of any property rights in NFTs—through comparison of their characteristics with those of negotiable instruments, securities, deeds of real property, bills of lading and other legal tokens—reasoning that NFTs lack the tethering effect that other properties have and that it is meaningless to view them as such, thus NFT holders do not control anything substantive.27

Exclusively use the information found in the prompt to provide responses limited to 300 words. Use bullet formatting if listing more than 2 items. Use numerical formatting is the response includes instructions. If there's is not enough information to answer some or all of an user's prompt then state so but answer the parts that you can, if any. Cite examples supporting main statements in your response when available.

How does Executive Order (E.O.) 14110 address concerns that were previously outlined in the E.O. on _Advancing Effective, Accountable Policing and Criminal Justice Practices to Enhance Public Trust and Public Safety_?

A number of concerns have been raised about law enforcement use of AI, including whether its use perpetuates biases; one criticism is that the data on which the software are trained contain bias, thus training bias into the AI systems. Another concern is whether reliance on AI technology may lead police to ignore contradictory evidence. Policymakers may consider increased oversight over police use of AI systems to help evaluate and alleviate some of the shortcomings. On October 30, 2023, President Biden issued Executive Order (E.O.) 14110 on the Safe, Secure, and Trustworthy Development and Use of Artificial Intelligence. This E.O. advances a government-wide approach to “governing the development and use of AI safely and responsibly” and directs efforts in AI policy areas involving safety and security, innovation and competition, worker support, equity and civil rights, individual protections, privacy protections, federal AI use, and international leadership. E.O. 14110 acknowledges the risk of AI exacerbating discrimination and directs federal law enforcement in various ways. (In doing so, it references accountability focused directives for federal law enforcement previously outlined in the May 25, 2022, E.O. 14074 on Advancing Effective, Accountable Policing and Criminal Justice Practices to Enhance Public Trust and Public Safety.) Directives in E.O. 14110 include the following: • The Attorney General (AG) shall coordinate and support enforcement of federal laws addressing discrimination and violations of civil rights and civil liberties related to AI. The Department of Justice’s Civil Rights Division shall also coordinate with other federal civil rights offices to assess how their offices can prevent and address discrimination in automated systems—including algorithmic discrimination. • The AG, with the Homeland Security Secretary and Office of Science and Technology Policy Director, shall submit a report to the President on the use of AI in the criminal justice system, including how AI can enhance law enforcement efficiency and accuracy, consistent with privacy, civil rights, and civil liberties protections. The report should also recommend best practices for law enforcement, including guidance on AI use, to address concerns outlined in E.O. 14074 with respect to law enforcement use of “facial recognition technology, other technologies using biometric information, and predictive algorithms, as well as data storage and access regarding such technologies.” • The interagency working group established by E.O. 14074 shall share best practices for recruiting law enforcement professionals with AI expertise and training them on responsible AI use. The AG, along with the Homeland Security Secretary, may review these and recommend best practices for state, local, tribal, and territorial law enforcement. • The AG shall review the Justice Department’s capacity to “investigate law enforcement deprivation of rights under color of law resulting from the use of AI,” including through increasing or improving training for federal law enforcement officers and prosecutors. Congressional Research Service 3 Policymakers conducting oversight of executive branch activities to ensure that AI is used in a fair and equitable manner may examine not only these elements of E.O. 14110 that specifically relate to federal law enforcement but also other elements—such as the development of industry standards on AI—that may in turn affect law enforcement use of AI. They may also explore whether there should be specific standards for AI use in the criminal justice sector or AI-specific requirements for criminal justice entities receiving federal grants. Additionally, policymakers may continue to debate law enforcement use of specific AI technologies in its toolbox such as facial recognition technology.

System instruction: Exclusively use the information found in the prompt to provide responses limited to 300 words. Use bullet formatting if listing more than 2 items. Use numerical formatting is the response includes instructions. If there's is not enough information to answer some or all of an user's prompt then state so but answer the parts that you can, if any. Cite examples supporting main statements in your response when available. context: A number of concerns have been raised about law enforcement use of AI, including whether its use perpetuates biases; one criticism is that the data on which the software are trained contain bias, thus training bias into the AI systems. Another concern is whether reliance on AI technology may lead police to ignore contradictory evidence. Policymakers may consider increased oversight over police use of AI systems to help evaluate and alleviate some of the shortcomings. On October 30, 2023, President Biden issued Executive Order (E.O.) 14110 on the Safe, Secure, and Trustworthy Development and Use of Artificial Intelligence. This E.O. advances a government-wide approach to “governing the development and use of AI safely and responsibly” and directs efforts in AI policy areas involving safety and security, innovation and competition, worker support, equity and civil rights, individual protections, privacy protections, federal AI use, and international leadership. E.O. 14110 acknowledges the risk of AI exacerbating discrimination and directs federal law enforcement in various ways. (In doing so, it references accountability focused directives for federal law enforcement previously outlined in the May 25, 2022, E.O. 14074 on Advancing Effective, Accountable Policing and Criminal Justice Practices to Enhance Public Trust and Public Safety.) Directives in E.O. 14110 include the following: • The Attorney General (AG) shall coordinate and support enforcement of federal laws addressing discrimination and violations of civil rights and civil liberties related to AI. The Department of Justice’s Civil Rights Division shall also coordinate with other federal civil rights offices to assess how their offices can prevent and address discrimination in automated systems—including algorithmic discrimination. • The AG, with the Homeland Security Secretary and Office of Science and Technology Policy Director, shall submit a report to the President on the use of AI in the criminal justice system, including how AI can enhance law enforcement efficiency and accuracy, consistent with privacy, civil rights, and civil liberties protections. The report should also recommend best practices for law enforcement, including guidance on AI use, to address concerns outlined in E.O. 14074 with respect to law enforcement use of “facial recognition technology, other technologies using biometric information, and predictive algorithms, as well as data storage and access regarding such technologies.” • The interagency working group established by E.O. 14074 shall share best practices for recruiting law enforcement professionals with AI expertise and training them on responsible AI use. The AG, along with the Homeland Security Secretary, may review these and recommend best practices for state, local, tribal, and territorial law enforcement. • The AG shall review the Justice Department’s capacity to “investigate law enforcement deprivation of rights under color of law resulting from the use of AI,” including through increasing or improving training for federal law enforcement officers and prosecutors. Congressional Research Service 3 Policymakers conducting oversight of executive branch activities to ensure that AI is used in a fair and equitable manner may examine not only these elements of E.O. 14110 that specifically relate to federal law enforcement but also other elements—such as the development of industry standards on AI—that may in turn affect law enforcement use of AI. They may also explore whether there should be specific standards for AI use in the criminal justice sector or AI-specific requirements for criminal justice entities receiving federal grants. Additionally, policymakers may continue to debate law enforcement use of specific AI technologies in its toolbox such as facial recognition technology. question: How does Executive Order (E.O.) 14110 address concerns that were previously outlined in the E.O. on _Advancing Effective, Accountable Policing and Criminal Justice Practices to Enhance Public Trust and Public Safety_?

[question] [user request] ===================== [text] [context document] ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

Provide me a summary of EI based on this reference, but organize it into two sections with one about the system itself and one about the actual benefits.

1.1.1 Summary The EI program, which is insurance-based, is designed to protect individuals who have lost their job for reasons outside their control, while they look for new employment or upgrade their skills. It may also help unemployed individuals across the country find employment. The EI program also provides temporary financial assistance to workers who are sick, pregnant, caring for a newborn or newly adopted child, or caring for a family member who has a serious medical condition. The EI program marked its 75th year in 2015, having been implemented in 1940. The last major reform occurred in 1996. At that time, the program introduced changes to better reflect its primary objective of promoting employment, and to better emphasize that access to the program is linked to significant work attachment. 1.1.2 Roles and responsibilities Employment and Social Development Canada (ESDC) is the department of the Government of Canada responsible for developing, managing and delivering programs and services. The Minister of Employment and Social Development is responsible for the EI act, except for PART IV - Insurable Earnings and Collection of Premiums, and PART VII - Benefit Repayment. The Canada Revenue Agency is responsible for resolving any questions pertaining to the insurability of employment or earnings (Part IV), and for the collection of EI premiums (Part VII). Service Canada is a federal institution that is part of ESDC. Service Canada oversees all legislative provisions of the act, including the determination of benefit eligibility and entitlement, and issues EI benefits (Part I) directly to EI claimants. Its role is to provide timely and accurate EI benefit payments and services, and to support EI claimants through each stage of the service delivery process. It strives to accurately and efficiently provide benefit information, respond to enquiries, assist employers, process claims and provide the means to request a formal reconsideration of a decision, or to appeal decisions. Provinces and territories deliver the majority of Employment Benefits and National Employment Services (Part II). These benefits and services are delivered through Labour Market Development Agreements (LMDA) funded by the Government of Canada. Through these agreements, Government of Canada funding enables provinces and territories to design, deliver and manage skills and employment programs for unemployed individuals, particularly for those who are eligible for EI benefits. The Canada Employment Insurance Commission (CEIC) is a departmental corporation of ESDC. It plays a key role in administering the EI program, including the making of regulations, with the approval of the Governor-in-Council, and reviewing, as well as approving, policies related to the EI program administration and delivery. In addition to its role in EI premium rate setting, the CEIC produces the annual EI Monitoring and Assessment Report. The Social Security Tribunal of Canada (SST) is an independent administrative body composed of a General Division and Appeal Division, that makes decisions on appeals related to the Act. 1.1.3 EI premiums & Insurable Employment All workers employed in insurable employment are required to pay EI premiums. The fact that a worker can or cannot qualify for EI benefits is not a criterion to determine whether EI premiums are payable, as it is the employment, and not the individual that is insured. The fundamental requirement for an employment to be insurable is that there is an employer-employee relationship; i.e. the person is not self-employed. CRA holds the responsibility for making decisions as to whether an employment is insurable or not, and whether EI premiums are payable with respect to that employment. 1.1.4 Purpose of Employment Insurance benefits As previously stated, Part I of the EI program provides temporary income support to workers who have lost their job for reasons outside their control, while they look for new employment or upgrade their skills. EI Part I also provides temporary financial assistance to workers who are sick, pregnant, caring for a newborn or newly adopted child, or caring for a family member who has a serious medical condition. The purpose of Part II of the EI Act is to provide employment assistance to eligible insured participants, through various programs and services. 1.1.5 Types of Employment Insurance benefits There are a number of types of EI benefits available: Regular benefits are available to individuals who lose their jobs for reasons outside their control and who are available for and actively seeking employment. Special benefits are available to insured workers and self-employed individuals who are too sick to work, are pregnant or have recently given birth, are providing care to a newborn or newly adopted child, or who must be away from work temporarily to provide care or support to a family member with a serious medical condition. Special benefits include: Maternity benefits: for biological mothers who are pregnant or have given birth. These benefits cover the period surrounding the child's birth (up to 15 weeks). Parental benefits: for any legal parent to care for their newborn or newly adopted child or children. One parent can receive these benefits, or they can share benefits between them (up to 40 weeks of standard parental benefits or 69 weeks of extended parental benefits when sharing). However, one parent cannot receive more than 35 weeks of standard parental benefits or 61 weeks of extended parental benefits. Sickness benefits: for people who cannot work due to injury, illness, or the need to be isolated in quarantine because they may be carrying a disease (up to 26Footnote1 weeks). Compassionate Care benefits: for people who must be away from work temporarily to provide care or support to a family member who is gravely ill with a significant risk of death within 26 weeks. One family member can receive these benefits, or they can be shared between several family members (up to 26 weeks). Family Caregiver benefits: for family members who must be away from work temporarily to care for or support a critically ill or injured family member. One family member can receive these benefits or they can be shared between several family members (up to 35 weeks for caring for a child; up to 15 weeks for caring for an adult). In certain circumstances various types of special benefits may be combined up to a maximum of 102 weeks of benefits within a maximum 104 week benefit period. Fishing benefits – are for eligible self-employed fishers who do not meet the eligibility requirements for EI regular benefits in their region. Job creation partnerships, work sharing, training benefits: for clients participating in developmental programs. [March 2019]

[question] Provide me a summary of EI based on this reference, but organize it into two sections with one about the system itself and one about the actual benefits. ===================== [text] 1.1.1 Summary The EI program, which is insurance-based, is designed to protect individuals who have lost their job for reasons outside their control, while they look for new employment or upgrade their skills. It may also help unemployed individuals across the country find employment. The EI program also provides temporary financial assistance to workers who are sick, pregnant, caring for a newborn or newly adopted child, or caring for a family member who has a serious medical condition. The EI program marked its 75th year in 2015, having been implemented in 1940. The last major reform occurred in 1996. At that time, the program introduced changes to better reflect its primary objective of promoting employment, and to better emphasize that access to the program is linked to significant work attachment. 1.1.2 Roles and responsibilities Employment and Social Development Canada (ESDC) is the department of the Government of Canada responsible for developing, managing and delivering programs and services. The Minister of Employment and Social Development is responsible for the EI act, except for PART IV - Insurable Earnings and Collection of Premiums, and PART VII - Benefit Repayment. The Canada Revenue Agency is responsible for resolving any questions pertaining to the insurability of employment or earnings (Part IV), and for the collection of EI premiums (Part VII). Service Canada is a federal institution that is part of ESDC. Service Canada oversees all legislative provisions of the act, including the determination of benefit eligibility and entitlement, and issues EI benefits (Part I) directly to EI claimants. Its role is to provide timely and accurate EI benefit payments and services, and to support EI claimants through each stage of the service delivery process. It strives to accurately and efficiently provide benefit information, respond to enquiries, assist employers, process claims and provide the means to request a formal reconsideration of a decision, or to appeal decisions. Provinces and territories deliver the majority of Employment Benefits and National Employment Services (Part II). These benefits and services are delivered through Labour Market Development Agreements (LMDA) funded by the Government of Canada. Through these agreements, Government of Canada funding enables provinces and territories to design, deliver and manage skills and employment programs for unemployed individuals, particularly for those who are eligible for EI benefits. The Canada Employment Insurance Commission (CEIC) is a departmental corporation of ESDC. It plays a key role in administering the EI program, including the making of regulations, with the approval of the Governor-in-Council, and reviewing, as well as approving, policies related to the EI program administration and delivery. In addition to its role in EI premium rate setting, the CEIC produces the annual EI Monitoring and Assessment Report. The Social Security Tribunal of Canada (SST) is an independent administrative body composed of a General Division and Appeal Division, that makes decisions on appeals related to the Act. 1.1.3 EI premiums & Insurable Employment All workers employed in insurable employment are required to pay EI premiums. The fact that a worker can or cannot qualify for EI benefits is not a criterion to determine whether EI premiums are payable, as it is the employment, and not the individual that is insured. The fundamental requirement for an employment to be insurable is that there is an employer-employee relationship; i.e. the person is not self-employed. CRA holds the responsibility for making decisions as to whether an employment is insurable or not, and whether EI premiums are payable with respect to that employment. 1.1.4 Purpose of Employment Insurance benefits As previously stated, Part I of the EI program provides temporary income support to workers who have lost their job for reasons outside their control, while they look for new employment or upgrade their skills. EI Part I also provides temporary financial assistance to workers who are sick, pregnant, caring for a newborn or newly adopted child, or caring for a family member who has a serious medical condition. The purpose of Part II of the EI Act is to provide employment assistance to eligible insured participants, through various programs and services. 1.1.5 Types of Employment Insurance benefits There are a number of types of EI benefits available: Regular benefits are available to individuals who lose their jobs for reasons outside their control and who are available for and actively seeking employment. Special benefits are available to insured workers and self-employed individuals who are too sick to work, are pregnant or have recently given birth, are providing care to a newborn or newly adopted child, or who must be away from work temporarily to provide care or support to a family member with a serious medical condition. Special benefits include: Maternity benefits: for biological mothers who are pregnant or have given birth. These benefits cover the period surrounding the child's birth (up to 15 weeks). Parental benefits: for any legal parent to care for their newborn or newly adopted child or children. One parent can receive these benefits, or they can share benefits between them (up to 40 weeks of standard parental benefits or 69 weeks of extended parental benefits when sharing). However, one parent cannot receive more than 35 weeks of standard parental benefits or 61 weeks of extended parental benefits. Sickness benefits: for people who cannot work due to injury, illness, or the need to be isolated in quarantine because they may be carrying a disease (up to 26Footnote1 weeks). Compassionate Care benefits: for people who must be away from work temporarily to provide care or support to a family member who is gravely ill with a significant risk of death within 26 weeks. One family member can receive these benefits, or they can be shared between several family members (up to 26 weeks). Family Caregiver benefits: for family members who must be away from work temporarily to care for or support a critically ill or injured family member. One family member can receive these benefits or they can be shared between several family members (up to 35 weeks for caring for a child; up to 15 weeks for caring for an adult). In certain circumstances various types of special benefits may be combined up to a maximum of 102 weeks of benefits within a maximum 104 week benefit period. Fishing benefits – are for eligible self-employed fishers who do not meet the eligibility requirements for EI regular benefits in their region. Job creation partnerships, work sharing, training benefits: for clients participating in developmental programs. [March 2019] https://www.canada.ca/en/employment-social-development/programs/ei/ei-list/reports/digest/chapter-1/authority.html#a1_1_1 ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. [user request] [context document]

Do local credit unions review and assess loan applications differently from a national chain such as Bank of America? What are the differences between their loan approval processes?

Over 93% of Americans have some type of financial transactional account, including checking, savings, money market, and call accounts. However, despite desiring a variety of choices in order to make informed decisions for their families and businesses, most Americans choose large national and regional banking institutions for their financial needs. In fact, big banks account for 74.8% of the total financial account market while smaller banking institutions and credit unions account for only 18.2% and 7%, respectively. Why the disparity? Although credit unions have been providing financial services in the U.S. for over 100 years, many people simply don’t know how they differ from a typical bank. The popularity of credit unions exploded in the first half of the 20th century and especially during the Great Depression. During this time, consumer credit from banking institutions was tight, leading many Americans to demand alternative banking choices. Credit unions were more likely to approve “risky” loans and provide services to people with less-than-perfect credit. Credit unions gained so much popularity that President Franklin Roosevelt enacted the Federal Credit Union Act in 1934, which established the National Credit Union Administration (“NCUA”) in order to better regulate federal credit unions and insure money deposited into credit union accounts. Credit unions and banks have a variety of major and minor differences, which boil down to business structure, product offerings, customer service, and membership requirements. These differences may be viewed as advantages or drawbacks, depending on your financial needs and preferences. One of the most important and major differences between banks and credit unions is business structure. A bank – whether it’s a small local provider or a national chain – is a for-profit enterprise. Similar to any other for-profit business, banks want to increase sales while reducing costs. If a bank is a public company, it’s governed by a board of directors and sells shares of its stock to investors. Conversely, credit unions are member-owned not-for-profit cooperatives. Specifically, if you open any type of account at a credit union, you’re considered a part-owner of that union. As such, credit union members enjoy certain benefits such as the ability to elect a volunteer board in charge of making important decisions on services, fees, and overall credit union management. Members also benefit from profit sharing in the form of reduced fees and dividends. As a result, credit unions typically consist of small, independent businesses or local chains. When it comes to customer service, credit unions outrank other financial institutions. According to the most recent annual American Customer Satisfaction Index (“ACSI”) report, credit unions scored an 85 for customer satisfaction, while the average bank scored a 76. The ACSI measured a variety of factors, including expectations, quality, value, loyalty, and complaint rates. Credit unions have outscored banks on all major factors for seven consecutive years. What makes credit unions so customer friendly? The reasons relate not only to their lower product rates and fees, but also to how they operate. As small not-for-profit cooperatives serving the local community, credit unions are more likely to work with people with poor or no credit that have been turned down by larger banks to obtain loans. Furthermore, some credit unions that serve low-income populations quality for the NCUA low-income designation, which entitles them and their members to additional benefits. In addition, credit unions work toward the betterment of their members and the surrounding community by offering a variety of local supports, such as sponsoring neighborhood or town projects, offering personal finance classes, providing microloans to people or businesses that don’t qualify for more traditional loans, and even offering scholarships and grants for local students. Similar to shopping at a large national big-box retailer versus a small mom-and-pop store, banks and credit unions provide similar financial benefits – but the products and types of services can be significantly different. Banks, especially large, national chains, generally provide more products – such as a variety of checking and saving account types, CDs, IRAs, and even credit cards. The variety allows individuals and businesses to find what works best for them. Credit unions, on the other hand, don’t always have the resources to offer the product variety that a larger bank could. However, as they are not-for-profit organizations, credit unions are able to offer lower fees and higher interest rates on the products they do carry as compared to a traditional bank. In addition to fewer product offerings, credit unions typically do not offer the same amenities as banks. With advanced online and mobile banking options, remote check deposits, and ubiquitous branches and ATMs – there’s a reason why banks control 93% of the financial account market. Quite simply, banks have the resources and economy of scale to invest in state-of-the-art, convenient services that customers want. Conversely, as credit unions are dedicated to serving a small, local population, there are typically only a few branches. Most credit unions do not maintain the capital to invest in cutting-edge services, and typically only offer rudimentary online banking options. However, although individual credit unions do not maintain a large number of branches, many credit unions belong to larger cooperatives that share resources, such as ATMs. This is especially important for today’s banking customer that requires on-the-go convenience and access to free ATMs. Lastly, a major difference between credit unions and banks is membership requirements. As mentioned, credit unions are member-owned and operated cooperatives, while banks are either private or public business enterprises. Banks are open to the public, and are free to do business with whomever they want. Credit unions, on the other hand, are required by law to restrict membership to certain communities tied by a “membership field” based on common occupations or association membership, family ties, or location. Most credit unions base their membership on locality, such as a town or region, while others may only serve certain professions, such as teachers or those in law enforcement. The NCUA changed its field of membership regulations in 2003 in order to increase credit union membership. The new rules expand what constitutes an occupational common bond as well as a community. The new regulations also eliminated several mandatory factors determining common bonds and membership fields. This has allowed credit unions that were once relatively inaccessible to open their doors to more types of consumers. Credit unions are enjoying increased interest in the wake of the recession and amidst consumer backlash against “too big to fail” banks. In 2011, a grassroots movement capitalized on feelings of consumer unrest by promoting Bank Transfer Day, urging Americans to move their accounts from big, national banks to community banks or credit unions. While over 600,000 people reportedly made the switch on Bank Transfer Day, the much-publicized movement continued to gain momentum. Approximately 5.6 million people moved their bank accounts in the fourth quarter of 2011, of which 11% was attributed to the Bank Transfer Day movement. Since that time, interest in credit unions has continued to gain momentum. Credit union membership increased 3.5% in 2015, the fastest annual advance since 1994. As with any decision, there are advantages and disadvantages to choosing either institution for your financial needs; it’s important to consider your needs, lifestyle, and goals. For example, an individual running a small consulting firm who regularly travels internationally may opt for a large bank due to its plethora of technology amenities and international presence. Conversely, the owner of a local shop may choose a credit union, preferring to support another local business and who appreciates the no frill, hands-on customer service.

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. Do local credit unions review and assess loan applications differently from a national chain such as Bank of America? What are the differences between their loan approval processes? Over 93% of Americans have some type of financial transactional account, including checking, savings, money market, and call accounts. However, despite desiring a variety of choices in order to make informed decisions for their families and businesses, most Americans choose large national and regional banking institutions for their financial needs. In fact, big banks account for 74.8% of the total financial account market while smaller banking institutions and credit unions account for only 18.2% and 7%, respectively. Why the disparity? Although credit unions have been providing financial services in the U.S. for over 100 years, many people simply don’t know how they differ from a typical bank. The popularity of credit unions exploded in the first half of the 20th century and especially during the Great Depression. During this time, consumer credit from banking institutions was tight, leading many Americans to demand alternative banking choices. Credit unions were more likely to approve “risky” loans and provide services to people with less-than-perfect credit. Credit unions gained so much popularity that President Franklin Roosevelt enacted the Federal Credit Union Act in 1934, which established the National Credit Union Administration (“NCUA”) in order to better regulate federal credit unions and insure money deposited into credit union accounts. Credit unions and banks have a variety of major and minor differences, which boil down to business structure, product offerings, customer service, and membership requirements. These differences may be viewed as advantages or drawbacks, depending on your financial needs and preferences. One of the most important and major differences between banks and credit unions is business structure. A bank – whether it’s a small local provider or a national chain – is a for-profit enterprise. Similar to any other for-profit business, banks want to increase sales while reducing costs. If a bank is a public company, it’s governed by a board of directors and sells shares of its stock to investors. Conversely, credit unions are member-owned not-for-profit cooperatives. Specifically, if you open any type of account at a credit union, you’re considered a part-owner of that union. As such, credit union members enjoy certain benefits such as the ability to elect a volunteer board in charge of making important decisions on services, fees, and overall credit union management. Members also benefit from profit sharing in the form of reduced fees and dividends. As a result, credit unions typically consist of small, independent businesses or local chains. When it comes to customer service, credit unions outrank other financial institutions. According to the most recent annual American Customer Satisfaction Index (“ACSI”) report, credit unions scored an 85 for customer satisfaction, while the average bank scored a 76. The ACSI measured a variety of factors, including expectations, quality, value, loyalty, and complaint rates. Credit unions have outscored banks on all major factors for seven consecutive years. What makes credit unions so customer friendly? The reasons relate not only to their lower product rates and fees, but also to how they operate. As small not-for-profit cooperatives serving the local community, credit unions are more likely to work with people with poor or no credit that have been turned down by larger banks to obtain loans. Furthermore, some credit unions that serve low-income populations quality for the NCUA low-income designation, which entitles them and their members to additional benefits. In addition, credit unions work toward the betterment of their members and the surrounding community by offering a variety of local supports, such as sponsoring neighborhood or town projects, offering personal finance classes, providing microloans to people or businesses that don’t qualify for more traditional loans, and even offering scholarships and grants for local students. Similar to shopping at a large national big-box retailer versus a small mom-and-pop store, banks and credit unions provide similar financial benefits – but the products and types of services can be significantly different. Banks, especially large, national chains, generally provide more products – such as a variety of checking and saving account types, CDs, IRAs, and even credit cards. The variety allows individuals and businesses to find what works best for them. Credit unions, on the other hand, don’t always have the resources to offer the product variety that a larger bank could. However, as they are not-for-profit organizations, credit unions are able to offer lower fees and higher interest rates on the products they do carry as compared to a traditional bank. In addition to fewer product offerings, credit unions typically do not offer the same amenities as banks. With advanced online and mobile banking options, remote check deposits, and ubiquitous branches and ATMs – there’s a reason why banks control 93% of the financial account market. Quite simply, banks have the resources and economy of scale to invest in state-of-the-art, convenient services that customers want. Conversely, as credit unions are dedicated to serving a small, local population, there are typically only a few branches. Most credit unions do not maintain the capital to invest in cutting-edge services, and typically only offer rudimentary online banking options. However, although individual credit unions do not maintain a large number of branches, many credit unions belong to larger cooperatives that share resources, such as ATMs. This is especially important for today’s banking customer that requires on-the-go convenience and access to free ATMs. Lastly, a major difference between credit unions and banks is membership requirements. As mentioned, credit unions are member-owned and operated cooperatives, while banks are either private or public business enterprises. Banks are open to the public, and are free to do business with whomever they want. Credit unions, on the other hand, are required by law to restrict membership to certain communities tied by a “membership field” based on common occupations or association membership, family ties, or location. Most credit unions base their membership on locality, such as a town or region, while others may only serve certain professions, such as teachers or those in law enforcement. The NCUA changed its field of membership regulations in 2003 in order to increase credit union membership. The new rules expand what constitutes an occupational common bond as well as a community. The new regulations also eliminated several mandatory factors determining common bonds and membership fields. This has allowed credit unions that were once relatively inaccessible to open their doors to more types of consumers. Credit unions are enjoying increased interest in the wake of the recession and amidst consumer backlash against “too big to fail” banks. In 2011, a grassroots movement capitalized on feelings of consumer unrest by promoting Bank Transfer Day, urging Americans to move their accounts from big, national banks to community banks or credit unions. While over 600,000 people reportedly made the switch on Bank Transfer Day, the much-publicized movement continued to gain momentum. Approximately 5.6 million people moved their bank accounts in the fourth quarter of 2011, of which 11% was attributed to the Bank Transfer Day movement. Since that time, interest in credit unions has continued to gain momentum. Credit union membership increased 3.5% in 2015, the fastest annual advance since 1994. As with any decision, there are advantages and disadvantages to choosing either institution for your financial needs; it’s important to consider your needs, lifestyle, and goals. For example, an individual running a small consulting firm who regularly travels internationally may opt for a large bank due to its plethora of technology amenities and international presence. Conversely, the owner of a local shop may choose a credit union, preferring to support another local business and who appreciates the no frill, hands-on customer service. https://blog.glia.com/4-major-differences-credit-unions-banks/

[This task requires you to answer questions based solely on the information provided in the prompt. You are not allowed to use any external resources or prior knowledge. Your answer should be between five and eight sentences long.]

[Will I get hungry and thirstier during a fast?]

Intermittent Fasting Myths “It’s just starving yourself.” Fasting is a planned action to avoid food for a set period of time. The body can still use energy from its own fat stores during a fast, so it isn’t being deprived. Starvation is completely different. It is unplanned, it doesn’t have a chosen end point, and the body doesn’t have much stored energy that it can use. It is simply untrue to say that fasting is the same as starving yourself! “It will slow your metabolism.” When someone follows a reduced calorie diet but continues to eat regularly (i.e., “little and often”), insulin levels remain high for most of the day. This stops the body from using stored fat for energy. It responds by reducing the amount of calories it burns, to save what energy it does have (i.e., it slows your metabolism). Fasting is different. During a fast, insulin levels are reduced, so fat stored in the body can be used for energy. This means that metabolism does not need to be slowed down, as the body does not think it is being deprived. “Breakfast is the most important meal of the day.” In the morning, the body’s releases hormones to get us ready to start the day. This causes the release of energy from the body’s stores, which means we don’t actually need to eat something first thing in the morning, as the body is being fed whether you eat something or not! No meal is more important than any other. What does matter is that you get all the nutrients you need from what you do eat. “You’ll be deprived of essential nutrients.” As long as a range of real foods are eaten in the non-fasting periods, there is no reason that people who try intermittent fasting should experience any nutrient deficiencies. “It’ll make your body break down muscle.” If available, the body will always use glucose and/or fat for fuel. Your muscles, and the proteins they are made up of, are only a last resort for this. Studies have shown that intermittent fasting does not cause significant muscle loss, and that levels of a growth hormone that protects muscles from being used for energy are increased during a fast. It is important that sufficient protein is eaten in the non-fasting periods though in order to support the growth and maintenance of muscle mass. “You’ll be hungry all the time and will just eat much more at the next meal.” Studies have shown that missing a meal may result in slightly more food being eaten at the next meal, but the total energy intake will still be less than if you had eaten both meals. Fasting decreases hunger hormones and increases fullness. So although you may feel hungry when you first try fasting, many people actually report reduced hunger once they are used to it. www.xperthealth.org.uk Stay hydrated When you eat, you get some water from your food. So during a fast, you are missing out on some of the fluids you normally get. This can lead to you becoming dehydrated, causing side effects such as tiredness and headaches. Dehydration can also be mistaken for hunger, which can make it more difficult to stick to your planned fast. The best option for staying hydrated is water. If you want to make it a bit more exciting then you can flavour it, with a slice of lemon, orange, lime or cucumber for example. Coffee (black or flavoured with natural extracts), tea (black, green, herbal or fruit), or broth (bone or vegetable) are all also suitable options. Stick with it You may struggle at first if you are not used to going for extended periods of time without food, but much of this could be down to habit. If you have had a set routine for a long time your body will expect to receive food at certain times of the day. So when it doesn’t get the food it is expecting, this can trigger feelings of hunger. Most people adapt quite quickly though, so find it increasingly easy to fast. But in the short-term, make sure you have thought about what you could do to try and distract yourself when you feel hungry. Break your fast with nutritious foods At the end of your fast, have a meal that includes plenty of real, minimally processed food. Make sure this meal includes one or two portions of good quality protein. This will help to satisfy your appetite, and to make sure your body gets plenty of nutrients. Planning a meal that supports your dietary approach but also includes some of your favourite foods to break your fast with can help to motivate you to stick with it too. Make sure you get enough salt People often think salt is unhealthy, but we do need some in our diet. Sodium is an essential nutrient, and the main source of it is salt. When you are not eating (i.e., during a fast), you are not taking in any salt. On top of this, the reduction in insulin levels during fasting results in less salt being held in the blood. Signs of having low sodium levels include dizziness (caused by a drop in blood pressure), muscle cramps, headaches and tiredness. These symptoms can be fixed by making sure you get enough salt and water. Salt can be added to meals in non-fasting periods, or you can get more by having salted water or bone broth during fasting periods. Don’t worry if you regain a bit of weight after a fast When you fast you will lose weight because your body is using up some of your stored fat for fuel. But you will also lose some weight for other reasons, including that there will be less food and waste passing through your body. This means that when you break your fast you might actually regain a little bit of weight. This is completely normal though, so you should not feel disappointed. The good news is that you will still have reduced the amount of fat stored in your body!

[Intermittent Fasting Myths “It’s just starving yourself.” Fasting is a planned action to avoid food for a set period of time. The body can still use energy from its own fat stores during a fast, so it isn’t being deprived. Starvation is completely different. It is unplanned, it doesn’t have a chosen end point, and the body doesn’t have much stored energy that it can use. It is simply untrue to say that fasting is the same as starving yourself! “It will slow your metabolism.” When someone follows a reduced calorie diet but continues to eat regularly (i.e., “little and often”), insulin levels remain high for most of the day. This stops the body from using stored fat for energy. It responds by reducing the amount of calories it burns, to save what energy it does have (i.e., it slows your metabolism). Fasting is different. During a fast, insulin levels are reduced, so fat stored in the body can be used for energy. This means that metabolism does not need to be slowed down, as the body does not think it is being deprived. “Breakfast is the most important meal of the day.” In the morning, the body’s releases hormones to get us ready to start the day. This causes the release of energy from the body’s stores, which means we don’t actually need to eat something first thing in the morning, as the body is being fed whether you eat something or not! No meal is more important than any other. What does matter is that you get all the nutrients you need from what you do eat. “You’ll be deprived of essential nutrients.” As long as a range of real foods are eaten in the non-fasting periods, there is no reason that people who try intermittent fasting should experience any nutrient deficiencies. “It’ll make your body break down muscle.” If available, the body will always use glucose and/or fat for fuel. Your muscles, and the proteins they are made up of, are only a last resort for this. Studies have shown that intermittent fasting does not cause significant muscle loss, and that levels of a growth hormone that protects muscles from being used for energy are increased during a fast. It is important that sufficient protein is eaten in the non-fasting periods though in order to support the growth and maintenance of muscle mass. “You’ll be hungry all the time and will just eat much more at the next meal.” Studies have shown that missing a meal may result in slightly more food being eaten at the next meal, but the total energy intake will still be less than if you had eaten both meals. Fasting decreases hunger hormones and increases fullness. So although you may feel hungry when you first try fasting, many people actually report reduced hunger once they are used to it. www.xperthealth.org.uk Stay hydrated When you eat, you get some water from your food. So during a fast, you are missing out on some of the fluids you normally get. This can lead to you becoming dehydrated, causing side effects such as tiredness and headaches. Dehydration can also be mistaken for hunger, which can make it more difficult to stick to your planned fast. The best option for staying hydrated is water. If you want to make it a bit more exciting then you can flavour it, with a slice of lemon, orange, lime or cucumber for example. Coffee (black or flavoured with natural extracts), tea (black, green, herbal or fruit), or broth (bone or vegetable) are all also suitable options. Stick with it You may struggle at first if you are not used to going for extended periods of time without food, but much of this could be down to habit. If you have had a set routine for a long time your body will expect to receive food at certain times of the day. So when it doesn’t get the food it is expecting, this can trigger feelings of hunger. Most people adapt quite quickly though, so find it increasingly easy to fast. But in the short-term, make sure you have thought about what you could do to try and distract yourself when you feel hungry. Break your fast with nutritious foods At the end of your fast, have a meal that includes plenty of real, minimally processed food. Make sure this meal includes one or two portions of good quality protein. This will help to satisfy your appetite, and to make sure your body gets plenty of nutrients. Planning a meal that supports your dietary approach but also includes some of your favourite foods to break your fast with can help to motivate you to stick with it too. Make sure you get enough salt People often think salt is unhealthy, but we do need some in our diet. Sodium is an essential nutrient, and the main source of it is salt. When you are not eating (i.e., during a fast), you are not taking in any salt. On top of this, the reduction in insulin levels during fasting results in less salt being held in the blood. Signs of having low sodium levels include dizziness (caused by a drop in blood pressure), muscle cramps, headaches and tiredness. These symptoms can be fixed by making sure you get enough salt and water. Salt can be added to meals in non-fasting periods, or you can get more by having salted water or bone broth during fasting periods. Don’t worry if you regain a bit of weight after a fast When you fast you will lose weight because your body is using up some of your stored fat for fuel. But you will also lose some weight for other reasons, including that there will be less food and waste passing through your body. This means that when you break your fast you might actually regain a little bit of weight. This is completely normal though, so you should not feel disappointed. The good news is that you will still have reduced the amount of fat stored in your body!] [Will I get hungry and thirstier during a fast?] [This task requires you to answer questions based solely on the information provided in the prompt. You are not allowed to use any external resources or prior knowledge. Your answer should be between five and eight sentences long.]

"================ <TEXT PASSAGE> ======= [context document] ================ <QUESTION> ======= [user request] ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

My aunt was just diagnosed with sickle cell anemia. I want to know more about the disease. Using this article as a reference, please explain the symptom and treatments for SCA.

How common is sickle cell anemia Prevalence Risk factors Symptoms Diagnosis Treatment Summary Sickle cell anemia (SCA) is a disorder that affects a person’s blood. Some research indicates that hundreds of thousands of people around the world experience this condition. SCA is a genetic blood disorder that affects red blood cells, which carry oxygen throughout the body. In people with SCA, these red blood cells change shape from round to crescent, or sickle shaped, due to problems with the hemoglobin in the cells. This can block blood flow to a person’s smaller blood vessels, causing pain and organ damage. SCA is one of a group of inherited red blood cell conditions that doctors refer to as sickle cell disease (SCD). SCA is usually the most severe form of SCD. SCD and SCA affect significant numbers of people globally. This article discusses SCA prevalence, risk factors, symptoms, diagnosis, and treatment. Sickle cell anemia prevalence yacobchuk/Getty Images According to the Centers for Disease Control and Prevention (CDC)Trusted Source, SCD affects millions of people throughout the world. The National Heart, Lung, and Blood Institute states that SCD affects more than 20 millionTrusted Source individuals worldwide. However, the CDC also states the exact number of people in the United States with SCD is unknown. They estimate that: SCD affects approximately 100,000 people in the United States. around 1 out of every 365 Black or African American babies have SCD around 1 out of every 16,300 Hispanic American babies have SCD There is a lack of current scientific data about how many people have SCA, which is a severe formTrusted Source of SCD. A 2022 review of research stated that more than 312,000Trusted Source children are born with SCA annually. However, the review used older data from 2011 to 2013 to provide this statistic. Sickle cell anemia risk factors SCA is a genetic condition that a person has from birthTrusted Source, so people cannot develop it any other way. People refer to the atypical genes that characterize the condition and cause SCA as sickle cell genes. If a person has one sickle cell gene, they have sickle cell trait (SCT). People with SCT typically do not have health problems as a result of the gene. However, they can still pass the sickle cell gene on if they have children. If someone inherits two sickle cell genes, they will have a form of SCD that may include SCA. They inherit one gene from each biological parent. If they have SCA, both their parents must have had SCD, SCT, or SCA. SCD is more common in some ethnic groups, such as: people of African descent Hispanic Americans from Central and South America people with Middle Eastern heritage individuals of Asian descent people with Indian heritage individuals of Mediterranean descent According to the CDC, approximately 1 in 13Trusted Source Black or African American babies have SCT. Learn more about SCA in African Americans. Symptoms to look out for People with SCA may have symptoms that appear at ages 5–6 months, including: painful swelling in hands and feet tiredness fussiness jaundice, which describes yellowing of the skin and whites of the eyes SCA symptoms can vary between people. Individuals with SCA may also developTrusted Source severe complications, such as: acute chest syndrome frequent serious infections severe anemia, which may cause shortness of breath and tiredness, among other symptoms sickle cell pain crises delayed growth lung problems strokes Sickle cell anemia diagnosis Healthcare professionals typically diagnoseTrusted Source SCA blood tests. They usually do so during pregnancy or soon after birth as part of routine screening. Healthcare professionals now test all newborns in the United States for SCA. People can have testing at any age to determine if they have SCA. They can also have blood or genetic testing to find out if they are at risk of having a child with the condition. They may carry the genes necessary for their children to have SCA, even if they do not have it themselves. Sickle cell anemia treatment People with SCA need lifelong treatment, which may include: preventing or managing painful episodes with self-care methods, such as staying hydrated and warm regular blood transfusions for a person’s symptoms or damage due to SCA emergency blood transfusions if a person develops severe anemia medication to reduce symptoms, such as hydroxyurea pain relief medications daily antibiotics for children under 5 yearsTrusted Source and regular vaccinations to reduce their risk of infection The only approved therapies that may be able to cure SCD are bone marrow or stem cell transplants. However, both these treatments carry significant risks — they may have serious side effects or be fatal. Summary Sickle cell anemia (SCA) is an inherited condition that affects a person’s red blood cells. It is a severe form of sickle cell disease (CSD). Some estimates suggest SCA affects hundreds of thousandsTrusted Source of people worldwide, while other health experts believe SCD affects millionsTrusted Source. People with forms of SCD have symptoms that can vary in severity, and some complications of SCD can be potentially fatal. However, there are a range of treatments to help manage the symptoms of SCD.

"================ <TEXT PASSAGE> ======= How common is sickle cell anemia Prevalence Risk factors Symptoms Diagnosis Treatment Summary Sickle cell anemia (SCA) is a disorder that affects a person’s blood. Some research indicates that hundreds of thousands of people around the world experience this condition. SCA is a genetic blood disorder that affects red blood cells, which carry oxygen throughout the body. In people with SCA, these red blood cells change shape from round to crescent, or sickle shaped, due to problems with the hemoglobin in the cells. This can block blood flow to a person’s smaller blood vessels, causing pain and organ damage. SCA is one of a group of inherited red blood cell conditions that doctors refer to as sickle cell disease (SCD). SCA is usually the most severe form of SCD. SCD and SCA affect significant numbers of people globally. This article discusses SCA prevalence, risk factors, symptoms, diagnosis, and treatment. Sickle cell anemia prevalence yacobchuk/Getty Images According to the Centers for Disease Control and Prevention (CDC)Trusted Source, SCD affects millions of people throughout the world. The National Heart, Lung, and Blood Institute states that SCD affects more than 20 millionTrusted Source individuals worldwide. However, the CDC also states the exact number of people in the United States with SCD is unknown. They estimate that: SCD affects approximately 100,000 people in the United States. around 1 out of every 365 Black or African American babies have SCD around 1 out of every 16,300 Hispanic American babies have SCD There is a lack of current scientific data about how many people have SCA, which is a severe formTrusted Source of SCD. A 2022 review of research stated that more than 312,000Trusted Source children are born with SCA annually. However, the review used older data from 2011 to 2013 to provide this statistic. Sickle cell anemia risk factors SCA is a genetic condition that a person has from birthTrusted Source, so people cannot develop it any other way. People refer to the atypical genes that characterize the condition and cause SCA as sickle cell genes. If a person has one sickle cell gene, they have sickle cell trait (SCT). People with SCT typically do not have health problems as a result of the gene. However, they can still pass the sickle cell gene on if they have children. If someone inherits two sickle cell genes, they will have a form of SCD that may include SCA. They inherit one gene from each biological parent. If they have SCA, both their parents must have had SCD, SCT, or SCA. SCD is more common in some ethnic groups, such as: people of African descent Hispanic Americans from Central and South America people with Middle Eastern heritage individuals of Asian descent people with Indian heritage individuals of Mediterranean descent According to the CDC, approximately 1 in 13Trusted Source Black or African American babies have SCT. Learn more about SCA in African Americans. Symptoms to look out for People with SCA may have symptoms that appear at ages 5–6 months, including: painful swelling in hands and feet tiredness fussiness jaundice, which describes yellowing of the skin and whites of the eyes SCA symptoms can vary between people. Individuals with SCA may also developTrusted Source severe complications, such as: acute chest syndrome frequent serious infections severe anemia, which may cause shortness of breath and tiredness, among other symptoms sickle cell pain crises delayed growth lung problems strokes Sickle cell anemia diagnosis Healthcare professionals typically diagnoseTrusted Source SCA blood tests. They usually do so during pregnancy or soon after birth as part of routine screening. Healthcare professionals now test all newborns in the United States for SCA. People can have testing at any age to determine if they have SCA. They can also have blood or genetic testing to find out if they are at risk of having a child with the condition. They may carry the genes necessary for their children to have SCA, even if they do not have it themselves. Sickle cell anemia treatment People with SCA need lifelong treatment, which may include: preventing or managing painful episodes with self-care methods, such as staying hydrated and warm regular blood transfusions for a person’s symptoms or damage due to SCA emergency blood transfusions if a person develops severe anemia medication to reduce symptoms, such as hydroxyurea pain relief medications daily antibiotics for children under 5 yearsTrusted Source and regular vaccinations to reduce their risk of infection The only approved therapies that may be able to cure SCD are bone marrow or stem cell transplants. However, both these treatments carry significant risks — they may have serious side effects or be fatal. Summary Sickle cell anemia (SCA) is an inherited condition that affects a person’s red blood cells. It is a severe form of sickle cell disease (CSD). Some estimates suggest SCA affects hundreds of thousandsTrusted Source of people worldwide, while other health experts believe SCD affects millionsTrusted Source. People with forms of SCD have symptoms that can vary in severity, and some complications of SCD can be potentially fatal. However, there are a range of treatments to help manage the symptoms of SCD. https://www.medicalnewstoday.com/articles/how-common-is-sickle-cell-anemia#summary ================ <QUESTION> ======= My aunt was just diagnosed with sickle cell anemia. I want to know more about the disease. Using this article as a reference, please explain the symptom and treatments for SCA. ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. [user request] [context document]

Can you extract the key information from this text, and summarize what IPv6 Quality-of-Service is and how it applies to a software engineer who primarily works on web-based technologies?

IPv6 Quality-of-Service Capabilities A host can use the flow label and the traffic fields in the IPv6 header. A host uses these fields to identify those packets for which the host requests special handling by IPv6 routers. For example, the host can request non-default quality of service or real-time service. This important capability enables the support of applications that require some degree of consistent throughput, delay, or jitter. These types of applications are known as multi media or real-time applications. Flow Labels A source can use the 20-bit flow label field in the IPv6 header. A source can use this field to label those packets for which the source requests special handling by the IPv6 routers. For example, a source can request non-default quality of service or real-time service. This aspect of IPv6 is still experimental and subject to change as the requirements for flow support in the Internet become clearer. Some hosts or routers do not support the functions of the flow label field. These hosts or routers are required to set the field to zero when originating a packet. Hosts or routers forward the field without changes when forwarding a packet. Hosts or routers ignore the field when receiving a packet. What Is a Flow? A flow is a sequence of packets that are sent from a particular source to a particular, unicast or multicast, destination. The source also requires special handling by the intervening routers. The nature of the special handling might be conveyed to the routers by a control protocol. The control protocol can be a resource reservation protocol. The special handling also might be conveyed by information within the flow's packets, for example, in a hop-by-hop option. Active flows from a source to a destination can be multiple. Active flows can also contain traffic that is not associated with any flow. The combination of a source address and a nonzero flow label uniquely identifies a flow. Packets that do not belong to a flow carry a flow label of zero. The flow's source node assigns a flow label to a flow. New flow labels must be chosen randomly, in a “pseudo” manner. New flow labels must also be chosen uniformly from the range 1 to FFFFF hex. This random allocation makes any set of bits within the flow label field suitable for use as a hash key by routers. The routers can use the hash key to look up the state that is associated with the flow. Packets Belonging to the Same Flow All packets that belong to the same flow must be sent with the same source address, same destination address, and same nonzero flow label. If any of those packets include a hop-by-hop options header, then the packets must be originated with the contents of the hop-by-hop options header. The next header field of the hop-by-hop options header is excluded. If any of those packets include a routing header, then the packets must be originated with the same contents in all extension headers. The same contents include all extensions before the routing header and the routing header. The next header field in the routing header is excluded. The routers or destinations are permitted, but not required, to verify that these conditions are satisfied. If a violation is detected, the violation should be reported to the source. The violation is reported by a problem message for an ICMP parameter, Code 0. The violation points to the high-order octet of the flow label field. The high-order octet is offset one octet within the IPv6 packet. Routers are free to set up the flow-handling state for any flow. Routers do not need explicit flow establishment information from a control protocol, a hop-by-hop option, or other means. For example, when a router receives a packet from a particular source with an unknown, non-zero flow label, a router can process its IPv6 header. The router processes any necessary extension headers in the same way that the router processes extension headers with the flow label field set to zero. The routers also determine the next-hop interface. The routers might also update a hop-by-hop option, advance the pointer and addresses in a routing header, or decide how to queue the packet. The decision to queue the packet is based on the Traffic Class field of the packet. The routers can then choose to remember the results of the processing steps. Then, the routers can cache the information. The routers use the source address and the flow label as the cache key. Subsequent packets, with the same source address and flow label, can then be handled by referring to the cached information. The routers do not need to examine all those fields. The routers can assume that the fields are unchanged from the first packet that is checked in the flow. Traffic Class The nodes that originate a packet must identify different classes or different priorities of IPv6 packets. The nodes use the Traffic Class field in the IPv6 header to make this identification. The routers that forward the packets also use the Traffic Class field for the same purpose. The following general requirements apply to the Traffic Class field: The service interface to the IPv6 service within a node must supply the value of the Traffic Class bits for an upper-layer protocol. The Traffic Class bits must be in packets that are originated by that upper-layer protocol. The default value must be zero for all of the 8 bits. Nodes that support some of the Traffic Class bits or all of the Traffic Class bits can change the value of those bits. The nodes can change only the values in packets that the nodes originate, forward, or receive, as required for that specific use. Nodes should ignore and leave unchanged any bits of the Traffic Class field for which the nodes do not support a specific use. The Traffic Class bits in a received packet might not be the same value that is sent by the packet's source. Therefore, the upper-layer protocol must not assume that the values are the same.

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. Can you extract the key information from this text, and summarize what IPv6 Quality-of-Service is and how it applies to a software engineer who primarily works on web-based technologies? IPv6 Quality-of-Service Capabilities A host can use the flow label and the traffic fields in the IPv6 header. A host uses these fields to identify those packets for which the host requests special handling by IPv6 routers. For example, the host can request non-default quality of service or real-time service. This important capability enables the support of applications that require some degree of consistent throughput, delay, or jitter. These types of applications are known as multi media or real-time applications. Flow Labels A source can use the 20-bit flow label field in the IPv6 header. A source can use this field to label those packets for which the source requests special handling by the IPv6 routers. For example, a source can request non-default quality of service or real-time service. This aspect of IPv6 is still experimental and subject to change as the requirements for flow support in the Internet become clearer. Some hosts or routers do not support the functions of the flow label field. These hosts or routers are required to set the field to zero when originating a packet. Hosts or routers forward the field without changes when forwarding a packet. Hosts or routers ignore the field when receiving a packet. What Is a Flow? A flow is a sequence of packets that are sent from a particular source to a particular, unicast or multicast, destination. The source also requires special handling by the intervening routers. The nature of the special handling might be conveyed to the routers by a control protocol. The control protocol can be a resource reservation protocol. The special handling also might be conveyed by information within the flow's packets, for example, in a hop-by-hop option. Active flows from a source to a destination can be multiple. Active flows can also contain traffic that is not associated with any flow. The combination of a source address and a nonzero flow label uniquely identifies a flow. Packets that do not belong to a flow carry a flow label of zero. The flow's source node assigns a flow label to a flow. New flow labels must be chosen randomly, in a “pseudo” manner. New flow labels must also be chosen uniformly from the range 1 to FFFFF hex. This random allocation makes any set of bits within the flow label field suitable for use as a hash key by routers. The routers can use the hash key to look up the state that is associated with the flow. Packets Belonging to the Same Flow All packets that belong to the same flow must be sent with the same source address, same destination address, and same nonzero flow label. If any of those packets include a hop-by-hop options header, then the packets must be originated with the contents of the hop-by-hop options header. The next header field of the hop-by-hop options header is excluded. If any of those packets include a routing header, then the packets must be originated with the same contents in all extension headers. The same contents include all extensions before the routing header and the routing header. The next header field in the routing header is excluded. The routers or destinations are permitted, but not required, to verify that these conditions are satisfied. If a violation is detected, the violation should be reported to the source. The violation is reported by a problem message for an ICMP parameter, Code 0. The violation points to the high-order octet of the flow label field. The high-order octet is offset one octet within the IPv6 packet. Routers are free to set up the flow-handling state for any flow. Routers do not need explicit flow establishment information from a control protocol, a hop-by-hop option, or other means. For example, when a router receives a packet from a particular source with an unknown, non-zero flow label, a router can process its IPv6 header. The router processes any necessary extension headers in the same way that the router processes extension headers with the flow label field set to zero. The routers also determine the next-hop interface. The routers might also update a hop-by-hop option, advance the pointer and addresses in a routing header, or decide how to queue the packet. The decision to queue the packet is based on the Traffic Class field of the packet. The routers can then choose to remember the results of the processing steps. Then, the routers can cache the information. The routers use the source address and the flow label as the cache key. Subsequent packets, with the same source address and flow label, can then be handled by referring to the cached information. The routers do not need to examine all those fields. The routers can assume that the fields are unchanged from the first packet that is checked in the flow. Traffic Class The nodes that originate a packet must identify different classes or different priorities of IPv6 packets. The nodes use the Traffic Class field in the IPv6 header to make this identification. The routers that forward the packets also use the Traffic Class field for the same purpose. The following general requirements apply to the Traffic Class field: The service interface to the IPv6 service within a node must supply the value of the Traffic Class bits for an upper-layer protocol. The Traffic Class bits must be in packets that are originated by that upper-layer protocol. The default value must be zero for all of the 8 bits. Nodes that support some of the Traffic Class bits or all of the Traffic Class bits can change the value of those bits. The nodes can change only the values in packets that the nodes originate, forward, or receive, as required for that specific use. Nodes should ignore and leave unchanged any bits of the Traffic Class field for which the nodes do not support a specific use. The Traffic Class bits in a received packet might not be the same value that is sent by the packet's source. Therefore, the upper-layer protocol must not assume that the values are the same. https://docs.oracle.com/cd/E19683-01/817-0573/chapter1-25/index.html

You may only use information in the context block when responding to the prompt

What specific disease in AR currently used for on the patient end?

AR applications for physicians and healthcare professionals cover by far the largest user group [6]. However, especially for AR-supported image guidance and navigation, very high accuracy and reliability may be needed [9]. Applications, for which sub-millimeter precision is not necessary, are, for example, ablations, ventriculostomy [10-14] or certain orthopedic interventions [15]. Here, the HoloLens is with its inside-out tracking already a promising tool, but for applications that need, for example, sub-millimeter precision, it cannot be used reliably yet. An example is the deep brain stimulation (DBS) procedure used for treating essential tremor and Parkinson’s disease, where millimeter-to-submillimeter accuracy in DBS targeting (an electrode placement inside the brain) can be important [16]. Another study exploring the clinical accuracy of the HoloLens for neuronavigation concludes also that it is currently not within clinically acceptable levels [17]. The same holds true for some application scenarios in orthopedic surgery [18], like screw placement, where there is still room for improvement [19]. We expect the Vision Pro to move the needle in terms of accuracy, because of its strong inside-out tracking through 12 built-in cameras and LiDAR (Light Detection and Ranging) sensing method, which is the key aspect for increasing the accuracy of AR. We do not see the often-criticized end-user price of $3,499 (without tax) for the Vision Pro as an issue for this user group. The price is similar to the HoloLens and much cheaper at a fraction of the costs compared to existing, and clinically used conventional medical navigation systems, e.g., from Brainlab or Medtronic. In this context, it is important to mention that the use of AR head-mounted displays (HMDs) with direct patient reference (and outside of research in the context of feasibility studies) requires an appropriate regulatory approval and a certification/classification as medical device. The Magic Leap 2, for example, received certification for usage in an operating room in January of this year (2023). Moreover, and especially in a medical context, the display may also require an image focus in surgical table distance [20]. Students are the second most common intended user group [6] with applications, for example, in educational training, like the HoloPointer, a virtual AR pointer for laparoscopic surgery training [21]. Another example is the usage of MR to teach medical students catheter placement [22] or a phantom experiment to study the effectiveness of learning using AR in the access of the central venous [23]. We found that the effects of HoloLens-based learning compared to conventional learning, e.g., by using cadavers or other computerized methods, seem to be rather small. A reason for this is that the learning tools usually used are relatively simple, conventional 3D models and more innovative visualizations, including interactive, dynamic content, which cannot be easily delivered by regular computerized methods, have not been explored in depth yet [6]. Here, we believe that the Vision Pro can raise the bar, because of its high-resolution visualization (consisting of two micro-OLED displays with a total of 23 megapixels) that uses eye-tracking to make the headset also usable as a desktop screen with its fine textual details. In addition, the 3D user interface, using precise and intuitive finger tracking, can be a game changer. Despite these advances, it remains to be seen if an AR headset has a major advantage over a conventional screen. The cost of the Vision Pro is also a concern, especially for students with a limited financial budget, but the “Pro” might indicate that there will also be a “regular” version released. Patients are currently the least frequented target user group with AR devices[6]. An example is MemHolo, which provides MR experiences for subjects with Alzheimer’s disease [24]. Other examples in this area include the usage of the HoloLens as an assistant and monitoring tool for medication adherence [25] and the usage of a HoloLens-based system for functional mobility assessment [26]. However, many interesting assistance and monitoring applications are limited by the restricted possible usage time of untethered AR headsets primarily due to battery life, and this problem seems to remain with the Vision Pro, which has a similar battery life of approximately two hours, like the HoloLens. The only consolation is the “external” battery pack that can be swapped for the Vision Pro. Finally, the Apple M2 and the new R1 chip of the Vision Pro could potentially boost the relatively small number of applications that have been explored so far, e.g., by reducing motion sickness, especially for elderly patients, which are more susceptible to MR sickness than younger users.

system instruction: [You may only use information in the context block when responding to the prompt] Content block: [AR applications for physicians and healthcare professionals cover by far the largest user group [6]. However, especially for AR-supported image guidance and navigation, very high accuracy and reliability may be needed [9]. Applications, for which sub-millimeter precision is not necessary, are, for example, ablations, ventriculostomy [10-14] or certain orthopedic interventions [15]. Here, the HoloLens is with its inside-out tracking already a promising tool, but for applications that need, for example, sub-millimeter precision, it cannot be used reliably yet. An example is the deep brain stimulation (DBS) procedure used for treating essential tremor and Parkinson’s disease, where millimeter-to-submillimeter accuracy in DBS targeting (an electrode placement inside the brain) can be important [16]. Another study exploring the clinical accuracy of the HoloLens for neuronavigation concludes also that it is currently not within clinically acceptable levels [17]. The same holds true for some application scenarios in orthopedic surgery [18], like screw placement, where there is still room for improvement [19]. We expect the Vision Pro to move the needle in terms of accuracy, because of its strong inside-out tracking through 12 built-in cameras and LiDAR (Light Detection and Ranging) sensing method, which is the key aspect for increasing the accuracy of AR. We do not see the often-criticized end-user price of $3,499 (without tax) for the Vision Pro as an issue for this user group. The price is similar to the HoloLens and much cheaper at a fraction of the costs compared to existing, and clinically used conventional medical navigation systems, e.g., from Brainlab or Medtronic. In this context, it is important to mention that the use of AR head-mounted displays (HMDs) with direct patient reference (and outside of research in the context of feasibility studies) requires an appropriate regulatory approval and a certification/classification as medical device. The Magic Leap 2, for example, received certification for usage in an operating room in January of this year (2023). Moreover, and especially in a medical context, the display may also require an image focus in surgical table distance [20]. Students are the second most common intended user group [6] with applications, for example, in educational training, like the HoloPointer, a virtual AR pointer for laparoscopic surgery training [21]. Another example is the usage of MR to teach medical students catheter placement [22] or a phantom experiment to study the effectiveness of learning using AR in the access of the central venous [23]. We found that the effects of HoloLens-based learning compared to conventional learning, e.g., by using cadavers or other computerized methods, seem to be rather small. A reason for this is that the learning tools usually used are relatively simple, conventional 3D models and more innovative visualizations, including interactive, dynamic content, which cannot be easily delivered by regular computerized methods, have not been explored in depth yet [6]. Here, we believe that the Vision Pro can raise the bar, because of its high-resolution visualization (consisting of two micro-OLED displays with a total of 23 megapixels) that uses eye-tracking to make the headset also usable as a desktop screen with its fine textual details. In addition, the 3D user interface, using precise and intuitive finger tracking, can be a game changer. Despite these advances, it remains to be seen if an AR headset has a major advantage over a conventional screen. The cost of the Vision Pro is also a concern, especially for students with a limited financial budget, but the “Pro” might indicate that there will also be a “regular” version released. Patients are currently the least frequented target user group with AR devices[6]. An example is MemHolo, which provides MR experiences for subjects with Alzheimer’s disease [24]. Other examples in this area include the usage of the HoloLens as an assistant and monitoring tool for medication adherence [25] and the usage of a HoloLens-based system for functional mobility assessment [26]. However, many interesting assistance and monitoring applications are limited by the restricted possible usage time of untethered AR headsets primarily due to battery life, and this problem seems to remain with the Vision Pro, which has a similar battery life of approximately two hours, like the HoloLens. The only consolation is the “external” battery pack that can be swapped for the Vision Pro. Finally, the Apple M2 and the new R1 chip of the Vision Pro could potentially boost the relatively small number of applications that have been explored so far, e.g., by reducing motion sickness, especially for elderly patients, which are more susceptible to MR sickness than younger users.] question: [What specific disease in AR currently used for on the patient end?]

You may not reference any other resources or find the answer to the prompt from any other resources beyond the provided text. If the answer is not given in the text, you must clearly state that. You may not assume or allude to potential meanings of the answers if the text does not explicitly state the answer. Do not expand upon the meanings of the answer if the text does not.

What advantages do offline vs online retailers have?

Due to savings in inventory costs, online retailing has a big advantage in selling less popular items (the long tail) and in removing geographic barriers to purchase. Brynjolfsson et al. (2003) estimated that the significantly increased assortment of books available online increased consumer welfare by $700 million to a billion dollars in 2000. In comparing the online sales of a clothing retailer with the catalog sales of the same item, Brynjolfsson et al. (2009) showed that online sales of niche items were less sensitive to competition from offline stores than from catalog sales because the online sales were skewed toward niche items. Brynjolfsson et al. (2011) showed that online sales of niche items increased with recommendations and search tools, indicating that these tools lowered search costs, making it easier for consumers to locate them. In sum, because of the ability to handle more extensive inventories and provide search tools that facilitate locating niche items, online retailing has a comparative advantage in selling less popular items, translating into substantial benefits for consumers. As noted above, online sellers have an advantage in facilitating a search for information on digital attributes (including price). In contrast, offline sellers have an advantage in providing information on non- digital attributes and providing faster delivery. This leads to the possibility that consumers will search among both online and offline retailers.

You may not reference any other resources or find the answer to the prompt from any other resources beyond the provided text. If the answer is not given in the text, you must clearly state that. You may not assume or allude to potential meanings of the answers if the text does not explicitly state the answer. Do not expand upon the meanings of the answer if the text does not. What advantages do offline vs online retailers have? Due to savings in inventory costs, online retailing has a big advantage in selling less popular items (the long tail) and in removing geographic barriers to purchase. Brynjolfsson et al. (2003) estimated that the significantly increased assortment of books available online increased consumer welfare by $700 million to a billion dollars in 2000. In comparing the online sales of a clothing retailer with the catalog sales of the same item, Brynjolfsson et al. (2009) showed that online sales of niche items were less sensitive to competition from offline stores than from catalog sales because the online sales were skewed toward niche items. Brynjolfsson et al. (2011) showed that online sales of niche items increased with recommendations and search tools, indicating that these tools lowered search costs, making it easier for consumers to locate them. In sum, because of the ability to handle more extensive inventories and provide search tools that facilitate locating niche items, online retailing has a comparative advantage in selling less popular items, translating into substantial benefits for consumers. As noted above, online sellers have an advantage in facilitating a search for information on digital attributes (including price). In contrast, offline sellers have an advantage in providing information on non- digital attributes and providing faster delivery. This leads to the possibility that consumers will search among both online and offline retailers.

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> [user request] <TEXT> [context document]

What is the effects of the Triple E virus on humans? Should we be worried? How is the Triple E virus spreading in the U.S. and what measures can be taken to combat?

A 41-year-old man in New Hampshire died last week after contracting a rare mosquito-borne illness called eastern equine encephalitis virus, also known as EEE or “triple E.” It was New Hampshire’s first human case of the disease in a decade. Four other human EEE infections have been reported this year in Wisconsin, New Jersey, Massachusetts, and Vermont. Though this outbreak is small and triple E does not pose a risk to most people living in the United States, public health officials and researchers alike are concerned about the threat the deadly virus poses to the public, both this year and in future summers. There is no known cure for the disease, which can cause severe flu-like symptoms and seizures in humans 4 to 10 days after exposure and kills between 30 and 40 percent of the people it infects. Half of the people who survive a triple E infection are left with permanent neurological damage. Because of EEE’s high mortality rate, state officials have begun spraying insecticide in Massachusetts, where 10 communities have been designated “critical” or “high risk” for triple E. Towns in the state shuttered their parks from dusk to dawn and warned people to stay inside after 6 p.m., when mosquitoes are most active. Like West Nile virus, another mosquito-borne illness that poses a risk to people in the U.S. every summer, triple E is constrained by environmental factors that are changing rapidly as the planet warms. That’s because mosquitoes thrive in the hotter, wetter conditions that climate change is producing. “We have seen a resurgence of activity with eastern equine encephalitis virus over the course of the past 10 or so years,” said Theodore G. Andreadis, a researcher who studied mosquito-borne diseases at the Connecticut Agricultural Experiment Station, a state government research and public outreach outfit, for 35 years. “And we’ve seen an advancement into more northern regions where it had previously not been detected.” Researchers don’t know what causes the virus to surge and abate, but Andreadis said it’s clear that climate change is one of the factors spurring its spread, particularly into new regions. The first triple E outbreak on record occurred in Massachusetts in the 1830s in horses — the reason one of the three Es stands for “equine.” It wasn’t until a full century later, in 1934, that mosquitoes were incriminated as potential vectors for the disease. The first recorded human cases of the disease also occurred in Massachusetts four years later, in 1938. There were 38 human cases in the state that year; 25 of them were fatal. Since then, human cases have mostly been registered in Gulf Coast states and, increasingly, the Northeast. From 1964 to 2002, in the Northeast, there was less than one case of the disease per year. From 2003 to 2019, the average in the region increased to between four and five cases per year. The disease is spread by two types of mosquito. The first is a species called Culiseta melanura, or the black-tailed mosquito. This mosquito tends to live in hardwood bogs and feeds on birds like robins, herons, and wrens, spreading the virus among them. But the melanura mosquito doesn’t often bite mammals. A different mosquito species, Coquillettidia perturbans, is primarily responsible for most of the human cases of the disease reported in the U.S. The perturbans mosquito picks up the EEE virus when it feeds on birds and then infects the humans and horses that it bites. Toward the end of the summer, when mosquitoes have reached their peak numbers and start jostling for any available blood meal, human cases start cropping up. Andreadis, who published a historical retrospective on the progression of triple E in the northeastern U.S. in 2021, said climate change has emerged as a major driver of the disease. “We’ve got milder winters, we’ve got warmer summers, and we’ve got extremes in both precipitation and drought,” he said. “The impact that this has on mosquito populations is probably quite profound.” Warmer global average temperatures generally produce more mosquitoes, no matter the species. Studies have shown that warmer air temperatures up to a certain threshold, around 90 degrees Fahrenheit, shorten the amount of time it takes for C. melanura eggs to hatch. Higher temperatures in the spring and fall extend the number of days mosquitoes have to breed and feed. And they’ll feed more times in a summer season if it’s warmer — mosquitoes are ectothermic, meaning their metabolism speeds up in higher temperatures. Rainfall, too, plays a role in mosquito breeding and activity, since mosquito eggs need water to hatch. A warmer atmosphere holds more moisture, which means that even small rainfall events dump more water today than they would have last century. The more standing water there is in roadside ditches, abandoned car tires, ponds, bogs, and potholes, the more opportunities mosquitoes have to breed. And warmer water decreases the incubation period for C. melanura eggs, leading one study to conclude that warmer-than-average water temperatures “increase the probability for amplification of EEE.” Climate change isn’t the only factor encouraging the spread of disease vectors like mosquitoes. The slow reforestation of areas that were clear-cut for industry and agriculture many decades ago is creating new habitat for insects. At the same time, developers are building new homes in wooded or half-wooded zones in ever larger numbers, putting humans in closer proximity to the natural world and the bugs that live in it. On an individual level, the best way to stay safe from EEE and other mosquito-borne diseases is to prevent bites: Wear long sleeves and pants at dusk and dawn, when mosquitoes are most prone to biting, and regularly apply an effective mosquito spray. But there are also steps that local health departments can take to safeguard public health, like testing pools of water for mosquito larvae and conducting public awareness and insecticide spraying campaigns when triple E is detected. Massachusetts is an example of a state that has been proactive about testing mosquitoes for triple E in recent summers. The most effective way to protect people from this disease would be to develop a vaccine against it. A vaccine already exists for horses, but there is little incentive for vaccine manufacturers to develop a preventative for triple E in humans because the illness is so rare. “Although EEE is not yet a global health emergency, the recent uptick in cases has highlighted our lack of preparedness for unexpected infectious disease outbreaks,” a group of biologists wrote last year in the open-access scientific journal Frontiers. “It would be wise to follow proactive active control measures and increase vigilance in the face of these threats.”

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> What is the effects of the Triple E virus on humans? Should we be worried? How is the Triple E virus spreading in the U.S. and what measures can be taken to combat? <TEXT> A 41-year-old man in New Hampshire died last week after contracting a rare mosquito-borne illness called eastern equine encephalitis virus, also known as EEE or “triple E.” It was New Hampshire’s first human case of the disease in a decade. Four other human EEE infections have been reported this year in Wisconsin, New Jersey, Massachusetts, and Vermont. Though this outbreak is small and triple E does not pose a risk to most people living in the United States, public health officials and researchers alike are concerned about the threat the deadly virus poses to the public, both this year and in future summers. There is no known cure for the disease, which can cause severe flu-like symptoms and seizures in humans 4 to 10 days after exposure and kills between 30 and 40 percent of the people it infects. Half of the people who survive a triple E infection are left with permanent neurological damage. Because of EEE’s high mortality rate, state officials have begun spraying insecticide in Massachusetts, where 10 communities have been designated “critical” or “high risk” for triple E. Towns in the state shuttered their parks from dusk to dawn and warned people to stay inside after 6 p.m., when mosquitoes are most active. Like West Nile virus, another mosquito-borne illness that poses a risk to people in the U.S. every summer, triple E is constrained by environmental factors that are changing rapidly as the planet warms. That’s because mosquitoes thrive in the hotter, wetter conditions that climate change is producing. “We have seen a resurgence of activity with eastern equine encephalitis virus over the course of the past 10 or so years,” said Theodore G. Andreadis, a researcher who studied mosquito-borne diseases at the Connecticut Agricultural Experiment Station, a state government research and public outreach outfit, for 35 years. “And we’ve seen an advancement into more northern regions where it had previously not been detected.” Researchers don’t know what causes the virus to surge and abate, but Andreadis said it’s clear that climate change is one of the factors spurring its spread, particularly into new regions. The first triple E outbreak on record occurred in Massachusetts in the 1830s in horses — the reason one of the three Es stands for “equine.” It wasn’t until a full century later, in 1934, that mosquitoes were incriminated as potential vectors for the disease. The first recorded human cases of the disease also occurred in Massachusetts four years later, in 1938. There were 38 human cases in the state that year; 25 of them were fatal. Since then, human cases have mostly been registered in Gulf Coast states and, increasingly, the Northeast. From 1964 to 2002, in the Northeast, there was less than one case of the disease per year. From 2003 to 2019, the average in the region increased to between four and five cases per year. The disease is spread by two types of mosquito. The first is a species called Culiseta melanura, or the black-tailed mosquito. This mosquito tends to live in hardwood bogs and feeds on birds like robins, herons, and wrens, spreading the virus among them. But the melanura mosquito doesn’t often bite mammals. A different mosquito species, Coquillettidia perturbans, is primarily responsible for most of the human cases of the disease reported in the U.S. The perturbans mosquito picks up the EEE virus when it feeds on birds and then infects the humans and horses that it bites. Toward the end of the summer, when mosquitoes have reached their peak numbers and start jostling for any available blood meal, human cases start cropping up. Andreadis, who published a historical retrospective on the progression of triple E in the northeastern U.S. in 2021, said climate change has emerged as a major driver of the disease. “We’ve got milder winters, we’ve got warmer summers, and we’ve got extremes in both precipitation and drought,” he said. “The impact that this has on mosquito populations is probably quite profound.” Warmer global average temperatures generally produce more mosquitoes, no matter the species. Studies have shown that warmer air temperatures up to a certain threshold, around 90 degrees Fahrenheit, shorten the amount of time it takes for C. melanura eggs to hatch. Higher temperatures in the spring and fall extend the number of days mosquitoes have to breed and feed. And they’ll feed more times in a summer season if it’s warmer — mosquitoes are ectothermic, meaning their metabolism speeds up in higher temperatures. Rainfall, too, plays a role in mosquito breeding and activity, since mosquito eggs need water to hatch. A warmer atmosphere holds more moisture, which means that even small rainfall events dump more water today than they would have last century. The more standing water there is in roadside ditches, abandoned car tires, ponds, bogs, and potholes, the more opportunities mosquitoes have to breed. And warmer water decreases the incubation period for C. melanura eggs, leading one study to conclude that warmer-than-average water temperatures “increase the probability for amplification of EEE.” Climate change isn’t the only factor encouraging the spread of disease vectors like mosquitoes. The slow reforestation of areas that were clear-cut for industry and agriculture many decades ago is creating new habitat for insects. At the same time, developers are building new homes in wooded or half-wooded zones in ever larger numbers, putting humans in closer proximity to the natural world and the bugs that live in it. On an individual level, the best way to stay safe from EEE and other mosquito-borne diseases is to prevent bites: Wear long sleeves and pants at dusk and dawn, when mosquitoes are most prone to biting, and regularly apply an effective mosquito spray. But there are also steps that local health departments can take to safeguard public health, like testing pools of water for mosquito larvae and conducting public awareness and insecticide spraying campaigns when triple E is detected. Massachusetts is an example of a state that has been proactive about testing mosquitoes for triple E in recent summers. The most effective way to protect people from this disease would be to develop a vaccine against it. A vaccine already exists for horses, but there is little incentive for vaccine manufacturers to develop a preventative for triple E in humans because the illness is so rare. “Although EEE is not yet a global health emergency, the recent uptick in cases has highlighted our lack of preparedness for unexpected infectious disease outbreaks,” a group of biologists wrote last year in the open-access scientific journal Frontiers. “It would be wise to follow proactive active control measures and increase vigilance in the face of these threats.” https://grist.org/health/eee-triple-e-climate-change-eastern-equine-encephalitis-mosquito-borne-illness/

You must answer in three paragraphs or less, using only information from the context block.

How does the adequacy decision impact data transfers?

CHAPTER V Transfers of personal data to third countries or international organisations Article 44 General principle for transfers Any transfer of personal data which are undergoing processing or are intended for processing after transfer to a third country or to an international organisation shall take place only if, subject to the other provisions of this Regulation, the conditions laid down in this Chapter are complied with by the controller and processor, including for onward transfers of personal data from the third country or an international organisation to another third country or to another international organisation. All provisions in this Chapter shall be applied in order to ensure that the level of protection of natural persons guaranteed by this Regulation is not undermined. L 119/60 EN Official Journal of the European Union 4.5.2016 Article 45 Transfers on the basis of an adequacy decision 1. A transfer of personal data to a third country or an international organisation may take place where the Commission has decided that the third country, a territory or one or more specified sectors within that third country, or the international organisation in question ensures an adequate level of protection. Such a transfer shall not require any specific authorisation. 2. When assessing the adequacy of the level of protection, the Commission shall, in particular, take account of the following elements: (a) the rule of law, respect for human rights and fundamental freedoms, relevant legislation, both general and sectoral, including concerning public security, defence, national security and criminal law and the access of public authorities to personal data, as well as the implementation of such legislation, data protection rules, professional rules and security measures, including rules for the onward transfer of personal data to another third country or international organisation which are complied with in that country or international organisation, case-law, as well as effective and enforceable data subject rights and effective administrative and judicial redress for the data subjects whose personal data are being transferred; (b) the existence and effective functioning of one or more independent supervisory authorities in the third country or to which an international organisation is subject, with responsibility for ensuring and enforcing compliance with the data protection rules, including adequate enforcement powers, for assisting and advising the data subjects in exercising their rights and for cooperation with the supervisory authorities of the Member States; and (c) the international commitments the third country or international organisation concerned has entered into, or other obligations arising from legally binding conventions or instruments as well as from its participation in multilateral or regional systems, in particular in relation to the protection of personal data. 3. The Commission, after assessing the adequacy of the level of protection, may decide, by means of implementing act, that a third country, a territory or one or more specified sectors within a third country, or an international organisation ensures an adequate level of protection within the meaning of paragraph 2 of this Article. The implementing act shall provide for a mechanism for a periodic review, at least every four years, which shall take into account all relevant developments in the third country or international organisation. The implementing act shall specify its territorial and sectoral application and, where applicable, identify the supervisory authority or authorities referred to in point (b) of paragraph 2 of this Article. The implementing act shall be adopted in accordance with the examination procedure referred to in Article 93(2). 4. The Commission shall, on an ongoing basis, monitor developments in third countries and international organisations that could affect the functioning of decisions adopted pursuant to paragraph 3 of this Article and decisions adopted on the basis of Article 25(6) of Directive 95/46/EC. 5. The Commission shall, where available information reveals, in particular following the review referred to in paragraph 3 of this Article, that a third country, a territory or one or more specified sectors within a third country, or an international organisation no longer ensures an adequate level of protection within the meaning of paragraph 2 of this Article, to the extent necessary, repeal, amend or suspend the decision referred to in paragraph 3 of this Article by means of implementing acts without retro-active effect. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 93(2). On duly justified imperative grounds of urgency, the Commission shall adopt immediately applicable implementing acts in accordance with the procedure referred to in Article 93(3). 6. The Commission shall enter into consultations with the third country or international organisation with a view to remedying the situation giving rise to the decision made pursuant to paragraph 5. 7. A decision pursuant to paragraph 5 of this Article is without prejudice to transfers of personal data to the third country, a territory or one or more specified sectors within that third country, or the international organisation in question pursuant to Articles 46 to 49. 8. The Commission shall publish in the Official Journal of the European Union and on its website a list of the third countries, territories and specified sectors within a third country and international organisations for which it has decided that an adequate level of protection is or is no longer ensured. 4.5.2016 EN Official Journal of the European Union L 119/61 9. Decisions adopted by the Commission on the basis of Article 25(6) of Directive 95/46/EC shall remain in force until amended, replaced or repealed by a Commission Decision adopted in accordance with paragraph 3 or 5 of this Article. Article 46 Transfers subject to appropriate safeguards 1. In the absence of a decision pursuant to Article 45(3), a controller or processor may transfer personal data to a third country or an international organisation only if the controller or processor has provided appropriate safeguards, and on condition that enforceable data subject rights and effective legal remedies for data subjects are available. 2. The appropriate safeguards referred to in paragraph 1 may be provided for, without requiring any specific authorisation from a supervisory authority, by: (a) a legally binding and enforceable instrument between public authorities or bodies; (b) binding corporate rules in accordance with Article 47; (c) standard data protection clauses adopted by the Commission in accordance with the examination procedure referred to in Article 93(2); (d) standard data protection clauses adopted by a supervisory authority and approved by the Commission pursuant to the examination procedure referred to in Article 93(2); (e) an approved code of conduct pursuant to Article 40 together with binding and enforceable commitments of the controller or processor in the third country to apply the appropriate safeguards, including as regards data subjects' rights; or (f) an approved certification mechanism pursuant to Article 42 together with binding and enforceable commitments of the controller or processor in the third country to apply the appropriate safeguards, including as regards data subjects' rights. 3. Subject to the authorisation from the competent supervisory authority, the appropriate safeguards referred to in paragraph 1 may also be provided for, in particular, by: (a) contractual clauses between the controller or processor and the controller, processor or the recipient of the personal data in the third country or international organisation; or (b) provisions to be inserted into administrative arrangements between public authorities or bodies which include enforceable and effective data subject rights. 4. The supervisory authority shall apply the consistency mechanism referred to in Article 63 in the cases referred to in paragraph 3 of this Article. 5. Authorisations by a Member State or supervisory authority on the basis of Article 26(2) of Directive 95/46/EC shall remain valid until amended, replaced or repealed, if necessary, by that supervisory authority. Decisions adopted by the Commission on the basis of Article 26(4) of Directive 95/46/EC shall remain in force until amended, replaced or repealed, if necessary, by a Commission Decision adopted in accordance with paragraph 2 of this Article.

System Instructions: You must answer only information from the context block. No external information can be used to supplement this. Context: CHAPTER V Transfers of personal data to third countries or international organisations Article 44 General principle for transfers Any transfer of personal data which are undergoing processing or are intended for processing after transfer to a third country or to an international organisation shall take place only if, subject to the other provisions of this Regulation, the conditions laid down in this Chapter are complied with by the controller and processor, including for onward transfers of personal data from the third country or an international organisation to another third country or to another international organisation. All provisions in this Chapter shall be applied in order to ensure that the level of protection of natural persons guaranteed by this Regulation is not undermined. L 119/60 EN Official Journal of the European Union 4.5.2016 Article 45 Transfers on the basis of an adequacy decision 1. A transfer of personal data to a third country or an international organisation may take place where the Commission has decided that the third country, a territory or one or more specified sectors within that third country, or the international organisation in question ensures an adequate level of protection. Such a transfer shall not require any specific authorisation. 2. When assessing the adequacy of the level of protection, the Commission shall, in particular, take account of the following elements: (a) the rule of law, respect for human rights and fundamental freedoms, relevant legislation, both general and sectoral, including concerning public security, defence, national security and criminal law and the access of public authorities to personal data, as well as the implementation of such legislation, data protection rules, professional rules and security measures, including rules for the onward transfer of personal data to another third country or international organisation which are complied with in that country or international organisation, case-law, as well as effective and enforceable data subject rights and effective administrative and judicial redress for the data subjects whose personal data are being transferred; (b) the existence and effective functioning of one or more independent supervisory authorities in the third country or to which an international organisation is subject, with responsibility for ensuring and enforcing compliance with the data protection rules, including adequate enforcement powers, for assisting and advising the data subjects in exercising their rights and for cooperation with the supervisory authorities of the Member States; and (c) the international commitments the third country or international organisation concerned has entered into, or other obligations arising from legally binding conventions or instruments as well as from its participation in multilateral or regional systems, in particular in relation to the protection of personal data. 3. The Commission, after assessing the adequacy of the level of protection, may decide, by means of implementing act, that a third country, a territory or one or more specified sectors within a third country, or an international organisation ensures an adequate level of protection within the meaning of paragraph 2 of this Article. The implementing act shall provide for a mechanism for a periodic review, at least every four years, which shall take into account all relevant developments in the third country or international organisation. The implementing act shall specify its territorial and sectoral application and, where applicable, identify the supervisory authority or authorities referred to in point (b) of paragraph 2 of this Article. The implementing act shall be adopted in accordance with the examination procedure referred to in Article 93(2). 4. The Commission shall, on an ongoing basis, monitor developments in third countries and international organisations that could affect the functioning of decisions adopted pursuant to paragraph 3 of this Article and decisions adopted on the basis of Article 25(6) of Directive 95/46/EC. 5. The Commission shall, where available information reveals, in particular following the review referred to in paragraph 3 of this Article, that a third country, a territory or one or more specified sectors within a third country, or an international organisation no longer ensures an adequate level of protection within the meaning of paragraph 2 of this Article, to the extent necessary, repeal, amend or suspend the decision referred to in paragraph 3 of this Article by means of implementing acts without retro-active effect. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 93(2). On duly justified imperative grounds of urgency, the Commission shall adopt immediately applicable implementing acts in accordance with the procedure referred to in Article 93(3). 6. The Commission shall enter into consultations with the third country or international organisation with a view to remedying the situation giving rise to the decision made pursuant to paragraph 5. 7. A decision pursuant to paragraph 5 of this Article is without prejudice to transfers of personal data to the third country, a territory or one or more specified sectors within that third country, or the international organisation in question pursuant to Articles 46 to 49. 8. The Commission shall publish in the Official Journal of the European Union and on its website a list of the third countries, territories and specified sectors within a third country and international organisations for which it has decided that an adequate level of protection is or is no longer ensured. 4.5.2016 EN Official Journal of the European Union L 119/61 9. Decisions adopted by the Commission on the basis of Article 25(6) of Directive 95/46/EC shall remain in force until amended, replaced or repealed by a Commission Decision adopted in accordance with paragraph 3 or 5 of this Article. Article 46 Transfers subject to appropriate safeguards 1. In the absence of a decision pursuant to Article 45(3), a controller or processor may transfer personal data to a third country or an international organisation only if the controller or processor has provided appropriate safeguards, and on condition that enforceable data subject rights and effective legal remedies for data subjects are available. 2. The appropriate safeguards referred to in paragraph 1 may be provided for, without requiring any specific authorisation from a supervisory authority, by: (a) a legally binding and enforceable instrument between public authorities or bodies; (b) binding corporate rules in accordance with Article 47; (c) standard data protection clauses adopted by the Commission in accordance with the examination procedure referred to in Article 93(2); (d) standard data protection clauses adopted by a supervisory authority and approved by the Commission pursuant to the examination procedure referred to in Article 93(2); (e) an approved code of conduct pursuant to Article 40 together with binding and enforceable commitments of the controller or processor in the third country to apply the appropriate safeguards, including as regards data subjects' rights; or (f) an approved certification mechanism pursuant to Article 42 together with binding and enforceable commitments of the controller or processor in the third country to apply the appropriate safeguards, including as regards data subjects' rights. 3. Subject to the authorisation from the competent supervisory authority, the appropriate safeguards referred to in paragraph 1 may also be provided for, in particular, by: (a) contractual clauses between the controller or processor and the controller, processor or the recipient of the personal data in the third country or international organisation; or (b) provisions to be inserted into administrative arrangements between public authorities or bodies which include enforceable and effective data subject rights. 4. The supervisory authority shall apply the consistency mechanism referred to in Article 63 in the cases referred to in paragraph 3 of this Article. 5. Authorisations by a Member State or supervisory authority on the basis of Article 26(2) of Directive 95/46/EC shall remain valid until amended, replaced or repealed, if necessary, by that supervisory authority. Decisions adopted by the Commission on the basis of Article 26(4) of Directive 95/46/EC shall remain in force until amended, replaced or repealed, if necessary, by a Commission Decision adopted in accordance with paragraph 2 of this Article. Question: How does the adequacy decision impact data transfers?

Only respond to the prompt using the information in the prompt. Format the response as a numbered list.

What are three failures of the WHO regarding fighting diseases and other health threats?

WHO achievements: A mixed track record Fighting infectious diseases One of the WHO's biggest achievements was in eradicating smallpox: in 1980, 21 years after launching an international vaccination campaign, it was finally able to declare the world free of the disease. In 1988, the WHO declared a target of similarly eliminating polio by the end of the millennium. That target was missed, and the stubborn persistence of infections prompted the WHO to declare a PHEIC in 2014. Nevertheless, considerable progress has been made, with the number of cases falling by 99 % over the past three decades. Unfortunately, tuberculosis is very far from disappearing; however, the WHO's Global Drug Facility has enabled millions of patients in developing countries to access high-quality anti-TB medicines, both through collective purchasing mechanisms that bring the cost of drugs down, and through grants that help the poorest countries to buy such medicines. The WHO has also been praised for its leadership during the 2003 SARS epidemic; within just four months, the disease had been contained. In 2009, fears that the swine flu virus could mutate into a more lethal form prompted the WHO to declare its first ever Public Health Emergency of International Concern (PHEIC – see Box). Governments rushed to stockpile vaccines, most of which were never used, as the epidemic turned out to be milder than expected. This 'disproportionate' response, as it was described in a 2011 European Parliament resolution, was blamed for wasting millions of euros of public money on unnecessary vaccines. Some critics even alleged that WHO decisions had been swayed by the interests of the pharmaceutical sector. An internal enquiry exonerated the WHO from most of these accusations, arguing that, in view of the evidence available at the time, it would not have been possible to predict the course of the epidemic, while also acknowledging that the situation could have been handled more transparently. Whereas the WHO was accused of over-reacting to swine flu, its response to the 2014 West African Ebola outbreak came too late to prevent tens of thousands of deaths. In what international health experts described as an 'egregious failure', the WHO waited months before declaring a PHEIC, despite warnings, including from its own staff, that the epidemic was out of control. The organisation's lumbering bureaucratic response contrasted unfavourably with more agile interventions by non-governmental bodies such as Médecins Sans Frontières. On the other hand, in 2018 efforts to contain a second outbreak of Ebola in the Democratic Republic of the Congo were more successful, with just 33 deaths in total; for some observers, the organisation's quick response, which included the release of emergency funding just hours after the start of the outbreak and a personal visit to Kinshasa by Director-General Tedros a few days later, suggested that it had learned lessons from its 2014 failures. Ebola remains a serious threat in West Africa; a subsequent outbreak triggered another PHEIC, and killed over 2 000. Non-communicable diseases and other health threats While media attention tends to focus on emergencies caused by infectious diseases, noncommunicable diseases such as cancer cost far more lives. However, the WHO's track record in this respect is, again, a mixed one. For example, many recommendations issued by the International Agency for Research on Cancer, a semi-autonomous branch of the WHO, are scientifically sound; however, critics allege that the body does not do enough to prevent conflicts of interest that might influence expert assessments on which its recommendations are based, nor is it very successful at communicating its conclusions with the public. On smoking, described by the WHO as a 'global epidemic', the main instrument is the 2003 Framework Convention on Tobacco Control, the first ever international treaty adopted within the WHO framework. The measures it envisages have played a key role in shaping national tobacco control policies, including in developing countries. Implementation is still patchy, but gradually improving: as of 2018, 12 % of the 181 countries which are parties to the Convention were failing to ensure protection from passive smoking (e.g. bans on smoking in public places), 23 % were not applying packaging and labelling requirements (such as health warnings on cigarette packets), 29 % did not have awareness-raising and educational measures in place, while 30 % were not restricting tobacco sales to and by minors. Tobacco still kills over 8 million people every year, most of them in developing countries, and consumption is only declining slowly. Obesity is another global health scourge that the WHO has taken on. For example, in 2016 it endorsed taxes on soft drinks as an effective means of reducing sugar consumption. However, it has run into resistance from the beverages industry, and the US government, which in 2018 blocked a WHO panel from issuing a global recommendation on sugar taxes. In developing countries, the high cost of medicines is often a barrier to effective treatment. Improving access to medicines has long been a priority for the WHO. The interests of producers, which are protected by patents, have to be balanced against patients' need for affordable treatment. However, WHO work in this area has been blocked by disagreements between countries which argue that intellectual property is not part of the organisation's remit – typically pharmaceutical exporters, such as the United States (US) – and others, including developing countries, which feel that it should be.

What are three failures of the WHO regarding fighting diseases and other health threats? Only respond to the prompt using the information in the prompt. Format the response as a numbered list. WHO achievements: A mixed track record Fighting infectious diseases One of the WHO's biggest achievements was in eradicating smallpox: in 1980, 21 years after launching an international vaccination campaign, it was finally able to declare the world free of the disease. In 1988, the WHO declared a target of similarly eliminating polio by the end of the millennium. That target was missed, and the stubborn persistence of infections prompted the WHO to declare a PHEIC in 2014. Nevertheless, considerable progress has been made, with the number of cases falling by 99 % over the past three decades. Unfortunately, tuberculosis is very far from disappearing; however, the WHO's Global Drug Facility has enabled millions of patients in developing countries to access high-quality anti-TB medicines, both through collective purchasing mechanisms that bring the cost of drugs down, and through grants that help the poorest countries to buy such medicines. The WHO has also been praised for its leadership during the 2003 SARS epidemic; within just four months, the disease had been contained. In 2009, fears that the swine flu virus could mutate into a more lethal form prompted the WHO to declare its first ever Public Health Emergency of International Concern (PHEIC – see Box). Governments rushed to stockpile vaccines, most of which were never used, as the epidemic turned out to be milder than expected. This 'disproportionate' response, as it was described in a 2011 European Parliament resolution, was blamed for wasting millions of euros of public money on unnecessary vaccines. Some critics even alleged that WHO decisions had been swayed by the interests of the pharmaceutical sector. An internal enquiry exonerated the WHO from most of these accusations, arguing that, in view of the evidence available at the time, it would not have been possible to predict the course of the epidemic, while also acknowledging that the situation could have been handled more transparently. Whereas the WHO was accused of over-reacting to swine flu, its response to the 2014 West African Ebola outbreak came too late to prevent tens of thousands of deaths. In what international health experts described as an 'egregious failure', the WHO waited months before declaring a PHEIC, despite warnings, including from its own staff, that the epidemic was out of control. The organisation's lumbering bureaucratic response contrasted unfavourably with more agile interventions by non-governmental bodies such as Médecins Sans Frontières. On the other hand, in 2018 efforts to contain a second outbreak of Ebola in the Democratic Republic of the Congo were more successful, with just 33 deaths in total; for some observers, the organisation's quick response, which included the release of emergency funding just hours after the start of the outbreak and a personal visit to Kinshasa by Director-General Tedros a few days later, suggested that it had learned lessons from its 2014 failures. Ebola remains a serious threat in West Africa; a subsequent outbreak triggered another PHEIC, and killed over 2 000. Non-communicable diseases and other health threats While media attention tends to focus on emergencies caused by infectious diseases, noncommunicable diseases such as cancer cost far more lives. However, the WHO's track record in this respect is, again, a mixed one. For example, many recommendations issued by the International Agency for Research on Cancer, a semi-autonomous branch of the WHO, are scientifically sound; however, critics allege that the body does not do enough to prevent conflicts of interest that might influence expert assessments on which its recommendations are based, nor is it very successful at communicating its conclusions with the public. On smoking, described by the WHO as a 'global epidemic', the main instrument is the 2003 Framework Convention on Tobacco Control, the first ever international treaty adopted within the WHO framework. The measures it envisages have played a key role in shaping national tobacco control policies, including in developing countries. Implementation is still patchy, but gradually improving: as of 2018, 12 % of the 181 countries which are parties to the Convention were failing to ensure protection from passive smoking (e.g. bans on smoking in public places), 23 % were not applying packaging and labelling requirements (such as health warnings on cigarette packets), 29 % did not have awareness-raising and educational measures in place, while 30 % were not restricting tobacco sales to and by minors. Tobacco still kills over 8 million people every year, most of them in developing countries, and consumption is only declining slowly. Obesity is another global health scourge that the WHO has taken on. For example, in 2016 it endorsed taxes on soft drinks as an effective means of reducing sugar consumption. However, it has run into resistance from the beverages industry, and the US government, which in 2018 blocked a WHO panel from issuing a global recommendation on sugar taxes. In developing countries, the high cost of medicines is often a barrier to effective treatment. Improving access to medicines has long been a priority for the WHO. The interests of producers, which are protected by patents, have to be balanced against patients' need for affordable treatment. However, WHO work in this area has been blocked by disagreements between countries which argue that intellectual property is not part of the organisation's remit – typically pharmaceutical exporters, such as the United States (US) – and others, including developing countries, which feel that it should be.

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. [user request] [context document]

Our social security numbers were stolen in a cyber-hack and I'm freaking out. We have accounts for the whole family, including our kids. We are pretty broke, but I'm worried they will open credit cards or something. What are some ways I can protect our credit because I can't decide between a credit freeze, lock or fraud alerts, what are the pros and cons for all three? I normally do all our banking online and have already changed all our passwords just in case but need some reassurance we will be ok.

A credit freeze is a free service, guaranteed under federal law, that can protect you from credit fraud by limiting most access to your credit report until you lift it, or "thaw" your report. When your credit report is frozen, any lender who asks to evaluate your report for purposes of issuing a loan or other credit is denied access to the report. A security freeze won't affect your credit scores, but it will prevent lenders evaluating credit applications from obtaining your credit scores. A security freeze prevents criminals from opening new credit accounts in your name, but it also blocks your legitimate credit applications. So, if you have a credit freeze in place, you'll need to thaw your credit reports before applying for a new loan, credit card or other consumer credit. Once your application is processed, you can reinstate the freeze. Alternatively, you can use a temporary thaw to lift the freeze for a set window of time, such as one day or one week, after which the freeze will be reinstated. Credit freezes must be activated and lifted separately at each of the national credit bureaus. Procedures differ somewhat with each bureau, but all three enable requesting and lifting of security freezes online, by phone and via postal mail. There is never a fee for applying or removing a credit freeze. The law also allows you to establish and freeze credit reports for your minor children, to avoid misuse of their personal information. To place a credit freeze, you must provide details and proof of your identity and address, per instructions provided by the respective credit bureau. These typically include: Full name Date of birth All addresses you've used in the past two years Social Security number One copy of a government-issued identification, such as a driver's license or state ID card A recent copy of a utility bill, bank or insurance statement or similar, as proof of address How to Freeze Your Credit at Each Credit Bureau Experian TransUnion Equifax Online 888-EXPERIAN Experian Security Freeze P.O. Box 9554 Allen, TX 75013 Online 800-916-8800 TransUnion P.O. Box 160 Woodlyn, PA 19094 Online 888-298-0045 Equifax Information Services LLC P.O. Box 105788 Atlanta, GA 30348-5788 You can remove a credit freeze using the same channels you use to set up a freeze. When lifting a credit freeze, you have the option of permanently unfreezing your credit, or lifting the freeze temporarily by indicating a length of time (one day or one week, for example) you want the freeze to be suspended. Policies vary by bureau, so make sure you understand what your options are before you begin the process. When you request a credit thaw by phone, your freeze will be lifted within one hour. If you use a credit bureau website or phone app to turn off a credit freeze, the process is virtually instantaneous. If you mail your request, the freeze will be lifted within three days of the credit bureau receiving your request. A credit lock lets you restrict and grant access to your credit reports essentially the same way a credit freeze does, but usually with extra features. Credit lock services provided by each credit bureau may differ in cost and functionality. For instance, in addition to enabling you to turn access to your Experian credit report on and off instantly, CreditLock from Experian also notifies you when anyone requests access to your locked credit report. This can help you spot unauthorized activity in your name. Experian CreditLock is available as part of a premium identity protection subscription for $24.99 per month, which also includes services such as: Monthly privacy scans and help getting information removed from covered people search sites Alerts to credit activity on your credit reports at all three national credit bureaus Quarterly FICO® Scores☉ based on your credit reports at all three national bureaus Daily FICO® Scores based on your Experian credit report Alerts when your personal data appears on the dark web Alerts to potential takeovers of your financial accounts Alerts when your Social Security number appears online Up to $1 million in identity theft insurance coverage Dedicated fraud resolution support Lost wallet assistance Equifax provides credit locks free to consumers through Lock & Alert, which also notifies users when anyone requests a credit check on a locked Equifax credit report. TransUnion includes credit file locking for both your TransUnion and Equifax credit files in its subscription service, which costs $29.95 per month. Each credit bureau requires entering your Social Security number and identity verification as part of its credit lock setup process. How to Lock Your Credit Enabling credit lock requires signing up for the service with the relevant credit bureau. Controls differ somewhat at each credit bureau, but each is a virtual on-off toggle that locks and unlocks the applicable credit report. The process for unlocking your credit report at each credit bureau is the reverse of the procedure for locking it: Using the credit bureau's app or website, locate the credit lock function and click the virtual switch to toggle from the locked setting to the unlocked If you're concerned your identity may have been stolen, or if you've discovered fraudulent activity on your credit reports, applying a security freeze or credit lock to your credit report will effectively prevent lenders from processing new credit applications filed in your name. Because they are free and guaranteed by law, credit freezes may be the better choice for consumers who don't want to pay for the service and don't want any extra features. When freezing or unfreezing your credit online, the process is essentially as quick and easy to use as a credit lock. A credit freeze is also the only option available if you want to restrict access to your minor children's credit information. Credit lock might be a better option if you're interested in the additional identity theft protection services included in the accompanying subscriptions. These might be particularly helpful in addressing the consequences of identity theft, and helping prevent additional fraud. When weighing the benefits of credit freeze and credit lock, it may also be worth considering a third option, the fraud alert. You have the right to place a fraud alert on your credit report, and doing so instructs lenders to verify your identity before processing a credit application in your name. This allows you to apply for loans and other forms of credit without having to remember to thaw or unlock your credit reports. What's more, placing a fraud alert with any one credit bureau automatically applies the alert to all three credit bureaus. You'll have to remove each separately, however. Learn more >> Fraud Alert vs. Credit Freeze: What's the Difference? The Bottom Line Credit freezes and credit locks offer valuable protection for your credit reports, as either a precaution or a response to criminal abuse of your credit. When managed online, both freezes and locks are quick and easy to use, and highly effective at blocking credit applications in your name—both fraudulent and legitimate ones. If you decide to apply a credit lock or security freeze, remember to disable it before you apply for a new loan or credit account.

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. Our social security numbers were stolen in a cyber-hack and I'm freaking out. We have accounts for the whole family, including our kids. We are pretty broke, but I'm worried they will open credit cards or something. What are some ways I can protect our credit because I can't decide between a credit freeze, lock or fraud alerts, what are the pros and cons for all three? I normally do all our banking online and have already changed all our passwords just in case but need some reassurance we will be ok. A credit freeze is a free service, guaranteed under federal law, that can protect you from credit fraud by limiting most access to your credit report until you lift it, or "thaw" your report. When your credit report is frozen, any lender who asks to evaluate your report for purposes of issuing a loan or other credit is denied access to the report. A security freeze won't affect your credit scores, but it will prevent lenders evaluating credit applications from obtaining your credit scores. A security freeze prevents criminals from opening new credit accounts in your name, but it also blocks your legitimate credit applications. So, if you have a credit freeze in place, you'll need to thaw your credit reports before applying for a new loan, credit card or other consumer credit. Once your application is processed, you can reinstate the freeze. Alternatively, you can use a temporary thaw to lift the freeze for a set window of time, such as one day or one week, after which the freeze will be reinstated. Credit freezes must be activated and lifted separately at each of the national credit bureaus. Procedures differ somewhat with each bureau, but all three enable requesting and lifting of security freezes online, by phone and via postal mail. There is never a fee for applying or removing a credit freeze. The law also allows you to establish and freeze credit reports for your minor children, to avoid misuse of their personal information. To place a credit freeze, you must provide details and proof of your identity and address, per instructions provided by the respective credit bureau. These typically include: Full name Date of birth All addresses you've used in the past two years Social Security number One copy of a government-issued identification, such as a driver's license or state ID card A recent copy of a utility bill, bank or insurance statement or similar, as proof of address How to Freeze Your Credit at Each Credit Bureau Experian TransUnion Equifax Online 888-EXPERIAN Experian Security Freeze P.O. Box 9554 Allen, TX 75013 Online 800-916-8800 TransUnion P.O. Box 160 Woodlyn, PA 19094 Online 888-298-0045 Equifax Information Services LLC P.O. Box 105788 Atlanta, GA 30348-5788 You can remove a credit freeze using the same channels you use to set up a freeze. When lifting a credit freeze, you have the option of permanently unfreezing your credit, or lifting the freeze temporarily by indicating a length of time (one day or one week, for example) you want the freeze to be suspended. Policies vary by bureau, so make sure you understand what your options are before you begin the process. When you request a credit thaw by phone, your freeze will be lifted within one hour. If you use a credit bureau website or phone app to turn off a credit freeze, the process is virtually instantaneous. If you mail your request, the freeze will be lifted within three days of the credit bureau receiving your request. A credit lock lets you restrict and grant access to your credit reports essentially the same way a credit freeze does, but usually with extra features. Credit lock services provided by each credit bureau may differ in cost and functionality. For instance, in addition to enabling you to turn access to your Experian credit report on and off instantly, CreditLock from Experian also notifies you when anyone requests access to your locked credit report. This can help you spot unauthorized activity in your name. Experian CreditLock is available as part of a premium identity protection subscription for $24.99 per month, which also includes services such as: Monthly privacy scans and help getting information removed from covered people search sites Alerts to credit activity on your credit reports at all three national credit bureaus Quarterly FICO® Scores☉ based on your credit reports at all three national bureaus Daily FICO® Scores based on your Experian credit report Alerts when your personal data appears on the dark web Alerts to potential takeovers of your financial accounts Alerts when your Social Security number appears online Up to $1 million in identity theft insurance coverage Dedicated fraud resolution support Lost wallet assistance Equifax provides credit locks free to consumers through Lock & Alert, which also notifies users when anyone requests a credit check on a locked Equifax credit report. TransUnion includes credit file locking for both your TransUnion and Equifax credit files in its subscription service, which costs $29.95 per month. Each credit bureau requires entering your Social Security number and identity verification as part of its credit lock setup process. How to Lock Your Credit Enabling credit lock requires signing up for the service with the relevant credit bureau. Controls differ somewhat at each credit bureau, but each is a virtual on-off toggle that locks and unlocks the applicable credit report. The process for unlocking your credit report at each credit bureau is the reverse of the procedure for locking it: Using the credit bureau's app or website, locate the credit lock function and click the virtual switch to toggle from the locked setting to the unlocked If you're concerned your identity may have been stolen, or if you've discovered fraudulent activity on your credit reports, applying a security freeze or credit lock to your credit report will effectively prevent lenders from processing new credit applications filed in your name. Because they are free and guaranteed by law, credit freezes may be the better choice for consumers who don't want to pay for the service and don't want any extra features. When freezing or unfreezing your credit online, the process is essentially as quick and easy to use as a credit lock. A credit freeze is also the only option available if you want to restrict access to your minor children's credit information. Credit lock might be a better option if you're interested in the additional identity theft protection services included in the accompanying subscriptions. These might be particularly helpful in addressing the consequences of identity theft, and helping prevent additional fraud. When weighing the benefits of credit freeze and credit lock, it may also be worth considering a third option, the fraud alert. You have the right to place a fraud alert on your credit report, and doing so instructs lenders to verify your identity before processing a credit application in your name. This allows you to apply for loans and other forms of credit without having to remember to thaw or unlock your credit reports. What's more, placing a fraud alert with any one credit bureau automatically applies the alert to all three credit bureaus. You'll have to remove each separately, however. Learn more >> Fraud Alert vs. Credit Freeze: What's the Difference? The Bottom Line Credit freezes and credit locks offer valuable protection for your credit reports, as either a precaution or a response to criminal abuse of your credit. When managed online, both freezes and locks are quick and easy to use, and highly effective at blocking credit applications in your name—both fraudulent and legitimate ones. If you decide to apply a credit lock or security freeze, remember to disable it before you apply for a new loan or credit account. https://www.experian.com/blogs/ask-experian/whats-the-difference-between-credit-freeze-and-a-credit-lock/

Answer questions based solely on the information provided in the prompt. You are not allowed to use any external resources or prior knowledge. If the answer contains more than one piece of information, utilize a numbered list.

If I need permission to use a work, where can I find the copyright owner?

In general, for works created on or after January 1, 1978, the term of copyright is the life of the author plus seventy years after the author’s death. If the work is a joint work with multiple authors, the term lasts for seventy years after the last surviving author’s death. For works made for hire and anonymous or pseudonymous works, the duration of copyright is 95 years from publication or 120 years from creation, whichever is shorter. For works created before January 1, 1978, that were not published or registered as of that date, the term of copyright is generally the same as for works created on or after January 1, 1978. The law, however, provides that in no case would the term have expired before December 31, 2002, and if the work was published on or before that date, the term will not expire before December 31, 2047. For works created before January 1, 1978, that were published or registered before that date, the initial term of copyright was twenty-eight years from the date of publication with notice or from the date of registration. At the end of the initial term, the copyright could be renewed for another sixtyseven years for a total term of protection of up to ninety-five years. To extend copyright into the renewal term, two registrations had to be made before the original term expired: one for the original term and the other for the renewal term. This requirement was eliminated on June 26, 1992, and renewal term registration is now optional. For more information on the term of copyright protection, see Duration of Copyright (Circular 15A) and Renewal of Copyright (Circular 6A). How Can I Protect My Work? Copyright exists automatically in an original work of authorship once it is fixed in a tangible medium, but a copyright owner can take steps to enhance the protections of copyright, the most important of which is registering the work. Although registering a work is not mandatory, for U.S. works, registration (or refusal) is necessary to enforce the exclusive rights of copyright through litigation. Applying a copyright notice to a work has not been required since March 1, 1989, but may still provide practical and legal benefits. Notice typically consists of the copyright symbol or the word “Copyright,” the name of the copyright owner, and the year of first publication. Placing a copyright notice on a work is not a substitute for registration. Copyright Basics 5 Benefits of Registration Registration establishes a claim to copyright with the Copyright Office. An application for copyright registration can be filed by the author or owner of an exclusive right in a work, the owner of all exclusive rights, or an agent on behalf of an author or owner. An application contains three essential elements: a completed application form, a nonrefundable filing fee, and a nonreturnable deposit— that is, a copy or copies of the work being registered and “deposited” with the Copyright Office. A certificate of registration creates a public record of key facts relating to the authorship and ownership of the claimed work, including the title of the work, the author of the work, the name and address of the claimant or copyright owner, the year of creation, and information about whether the work is published, has been previously registered, or includes preexisting material. You can submit an application online through www.copyright.gov or on a paper application. For more information on registering a work with the Copyright Office, see Copyright Registration (Circular 2). In addition to establishing a public record of a copyright claim, registration offers several other statutory advantages: • Before an infringement suit may be filed in court, registration (or refusal) is necessary for U.S. works.2 • Registration establishes prima facie evidence of the validity of the copyright and facts stated in the certificate when registration is made before or within five years of publication. • When registration is made prior to infringement or within three months after publication of a work, a copyright owner is eligible for statutory damages, attorneys’ fees, and costs. • Registration permits a copyright owner to establish a record with the U.S. Customs and Border Protection (CBP)4 for protection against the importation of infringing copies. Registration can be made at any time within the life of the copyright. If you register before publication, you do not have to re-register when the work is published, although you can register the published edition, if desired. Effective Date of Registration When the Copyright Office registers a work it assigns an effective date of registration to the certificate of registration. The effective date of registration is the day that the Office receives in proper form all required elements—an acceptable application, an acceptable deposit, and a nonrefundable filing fee. The date is not set until all the required elements are in the Office’s possession. If the Office receives incomplete materials, an unacceptable deposit, or an insufficient fee, the effective date of registration will be set on the date that the Office receives all the required materials in acceptable form. The date is not based on how long it takes the Office to examine the materials or mail the certificate of registration. You do not have to receive your certificate of registration before you publish or produce your work. Nor do you need permission from the Copyright Office to place a copyright notice on your work. But the Copyright Office must approve or refuse your application before you can file a lawsuit for copyright infringement, except in cases involving a non-U.S. work.5 You may seek statutory damages and attorneys’ fees in an infringement action provided that the infringement began after the effective date of registration. The law, however, provides a grace period of three months after publication during which full remedies can be recovered for any infringement begun during the three months after publication if registration is made before this period ends. Copyright Basics 6 Copyright Notice A copyright notice is a statement placed on copies or phonorecords of a work to inform the public that a copyright owner is claiming ownership of the work. A copyright notice consists of three elements: • The copyright symbol © or (p) for phonorecords, the word “Copyright,” or the abbreviation “Copr.”; • The year of first publication of the work (or of creation if the work is unpublished); and • The name of the copyright owner, an abbreviation by which the name can be recognized, or a generally known alternative designation. A notice should be affixed to copies or phonorecords of a work in a way that gives reasonable notice of the claim of copyright. Using a copyright notice is optional for unpublished works, non-U.S. works, and works published on or after March 1, 1989. However, notice conveys the following benefits: • It puts potential users on notice that copyright is claimed in the work. • For published works, notice may prevent a defendant from attempting to limit liability for damages or injunctive relief based on an “innocent infringement” defense. • It identifies the copyright owner at the time of first publication for parties seeking permission to use the work. • It identifies the year of first publication, which can be used to determine the term of copyright for anonymous or pseudonymous works or works made for hire. • It may prevent the work from becoming an “orphan” by identifying the copyright owner or specifying the term of copyright. Orphan works are original works of authorship for which prospective users cannot identify or locate copyright owners to request permission. Notice was required for works published in the United States before March 1, 1989. Works published without notice before that date may have entered the public domain in this country. For more information, see Copyright Notice (Circular 3

Answer questions based solely on the information provided in the prompt. You are not allowed to use any external resources or prior knowledge. If the answer contains more than one piece of information, utilize a numbered list. If I need permission to use a work, where can I find the copyright owner? In general, for works created on or after January 1, 1978, the term of copyright is the life of the author plus seventy years after the author’s death. If the work is a joint work with multiple authors, the term lasts for seventy years after the last surviving author’s death. For works made for hire and anonymous or pseudonymous works, the duration of copyright is 95 years from publication or 120 years from creation, whichever is shorter. For works created before January 1, 1978, that were not published or registered as of that date, the term of copyright is generally the same as for works created on or after January 1, 1978. The law, however, provides that in no case would the term have expired before December 31, 2002, and if the work was published on or before that date, the term will not expire before December 31, 2047. For works created before January 1, 1978, that were published or registered before that date, the initial term of copyright was twenty-eight years from the date of publication with notice or from the date of registration. At the end of the initial term, the copyright could be renewed for another sixtyseven years for a total term of protection of up to ninety-five years. To extend copyright into the renewal term, two registrations had to be made before the original term expired: one for the original term and the other for the renewal term. This requirement was eliminated on June 26, 1992, and renewal term registration is now optional. For more information on the term of copyright protection, see Duration of Copyright (Circular 15A) and Renewal of Copyright (Circular 6A). How Can I Protect My Work? Copyright exists automatically in an original work of authorship once it is fixed in a tangible medium, but a copyright owner can take steps to enhance the protections of copyright, the most important of which is registering the work. Although registering a work is not mandatory, for U.S. works, registration (or refusal) is necessary to enforce the exclusive rights of copyright through litigation. Applying a copyright notice to a work has not been required since March 1, 1989, but may still provide practical and legal benefits. Notice typically consists of the copyright symbol or the word “Copyright,” the name of the copyright owner, and the year of first publication. Placing a copyright notice on a work is not a substitute for registration. Copyright Basics 5 Benefits of Registration Registration establishes a claim to copyright with the Copyright Office. An application for copyright registration can be filed by the author or owner of an exclusive right in a work, the owner of all exclusive rights, or an agent on behalf of an author or owner. An application contains three essential elements: a completed application form, a nonrefundable filing fee, and a nonreturnable deposit— that is, a copy or copies of the work being registered and “deposited” with the Copyright Office. A certificate of registration creates a public record of key facts relating to the authorship and ownership of the claimed work, including the title of the work, the author of the work, the name and address of the claimant or copyright owner, the year of creation, and information about whether the work is published, has been previously registered, or includes preexisting material. You can submit an application online through www.copyright.gov or on a paper application. For more information on registering a work with the Copyright Office, see Copyright Registration (Circular 2). In addition to establishing a public record of a copyright claim, registration offers several other statutory advantages: • Before an infringement suit may be filed in court, registration (or refusal) is necessary for U.S. works.2 • Registration establishes prima facie evidence of the validity of the copyright and facts stated in the certificate when registration is made before or within five years of publication. • When registration is made prior to infringement or within three months after publication of a work, a copyright owner is eligible for statutory damages, attorneys’ fees, and costs. • Registration permits a copyright owner to establish a record with the U.S. Customs and Border Protection (CBP)4 for protection against the importation of infringing copies. Registration can be made at any time within the life of the copyright. If you register before publication, you do not have to re-register when the work is published, although you can register the published edition, if desired. Effective Date of Registration When the Copyright Office registers a work it assigns an effective date of registration to the certificate of registration. The effective date of registration is the day that the Office receives in proper form all required elements—an acceptable application, an acceptable deposit, and a nonrefundable filing fee. The date is not set until all the required elements are in the Office’s possession. If the Office receives incomplete materials, an unacceptable deposit, or an insufficient fee, the effective date of registration will be set on the date that the Office receives all the required materials in acceptable form. The date is not based on how long it takes the Office to examine the materials or mail the certificate of registration. You do not have to receive your certificate of registration before you publish or produce your work. Nor do you need permission from the Copyright Office to place a copyright notice on your work. But the Copyright Office must approve or refuse your application before you can file a lawsuit for copyright infringement, except in cases involving a non-U.S. work.5 You may seek statutory damages and attorneys’ fees in an infringement action provided that the infringement began after the effective date of registration. The law, however, provides a grace period of three months after publication during which full remedies can be recovered for any infringement begun during the three months after publication if registration is made before this period ends. Copyright Basics 6 Copyright Notice A copyright notice is a statement placed on copies or phonorecords of a work to inform the public that a copyright owner is claiming ownership of the work. A copyright notice consists of three elements: • The copyright symbol © or (p) for phonorecords, the word “Copyright,” or the abbreviation “Copr.”; • The year of first publication of the work (or of creation if the work is unpublished); and • The name of the copyright owner, an abbreviation by which the name can be recognized, or a generally known alternative designation. A notice should be affixed to copies or phonorecords of a work in a way that gives reasonable notice of the claim of copyright. Using a copyright notice is optional for unpublished works, non-U.S. works, and works published on or after March 1, 1989. However, notice conveys the following benefits: • It puts potential users on notice that copyright is claimed in the work. • For published works, notice may prevent a defendant from attempting to limit liability for damages or injunctive relief based on an “innocent infringement” defense. • It identifies the copyright owner at the time of first publication for parties seeking permission to use the work. • It identifies the year of first publication, which can be used to determine the term of copyright for anonymous or pseudonymous works or works made for hire. • It may prevent the work from becoming an “orphan” by identifying the copyright owner or specifying the term of copyright. Orphan works are original works of authorship for which prospective users cannot identify or locate copyright owners to request permission. Notice was required for works published in the United States before March 1, 1989. Works published without notice before that date may have entered the public domain in this country. For more information, see Copyright Notice (Circular 3

Do not use any knowledge other than the provided document. After answering the question, quote in parentheses the section of the document that you referred to for your answer. Use capital letters for this quotation.

Give me a list of all of the EV chargers found in this document.

**Electic Vehicle Charging Solutions for Home and Travel** PORTABLE PORTABLE EV CHARGER PPC16A35 • European standard plug SCHUKO • Length of cable: 5 meter (16.5 feet) EV CHARGER TYPE-2 to Schuko Adapter cable 5m lenght POWERED FROM 230V SCHUKO SOCKET - NO LIMITS The 16A portable charger is powered by a standard 230V mains socket (Schuko). Becasue of it, you do not need any special installation to charge the car - it’s simple. In addition, the portable charger is characterized by compact dimensions, which guarantees ease of transport and the possibility of using it anywhere. The charger will easily fit into any trunk. • Rated input voltage: 85-265V AC • Rated output voltage: 85-265V AC • Rated current: default -16A • Rated power: Up to 3700W (3,7kW) • Insulation resistance of cable: >1000MΩ (DC500V) • Contact resistance: 0.5mΩ MAX • Housing fire rating: UL94V-0 • Wiring harness size: 3 x 2.5mm2 + 2 x 0.5mm2 • Cable wrap shell design • With Leakage protection • With over-voltage or low-voltage protection • With over load protection (Self-checking recovery) • With lightning protection • With over-heat protection 16A TYPE 2 3,7kW INSURANCE! 200 000 eur.PLUG & PLAY - EASY OPERATIONS Plug & Play functionality is one of the many advantages of the charger - vehicle charging starts automatically after connecting the charger to the car. To finish charging, simply disconnect the charging plug from the car. 2IN1 PORTABLE EV QUICK CHARGER SCHUKO TO TYPE 2 ADAPTER is a great solution for charging your car, motorcycle or electric scooter. The cable has a Schuko socket on one side and a Type 2 plug on the other. With it, any electric car with a Schuko plug can be charged using a charger with a Type 2 socket. This is especially useful when we use a Schuko cable in an electric car and we want to charge it at a private or public Type 2 charging station. Cable length is 30cm. CEE to Schuko Adapter INCLUDED INSURANCE! 200 000 eur. TYPE 2 11kW PPC32AT 16A cable 5m lenght PORTABLE EV QUICK CHARGER • European standard plug (CEE red) • 3 Phases (trójfazowy) • Length of cable: 5 meter (16.5 feet) • Rated input voltage: 85-400V AC • Rated output voltage: 85-400V AC • Rated current: default - 8A, 10A, 13A, 16A • Rated power: up to 11KW quick charging • Insulation resistance of cable: >1000MΩ (DC500V) • Contact resistance: 0.5mΩ MAX • Housing fire rating: UL94V-0 • Wiring harness size: 3 x 2.5mm2 + 2 x 0.5mm2 • With LED display to show temperature, charging time, and real current • With leakage protection • With over-voltage or low-voltage protection • With over load protection (Self-checking recovery) • With lightning protection • With over-heat protectionPORTABLE EV QUICK CHARGER • European standard plug (CEE red) • 3 phases (trójfazowy) • Length of cable: 5 meter (16.5 feet) • Rated input voltage: 85-400V AC • Rated output voltage: 85-400V AC • Rated current: 8A, 10A, 13A, 16A, 20A, 24A, 32A • Rated power: Up to 22KW quick charging • Insulation resistance of cable: >1000MΩ (DC500V) • Contact resistance: 0.5mΩ MAX • Housing fire rating: UL94V-0 • Wiring harness size: 3 x 2.5mm2 + 2 x 0.5mm2 • With LED display to show temperature, charging time, and real current • With leakage protection • With over-voltage or low-voltage protection • With over load protection (Self-checking recovery) • With lightning protection • With over-heat protection PLUG & PLAY - EASY OPERATIONS Plug & Play functionality is one of the many advantages of the charger - vehicle charging starts automatically after connecting the charger to the car. To finish charging, simply disconnect the charging plug from the car. 2IN1 PORTABLE EV QUICK CHARGER SCHUKO TO TYPE 2 ADAPTER is a great solution for charging your car, motorcycle or electric scooter. The cable has a Schuko socket on one side and a Type 2 plug on the other. With it, any electric car with a Schuko plug can be charged using a charger with a Type 2 socket. This is especially useful when we use a Schuko cable in an electric car and we want to charge it at a private or public Type 2 charging station. Cable length is 30 cm. CEE to Schuko Adapter INCLUDED INSURANCE! 200 000 eur. TYPE 2 22kW PPC32AT22 32A cable 5m lenghtUNIVERSAL MOBILE Adapter PC050EV INCLUDED CHARGING STATION Traveler Set Charger connectors: Type 2 Charging mode: Mode 2 Charging current: 32 A Charging capacity: 16 kW Nominal voltage: 400 V, 230 V Cable length: 7.00 m IP rating: IP66 Colour: Black Width: 300 mm Height: 66 mm Depth: 86 mm Weight: 7.5 kg Type A: PG connector, UK connector, CEE connector (5-pin, 32 A), CEE connector (3-pin, 32 A), CEE connector (5-pin, 16 A), CEE connector (3-pin, 16 A) Type B: Type 2 No. of phases: 3-phase Nominal current: 16 A, 32 A Sustainability / eco-friendliness: Plastic free packaging Product type Mobile electric car charging station One charger for all possible outlet. All adapters for every conceivable 32A TYPE 2 16kW INSURANCE! European outlet. 200 000 eur.TYPE 2 TYPE 2 22kW 11kW 32A 16A INSURANCE! 200 000 eur. ELECTRIC VEHICLE CHARGING CABLE CHARGING CABLE TYPE 2-TYPE 2 • Phase: 3 phase • Rated current: 32A or 16A • Rated voltage: 480V • Max power: 22kW or 11kW • Cable spec 22kW: 5x6mm2 + 2x0,5 mm2 • Outer diameter 22kW: 16,5mm (+/- 0,4mm) • Cable spec 11kW: 5x2,5 mm2 + 2x0,5 mm2 • Outer diameter 11kW: 13,5mm (+/- 0,4mm) • Length: 5m, optional 4m • Protection rank: IP54 (when plugged) • Plug insertion force: >45N <80N • Operating temperature: -35OC to 50OC CHARGING WITH „NO-LIMITS” We can safely take the PLATINET Type 2 cable for charging electric cars on a trip throughout Europe. Becasue of the universal Type 2 plugs, they are compatible with all stations that support this type of charging. It allows you to charge electric cars with a power of up to 11kW or 22kW. It is terminated with Type 2 connectors, which are operated at charging stations all over Europe. Its low weight makes it easy to use, and the cable itself will not take up much space in the trunk of our vehicle. PEVC22KW5B PEVC11KW5B cable 5m (4m optional) lenghtELECTRIC VEHICLE PEVC22KW5B-B CHARGING CABLE lenght cable 5m (4m optional) CHARGING WITH „NO-LIMITS” We can safely take the PLATINET Type 2 cable for charging electric cars on a trip throughout Europe. Becasue of the universal Type 2 plugs, they are compatible with all stations that support this type of charging. It allows you to charge electric cars with a power of up to 11kW or 22kW. It is terminated with Type 2 connectors, which are operated at charging stations all over Europe. Its low weight makes it easy to use, and the cable itself will not take up much space in the trunk of our vehicle. CHARGING CABLE TYPE 2-TYPE 2 • Phase: 3 phase • Rated current: 32A or 16A • Rated voltage: 480V • Max power: 22kW or 11kW • Cable spec 22kW: 5x6mm2 + 2x0,5 mm2 • Outer diameter 22kW: 16,5mm (+/- 0,4mm) • Cable spec 11kW: 5x2,5 mm2 + 2x0,5 mm2 • Outer diameter 11kW: 13,5mm (+/- 0,4mm) • Length: 5m, optional 4m • Protection rank: IP54 (when plugged) • Plug insertion force: >45N <80N TYPE 2 32A 22kW PEVC11KW5B-B TYPE 2 16A 11kW INSURANCE! • Operating temperature: -35OC to 50OC 200 000 eur.EV TYPE 2 PEVA30 TO SCHUKO ADAPTER lenght 30cm PLATINET SCHUKO TO CEE ADAPTER is a great solution for charging your car, motorcycle or electric scooter. The cable has a CEE socket on one side and a Schuko plug on the other. Cable length is 30cm. TYPE 2 I

[Task Information] ================== Do not use any knowledge other than the provided document. After answering the question, quote in parentheses the section of the document that you referred to for your answer. Use capital letters for this quotation. ================ [Question] ================== Give me a list of all of the EV chargers found in this document. ================ [Passage] ================== **Electic Vehicle Charging Solutions for Home and Travel** PORTABLE PORTABLE EV CHARGER PPC16A35 • European standard plug SCHUKO • Length of cable: 5 meter (16.5 feet) EV CHARGER TYPE-2 to Schuko Adapter cable 5m lenght POWERED FROM 230V SCHUKO SOCKET - NO LIMITS The 16A portable charger is powered by a standard 230V mains socket (Schuko). Becasue of it, you do not need any special installation to charge the car - it’s simple. In addition, the portable charger is characterized by compact dimensions, which guarantees ease of transport and the possibility of using it anywhere. The charger will easily fit into any trunk. • Rated input voltage: 85-265V AC • Rated output voltage: 85-265V AC • Rated current: default -16A • Rated power: Up to 3700W (3,7kW) • Insulation resistance of cable: >1000MΩ (DC500V) • Contact resistance: 0.5mΩ MAX • Housing fire rating: UL94V-0 • Wiring harness size: 3 x 2.5mm2 + 2 x 0.5mm2 • Cable wrap shell design • With Leakage protection • With over-voltage or low-voltage protection • With over load protection (Self-checking recovery) • With lightning protection • With over-heat protection 16A TYPE 2 3,7kW INSURANCE! 200 000 eur.PLUG & PLAY - EASY OPERATIONS Plug & Play functionality is one of the many advantages of the charger - vehicle charging starts automatically after connecting the charger to the car. To finish charging, simply disconnect the charging plug from the car. 2IN1 PORTABLE EV QUICK CHARGER SCHUKO TO TYPE 2 ADAPTER is a great solution for charging your car, motorcycle or electric scooter. The cable has a Schuko socket on one side and a Type 2 plug on the other. With it, any electric car with a Schuko plug can be charged using a charger with a Type 2 socket. This is especially useful when we use a Schuko cable in an electric car and we want to charge it at a private or public Type 2 charging station. Cable length is 30cm. CEE to Schuko Adapter INCLUDED INSURANCE! 200 000 eur. TYPE 2 11kW PPC32AT 16A cable 5m lenght PORTABLE EV QUICK CHARGER • European standard plug (CEE red) • 3 Phases (trójfazowy) • Length of cable: 5 meter (16.5 feet) • Rated input voltage: 85-400V AC • Rated output voltage: 85-400V AC • Rated current: default - 8A, 10A, 13A, 16A • Rated power: up to 11KW quick charging • Insulation resistance of cable: >1000MΩ (DC500V) • Contact resistance: 0.5mΩ MAX • Housing fire rating: UL94V-0 • Wiring harness size: 3 x 2.5mm2 + 2 x 0.5mm2 • With LED display to show temperature, charging time, and real current • With leakage protection • With over-voltage or low-voltage protection • With over load protection (Self-checking recovery) • With lightning protection • With over-heat protectionPORTABLE EV QUICK CHARGER • European standard plug (CEE red) • 3 phases (trójfazowy) • Length of cable: 5 meter (16.5 feet) • Rated input voltage: 85-400V AC • Rated output voltage: 85-400V AC • Rated current: 8A, 10A, 13A, 16A, 20A, 24A, 32A • Rated power: Up to 22KW quick charging • Insulation resistance of cable: >1000MΩ (DC500V) • Contact resistance: 0.5mΩ MAX • Housing fire rating: UL94V-0 • Wiring harness size: 3 x 2.5mm2 + 2 x 0.5mm2 • With LED display to show temperature, charging time, and real current • With leakage protection • With over-voltage or low-voltage protection • With over load protection (Self-checking recovery) • With lightning protection • With over-heat protection PLUG & PLAY - EASY OPERATIONS Plug & Play functionality is one of the many advantages of the charger - vehicle charging starts automatically after connecting the charger to the car. To finish charging, simply disconnect the charging plug from the car. 2IN1 PORTABLE EV QUICK CHARGER SCHUKO TO TYPE 2 ADAPTER is a great solution for charging your car, motorcycle or electric scooter. The cable has a Schuko socket on one side and a Type 2 plug on the other. With it, any electric car with a Schuko plug can be charged using a charger with a Type 2 socket. This is especially useful when we use a Schuko cable in an electric car and we want to charge it at a private or public Type 2 charging station. Cable length is 30 cm. CEE to Schuko Adapter INCLUDED INSURANCE! 200 000 eur. TYPE 2 22kW PPC32AT22 32A cable 5m lenghtUNIVERSAL MOBILE Adapter PC050EV INCLUDED CHARGING STATION Traveler Set Charger connectors: Type 2 Charging mode: Mode 2 Charging current: 32 A Charging capacity: 16 kW Nominal voltage: 400 V, 230 V Cable length: 7.00 m IP rating: IP66 Colour: Black Width: 300 mm Height: 66 mm Depth: 86 mm Weight: 7.5 kg Type A: PG connector, UK connector, CEE connector (5-pin, 32 A), CEE connector (3-pin, 32 A), CEE connector (5-pin, 16 A), CEE connector (3-pin, 16 A) Type B: Type 2 No. of phases: 3-phase Nominal current: 16 A, 32 A Sustainability / eco-friendliness: Plastic free packaging Product type Mobile electric car charging station One charger for all possible outlet. All adapters for every conceivable 32A TYPE 2 16kW INSURANCE! European outlet. 200 000 eur.TYPE 2 TYPE 2 22kW 11kW 32A 16A INSURANCE! 200 000 eur. ELECTRIC VEHICLE CHARGING CABLE CHARGING CABLE TYPE 2-TYPE 2 • Phase: 3 phase • Rated current: 32A or 16A • Rated voltage: 480V • Max power: 22kW or 11kW • Cable spec 22kW: 5x6mm2 + 2x0,5 mm2 • Outer diameter 22kW: 16,5mm (+/- 0,4mm) • Cable spec 11kW: 5x2,5 mm2 + 2x0,5 mm2 • Outer diameter 11kW: 13,5mm (+/- 0,4mm) • Length: 5m, optional 4m • Protection rank: IP54 (when plugged) • Plug insertion force: >45N <80N • Operating temperature: -35OC to 50OC CHARGING WITH „NO-LIMITS” We can safely take the PLATINET Type 2 cable for charging electric cars on a trip throughout Europe. Becasue of the universal Type 2 plugs, they are compatible with all stations that support this type of charging. It allows you to charge electric cars with a power of up to 11kW or 22kW. It is terminated with Type 2 connectors, which are operated at charging stations all over Europe. Its low weight makes it easy to use, and the cable itself will not take up much space in the trunk of our vehicle. PEVC22KW5B PEVC11KW5B cable 5m (4m optional) lenghtELECTRIC VEHICLE PEVC22KW5B-B CHARGING CABLE lenght cable 5m (4m optional) CHARGING WITH „NO-LIMITS” We can safely take the PLATINET Type 2 cable for charging electric cars on a trip throughout Europe. Becasue of the universal Type 2 plugs, they are compatible with all stations that support this type of charging. It allows you to charge electric cars with a power of up to 11kW or 22kW. It is terminated with Type 2 connectors, which are operated at charging stations all over Europe. Its low weight makes it easy to use, and the cable itself will not take up much space in the trunk of our vehicle. CHARGING CABLE TYPE 2-TYPE 2 • Phase: 3 phase • Rated current: 32A or 16A • Rated voltage: 480V • Max power: 22kW or 11kW • Cable spec 22kW: 5x6mm2 + 2x0,5 mm2 • Outer diameter 22kW: 16,5mm (+/- 0,4mm) • Cable spec 11kW: 5x2,5 mm2 + 2x0,5 mm2 • Outer diameter 11kW: 13,5mm (+/- 0,4mm) • Length: 5m, optional 4m • Protection rank: IP54 (when plugged) • Plug insertion force: >45N <80N TYPE 2 32A 22kW PEVC11KW5B-B TYPE 2 16A 11kW INSURANCE! • Operating temperature: -35OC to 50OC 200 000 eur.EV TYPE 2 PEVA30 TO SCHUKO ADAPTER lenght 30cm PLATINET SCHUKO TO CEE ADAPTER is a great solution for charging your car, motorcycle or electric scooter. The cable has a CEE socket on one side and a Schuko plug on the other. Cable length is 30cm. TYPE 2 I

This task requires you to answer questions based solely on the information provided in the prompt. You are not allowed to use any external resources or prior knowledge.

What is the SDWA?

Detections of contaminants in public water supplies in numerous states have raised questions about drinking water quality and have increased congressional interest in the Environmental Protection Agency’s (EPA’s) efforts to regulate contaminants under the Safe Drinking Water Act (SDWA). Congress is particularly interested in the EPA’s process for evaluating new contaminants for potential regulation. Detections of already-regulated contaminants, such as lead, have also raised concerns about the effectiveness of certain existing regulations. SDWA is the key federal law that authorizes EPA to promulgate regulations to control contaminants in public water supplies. Since its enactment in 1974, EPA has issued drinking water regulations for 100 contaminants. Congress has twice revised the act’s process for evaluating contaminants and developing drinking water regulations (in 1986 and 1996). In 1986, Congress directed EPA to develop regulations for 83 contaminants within 3 years, and adopt regulations, every 3 years, for at least 25 new contaminants. In 1996, when this regulatory schedule proved unworkable, Congress amended SDWA to establish a riskbased process that prioritizes contaminants for regulation based on health effects and occurrence. Under SDWA, EPA follows a multistep process to evaluate and prioritize contaminants for regulation. This process includes identifying contaminants of potential concern, assessing health risks, collecting national occurrence data (and developing reliable and field-tested analytical methods necessary to do so), and making determinations as to whether a contaminant warrants regulation. Since 1996, EPA has considered over 7,500 contaminants for potential regulation, revised existing regulations, and established new regulations and standards for several contaminants. When EPA determines that a contaminant warrants regulation, SDWA directs EPA to propose a “national primary drinking water regulation” and request public comment within 24 months. Within 18 months of the proposal, EPA is required to promulgate a final rule. EPA is required to establish a nonenforceable maximum contaminant level goal (MCLG) at a level at which no known or anticipated adverse health effects occur and allowing for an adequate margin of safety. Drinking water regulations generally specify a maximum contaminant level (MCL)—an enforceable limit for a contaminant in public water supplies. SDWA requires EPA to set the MCL as close to the MCLG as “feasible,” taking treatment efficacy and costs into consideration. Concurrent with proposing a regulation, SDWA requires EPA to publish a “health risk reduction and cost analysis” for each contaminant covered by the proposed regulation and make a determination whether or not the benefits of regulation outweigh the compliance costs. EPA’s regulations generally take effect three years after promulgation, though the agency may allow up to two additional years, under certain conditions. For each drinking water regulation, SDWA requires EPA to identify a list of best available technologies, treatment techniques, and other means that EPA finds feasible for meeting the MCL. In addition, EPA is required to identify treatment technologies that achieve the MCL and are affordable for small systems. Each regulation also establishes associated monitoring and reporting requirements. SDWA requires EPA to review—and, if necessary, revise— each existing national primary drinking water regulation every six years. SDWA also requires that any revisions to drinking water regulations maintain or provide greater health protection. Under the current SDWA statutory framework, evaluating and developing regulations for contaminants requires data, including data from peer-reviewed scientific studies on potential health effects and nationally representative occurrence data. For some contaminants, the availability or development of (1) data, (2) analytical methods to detect contaminants in drinking water, and (3) treatment technologies pose technical and resource challenges. Congressional attention has centered on EPA’s implementation of SDWA regulatory development provisions. Some stakeholders also have raised concerns about regulatory costs for communities. In recent Congresses, some Members have raised concerns that the act’s process is lengthy and complicated and does not allow for the timely regulation of contaminants of concern in drinking water. Others have expressed concern that proposals to expedite regulation by removing elements of SDWA regulatory development provisions (e.g., the requirement to use peer-reviewed science or a health-risk-based approach) may result in increased costs to communities without commensurate public health protection. This debate was heightened prior to EPA’s determination to regulate per- and polyfluoroalkyl substances (PFAS) in 2021, yet stakeholders raised similar concerns after EPA’s 2024 finalization of a regulation for six PFAS.

This task requires you to answer questions based solely on the information provided in the prompt. You are not allowed to use any external resources or prior knowledge. What is the SDWA? Detections of contaminants in public water supplies in numerous states have raised questions about drinking water quality and have increased congressional interest in the Environmental Protection Agency’s (EPA’s) efforts to regulate contaminants under the Safe Drinking Water Act (SDWA). Congress is particularly interested in the EPA’s process for evaluating new contaminants for potential regulation. Detections of already-regulated contaminants, such as lead, have also raised concerns about the effectiveness of certain existing regulations. SDWA is the key federal law that authorizes EPA to promulgate regulations to control contaminants in public water supplies. Since its enactment in 1974, EPA has issued drinking water regulations for 100 contaminants. Congress has twice revised the act’s process for evaluating contaminants and developing drinking water regulations (in 1986 and 1996). In 1986, Congress directed EPA to develop regulations for 83 contaminants within 3 years, and adopt regulations, every 3 years, for at least 25 new contaminants. In 1996, when this regulatory schedule proved unworkable, Congress amended SDWA to establish a riskbased process that prioritizes contaminants for regulation based on health effects and occurrence. Under SDWA, EPA follows a multistep process to evaluate and prioritize contaminants for regulation. This process includes identifying contaminants of potential concern, assessing health risks, collecting national occurrence data (and developing reliable and field-tested analytical methods necessary to do so), and making determinations as to whether a contaminant warrants regulation. Since 1996, EPA has considered over 7,500 contaminants for potential regulation, revised existing regulations, and established new regulations and standards for several contaminants. When EPA determines that a contaminant warrants regulation, SDWA directs EPA to propose a “national primary drinking water regulation” and request public comment within 24 months. Within 18 months of the proposal, EPA is required to promulgate a final rule. EPA is required to establish a nonenforceable maximum contaminant level goal (MCLG) at a level at which no known or anticipated adverse health effects occur and allowing for an adequate margin of safety. Drinking water regulations generally specify a maximum contaminant level (MCL)—an enforceable limit for a contaminant in public water supplies. SDWA requires EPA to set the MCL as close to the MCLG as “feasible,” taking treatment efficacy and costs into consideration. Concurrent with proposing a regulation, SDWA requires EPA to publish a “health risk reduction and cost analysis” for each contaminant covered by the proposed regulation and make a determination whether or not the benefits of regulation outweigh the compliance costs. EPA’s regulations generally take effect three years after promulgation, though the agency may allow up to two additional years, under certain conditions. For each drinking water regulation, SDWA requires EPA to identify a list of best available technologies, treatment techniques, and other means that EPA finds feasible for meeting the MCL. In addition, EPA is required to identify treatment technologies that achieve the MCL and are affordable for small systems. Each regulation also establishes associated monitoring and reporting requirements. SDWA requires EPA to review—and, if necessary, revise— each existing national primary drinking water regulation every six years. SDWA also requires that any revisions to drinking water regulations maintain or provide greater health protection. Under the current SDWA statutory framework, evaluating and developing regulations for contaminants requires data, including data from peer-reviewed scientific studies on potential health effects and nationally representative occurrence data. For some contaminants, the availability or development of (1) data, (2) analytical methods to detect contaminants in drinking water, and (3) treatment technologies pose technical and resource challenges. Congressional attention has centered on EPA’s implementation of SDWA regulatory development provisions. Some stakeholders also have raised concerns about regulatory costs for communities. In recent Congresses, some Members have raised concerns that the act’s process is lengthy and complicated and does not allow for the timely regulation of contaminants of concern in drinking water. Others have expressed concern that proposals to expedite regulation by removing elements of SDWA regulatory development provisions (e.g., the requirement to use peer-reviewed science or a health-risk-based approach) may result in increased costs to communities without commensurate public health protection. This debate was heightened prior to EPA’s determination to regulate per- and polyfluoroalkyl substances (PFAS) in 2021, yet stakeholders raised similar concerns after EPA’s 2024 finalization of a regulation for six PFAS.

This task requires you to answer questions based solely on the information provided in the prompt. You are not allowed to use any external resources or prior knowledge. Respond in 100 words or less and you may not use less than five bullet points in your answer. If you cannot answer using the context alone, say "I cannot determine the answer to that due to lack of context"

Why do the types of mergers Congress is stating that Blizzard being acquired through Microsoft presents problems to consumers?

Acquisition of Activision Blizzard Microsoft’s proposed acquisition may be considered both a vertical merger, in which one firm is the supplier and the other is a customer in the supply chain, and a horizontal merger, in which the merging firms are direct competitors, offering similar products or services that are considered substitutes. One concern with vertical mergers is that they may lead to foreclosure, a situation in which a supplier that competes with the merged firm loses access to a potential customer or a buyer that competes with the merged firm is denied access to a supplier. A concern with horizontal mergers is that they may significantly increase the market share of the merged firm, increasing concentration in the market and reducing competition, thereby enabling the remaining firms to raise prices. Microsoft’s proposed acquisition may also raise other concerns that typically have not been raised in merger challenges in recent decades, such as dominance in markets that may develop in the future and labor market monopsony.36 A key question about Microsoft’s proposed acquisition may be the extent to which Microsoft might restrict the availability of Activision Blizzard’s video games to its consoles and its streaming and cloud gaming services. Such a restriction would mean that other companies’ consoles or streaming or cloud gaming services would not be able to offer Activision Blizzard’s games to consumers. Microsoft has stated that if the merger is approved, it would continue to make Call of Duty and other popular Activision games available on other gaming consoles in addition to its Xbox.37 The statement specifies that Activision’s popular content would be “available on competing platforms like Sony’s PlayStation.” It is unclear, however, if this commitment pertains only to Sony’s consoles or also applies to PlayStation Plus,38 Sony’s version of Game Pass. Additionally, it is unclear whether Activision Blizzard’s games would be available on other streaming or cloud gaming services. Microsoft could also limit the availability of other games that are or will be under development. In 2020, after acquiring ZeniMax Media, parent company of the video game developer Bethesda Softworks,39 Microsoft stated that it would honor the exclusivity commitments Bethesda made with Sony for certain games for one year,40 but that future Bethesda games would be made available for “other consoles on a case by case basis.” 41 The game Starfield, officially introduced by Bethesda in 2018,42 is scheduled to be released in November 2022 exclusively on Microsoft’s Xbox Series X and S consoles and Windows PCs; it will not be available on other consoles.43 One potential concern may be how Microsoft’s acquisition might affect competition among digital stores selling video games for PCs, a market in which both Microsoft and Activision Blizzard compete. Following the acquisition, Microsoft could operate both Microsoft Store and Battle.net. This may not have a significant effect on competition, however, because Valve Corp.’s Steam is considered to be the dominant market player among PC digital stores. In a 2021 lawsuit alleging anticompetitive practices by Valve, video game developer Wolfire Games estimated that Valve controlled at least 75% of PC desktop game distribution.44 With respect to subscription or cloud gaming services, Microsoft may be able to increase its market share with the acquisition by offering more content than other providers. In addition to developing its own games, Microsoft has entered partnerships with various developers and publishers. For example, some Game Pass subscribers can access games on Electronic Arts (EA) Play for no additional cost,45 and Fortnite is available for free on Xbox Cloud Gaming without a Game Pass membership, although users must have a Microsoft account.46 If Microsoft allows other subscription or cloud gaming services to distribute Activision Blizzard’s video games, it may charge these providers a fee to do so, meaning potential competitors could face an additional cost that Microsoft would not. Consumers would arguably benefit from having a greater selection of video games offered through Microsoft’s subscription and cloud gaming services. However, if other subscription and cloud gaming service providers are unable to increase their market shares, Microsoft may be able to dominate the market, potentially allowing Microsoft to increase prices in the future. The salience of this concern may reflect opinions on whether antitrust enforcement should consider potential effects on the industry that may affect competition in the future or focus exclusively on consumer welfare. Among video game publishers in the United States, Microsoft and Activision Blizzard are estimated to have the largest market shares.47 IBISWorld reports, however, that competition among publishers and developers is high, even though the success of new entrants, particularly among developers, is fairly low.48 Publishers and developers can face high levels of uncertainty and risk.49 Furthermore, measuring the market share of Microsoft and Activision Blizzard within the United States may not accurately reflect competition in these markets, given that these companies compete at a global level. Some industry analysts list Tencent, which is headquartered in China, as the largest video game publisher worldwide based on revenue;50 Microsoft and Activision Blizzard are listed among the top 10, along with Sony, Nintendo, EA, and Take-Two Interactive.51 Microsoft stated that after its acquisition of Activision Blizzard, it would “become the world’s third-largest gaming company by revenue, behind Tencent and Sony.” 52 Microsoft’s acquisition could reduce the number of potential employers in the video game industry. At an FTC forum, an Activision Blizzard employee raised concern that consolidation in the industry could enable firms to hire employees at lower wages than in a competitive market.58 During its acquisition of ZeniMax, Microsoft reportedly stated that it did not plan on making changes to ZeniMax and that ZeniMax would operate independently following the acquisition.59 One industry analyst viewed the acquisition as a means to support gaming studios under ZeniMax, which had been struggling financially; according to the analyst, without the acquisition, ZeniMax would have likely faced layoffs and released fewer games.60 If Microsoft were to utilize a similar approach with Activision Blizzard, allowing it to essentially operate as a separate entity within Microsoft, the acquisition might not significantly affect the labor market for developers. Furthermore, some employees may have skills that would be easily transferrable to firms outside of the video game industry, which could limit Microsoft’s ability to control wages. Nevertheless, Microsoft’s acquisition would reduce the number of large, established firms in the video game industry, which could provide it with greater negotiating power. Another concern may be that Microsoft’s proposed acquisition could affect ongoing efforts to reach a collective bargaining agreement for Activision Blizzard employees. This concern was raised by an Activision Blizzard employee at an FTC forum and by some Senators in a March 2022 letter to the FTC,61 which cited Microsoft’s dismissal of temporary quality assurance workers two years after they formed a union in 2014.62 However, on June 13, 2022, Microsoft and the Communications Workers of America—the union that has been assisting Activision Blizzard employees—announced that they had entered a labor neutrality agreement enabling workers “to freely and fairly make a choice about union representation,” which would apply beginning 60 days after Microsoft’s acquisition is completed.63 Furthermore, it is unclear whether working conditions would improve if Activision Blizzard were to remain an independent company rather than being acquired by Microsoft. Some antitrust enforcers are reportedly considering some of the concerns discussed in the previous section, including the potential effect of Microsoft’s proposed acquisition on competing gaming subscription services and the market for game developers.64 In response to the March 2022 letter from some Senators asking the FTC to consider whether the transaction might exacerbate anticompetitive conduct in the labor market,65 FTC Chair Lina Khan stated that she shares those Senators’ concerns about monopsony power in labor markets.

Why do the types of mergers Congress is stating that Blizzard being acquired through Microsoft presents problems to consumers? This task requires you to answer questions based solely on the information provided in the prompt. You are not allowed to use any external resources or prior knowledge. Respond in 100 words or less and you may not use less than five bullet points in your answer. If you cannot answer using the context alone, say "I cannot determine the answer to that due to lack of context" Acquisition of Activision Blizzard Microsoft’s proposed acquisition may be considered both a vertical merger, in which one firm is the supplier and the other is a customer in the supply chain, and a horizontal merger, in which the merging firms are direct competitors, offering similar products or services that are considered substitutes. One concern with vertical mergers is that they may lead to foreclosure, a situation in which a supplier that competes with the merged firm loses access to a potential customer or a buyer that competes with the merged firm is denied access to a supplier. A concern with horizontal mergers is that they may significantly increase the market share of the merged firm, increasing concentration in the market and reducing competition, thereby enabling the remaining firms to raise prices. Microsoft’s proposed acquisition may also raise other concerns that typically have not been raised in merger challenges in recent decades, such as dominance in markets that may develop in the future and labor market monopsony.36 A key question about Microsoft’s proposed acquisition may be the extent to which Microsoft might restrict the availability of Activision Blizzard’s video games to its consoles and its streaming and cloud gaming services. Such a restriction would mean that other companies’ consoles or streaming or cloud gaming services would not be able to offer Activision Blizzard’s games to consumers. Microsoft has stated that if the merger is approved, it would continue to make Call of Duty and other popular Activision games available on other gaming consoles in addition to its Xbox.37 The statement specifies that Activision’s popular content would be “available on competing platforms like Sony’s PlayStation.” It is unclear, however, if this commitment pertains only to Sony’s consoles or also applies to PlayStation Plus,38 Sony’s version of Game Pass. Additionally, it is unclear whether Activision Blizzard’s games would be available on other streaming or cloud gaming services. Microsoft could also limit the availability of other games that are or will be under development. In 2020, after acquiring ZeniMax Media, parent company of the video game developer Bethesda Softworks,39 Microsoft stated that it would honor the exclusivity commitments Bethesda made with Sony for certain games for one year,40 but that future Bethesda games would be made available for “other consoles on a case by case basis.” 41 The game Starfield, officially introduced by Bethesda in 2018,42 is scheduled to be released in November 2022 exclusively on Microsoft’s Xbox Series X and S consoles and Windows PCs; it will not be available on other consoles.43 One potential concern may be how Microsoft’s acquisition might affect competition among digital stores selling video games for PCs, a market in which both Microsoft and Activision Blizzard compete. Following the acquisition, Microsoft could operate both Microsoft Store and Battle.net. This may not have a significant effect on competition, however, because Valve Corp.’s Steam is considered to be the dominant market player among PC digital stores. In a 2021 lawsuit alleging anticompetitive practices by Valve, video game developer Wolfire Games estimated that Valve controlled at least 75% of PC desktop game distribution.44 With respect to subscription or cloud gaming services, Microsoft may be able to increase its market share with the acquisition by offering more content than other providers. In addition to developing its own games, Microsoft has entered partnerships with various developers and publishers. For example, some Game Pass subscribers can access games on Electronic Arts (EA) Play for no additional cost,45 and Fortnite is available for free on Xbox Cloud Gaming without a Game Pass membership, although users must have a Microsoft account.46 If Microsoft allows other subscription or cloud gaming services to distribute Activision Blizzard’s video games, it may charge these providers a fee to do so, meaning potential competitors could face an additional cost that Microsoft would not. Consumers would arguably benefit from having a greater selection of video games offered through Microsoft’s subscription and cloud gaming services. However, if other subscription and cloud gaming service providers are unable to increase their market shares, Microsoft may be able to dominate the market, potentially allowing Microsoft to increase prices in the future. The salience of this concern may reflect opinions on whether antitrust enforcement should consider potential effects on the industry that may affect competition in the future or focus exclusively on consumer welfare. Among video game publishers in the United States, Microsoft and Activision Blizzard are estimated to have the largest market shares.47 IBISWorld reports, however, that competition among publishers and developers is high, even though the success of new entrants, particularly among developers, is fairly low.48 Publishers and developers can face high levels of uncertainty and risk.49 Furthermore, measuring the market share of Microsoft and Activision Blizzard within the United States may not accurately reflect competition in these markets, given that these companies compete at a global level. Some industry analysts list Tencent, which is headquartered in China, as the largest video game publisher worldwide based on revenue;50 Microsoft and Activision Blizzard are listed among the top 10, along with Sony, Nintendo, EA, and Take-Two Interactive.51 Microsoft stated that after its acquisition of Activision Blizzard, it would “become the world’s third-largest gaming company by revenue, behind Tencent and Sony.” 52 Microsoft’s acquisition could reduce the number of potential employers in the video game industry. At an FTC forum, an Activision Blizzard employee raised concern that consolidation in the industry could enable firms to hire employees at lower wages than in a competitive market.58 During its acquisition of ZeniMax, Microsoft reportedly stated that it did not plan on making changes to ZeniMax and that ZeniMax would operate independently following the acquisition.59 One industry analyst viewed the acquisition as a means to support gaming studios under ZeniMax, which had been struggling financially; according to the analyst, without the acquisition, ZeniMax would have likely faced layoffs and released fewer games.60 If Microsoft were to utilize a similar approach with Activision Blizzard, allowing it to essentially operate as a separate entity within Microsoft, the acquisition might not significantly affect the labor market for developers. Furthermore, some employees may have skills that would be easily transferrable to firms outside of the video game industry, which could limit Microsoft’s ability to control wages. Nevertheless, Microsoft’s acquisition would reduce the number of large, established firms in the video game industry, which could provide it with greater negotiating power. Another concern may be that Microsoft’s proposed acquisition could affect ongoing efforts to reach a collective bargaining agreement for Activision Blizzard employees. This concern was raised by an Activision Blizzard employee at an FTC forum and by some Senators in a March 2022 letter to the FTC,61 which cited Microsoft’s dismissal of temporary quality assurance workers two years after they formed a union in 2014.62 However, on June 13, 2022, Microsoft and the Communications Workers of America—the union that has been assisting Activision Blizzard employees—announced that they had entered a labor neutrality agreement enabling workers “to freely and fairly make a choice about union representation,” which would apply beginning 60 days after Microsoft’s acquisition is completed.63 Furthermore, it is unclear whether working conditions would improve if Activision Blizzard were to remain an independent company rather than being acquired by Microsoft. Some antitrust enforcers are reportedly considering some of the concerns discussed in the previous section, including the potential effect of Microsoft’s proposed acquisition on competing gaming subscription services and the market for game developers.64 In response to the March 2022 letter from some Senators asking the FTC to consider whether the transaction might exacerbate anticompetitive conduct in the labor market,65 FTC Chair Lina Khan stated that she shares those Senators’ concerns about monopsony power in labor markets.

Refer only to the provided context document when answering the question.

List all the types of bonds only using information from the provided document.

𝐒𝐭𝐨𝐜𝐤𝐬 𝐚𝐧𝐝 𝐁𝐨𝐧𝐝𝐬 𝐂𝐨𝐦𝐩𝐚𝐫𝐢𝐬𝐨𝐧 Large companies and other entities use bonds as a form of debt borrowing or financing. Unlike loans, bonds are more transferrable and divisible by the lenders, allowing for multiple investors, which is appropriate when financing needs are very substantial. Bearing similarities to the concept of a first mortgage and a second mortgage, there are senior bonds and subordinated bonds; the senior bonds take precedence over the subordinated bonds in terms of payment priority, and therefore are safer for the lender or investor. Equity, on the other hand, represents a share of ownership in a for-profit corporation. It is what is “left over” from revenue brought in after all expenses (operating expenses, taxes, interest) have been paid. Because equity holders are entitled to what is “left over,” this means they are the investor class exposed to the greatest risk, but are also entitled to the greatest reward. A corporation’s capital structure is typically comprised of one or more forms of debt and one or more forms of equity. According to the chart below, there is an order of precedence governing how money flows in an entity from one class of investors to another. Because debt or bond holders have a senior claim relative to equity holders, business profits first go towards senior debt payments, then to any subordinate class of debt, and then to any preferred class of equity. From there, all remaining profits flow to common equity as a return on investment to be distributed to the owners of common equity. Pending the direction and approval of the company’s board of directors, this distribution can come in the form of a dividend (or stock buyback), reinvested into the company, or most likely a combination of both. If business prospects are extremely good, a common equity shareholder may receive a theoretically uncapped return on their investment. Over the long run, the return on equity of successful and stable corporations exceeds the cost of debt sufficiently enough to compensate investors for the additional risk they are taking. The source of the additional risk is the priority of payments when business conditions are weaker. If there is an economic cycle of weaker revenues, a business might find itself barely able to service its debt financing. In this case, it is unlikely any residual profits will be available to common shareholders for distribution; these circumstances may last for years and many require the business to resort to costly compromises to ensure its debt payments are met. Meanwhile, the senior debt holders can take comfort in the fact the return on their investment is of highest priority and will only be compromised as a last resort. This creates what can be referred to as a more open system of outcomes for stocks and a more closed system of outcomes for bonds; this feature will be expanded upon in greater detail later. These nuances in the capital structure may seem like semantics to some, but as was stated in the introduction, it is an essential component of developing a true understanding of investment options and has great implications on risk and return characteristics. Stock and Bond Investment Opportunities In terms of the number of different investments investors are able to choose from, there are overwhelmingly more bond opportunities than stock opportunities. This may come as a surprise to some as market media attention is overwhelmingly slanted towards stock investing instead of bond investing. Investment products are: • Not a Deposit • Not FDIC Insured • Not Insured by any Federal Government Agency • Not Guaranteed by the Bank • May Go Down in Value In fact, there are 68 times more bond issuances than there are publicly owned stocks. If a person only includes the stocks actively traded on an exchange, there would be 277 times more bond issuances. Yet in terms of the amount of capital invested in each market, there is only 54% more invested in bonds than there is invested in equities. Similar to how the vast amount of market media attention is fixated on the relatively few amount of actively traded stocks, the amount of investment dollars chasing those actively traded stocks is disproportionately large compared to the amount of capital invested in the vast universe of bonds. Within the overemphasis on stocks, there is yet more of a disproportionate emphasis placed on the largest companies; of the aggregate investment in all of the 15,000 publicly traded corporations, 70% of that capital is concentrated in the 500 largest corporations. Put another way, 70% of the money is invested in 3% of the companies; these are the companies receiving the lion’s share of market media attention! In investing, when all of the attention and capital is placed in one area, it is unlikely there are undiscovered opportunities in that area. In fact, numerous studies have shown there is no outperformance potential when investing in the largest U.S. corporations. However, studies have consistently indicated outperformance potential is available investing in small U.S. corporations, various bond sectors, and in certain international investments. Different Types of Stocks Stock market opportunities are often segmented different ways. The three most prominent forms of categorization are market capitalization size, value or growth, and industry classification. The capitalization size of a company is measured by the market value of all outstanding shares of a company’s equity. Companies’ market capitalization is categorized between large cap, medium cap, and small cap. Companies are considered to be large cap when their market capitalization exceeds $10 billion. Companies between $2 billion and $10 billion market cap are considered mid cap companies. Those companies with less than $2 billion market cap are considered small cap companies. The next series of categorization is between value and growth and is often determined by the price of a company’s equity in relation to its earnings, its future earnings prospects, and the amount of profits the corporations retain versus what is returned to shareholders. All else unchanged, the lower the company’s price relative to earnings (measured by the Price to Earnings (P/E) ratio, or other relative value measurements) the more likely it is to be classified as a value company instead of a growth company; Investment products are: • Not a Deposit • Not FDIC Insured • Not Insured by any Federal Government Agency • Not Guaranteed by the Bank • May Go Down in Value value companies tend to have a low stock price due to unfavorable growth or future earnings prospects. Growth companies tend to have very favorable earnings growth forecasts causing their equity prices to be much higher relative to the company’s current earnings. When categorizing equity mutual funds or ETFs, the Equity Style Box is a conventional way to categorize the predominant types of companies a fund is primarily invested in. The Equity Style a fund pursues may not provide an investor the capability to predict future returns, but it helps to understand the types of companies a fund is invested in and to compare the actual investment activities to the fund’s mandated objectives. The final categorization of stocks is the industry classifications; these are subsections of the equity investment market and are often referred to as equity subsectors. The predominant subsectors are: energy, materials, industrials, consumer goods (basic staples), consumer discretionary, health care, utilities, financials, and technology. This series of classifications is especially useful because an industry’s trends, opportunities, and risks bear a heavy influence on the future prospects of the earnings and stock price of companies within that industry. In fact, a key focal point in corporate investment analysis is to perform an industry analysis. As an industry is beneficially or negatively exposed to an economic cycle, the corresponding beneficial or negative implications are likely to be shared across the vast majority of companies in the industry. By categorizing between equity subsectors, an investor may be better able to develop informed expectations of how their equity portfolio will perform in a given economic cycle. Different Types of Bonds Three general categorizations of bonds are issuer type, maturity length, and credit strength. When discussing stocks, the discussion always pertained to shares of corporations. For-profit corporations are only one of many kinds of bond issuers. The overarching categorizations of bond issuers are: U.S. Treasury and other federal agencies, mortgage- related bonds, corporate bonds, asset-backed bonds, and municipal bonds. Within mortgage-related, asset- backed, and municipal bonds, there is a multitude of meaningfully different issuer types. For example: in municipal bonds, there are: cities, states, counties, toll roads, school districts, business and residential real estate developments, event centers, hospitals, prisons, sewer systems, tobacco bonds, etc. The type of issuer and its repayment source carry strong implications on a bond’s credit strength, its perceived risk, and ultimately the return opportunities for investors. The maturity length of a bond and whether it can be prepaid in advance of the maturity date has important implications on the long term returns on bond investing. All else unchanged, a bond with a longer maturity typically has a higher return and is considered to be a higher risk.2 Basic Bond Valuation and Maturity Trade-offs If a person owns a $100 bond that earns 5% return each year for 5 years in a world where the market expects 5% return, the market value on the bond would be $100. However, if the market instead expected a 4% return, what would the 2However, in the context of a portfolio of stocks and bonds, having longer maturity bonds while having greater individual risk can actually lower portfolio risk due to their historic negative correlation to stocks. market value be? In that case, the bond owner would benefit by an extra 1% per year over 5 years equating to a 5% aggregate benefit; ignoring compounding and preciseness, the market value on that bond would be 5% higher, or $105. For a 10 year bond instead of a 5 year bond, the differences in interest rates would have twice the magnitude of impact.

<context> ================== 𝐒𝐭𝐨𝐜𝐤𝐬 𝐚𝐧𝐝 𝐁𝐨𝐧𝐝𝐬 𝐂𝐨𝐦𝐩𝐚𝐫𝐢𝐬𝐨𝐧 Large companies and other entities use bonds as a form of debt borrowing or financing. Unlike loans, bonds are more transferrable and divisible by the lenders, allowing for multiple investors, which is appropriate when financing needs are very substantial. Bearing similarities to the concept of a first mortgage and a second mortgage, there are senior bonds and subordinated bonds; the senior bonds take precedence over the subordinated bonds in terms of payment priority, and therefore are safer for the lender or investor. Equity, on the other hand, represents a share of ownership in a for-profit corporation. It is what is “left over” from revenue brought in after all expenses (operating expenses, taxes, interest) have been paid. Because equity holders are entitled to what is “left over,” this means they are the investor class exposed to the greatest risk, but are also entitled to the greatest reward. A corporation’s capital structure is typically comprised of one or more forms of debt and one or more forms of equity. According to the chart below, there is an order of precedence governing how money flows in an entity from one class of investors to another. Because debt or bond holders have a senior claim relative to equity holders, business profits first go towards senior debt payments, then to any subordinate class of debt, and then to any preferred class of equity. From there, all remaining profits flow to common equity as a return on investment to be distributed to the owners of common equity. Pending the direction and approval of the company’s board of directors, this distribution can come in the form of a dividend (or stock buyback), reinvested into the company, or most likely a combination of both. If business prospects are extremely good, a common equity shareholder may receive a theoretically uncapped return on their investment. Over the long run, the return on equity of successful and stable corporations exceeds the cost of debt sufficiently enough to compensate investors for the additional risk they are taking. The source of the additional risk is the priority of payments when business conditions are weaker. If there is an economic cycle of weaker revenues, a business might find itself barely able to service its debt financing. In this case, it is unlikely any residual profits will be available to common shareholders for distribution; these circumstances may last for years and many require the business to resort to costly compromises to ensure its debt payments are met. Meanwhile, the senior debt holders can take comfort in the fact the return on their investment is of highest priority and will only be compromised as a last resort. This creates what can be referred to as a more open system of outcomes for stocks and a more closed system of outcomes for bonds; this feature will be expanded upon in greater detail later. These nuances in the capital structure may seem like semantics to some, but as was stated in the introduction, it is an essential component of developing a true understanding of investment options and has great implications on risk and return characteristics. Stock and Bond Investment Opportunities In terms of the number of different investments investors are able to choose from, there are overwhelmingly more bond opportunities than stock opportunities. This may come as a surprise to some as market media attention is overwhelmingly slanted towards stock investing instead of bond investing. Investment products are: • Not a Deposit • Not FDIC Insured • Not Insured by any Federal Government Agency • Not Guaranteed by the Bank • May Go Down in Value In fact, there are 68 times more bond issuances than there are publicly owned stocks. If a person only includes the stocks actively traded on an exchange, there would be 277 times more bond issuances. Yet in terms of the amount of capital invested in each market, there is only 54% more invested in bonds than there is invested in equities. Similar to how the vast amount of market media attention is fixated on the relatively few amount of actively traded stocks, the amount of investment dollars chasing those actively traded stocks is disproportionately large compared to the amount of capital invested in the vast universe of bonds. Within the overemphasis on stocks, there is yet more of a disproportionate emphasis placed on the largest companies; of the aggregate investment in all of the 15,000 publicly traded corporations, 70% of that capital is concentrated in the 500 largest corporations. Put another way, 70% of the money is invested in 3% of the companies; these are the companies receiving the lion’s share of market media attention! In investing, when all of the attention and capital is placed in one area, it is unlikely there are undiscovered opportunities in that area. In fact, numerous studies have shown there is no outperformance potential when investing in the largest U.S. corporations. However, studies have consistently indicated outperformance potential is available investing in small U.S. corporations, various bond sectors, and in certain international investments. Different Types of Stocks Stock market opportunities are often segmented different ways. The three most prominent forms of categorization are market capitalization size, value or growth, and industry classification. The capitalization size of a company is measured by the market value of all outstanding shares of a company’s equity. Companies’ market capitalization is categorized between large cap, medium cap, and small cap. Companies are considered to be large cap when their market capitalization exceeds $10 billion. Companies between $2 billion and $10 billion market cap are considered mid cap companies. Those companies with less than $2 billion market cap are considered small cap companies. The next series of categorization is between value and growth and is often determined by the price of a company’s equity in relation to its earnings, its future earnings prospects, and the amount of profits the corporations retain versus what is returned to shareholders. All else unchanged, the lower the company’s price relative to earnings (measured by the Price to Earnings (P/E) ratio, or other relative value measurements) the more likely it is to be classified as a value company instead of a growth company; Investment products are: • Not a Deposit • Not FDIC Insured • Not Insured by any Federal Government Agency • Not Guaranteed by the Bank • May Go Down in Value value companies tend to have a low stock price due to unfavorable growth or future earnings prospects. Growth companies tend to have very favorable earnings growth forecasts causing their equity prices to be much higher relative to the company’s current earnings. When categorizing equity mutual funds or ETFs, the Equity Style Box is a conventional way to categorize the predominant types of companies a fund is primarily invested in. The Equity Style a fund pursues may not provide an investor the capability to predict future returns, but it helps to understand the types of companies a fund is invested in and to compare the actual investment activities to the fund’s mandated objectives. The final categorization of stocks is the industry classifications; these are subsections of the equity investment market and are often referred to as equity subsectors. The predominant subsectors are: energy, materials, industrials, consumer goods (basic staples), consumer discretionary, health care, utilities, financials, and technology. This series of classifications is especially useful because an industry’s trends, opportunities, and risks bear a heavy influence on the future prospects of the earnings and stock price of companies within that industry. In fact, a key focal point in corporate investment analysis is to perform an industry analysis. As an industry is beneficially or negatively exposed to an economic cycle, the corresponding beneficial or negative implications are likely to be shared across the vast majority of companies in the industry. By categorizing between equity subsectors, an investor may be better able to develop informed expectations of how their equity portfolio will perform in a given economic cycle. Different Types of Bonds Three general categorizations of bonds are issuer type, maturity length, and credit strength. When discussing stocks, the discussion always pertained to shares of corporations. For-profit corporations are only one of many kinds of bond issuers. The overarching categorizations of bond issuers are: U.S. Treasury and other federal agencies, mortgage- related bonds, corporate bonds, asset-backed bonds, and municipal bonds. Within mortgage-related, asset- backed, and municipal bonds, there is a multitude of meaningfully different issuer types. For example: in municipal bonds, there are: cities, states, counties, toll roads, school districts, business and residential real estate developments, event centers, hospitals, prisons, sewer systems, tobacco bonds, etc. The type of issuer and its repayment source carry strong implications on a bond’s credit strength, its perceived risk, and ultimately the return opportunities for investors. The maturity length of a bond and whether it can be prepaid in advance of the maturity date has important implications on the long term returns on bond investing. All else unchanged, a bond with a longer maturity typically has a higher return and is considered to be a higher risk.2 Basic Bond Valuation and Maturity Trade-offs If a person owns a $100 bond that earns 5% return each year for 5 years in a world where the market expects 5% return, the market value on the bond would be $100. However, if the market instead expected a 4% return, what would the 2However, in the context of a portfolio of stocks and bonds, having longer maturity bonds while having greater individual risk can actually lower portfolio risk due to their historic negative correlation to stocks. market value be? In that case, the bond owner would benefit by an extra 1% per year over 5 years equating to a 5% aggregate benefit; ignoring compounding and preciseness, the market value on that bond would be 5% higher, or $105. For a 10 year bond instead of a 5 year bond, the differences in interest rates would have twice the magnitude of impact. <question> ================== List all the types of bonds only using information from the provided document. <instruction> ================== Refer only to the provided context document when answering the question.

The response should be accurate and concise, with little added conversational elements or tone. If you cannot provide the answer to the request based on the context given, make sure to simply state, "The information is not available at this time."

When evaluating legacy systems, how do we determine whether to replace or maintain these legacy systems?

Home > IT applications, infrastructure and operations FEATURE ~ 20F3 4 P Partof: The CIO's guide to legacy systems Replacing vs. maintaining legacy systems Understanding issues such as which systems hinder organizational performance can help IT leaders decide which legacy systems to replace and which to maintain. By Mary K. Pratt Published: 05 Jul 2023 Few CIOs escape the complexity of deciding whether to maintain legacy systems or replace them altogether. The right choice, as with most things in life, is: It depends. IT leaders might want to replace a legacy_system because of outdated hardware, increased security risks or a desire to enable a digital transformation initiative. But replacing existing systems isn't always in the company's best interest. Legacy systems can remain in place if the existing system is reliable. vclo” Q Prioritize a strategic assessment One alternative to completely replacing or maintaining legacy systems is to modernize them. Modernized systems might be more cost-effective, while increasing efficiency and improving existing processes at the same time. Michael Bradshaw is currently working through a multiyear plan to modernize the technology at Kyndryl, a New York-based IT services company. After about two years of planning and execution, the goal is to complete the big moves by November, he said. A strategic assessment of the company's existing systems and applications was the first step in the process. His modernization plan calls for the digitalization of the company's entire business chain, Bradshaw said. Previously, about 1,800 applications supported that chain, but the number should drop to 360 by year's end and eventually down to 300. His IT team partnered with the business to develop a target, as well as a roadmap on how to get there, he said. 20f34 P + The goal of this strategy is to streamline the modernization efforts. Up Next The strategic assessment enabled §Tdasisienliyashaylagaeysysiams laimmeripbiigraationmodriizgtion and which could wait, systems Bradshaw said. Slyingwit i-and-rue logacysysems can el ke Undertanding sses such s which ystr e safot vt Byl as 1o wad changes al a izzying organizatonal perormance can ol " T loax Afocus on competitive advantage heiped Steer the roadmap, foo. -~ el peroma "Ultimately, all the systems we provide are to support the execution of business, so you start with the business needs, what's most important for the business," he said. Organizations that want to modernize must choose systems that support their objectives. The company considered cybersecurity concerns, maintenance requirements and operational costs to determine which apps to prioritize for modernization, Bradshaw said. Replacing vs. maintaining legacy systems Many organizations still rely on legacy systems for some of their workloads, which can limit innovation efforts. Seventy-two percent of all respondents believe that their organization's digital transformation efforts are lagging due to technical debt, while 51% cite a complex legacy IT infrastructure as one of their key challenges over the next year, according to the 2023 report "CIO Pulse: 2023 budgets & priorities” from cloud software provider SoftwareOne, headquartered in Milwaukee. Yet, many CIOs don't always have a well-formulated path forward. A good portion of IT leaders are unclear on what they should modernize first and what legacy systems are OK to keep running. Some might end up shedding a legacy system under duress, said Joe Davey, partner at West Monroe, a digital services firm, headquartered in Chicago. "Often, it takes a catalyzing event," Davey said. In some cases, CIOs replace legacy technologies without a clear strategy in mind. "[The strategy is] technology for technology's sake." he said. “[But] there's a lack of understanding how that technology can help them get ahead.” Although companies eventually need to replace all legacy technology, CIOs don't need to modernize all systems at once - nor is an undertaking of that magnitude usually possible. Instead, CIOs must determine what legacy systems need to be replaced sooner and which can be replaced later, both Davey and Bradshaw said. 5 reasons to replace legacy systems Organizations should carefully evaluate their existing systems before making any changes. IT leaders should understand the following reasons why legacy systems should be prioritized for modernization. 1. The system creates an unacceptable security risk Many IT teams can't patch some legacy systems because vendors don't release new patches. Other systems have significant security. vulnerabilities IT can't address for another reason. Any such system with "security vulnerabiltties that could bring the [organization] to its knees should be a high priority for replacement,” said Dave Powner, executive director of the Center for Data-Driven Policy at Mitre Corp., a nonprofit research and development organization, based in McLean, Va., that provides technical and cybersecurity support to U.S. government agencies. 2. The system hinders the organization’s performance Inefficient systems can cause delays and decreased productivity. 20f34 P + Organizations should prioritize replacing systems that affect efficiency, said Minir Patel, vice president of cloud architecture at Apps Associates, a consultancy augl NP, headquartered in Acton, Mass. 6 reasons legacy systems are stillinuse Replacing vs. maintaining legac Systems by modernizing legacy systems, Powner said. Enterprises can pursue new opportunities or significantly improve mission cap4Biiieé Stying win rec-and-ruo legacy systems can feel ke Understanding issues uch as whih syster 3. The system doesn't fit into the oR§AHIZHESH S ERUFEEsgaoes ot davng organzatona poromancecanhalp I lac Alegacy system without immediate problems can still be a priority for modernization if the processes it supports aren't critical for the organization's long-term goals. When developing a modernization strategy, CIOs should focus on where the company wants to be, said Suneel Ghei, principal research director at Info-Tech Research Group, an IT services management company, based in London, Ont. 4. The system costs too much to maintain Al systems come with run costs. In some cases, a system’s maintenance costs might exceed its business value, including the cost of modernizing the system. Excessive run costs draw resources away from pursuing innovation and new opportunities, Patel said. CIOs need to do that math and know when they're approaching or have gone past that point so they can take appropriate action. 5. The system is at a high risk of failure Systems with no vendor support, that depend on obsolete programming languages or are highly customized with scant documentation and no remaining institutional knowledge of its buildout are highly fragile. Organizations could have a difficult time recovering if the system should fail. For example, some businesses have needed help with IT systems but couldn'tfind IT talent to service the systems. It's best to replace those systems before that happens to ensure business continuity. 3 reasons to maintain legacy systems Companies can maintain legacy systems under the right circumstances. Here are three reasons to maintain a legacy system that IT leaders should understand. 1. The system has an acceptable level of risk Asystem no longer supported by a vendor or built on an obsolete programming language does have security vulnerabilities. But it might not create unnecessary risks. For example, a company might rely on the system for a noncritical back-office function. There would be minimal effects on daily operations if the system failed. Or the CIO might have or could easily access the talent needed to keep it running at a reasonable cost. In such cases, the CIO might reasonably opt to make modernizing that system a lower priority. 2. The system still supports the organization's needs Asystem that meets the organization's needs, while not hindering its ability to pursue new competitive opportunities, is a strong candidate to stay in place. Organizations might do themselves a disservice by replacing legacy systems with modern versions they're not ready to use or optimize, Patel said. For example, replacing an existing system with a modern app featuring Al might seem like a good strategy. Still, a company needs to have the maturity required to use the Al component successfully to get ROI that justifies the modernization. 3. The system's processes can be sunsetted or shifted to other systems 20f34 P + CIOs might opt to keep a legacy system in place if they know that the business processes it supports will be sunsetted by the organization or shifted to other systems, pinie¥itin Naik, technical fellow at Mitre Corp. 6 reasons legacy systems are still inuse Replacing vs. maintaining legac il a system that won't't be needed in the future won'te deliver good ROI® Replacing % Next Steps Stying win rec-and-ruo legacy systems can el ke Ine slest roue. But 3 the wor changes ata dzzying vstems Understanding issues such as whih syster organizatonalperormance can help I eac How to modernize apps as part of the cloud migration process How to perform an application modernization assessment % Dig Deeper on IT applications, infrastructure and operations bimodal IT (bimodal information technology) How to modernize legacy applications By: Linda Tucci By: Mary Pratt IT transformation Defra's tech review reveals legacy IT issues across government By: Brian Holak By: Cliff Saran -ADS BY GOOGLE Latest TechTarget resources Cloud Computing [ Top 6 soft skills in IT that cloud teams need 20f34 P + Softskills play a bigger partin successiul cloud deployments than you might think. Technical skill are obviously essential in . MOBILE COMPUTING Up Next DATACENTER 6 reasons legacy systems a@mfi.msandzmef&%dwsgfi- cloud SUSTAINABILITY AND ESG. Staying with tried-and-lrue legacy systems carStaridieds for ndeeiifiodiirisawes chishgingwith Sheteapid pace of cloud adoption. certificatioreprograms he safest route. But as the world changes al EZisW oxpeRERVERISEARS URBBCEHLBRRIT leac About Us Contributors Guides Editorial Ethics Policy Reprints Opinions Meet The Editors Answers Photo Stories Contact Us Definitions Quizzes Advertisers E-Products Tips Partner with Us Events Tutorials Media Kit Fealures Videos Corporate Site AllRights Reserved, Copyright 2007 - 2024, TechTarget Privacy Policy D0 Not Sel or Share My Persona Information 20f34 P + 

The response should be accurate and concise, with little added conversational elements or tone. If you cannot provide the answer to the request based on the context given, make sure to simply state, "The information is not available at this time." When evaluating legacy systems, how do we determine whether to replace or maintain these legacy systems? Home > IT applications, infrastructure and operations FEATURE ~ 20F3 4 P Partof: The CIO's guide to legacy systems Replacing vs. maintaining legacy systems Understanding issues such as which systems hinder organizational performance can help IT leaders decide which legacy systems to replace and which to maintain. By Mary K. Pratt Published: 05 Jul 2023 Few CIOs escape the complexity of deciding whether to maintain legacy systems or replace them altogether. The right choice, as with most things in life, is: It depends. IT leaders might want to replace a legacy_system because of outdated hardware, increased security risks or a desire to enable a digital transformation initiative. But replacing existing systems isn't always in the company's best interest. Legacy systems can remain in place if the existing system is reliable. vclo” Q Prioritize a strategic assessment One alternative to completely replacing or maintaining legacy systems is to modernize them. Modernized systems might be more cost-effective, while increasing efficiency and improving existing processes at the same time. Michael Bradshaw is currently working through a multiyear plan to modernize the technology at Kyndryl, a New York-based IT services company. After about two years of planning and execution, the goal is to complete the big moves by November, he said. A strategic assessment of the company's existing systems and applications was the first step in the process. His modernization plan calls for the digitalization of the company's entire business chain, Bradshaw said. Previously, about 1,800 applications supported that chain, but the number should drop to 360 by year's end and eventually down to 300. His IT team partnered with the business to develop a target, as well as a roadmap on how to get there, he said. 20f34 P + The goal of this strategy is to streamline the modernization efforts. Up Next The strategic assessment enabled §Tdasisienliyashaylagaeysysiams laimmeripbiigraationmodriizgtion and which could wait, systems Bradshaw said. Slyingwit i-and-rue logacysysems can el ke Undertanding sses such s which ystr e safot vt Byl as 1o wad changes al a izzying organizatonal perormance can ol " T loax Afocus on competitive advantage heiped Steer the roadmap, foo. -~ el peroma "Ultimately, all the systems we provide are to support the execution of business, so you start with the business needs, what's most important for the business," he said. Organizations that want to modernize must choose systems that support their objectives. The company considered cybersecurity concerns, maintenance requirements and operational costs to determine which apps to prioritize for modernization, Bradshaw said. Replacing vs. maintaining legacy systems Many organizations still rely on legacy systems for some of their workloads, which can limit innovation efforts. Seventy-two percent of all respondents believe that their organization's digital transformation efforts are lagging due to technical debt, while 51% cite a complex legacy IT infrastructure as one of their key challenges over the next year, according to the 2023 report "CIO Pulse: 2023 budgets & priorities” from cloud software provider SoftwareOne, headquartered in Milwaukee. Yet, many CIOs don't always have a well-formulated path forward. A good portion of IT leaders are unclear on what they should modernize first and what legacy systems are OK to keep running. Some might end up shedding a legacy system under duress, said Joe Davey, partner at West Monroe, a digital services firm, headquartered in Chicago. "Often, it takes a catalyzing event," Davey said. In some cases, CIOs replace legacy technologies without a clear strategy in mind. "[The strategy is] technology for technology's sake." he said. “[But] there's a lack of understanding how that technology can help them get ahead.” Although companies eventually need to replace all legacy technology, CIOs don't need to modernize all systems at once - nor is an undertaking of that magnitude usually possible. Instead, CIOs must determine what legacy systems need to be replaced sooner and which can be replaced later, both Davey and Bradshaw said. 5 reasons to replace legacy systems Organizations should carefully evaluate their existing systems before making any changes. IT leaders should understand the following reasons why legacy systems should be prioritized for modernization. 1. The system creates an unacceptable security risk Many IT teams can't patch some legacy systems because vendors don't release new patches. Other systems have significant security. vulnerabilities IT can't address for another reason. Any such system with "security vulnerabiltties that could bring the [organization] to its knees should be a high priority for replacement,” said Dave Powner, executive director of the Center for Data-Driven Policy at Mitre Corp., a nonprofit research and development organization, based in McLean, Va., that provides technical and cybersecurity support to U.S. government agencies. 2. The system hinders the organization’s performance Inefficient systems can cause delays and decreased productivity. 20f34 P + Organizations should prioritize replacing systems that affect efficiency, said Minir Patel, vice president of cloud architecture at Apps Associates, a consultancy augl NP, headquartered in Acton, Mass. 6 reasons legacy systems are stillinuse Replacing vs. maintaining legac Systems by modernizing legacy systems, Powner said. Enterprises can pursue new opportunities or significantly improve mission cap4Biiieé Stying win rec-and-ruo legacy systems can feel ke Understanding issues uch as whih syster 3. The system doesn't fit into the oR§AHIZHESH S ERUFEEsgaoes ot davng organzatona poromancecanhalp I lac Alegacy system without immediate problems can still be a priority for modernization if the processes it supports aren't critical for the organization's long-term goals. When developing a modernization strategy, CIOs should focus on where the company wants to be, said Suneel Ghei, principal research director at Info-Tech Research Group, an IT services management company, based in London, Ont. 4. The system costs too much to maintain Al systems come with run costs. In some cases, a system’s maintenance costs might exceed its business value, including the cost of modernizing the system. Excessive run costs draw resources away from pursuing innovation and new opportunities, Patel said. CIOs need to do that math and know when they're approaching or have gone past that point so they can take appropriate action. 5. The system is at a high risk of failure Systems with no vendor support, that depend on obsolete programming languages or are highly customized with scant documentation and no remaining institutional knowledge of its buildout are highly fragile. Organizations could have a difficult time recovering if the system should fail. For example, some businesses have needed help with IT systems but couldn'tfind IT talent to service the systems. It's best to replace those systems before that happens to ensure business continuity. 3 reasons to maintain legacy systems Companies can maintain legacy systems under the right circumstances. Here are three reasons to maintain a legacy system that IT leaders should understand. 1. The system has an acceptable level of risk Asystem no longer supported by a vendor or built on an obsolete programming language does have security vulnerabilities. But it might not create unnecessary risks. For example, a company might rely on the system for a noncritical back-office function. There would be minimal effects on daily operations if the system failed. Or the CIO might have or could easily access the talent needed to keep it running at a reasonable cost. In such cases, the CIO might reasonably opt to make modernizing that system a lower priority. 2. The system still supports the organization's needs Asystem that meets the organization's needs, while not hindering its ability to pursue new competitive opportunities, is a strong candidate to stay in place. Organizations might do themselves a disservice by replacing legacy systems with modern versions they're not ready to use or optimize, Patel said. For example, replacing an existing system with a modern app featuring Al might seem like a good strategy. Still, a company needs to have the maturity required to use the Al component successfully to get ROI that justifies the modernization. 3. The system's processes can be sunsetted or shifted to other systems 20f34 P + CIOs might opt to keep a legacy system in place if they know that the business processes it supports will be sunsetted by the organization or shifted to other systems, pinie¥itin Naik, technical fellow at Mitre Corp. 6 reasons legacy systems are still inuse Replacing vs. maintaining legac il a system that won't't be needed in the future won'te deliver good ROI® Replacing % Next Steps Stying win rec-and-ruo legacy systems can el ke Ine slest roue. But 3 the wor changes ata dzzying vstems Understanding issues such as whih syster organizatonalperormance can help I eac How to modernize apps as part of the cloud migration process How to perform an application modernization assessment % Dig Deeper on IT applications, infrastructure and operations bimodal IT (bimodal information technology) How to modernize legacy applications By: Linda Tucci By: Mary Pratt IT transformation Defra's tech review reveals legacy IT issues across government By: Brian Holak By: Cliff Saran -ADS BY GOOGLE Latest TechTarget resources Cloud Computing [ Top 6 soft skills in IT that cloud teams need 20f34 P + Softskills play a bigger partin successiul cloud deployments than you might think. Technical skill are obviously essential in . MOBILE COMPUTING Up Next DATACENTER 6 reasons legacy systems a@mfi.msandzmef&%dwsgfi- cloud SUSTAINABILITY AND ESG. Staying with tried-and-lrue legacy systems carStaridieds for ndeeiifiodiirisawes chishgingwith Sheteapid pace of cloud adoption. certificatioreprograms he safest route. But as the world changes al EZisW oxpeRERVERISEARS URBBCEHLBRRIT leac About Us Contributors Guides Editorial Ethics Policy Reprints Opinions Meet The Editors Answers Photo Stories Contact Us Definitions Quizzes Advertisers E-Products Tips Partner with Us Events Tutorials Media Kit Fealures Videos Corporate Site AllRights Reserved, Copyright 2007 - 2024, TechTarget Privacy Policy D0 Not Sel or Share My Persona Information 20f34 P + 

{instruction} ========== In your answer, refer only to the context document. Do not employ any outside knowledge {question} ========== [user request] {passage 0} ========== [context document]

What does it mean to have gerd and how does it affect my body? Is it preventable? How do I know if I need to go to a doctor? Are there any foods or drinks I should avoid? Answer in 200 words or less.

Gastroesophageal reflux disease is a condition in which stomach acid repeatedly flows back up into the tube connecting the mouth and stomach, called the esophagus. It's often called GERD for short. This backwash is known as acid reflux, and it can irritate the lining of the esophagus. Many people experience acid reflux now and then. However, when acid reflux happens repeatedly over time, it can cause GERD. Most people can manage the discomfort of GERD with lifestyle changes and medicines. And though it's uncommon, some may need surgery to help with symptoms. Symptoms Common symptoms of GERD include: A burning sensation in the chest, often called heartburn. Heartburn usually happens after eating and might be worse at night or while lying down. Backwash of food or sour liquid in the throat. Upper belly or chest pain. Trouble swallowing, called dysphagia. Sensation of a lump in the throat. If you have nighttime acid reflux, you also might experience: An ongoing cough. Inflammation of the vocal cords, known as laryngitis. New or worsening asthma. When to see a doctor Seek medical help right away if you have chest pain, especially if you also have shortness of breath, or jaw or arm pain. These may be symptoms of a heart attack. Make an appointment with a healthcare professional if you: Have severe or frequent GERD symptoms. Take nonprescription medicines for heartburn more than twice a week. GERD is caused by frequent acid reflux or reflux of nonacidic content from the stomach. When you swallow, a circular band of muscle around the bottom of the esophagus, called the lower esophageal sphincter, relaxes to allow food and liquid to flow into the stomach. Then the sphincter closes again. If the sphincter does not relax as is typical or it weakens, stomach acid can flow back into the esophagus. This constant backwash of acid irritates the lining of the esophagus, often causing it to become inflamed. Conditions that can increase the risk of GERD include: Obesity. Bulging of the top of the stomach up above the diaphragm, known as a hiatal hernia. Pregnancy. Connective tissue disorders, such as scleroderma. Delayed stomach emptying. Factors that can aggravate acid reflux include: Smoking. Eating large meals or eating late at night. Eating certain foods, such as fatty or fried foods. Drinking certain beverages, such as alcohol or coffee. Taking certain medicines, such as aspirin. Complications Over time, long-lasting inflammation in the esophagus can cause: Inflammation of the tissue in the esophagus, known as esophagitis. Stomach acid can break down tissue in the esophagus. This can cause inflammation, bleeding and sometimes an open sore, called an ulcer. Esophagitis can cause pain and make swallowing difficult. Narrowing of the esophagus, called an esophageal stricture. Damage to the lower esophagus from stomach acid causes scar tissue to form. The scar tissue narrows the food pathway, leading to problems with swallowing. Precancerous changes to the esophagus, known as Barrett esophagus. Damage from acid can cause changes in the tissue lining the lower esophagus. These changes are associated with an increased risk of esophageal cancer.

{instruction} ========== In your answer, refer only to the context document. Do not employ any outside knowledge {question} ========== What does it mean to have gerd and how does it affect my body? Is it preventable? How do I know if I need to go to a doctor? Are there any foods or drinks I should avoid? Answer in 200 words or less. {passage 0} ========== Gastroesophageal reflux disease is a condition in which stomach acid repeatedly flows back up into the tube connecting the mouth and stomach, called the esophagus. It's often called GERD for short. This backwash is known as acid reflux, and it can irritate the lining of the esophagus. Many people experience acid reflux now and then. However, when acid reflux happens repeatedly over time, it can cause GERD. Most people can manage the discomfort of GERD with lifestyle changes and medicines. And though it's uncommon, some may need surgery to help with symptoms. Symptoms Common symptoms of GERD include: A burning sensation in the chest, often called heartburn. Heartburn usually happens after eating and might be worse at night or while lying down. Backwash of food or sour liquid in the throat. Upper belly or chest pain. Trouble swallowing, called dysphagia. Sensation of a lump in the throat. If you have nighttime acid reflux, you also might experience: An ongoing cough. Inflammation of the vocal cords, known as laryngitis. New or worsening asthma. When to see a doctor Seek medical help right away if you have chest pain, especially if you also have shortness of breath, or jaw or arm pain. These may be symptoms of a heart attack. Make an appointment with a healthcare professional if you: Have severe or frequent GERD symptoms. Take nonprescription medicines for heartburn more than twice a week. GERD is caused by frequent acid reflux or reflux of nonacidic content from the stomach. When you swallow, a circular band of muscle around the bottom of the esophagus, called the lower esophageal sphincter, relaxes to allow food and liquid to flow into the stomach. Then the sphincter closes again. If the sphincter does not relax as is typical or it weakens, stomach acid can flow back into the esophagus. This constant backwash of acid irritates the lining of the esophagus, often causing it to become inflamed. Conditions that can increase the risk of GERD include: Obesity. Bulging of the top of the stomach up above the diaphragm, known as a hiatal hernia. Pregnancy. Connective tissue disorders, such as scleroderma. Delayed stomach emptying. Factors that can aggravate acid reflux include: Smoking. Eating large meals or eating late at night. Eating certain foods, such as fatty or fried foods. Drinking certain beverages, such as alcohol or coffee. Taking certain medicines, such as aspirin. Complications Over time, long-lasting inflammation in the esophagus can cause: Inflammation of the tissue in the esophagus, known as esophagitis. Stomach acid can break down tissue in the esophagus. This can cause inflammation, bleeding and sometimes an open sore, called an ulcer. Esophagitis can cause pain and make swallowing difficult. Narrowing of the esophagus, called an esophageal stricture. Damage to the lower esophagus from stomach acid causes scar tissue to form. The scar tissue narrows the food pathway, leading to problems with swallowing. Precancerous changes to the esophagus, known as Barrett esophagus. Damage from acid can cause changes in the tissue lining the lower esophagus. These changes are associated with an increased risk of esophageal cancer. https://www.mayoclinic.org/diseases-conditions/gerd/symptoms-causes/syc-20361940

Do not use any prior knowledge or external resources. You must answer questions solely on the basis of the information provided in the prompt.

What are the main legal arguments for and against the FTC's Non-Compete Rule?

Legal Authority The FTC relied on Sections 5 and 6(g) of the Federal Trade Commission Act (FTC Act) in promulgating the Non-Compete Rule. Section 5 prohibits “unfair methods of competition” (UMC) and empowers the FTC to enforce that prohibition through adjudication. Section 6 is titled “Additional powers of Commission.” It confers a range of authorities, most of which involve investigations and the publication of reports. The provision also includes Section 6(g), which empowers the FTC to “from time to time classify corporations and . . . to make rules and regulations for the purpose of carrying out” the FTC Act. Sections 5 and 6(g) were both part of the original FTC Act, which Congress enacted in 1914. Since the statute’s enactment, Congress has adopted several laws granting the FTC rulemaking authority over discrete subjects, including the Wool Products Labeling Act, the Textile Fiber Products Identification Act, the Fur Products Labeling Act, the Flammable Fabrics Act, and the Fair Packaging and Labeling Act. The FTC first asserted that Section 6(g) endows it with general substantive rulemaking power in 1962, and the agency adopted a number of trade regulation rules in the years that followed. Some of those rules defined certain conduct as both a UMC and an “unfair or deceptive act or practice” (UDAP)—a separate category of conduct prohibited by Section 5. Other rules relied only on the FTC’s UDAP power. One rule relied solely on the FTC’s competition authority, but was never enforced and has been repealed. In the 1970s, a trade association challenged the FTC’s authority to issue substantive rules under Section 6(g) in National Petroleum Refiners Association v. FTC. The trade association argued that Section 6(g) authorized only procedural rules, emphasizing that the FTC had not asserted substantive rulemaking authority under Section 6(g) until 1962 and that FTC officials had occasionally denied the existence of such authority. The trade association also contended that Congress’s enactment of several statutes granting the FTC specific rulemaking authorities implied that the FTC lacked general rulemaking authority. The U.S. Court of Appeals for the D.C. Circuit rejected those arguments. In affirming the FTC’s power to issue legislative rules under Section 6(g), the court relied on appellate decisions construing similar statutes as authorizing substantive rulemaking, the advantages of rulemaking in effectuating the FTC Congressional Research Service 3 Act’s purposes, and the absence of any limiting language in the statutory text. The D.C. Circuit downplayed the fact that the FTC had not claimed general rulemaking authority until 1962, reasoning that the agency’s earlier interpretation of its legal authority did not warrant judicial deference. The court also concluded that Congress may have provided the FTC with more specific rulemaking authorities based on “uncertainty, understandable caution, and a desire to avoid litigation,” rather than a firm conviction that the FTC lacked general rulemaking authority. Two years after the National Petroleum Refiners decision, Congress enacted the Magnuson-Moss Act, which imposed special procedural requirements for the FTC’s UDAP rules and eliminated the FTC’s authority to issue such rules under Section 6(g). Magnuson-Moss did not by its terms affect the FTC’s authority to issue UMC rules: the statute included a provision disclaiming an intent to affect “any authority of the Commission to prescribe rules (including interpretive rules), and general statements of policy, with respect to unfair methods of competition.” Despite this language in Magnuson-Moss, the FTC’s putative authority to issue UMC rules has been dormant since the enactment of that statute. The Non-Compete Rule marks the first rule promulgated under Section 6(g) since the 1970s and the second rule ever that relies solely upon the FTC’s competition authority. A 1983 decision from the U.S. Court of Appeals for the Seventh Circuit agreed with the D.C. Circuit’s reasoning in National Petroleum Refiners, but no other federal appellate court has addressed the FTC’s authority to issue legislative rules under Section 6(g). Whether the FTC possesses such authority remains unsettled; some commentators have argued that National Petroleum Refiners was wrongly decided and that it is unlikely that modern courts would reach the same conclusion. In issuing the Non-Compete Rule, the FTC defended its authority to issue substantive rules under Section 6(g) by pointing to the provision’s plain meaning and the D.C. Circuit’s decision in National Petroleum Refiners. The FTC also argued that Congress implicitly ratified the D.C. Circuit’s decision in both the Magnuson-Moss Act and the Federal Trade Commission Improvements Act of 1980 (the 1980 Amendments). The 1980 Amendments imposed procedural requirements that the FTC must follow in issuing any “rule.” It defined the term “rule” to include rules promulgated under Section 6 or Magnuson-Moss. The statute excluded from that definition “interpretive rules, rules involving Commission management or personnel, general statements of policy, or rules relating to Commission organization, procedure, or practice.” The FTC argued that this exclusion confirms its authority to issue rules under Section 6 that are not merely “interpretive rules, rules involving Commission management or personnel, general statements of policy, or rules relating to Commission organization, procedure, or practice.” The FTC’s authority to issue the Non-Compete Rule depends not only on whether Section 6(g) authorizes legislative rulemaking, but also on the scope of Section 5’s prohibition of UMC. The Supreme Court has repeatedly said that Section 5 is broader than the Sherman Act and the Clayton Act (the other core federal antitrust laws). However, the scope of this additional coverage—often called the FTC’s “standalone” Section 5 authority—is unsettled. Under previous leadership, the FTC took a narrow view of its standalone Section 5 authority. In a 2015 policy statement, the FTC indicated that decisions to bring standalone Section 5 actions would be guided by considerations of consumer welfare, that the FTC would evaluate challenged conduct under “a framework similar to the rule of reason,” and that the FTC was less likely to bring a standalone Section 5 action if enforcement of the Sherman Act or Clayton Act was sufficient to address the relevant competitive harm. The FTC rescinded this policy statement in 2021 and issued a new Section 5 policy statement the following year. In the 2022 policy statement, the FTC identified “two key criteria” it will consider in evaluating whether a “method of competition” is “unfair.” First, the FTC indicated that “unfair” conduct Congressional Research Service 4 “may be coercive, exploitative, collusive, abusive, deceptive, predatory, or involve the use of economic power of a similar nature,” and “may also be otherwise restrictive or exclusionary.” Second, the FTC explained that such conduct “must tend to negatively affect competitive conditions”—for example, by foreclosing or impairing the opportunities of market participants, reducing competition between rivals, limiting choice, or otherwise harming consumers. The 2022 policy statement indicated that this second inquiry will not turn on whether conduct directly causes harm in particular cases, but instead will focus on whether conduct “has a tendency to generate negative consequences.” In promulgating the Non-Compete Rule, the FTC found that non-competes violate Section 5 because they represent “restrictive and exclusionary conduct that tends to negatively affect competitive conditions” in labor markets and product and service markets. The FTC also determined that non-competes for workers other than senior executives violate Section 5 because they constitute “exploitative and coercive conduct that tends to negatively affect competitive conditions” in labor markets and product and service markets. (A previous Legal Sidebar provides a more extensive discussion of the FTC’s justification for the Non-Compete Rule.) Two FTC Commissioners voted against the Non-Compete Rule, arguing that the FTC lacks the authority to issue substantive competition regulations and that the evidence did not justify a categorical prohibition of non-competes.

Do not use any prior knowledge or external resources. You must answer questions solely on the basis of the information provided in the prompt. What are the main legal arguments for and against the FTC's Non-Compete Rule? Legal Authority The FTC relied on Sections 5 and 6(g) of the Federal Trade Commission Act (FTC Act) in promulgating the Non-Compete Rule. Section 5 prohibits “unfair methods of competition” (UMC) and empowers the FTC to enforce that prohibition through adjudication. Section 6 is titled “Additional powers of Commission.” It confers a range of authorities, most of which involve investigations and the publication of reports. The provision also includes Section 6(g), which empowers the FTC to “from time to time classify corporations and . . . to make rules and regulations for the purpose of carrying out” the FTC Act. Sections 5 and 6(g) were both part of the original FTC Act, which Congress enacted in 1914. Since the statute’s enactment, Congress has adopted several laws granting the FTC rulemaking authority over discrete subjects, including the Wool Products Labeling Act, the Textile Fiber Products Identification Act, the Fur Products Labeling Act, the Flammable Fabrics Act, and the Fair Packaging and Labeling Act. The FTC first asserted that Section 6(g) endows it with general substantive rulemaking power in 1962, and the agency adopted a number of trade regulation rules in the years that followed. Some of those rules defined certain conduct as both a UMC and an “unfair or deceptive act or practice” (UDAP)—a separate category of conduct prohibited by Section 5. Other rules relied only on the FTC’s UDAP power. One rule relied solely on the FTC’s competition authority, but was never enforced and has been repealed. In the 1970s, a trade association challenged the FTC’s authority to issue substantive rules under Section 6(g) in National Petroleum Refiners Association v. FTC. The trade association argued that Section 6(g) authorized only procedural rules, emphasizing that the FTC had not asserted substantive rulemaking authority under Section 6(g) until 1962 and that FTC officials had occasionally denied the existence of such authority. The trade association also contended that Congress’s enactment of several statutes granting the FTC specific rulemaking authorities implied that the FTC lacked general rulemaking authority. The U.S. Court of Appeals for the D.C. Circuit rejected those arguments. In affirming the FTC’s power to issue legislative rules under Section 6(g), the court relied on appellate decisions construing similar statutes as authorizing substantive rulemaking, the advantages of rulemaking in effectuating the FTC Congressional Research Service 3 Act’s purposes, and the absence of any limiting language in the statutory text. The D.C. Circuit downplayed the fact that the FTC had not claimed general rulemaking authority until 1962, reasoning that the agency’s earlier interpretation of its legal authority did not warrant judicial deference. The court also concluded that Congress may have provided the FTC with more specific rulemaking authorities based on “uncertainty, understandable caution, and a desire to avoid litigation,” rather than a firm conviction that the FTC lacked general rulemaking authority. Two years after the National Petroleum Refiners decision, Congress enacted the Magnuson-Moss Act, which imposed special procedural requirements for the FTC’s UDAP rules and eliminated the FTC’s authority to issue such rules under Section 6(g). Magnuson-Moss did not by its terms affect the FTC’s authority to issue UMC rules: the statute included a provision disclaiming an intent to affect “any authority of the Commission to prescribe rules (including interpretive rules), and general statements of policy, with respect to unfair methods of competition.” Despite this language in Magnuson-Moss, the FTC’s putative authority to issue UMC rules has been dormant since the enactment of that statute. The Non-Compete Rule marks the first rule promulgated under Section 6(g) since the 1970s and the second rule ever that relies solely upon the FTC’s competition authority. A 1983 decision from the U.S. Court of Appeals for the Seventh Circuit agreed with the D.C. Circuit’s reasoning in National Petroleum Refiners, but no other federal appellate court has addressed the FTC’s authority to issue legislative rules under Section 6(g). Whether the FTC possesses such authority remains unsettled; some commentators have argued that National Petroleum Refiners was wrongly decided and that it is unlikely that modern courts would reach the same conclusion. In issuing the Non-Compete Rule, the FTC defended its authority to issue substantive rules under Section 6(g) by pointing to the provision’s plain meaning and the D.C. Circuit’s decision in National Petroleum Refiners. The FTC also argued that Congress implicitly ratified the D.C. Circuit’s decision in both the Magnuson-Moss Act and the Federal Trade Commission Improvements Act of 1980 (the 1980 Amendments). The 1980 Amendments imposed procedural requirements that the FTC must follow in issuing any “rule.” It defined the term “rule” to include rules promulgated under Section 6 or Magnuson-Moss. The statute excluded from that definition “interpretive rules, rules involving Commission management or personnel, general statements of policy, or rules relating to Commission organization, procedure, or practice.” The FTC argued that this exclusion confirms its authority to issue rules under Section 6 that are not merely “interpretive rules, rules involving Commission management or personnel, general statements of policy, or rules relating to Commission organization, procedure, or practice.” The FTC’s authority to issue the Non-Compete Rule depends not only on whether Section 6(g) authorizes legislative rulemaking, but also on the scope of Section 5’s prohibition of UMC. The Supreme Court has repeatedly said that Section 5 is broader than the Sherman Act and the Clayton Act (the other core federal antitrust laws). However, the scope of this additional coverage—often called the FTC’s “standalone” Section 5 authority—is unsettled. Under previous leadership, the FTC took a narrow view of its standalone Section 5 authority. In a 2015 policy statement, the FTC indicated that decisions to bring standalone Section 5 actions would be guided by considerations of consumer welfare, that the FTC would evaluate challenged conduct under “a framework similar to the rule of reason,” and that the FTC was less likely to bring a standalone Section 5 action if enforcement of the Sherman Act or Clayton Act was sufficient to address the relevant competitive harm. The FTC rescinded this policy statement in 2021 and issued a new Section 5 policy statement the following year. In the 2022 policy statement, the FTC identified “two key criteria” it will consider in evaluating whether a “method of competition” is “unfair.” First, the FTC indicated that “unfair” conduct Congressional Research Service 4 “may be coercive, exploitative, collusive, abusive, deceptive, predatory, or involve the use of economic power of a similar nature,” and “may also be otherwise restrictive or exclusionary.” Second, the FTC explained that such conduct “must tend to negatively affect competitive conditions”—for example, by foreclosing or impairing the opportunities of market participants, reducing competition between rivals, limiting choice, or otherwise harming consumers. The 2022 policy statement indicated that this second inquiry will not turn on whether conduct directly causes harm in particular cases, but instead will focus on whether conduct “has a tendency to generate negative consequences.” In promulgating the Non-Compete Rule, the FTC found that non-competes violate Section 5 because they represent “restrictive and exclusionary conduct that tends to negatively affect competitive conditions” in labor markets and product and service markets. The FTC also determined that non-competes for workers other than senior executives violate Section 5 because they constitute “exploitative and coercive conduct that tends to negatively affect competitive conditions” in labor markets and product and service markets. (A previous Legal Sidebar provides a more extensive discussion of the FTC’s justification for the Non-Compete Rule.) Two FTC Commissioners voted against the Non-Compete Rule, arguing that the FTC lacks the authority to issue substantive competition regulations and that the evidence did not justify a categorical prohibition of non-competes.

[question] [user request] ===================== [text] [context document] ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

Attached is a portion of an article that discusses the clinical trial results of patients who tried ozempic. Can you provide me with four sections, each titled the same as the paragraphs in the text. For each section, tell me what sustain group is being discussed, and provide a bullet-point list including: how much weight was lost for each SEM group, and what the BMI change was for each SEM group. Be sure to include information about the control groups as well. If the information is redacted, do not include it in the response.

SEM Used as First-Line Therapy SUSTAIN-1 reported change in body weight from baseline to week 30 in drug-naive patients with T2DM and had inadequate glycemic control after therapy with diet and exercise. At week 30, the mean change in body weight was -3.73 kg (SE 0.41), -4.53 kg (SE 0.41), and -0.98 kg (SE 0.43) for patients who received SEM 0.5 mg, SEM 1 mg, and placebo, respectively. The mean differences were statistically significant for both SEM groups compared with placebo (SEM 0.5 mg: -2.75 kg, 95% CI -3.92 to -1.58, P < 0.0001; SEM 1 mg: -3.56 kg, 95% CI -4.74 to -2.38) (Table 30). Because the upper limit of the two-sided 95% CI for the estimated differences was below 0 kg, superiority of SEM 0.5 mg or SEM 1 mg versus placebo in change in body weight was demonstrated. According to the clinical expert consulted for this review, the between-group differences were considered clinically important. SUSTAIN-1 also reported change in BMI from baseline to week 30 in drug-naive patients. At week 30, the mean change in BMI was -1.36 kg/m2 (SE 0.15), -1.61 kg/m2 (SE 0.14) and -0.38 kg/m2 (SE 0.15) for patients who received SEM 0.5 mg, SEM 1 mg, and placebo, respectively. The mean differences were statistically significant for both SEM groups compared with placebo (SEM 0.5 mg: -0.98 kg/m2, 95% CI -1.40 to -0.56, P < 0.0001; SEM 1 mg: -1.23 kg/m2, 95% CI -1.65 to -0.82) (Table 30). SEM Used as Second-Line Therapy (Add-On to MET) Results of post hoc subgroup analyses on body weight in SUSTAIN-2, SUSTAIN-3, and SUSTAIN-4 are presented. Patients in SUSTAIN-7 received treatment with SEM or DUL with background therapy of MET monotherapy. In patients with T2DM and received SEM as the second-line therapy (add-on to MET), treatment with either dose of SEM for 30 to 56 weeks was associated with greater reduction in body weight, compared with SIT, EXE, or IG (Table 31). The mean change from baseline in body weight ranged from ▬ for the SEM 0.5 mg group, and from ▬ for the SEM 1 mg group. Compared with SIT, the mean between-group differences were ▬ for the SEM 0.5 mg group and ▬ for the SEM 1 mg group. Compared with EXE, the mean between-group difference was ▬ for the SEM 1 mg group. Compared with IG, the mean between-group differences were ▬ for the SEM 0.5 mg group and ▬ for the SEM 1 mg group. Compared with DUL, the mean between-group differences were -2.26 kg (95% CI -3.02 to -1.51, P < 0.0001) for the SEM 0.5 mg group and -3.55 kg (95% CI -4.32 to -2.78, P < 0.0001) for the SEM 1 mg group. According to the clinical expert consulted for this review, the between-group differences in body weight were considered clinically relevant. In SUSTAIN-7, superiority in reducing body weight was concluded for each dose of SEM compared with the respective dose level of DUL. Results of post hoc subgroup analyses on BMI in SUSTAIN-2 to SUSTAIN-4 are presented. In the subgroups of patients with T2DM and received SEM as the second-line therapy (add-on to MET), treatment with either dose of SEM for 30 weeks to 56 weeks was associated with greater reduction in BMI, compared with SIT, EXE, or IG (Table 31). Patients in SUSTAIN-7 received treatment with SEM or DUL with background therapy of MET monotherapy. The mean change from baseline in BMI ranged from ▬ for the SEM 0.5 mg group, and from ▬ for the SEM 1 mg group. Compared with SIT, the mean between-group differences were ▬ for the SEM 0.5 mg group and ▬ for the SEM 1 mg group. Compared with EXE, the mean between-group difference was ▬ for the SEM 1 mg group. Compared with IG, the mean between-group differences were ▬ for the SEM 0.5 mg group and ▬ for the SEM 1 mg group. Compared with DUL, the mean between-group differences were -0.81 kg/m2 (95% CI -1.08 to -0.54) for the SEM 0.5 mg group and -1.25 kg/m2 (95% CI -1.52 to -0.98) for the SEM 1 mg group. SEM Used as Third-Line Therapy (Add-On to MET + TZD or MET + SU) Results of post hoc subgroup analyses on body weight in SUSTAIN-2 to SUSTAIN-4 are presented. In the patients receiving SEM as the third-line therapy (add-on to MET + TZD or MET + SU), treatment with either dose of SEM for 30 weeks to 56 weeks was associated with greater reduction in body weight, compared with SIT, EXE, or IG (Table 32). The mean change from baseline in A1C ranged from ▬ for the SEM 0.5 mg group, and from ▬ for the SEM 1 mg group. Compared with SIT, the mean between-group differences were ▬ for the SEM 0.5 mg group and ▬ for the SEM 1 mg group. Compared with EXE, the mean between-group difference was ▬ for the SEM 1 mg group. Compared with IG, the mean between-group differences were ▬ for the SEM 0.5 mg group and ▬ for the SEM 1 mg group. According to the clinical expert consulted for this review, the between-group differences in body weight were considered clinically relevant. Results of post hoc subgroup analyses on BMI from SUSTAIN-2 to SUSTAIN-4 are presented. In the subgroups of patients with T2DM and received SEM as the third-line therapy (add-on to MET + TZD or MET + SU), treatment with either dose of SEM for 30 weeks to 56 weeks was associated with greater reduction in BMI, compared with SIT, EXE, or IG (Table 32). The mean change from baseline in BMI ranged from ▬ for the SEM 0.5 mg group, and from ▬ for the SEM 1 mg group. Compared with SIT, the mean between-group differences were ▬ for the SEM 0.5 mg group and ▬ for the SEM 1 mg group. Compared with EXE, the mean between-group difference was ▬ for the SEM 1 mg group. Compared with IG, the mean between-group differences were ▬ for the SEM 0.5 mg group and ▬ for the SEM 1 mg group.

[question] Attached is a portion of an article that discusses the clinical trial results of patients who tried ozempic. Can you provide me with four sections, each titled the same as the paragraphs in the text. For each section, tell me what sustain group is being discussed, and provide a bullet-point list including: how much weight was lost for each SEM group, and what the BMI change was for each SEM group. Be sure to include information about the control groups as well. If the information is redacted, do not include it in the response. ===================== [text] SEM Used as First-Line Therapy SUSTAIN-1 reported change in body weight from baseline to week 30 in drug-naive patients with T2DM and had inadequate glycemic control after therapy with diet and exercise. At week 30, the mean change in body weight was -3.73 kg (SE 0.41), -4.53 kg (SE 0.41), and -0.98 kg (SE 0.43) for patients who received SEM 0.5 mg, SEM 1 mg, and placebo, respectively. The mean differences were statistically significant for both SEM groups compared with placebo (SEM 0.5 mg: -2.75 kg, 95% CI -3.92 to -1.58, P < 0.0001; SEM 1 mg: -3.56 kg, 95% CI -4.74 to -2.38) (Table 30). Because the upper limit of the two-sided 95% CI for the estimated differences was below 0 kg, superiority of SEM 0.5 mg or SEM 1 mg versus placebo in change in body weight was demonstrated. According to the clinical expert consulted for this review, the between-group differences were considered clinically important. SUSTAIN-1 also reported change in BMI from baseline to week 30 in drug-naive patients. At week 30, the mean change in BMI was -1.36 kg/m2 (SE 0.15), -1.61 kg/m2 (SE 0.14) and -0.38 kg/m2 (SE 0.15) for patients who received SEM 0.5 mg, SEM 1 mg, and placebo, respectively. The mean differences were statistically significant for both SEM groups compared with placebo (SEM 0.5 mg: -0.98 kg/m2, 95% CI -1.40 to -0.56, P < 0.0001; SEM 1 mg: -1.23 kg/m2, 95% CI -1.65 to -0.82) (Table 30). SEM Used as Second-Line Therapy (Add-On to MET) Results of post hoc subgroup analyses on body weight in SUSTAIN-2, SUSTAIN-3, and SUSTAIN-4 are presented. Patients in SUSTAIN-7 received treatment with SEM or DUL with background therapy of MET monotherapy. In patients with T2DM and received SEM as the second-line therapy (add-on to MET), treatment with either dose of SEM for 30 to 56 weeks was associated with greater reduction in body weight, compared with SIT, EXE, or IG (Table 31). The mean change from baseline in body weight ranged from ▬ for the SEM 0.5 mg group, and from ▬ for the SEM 1 mg group. Compared with SIT, the mean between-group differences were ▬ for the SEM 0.5 mg group and ▬ for the SEM 1 mg group. Compared with EXE, the mean between-group difference was ▬ for the SEM 1 mg group. Compared with IG, the mean between-group differences were ▬ for the SEM 0.5 mg group and ▬ for the SEM 1 mg group. Compared with DUL, the mean between-group differences were -2.26 kg (95% CI -3.02 to -1.51, P < 0.0001) for the SEM 0.5 mg group and -3.55 kg (95% CI -4.32 to -2.78, P < 0.0001) for the SEM 1 mg group. According to the clinical expert consulted for this review, the between-group differences in body weight were considered clinically relevant. In SUSTAIN-7, superiority in reducing body weight was concluded for each dose of SEM compared with the respective dose level of DUL. Results of post hoc subgroup analyses on BMI in SUSTAIN-2 to SUSTAIN-4 are presented. In the subgroups of patients with T2DM and received SEM as the second-line therapy (add-on to MET), treatment with either dose of SEM for 30 weeks to 56 weeks was associated with greater reduction in BMI, compared with SIT, EXE, or IG (Table 31). Patients in SUSTAIN-7 received treatment with SEM or DUL with background therapy of MET monotherapy. The mean change from baseline in BMI ranged from ▬ for the SEM 0.5 mg group, and from ▬ for the SEM 1 mg group. Compared with SIT, the mean between-group differences were ▬ for the SEM 0.5 mg group and ▬ for the SEM 1 mg group. Compared with EXE, the mean between-group difference was ▬ for the SEM 1 mg group. Compared with IG, the mean between-group differences were ▬ for the SEM 0.5 mg group and ▬ for the SEM 1 mg group. Compared with DUL, the mean between-group differences were -0.81 kg/m2 (95% CI -1.08 to -0.54) for the SEM 0.5 mg group and -1.25 kg/m2 (95% CI -1.52 to -0.98) for the SEM 1 mg group. SEM Used as Third-Line Therapy (Add-On to MET + TZD or MET + SU) Results of post hoc subgroup analyses on body weight in SUSTAIN-2 to SUSTAIN-4 are presented. In the patients receiving SEM as the third-line therapy (add-on to MET + TZD or MET + SU), treatment with either dose of SEM for 30 weeks to 56 weeks was associated with greater reduction in body weight, compared with SIT, EXE, or IG (Table 32). The mean change from baseline in A1C ranged from ▬ for the SEM 0.5 mg group, and from ▬ for the SEM 1 mg group. Compared with SIT, the mean between-group differences were ▬ for the SEM 0.5 mg group and ▬ for the SEM 1 mg group. Compared with EXE, the mean between-group difference was ▬ for the SEM 1 mg group. Compared with IG, the mean between-group differences were ▬ for the SEM 0.5 mg group and ▬ for the SEM 1 mg group. According to the clinical expert consulted for this review, the between-group differences in body weight were considered clinically relevant. Results of post hoc subgroup analyses on BMI from SUSTAIN-2 to SUSTAIN-4 are presented. In the subgroups of patients with T2DM and received SEM as the third-line therapy (add-on to MET + TZD or MET + SU), treatment with either dose of SEM for 30 weeks to 56 weeks was associated with greater reduction in BMI, compared with SIT, EXE, or IG (Table 32). The mean change from baseline in BMI ranged from ▬ for the SEM 0.5 mg group, and from ▬ for the SEM 1 mg group. Compared with SIT, the mean between-group differences were ▬ for the SEM 0.5 mg group and ▬ for the SEM 1 mg group. Compared with EXE, the mean between-group difference was ▬ for the SEM 1 mg group. Compared with IG, the mean between-group differences were ▬ for the SEM 0.5 mg group and ▬ for the SEM 1 mg group. https://www.ncbi.nlm.nih.gov/books/NBK544016/ ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

You can only respond to the prompt using information in the context block and no other sources. Your role is to explain complicated tax information to consumers using clear and understandable language.

Explain the rationale behind the global minimum tax on multinational enterprises for Canadian businesses as outlined in the context document.

International Tax Reform Canada is one of 138 members of the Organisation for Economic Co-operation and Development (OECD)/Group of 20 (G20) Inclusive Framework on Base Erosion and Profit Shifting (the Inclusive Framework) that have joined a two-pillar plan for international tax reform agreed to on October 8, 2021. The historic “Statement on a Two-Pillar Solution to Address the Tax Challenges Arising from the Digitalisation of the Economy” (the October 2021 Statement) agreed to on that day has since been endorsed by G20 Finance Ministers and Leaders. Pillar One is intended to reallocate a portion of taxing rights over the profits of the largest and most profitable multinational enterprises (MNEs) to market countries (i.e., where their users and customers are located). Pillar Two is intended to ensure that the profits of large MNEs are subject to an effective tax rate of at least 15 per cent, regardless of where they are earned. The following provides an update on recent developments and upcoming implementation steps in relation to the pillars. Pillar One – Reallocation of Taxing Rights Pillar One is an update to the framework that underlies current tax treaties, which allocates the income of MNEs between countries for tax purposes. The existing framework relies on principles of connection with a country based on physical presence that were designed for traditional bricks-and-mortar businesses; they do not produce appropriate results in today’s digitalized economy. Pillar One instead uses a broader test of connection and a formulary allocation of residual profits to ensure that the largest and most profitable MNEs pay a fair share of tax in the countries where their users and customers are located. The government is working with its international partners in an OECD-led process to develop the model rules and the multilateral convention needed to establish this new multilateral tax framework and bring it into effect. To help ensure that the final rules will be effective and administrable, the OECD has been releasing draft model rules for public comment as each element reaches maturity. The draft rules were consolidated in two major progress reports released in July and October of 2022. Countries are working toward completing multilateral negotiations so that the convention to implement Pillar One can be signed by mid-2023, with a view to it entering into force in 2024. To ensure that Canadians' interests are protected, the government released draft legislative proposals for a Digital Services Tax (DST) in December 2021. The government intends to release a revised draft of the legislative proposals for public comment before introducing a bill in Parliament. Consistent with the October 2021 Statement, the DST could be imposed as of January 1, 2024, but only if the multilateral convention implementing the Pillar One framework has not come into force. In that event, the DST would be payable as of 2024 in respect of revenues earned as of January 1, 2022. It remains the government’s hope and underlying assumption that the timely implementation of the new multilateral framework will make this unnecessary. Pillar Two – Global Minimum Tax Pillar Two is a multilateral framework for a global minimum tax regime that is designed to ensure that MNEs with annual revenues of €750 million or more are subject to a minimum effective tax rate of 15 per cent on their profits in every jurisdiction in which they operate. It is intended to reduce the incentive for MNEs to shift profits into low-tax jurisdictions and, at the same time, end the “race to the bottom” in international corporate taxation by setting a floor on tax competition. The primary charging rule for Pillar Two is known as the Income Inclusion Rule (IIR). In general terms, if the jurisdiction where the ultimate parent entity of an MNE is located has implemented the IIR, it has the primary right to impose a top-up tax on the ultimate parent entity with respect to income from the MNE’s operations in any jurisdiction where it is taxed at an effective tax rate below 15 per cent. Pillar Two also contains a “backstop” rule, known as the Undertaxed Profits Rule (UTPR). If a parent jurisdiction of an MNE has not implemented the IIR, other jurisdictions in which the MNE operates that have implemented the UTPR would impose the top-up tax on the group entities located in their jurisdiction, with the top-up tax being allocated among those jurisdictions on a formulary basis. This ensures that MNEs whose parent entities are located in non-implementing jurisdictions are nonetheless subject to top-up tax in respect of their low-taxed income. The details of the IIR and UTPR are set out in the model rules (the Global Anti-Base Erosion or GloBE Rules), and related commentary and administrative guidance, all agreed by the Inclusive Framework. The Pillar Two framework contemplates that a jurisdiction may enact a domestic minimum top-up tax that would apply a top-up tax on low-taxed income of its domestic entities. If such a tax is designed to achieve the intended outcomes under Pillar Two, it is treated as a “qualified” domestic minimum top-up tax and is creditable dollar-for-dollar against the top-up tax liability that would otherwise arise under Pillar Two. In effect, this allows a jurisdiction to collect the top-up tax applicable to any low-taxed income of its domestic entities, rather than allowing the top-up tax to accrue to the treasuries of other countries under the IIR or UTPR. A more detailed outline of the Pillar Two framework is set out in the Supplementary Information to Budget 2022 (https://www.budget.canada.ca/2022/report-rapport/tm-mf-en.html#a4), which launched a public consultation on the implementation of Pillar Two in Canada, which ended on July 7, 2022.

You can only respond to the prompt using information in the context block and no other sources. Your role is to explain complicated tax information to consumers using clear and understandable language. Explain the rationale behind the global minimum tax on multinational enterprises for Canadian businesses as outlined in the context document. International Tax Reform Canada is one of 138 members of the Organisation for Economic Co-operation and Development (OECD)/Group of 20 (G20) Inclusive Framework on Base Erosion and Profit Shifting (the Inclusive Framework) that have joined a two-pillar plan for international tax reform agreed to on October 8, 2021. The historic “Statement on a Two-Pillar Solution to Address the Tax Challenges Arising from the Digitalisation of the Economy” (the October 2021 Statement) agreed to on that day has since been endorsed by G20 Finance Ministers and Leaders. Pillar One is intended to reallocate a portion of taxing rights over the profits of the largest and most profitable multinational enterprises (MNEs) to market countries (i.e., where their users and customers are located). Pillar Two is intended to ensure that the profits of large MNEs are subject to an effective tax rate of at least 15 per cent, regardless of where they are earned. The following provides an update on recent developments and upcoming implementation steps in relation to the pillars. Pillar One – Reallocation of Taxing Rights Pillar One is an update to the framework that underlies current tax treaties, which allocates the income of MNEs between countries for tax purposes. The existing framework relies on principles of connection with a country based on physical presence that were designed for traditional bricks-and-mortar businesses; they do not produce appropriate results in today’s digitalized economy. Pillar One instead uses a broader test of connection and a formulary allocation of residual profits to ensure that the largest and most profitable MNEs pay a fair share of tax in the countries where their users and customers are located. The government is working with its international partners in an OECD-led process to develop the model rules and the multilateral convention needed to establish this new multilateral tax framework and bring it into effect. To help ensure that the final rules will be effective and administrable, the OECD has been releasing draft model rules for public comment as each element reaches maturity. The draft rules were consolidated in two major progress reports released in July and October of 2022. Countries are working toward completing multilateral negotiations so that the convention to implement Pillar One can be signed by mid-2023, with a view to it entering into force in 2024. To ensure that Canadians' interests are protected, the government released draft legislative proposals for a Digital Services Tax (DST) in December 2021. The government intends to release a revised draft of the legislative proposals for public comment before introducing a bill in Parliament. Consistent with the October 2021 Statement, the DST could be imposed as of January 1, 2024, but only if the multilateral convention implementing the Pillar One framework has not come into force. In that event, the DST would be payable as of 2024 in respect of revenues earned as of January 1, 2022. It remains the government’s hope and underlying assumption that the timely implementation of the new multilateral framework will make this unnecessary. Pillar Two – Global Minimum Tax Pillar Two is a multilateral framework for a global minimum tax regime that is designed to ensure that MNEs with annual revenues of €750 million or more are subject to a minimum effective tax rate of 15 per cent on their profits in every jurisdiction in which they operate. It is intended to reduce the incentive for MNEs to shift profits into low-tax jurisdictions and, at the same time, end the “race to the bottom” in international corporate taxation by setting a floor on tax competition. The primary charging rule for Pillar Two is known as the Income Inclusion Rule (IIR). In general terms, if the jurisdiction where the ultimate parent entity of an MNE is located has implemented the IIR, it has the primary right to impose a top-up tax on the ultimate parent entity with respect to income from the MNE’s operations in any jurisdiction where it is taxed at an effective tax rate below 15 per cent. Pillar Two also contains a “backstop” rule, known as the Undertaxed Profits Rule (UTPR). If a parent jurisdiction of an MNE has not implemented the IIR, other jurisdictions in which the MNE operates that have implemented the UTPR would impose the top-up tax on the group entities located in their jurisdiction, with the top-up tax being allocated among those jurisdictions on a formulary basis. This ensures that MNEs whose parent entities are located in non-implementing jurisdictions are nonetheless subject to top-up tax in respect of their low-taxed income. The details of the IIR and UTPR are set out in the model rules (the Global Anti-Base Erosion or GloBE Rules), and related commentary and administrative guidance, all agreed by the Inclusive Framework. The Pillar Two framework contemplates that a jurisdiction may enact a domestic minimum top-up tax that would apply a top-up tax on low-taxed income of its domestic entities. If such a tax is designed to achieve the intended outcomes under Pillar Two, it is treated as a “qualified” domestic minimum top-up tax and is creditable dollar-for-dollar against the top-up tax liability that would otherwise arise under Pillar Two. In effect, this allows a jurisdiction to collect the top-up tax applicable to any low-taxed income of its domestic entities, rather than allowing the top-up tax to accrue to the treasuries of other countries under the IIR or UTPR. A more detailed outline of the Pillar Two framework is set out in the Supplementary Information to Budget 2022 (https://www.budget.canada.ca/2022/report-rapport/tm-mf-en.html#a4), which launched a public consultation on the implementation of Pillar Two in Canada, which ended on July 7, 2022.

The information in this prompt is all you may use to answer any questions. You are not allowed to use any external resources or prior knowledge. When using acronyms, include the full form beside it for the first use.

Summarise all information relevant to law.

Congress passed and the President signed into law the National Quantum Initiative Act (NQI Act; P.L. 115-368; codified at 15 U.S.C. §§8801 et seq.) in December 2018 to accelerate quantum research and development (R&D) for the economic and national security of the United States and ensure the continued U.S. leadership in quantum information science and its technology applications. Since the enactment of the NQI Act, researchers have made progress in quantum R&D. The authorization of funding for several federal R&D activities under the NQI Act is set to expire at the end of FY2023. In the NQI Act, Congress defined the term quantum information science as “the use of the laws of quantum physics for the storage, transmission, manipulation, computing, or measurement of information.” Quantum computing, one of technology applications of quantum information science, uses a quantum bit, or qubit, as its basic data unit, to harness quantum properties such as superposition and entanglement. By generating and manipulating qubits, a quantum computer is capable of performing certain calculations significantly faster than conventional, non-quantum computers, known as classical computers, leading to new ways to solve some complex problems that were previously unsolvable. Researchers have demonstrated the potential for quantum computing applications in areas such as cryptography, machine learning, and scientific and engineering research, particularly using modeling, optimization, and simulation. The NQI Act is the primary federal law that supports R&D activities in quantum computing. It has been amended by the National Defense Authorization Act (NDAA) for FY2022 (P.L. 117-81) and the CHIPS and Science Act (Division B of P.L. 117-167). The current act contains four titles, directing (1) the President to implement an NQI Program with a 10-year plan to accelerate quantum R&D, invest in and coordinate fundamental federal R&D activities, and partner with industry and universities to advance goals and priorities in the NQI Program; (2) the National Institute of Standards and Technology (NIST) to carry out specified R&D activities and convene a stakeholder consortium to identify the future measurement, standards, cybersecurity, and needs for a robust quantum industry; (3) the National Science Foundation (NSF) to carry out a basic research and education program and award grants to establish Multidisciplinary Centers for Quantum Research and Education; and (4) the Department of Energy (DOE) to administer a number of programs, including a basic research program, National Quantum Information Science Research Centers, a program to accelerate innovation in quantum network infrastructure, and the Quantum User Expansion for Science and Technology program. The authorization of funding for the following activities under the NQI Act is set to expire in September 2023: NSF’s five university-based Quantum Leap Challenge Institutes, DOE’s five national lab-led research centers, and NIST’s R&D activities, including the industry-led Quantum Economic Development Consortium. Since the enactment of the NQI Act in 2018, researchers have made notable advances in quantum computing in three areas: demonstrating that a quantum processor could execute a complex computational task much faster than a classical supercomputer in an experiment; demonstrating the mitigation of calculation errors caused by the loss of information held by qubits—a major outstanding challenge to quantum computing—in an experiment; and scaling up quantum computing processors, thus enhancing their power and potential reliability. Some experts argue that sustained federal R&D investment is necessary to accelerate progress toward practical quantum computing and to maintain the leading role of U.S. researchers and institutions globally. There is less consensus, however, on the specific role the federal government should play in quantum R&D and how resources and support should be specifically targeted and prioritized. Congress faces policymaking in three areas. First, Congress may decide whether and how to reauthorize or expand federal R&D activities and support under the NQI Act. Second, Congress may choose whether to set policy priorities to ensure U.S. leadership in quantum computing, including (1) accelerating the development of practical quantum computers with near-term, useful applications; (2) supporting the development of an accessible, sustainable, and secure supply chain and domestic manufacturing capabilities; and (3) facilitating the development of a quantum-literate workforce. Congress may also consider whether to set policy priorities to protect national security interests in quantum computing by addressing risks; in particular, the anticipated compromise of current cryptographic systems that protect sensitive data and communications among government agencies, financial institutions, health service providers, and others.

system instructions: [The information in this prompt is all you may use to answer any questions. You are not allowed to use any external resources or prior knowledge. When using acronyms, include the full form beside it for the first use.] question: [Summarise all information relevant to law.] context block: [Congress passed and the President signed into law the National Quantum Initiative Act (NQI Act; P.L. 115-368; codified at 15 U.S.C. §§8801 et seq.) in December 2018 to accelerate quantum research and development (R&D) for the economic and national security of the United States and ensure the continued U.S. leadership in quantum information science and its technology applications. Since the enactment of the NQI Act, researchers have made progress in quantum R&D. The authorization of funding for several federal R&D activities under the NQI Act is set to expire at the end of FY2023. In the NQI Act, Congress defined the term quantum information science as “the use of the laws of quantum physics for the storage, transmission, manipulation, computing, or measurement of information.” Quantum computing, one of technology applications of quantum information science, uses a quantum bit, or qubit, as its basic data unit, to harness quantum properties such as superposition and entanglement. By generating and manipulating qubits, a quantum computer is capable of performing certain calculations significantly faster than conventional, non-quantum computers, known as classical computers, leading to new ways to solve some complex problems that were previously unsolvable. Researchers have demonstrated the potential for quantum computing applications in areas such as cryptography, machine learning, and scientific and engineering research, particularly using modeling, optimization, and simulation. The NQI Act is the primary federal law that supports R&D activities in quantum computing. It has been amended by the National Defense Authorization Act (NDAA) for FY2022 (P.L. 117-81) and the CHIPS and Science Act (Division B of P.L. 117-167). The current act contains four titles, directing (1) the President to implement an NQI Program with a 10-year plan to accelerate quantum R&D, invest in and coordinate fundamental federal R&D activities, and partner with industry and universities to advance goals and priorities in the NQI Program; (2) the National Institute of Standards and Technology (NIST) to carry out specified R&D activities and convene a stakeholder consortium to identify the future measurement, standards, cybersecurity, and needs for a robust quantum industry; (3) the National Science Foundation (NSF) to carry out a basic research and education program and award grants to establish Multidisciplinary Centers for Quantum Research and Education; and (4) the Department of Energy (DOE) to administer a number of programs, including a basic research program, National Quantum Information Science Research Centers, a program to accelerate innovation in quantum network infrastructure, and the Quantum User Expansion for Science and Technology program. The authorization of funding for the following activities under the NQI Act is set to expire in September 2023: NSF’s five university-based Quantum Leap Challenge Institutes, DOE’s five national lab-led research centers, and NIST’s R&D activities, including the industry-led Quantum Economic Development Consortium. Since the enactment of the NQI Act in 2018, researchers have made notable advances in quantum computing in three areas: demonstrating that a quantum processor could execute a complex computational task much faster than a classical supercomputer in an experiment; demonstrating the mitigation of calculation errors caused by the loss of information held by qubits—a major outstanding challenge to quantum computing—in an experiment; and scaling up quantum computing processors, thus enhancing their power and potential reliability. Some experts argue that sustained federal R&D investment is necessary to accelerate progress toward practical quantum computing and to maintain the leading role of U.S. researchers and institutions globally. There is less consensus, however, on the specific role the federal government should play in quantum R&D and how resources and support should be specifically targeted and prioritized. Congress faces policymaking in three areas. First, Congress may decide whether and how to reauthorize or expand federal R&D activities and support under the NQI Act. Second, Congress may choose whether to set policy priorities to ensure U.S. leadership in quantum computing, including (1) accelerating the development of practical quantum computers with near-term, useful applications; (2) supporting the development of an accessible, sustainable, and secure supply chain and domestic manufacturing capabilities; and (3) facilitating the development of a quantum-literate workforce. Congress may also consider whether to set policy priorities to protect national security interests in quantum computing by addressing risks; in particular, the anticipated compromise of current cryptographic systems that protect sensitive data and communications among government agencies, financial institutions, health service providers, and others.]

{instruction} ========== In your answer, refer only to the context document. Do not employ any outside knowledge {question} ========== [user request] {passage 0} ========== [context document]

My final research project is on fungal immunity. Read this section from a recent publication and explain the effects of the different interleukins mentioned in the section. Do not give an overview of the molecules, I only want to know their specific functions in fungal immunity. Limit to one sentence per interleukin.

Innate Immunity Innate Detection and Immune Evasion The lungs maintain many defense mechanisms to survey and eliminate airborne threats. Lung epithelial cells (LECs) secrete anti-microbial peptides, complement proteins, and defensins which enhance granulocyte activity and create a less hospitable environment for Coccidioides (Hernández-Santos et al., 2018). To survive, Coccidioides must successfully avoid detection from surveying and patrolling innate immune cells. Lung-resident macrophages, also known as alveolar macrophages, comprise up to 95% of pulmonary leukocytes and participate in early immune detection of pathogens and maintain the lung microenvironment (Wynn and Vannella, 2016). In Aspergillus infections, tissue-specific neutrophils are recruited by LECs and enter the lung early after infection due to β-glucan and chitin (Dubey et al., 2014). Innate leukocytes control early pathogen invasion via phagocytosis and production of reactive oxide and reactive nitrogen species (RNS) (Xu and Shinohara, 2017). β-glucan and chitin are conserved across many fungal species, including Coccidioides, so these molecules could interact with epithelial cells and aid in neutrophil recruitment. In cases where host immune responses cannot control infection, disease becomes chronic. Host responses sometimes control infections through granuloma formation in the lung as fungi is walled off instead of destroyed (Nguyen et al., 2013; Johnson et al., 2014; Wynn and Vannella, 2016). To survive lung defenses and evade innate immune responses, Coccidioides expresses virulence factors for immune evasion and survival. Inside the lung, arthroconidia express ornithine decarboxylase, an enzyme implicated during growth from arthroconidia to spherule state (Guevara-Olvera et al., 2000). During transition, the spherule internal cell wall segments bud off into endospores. Lifecycle transition allows vulnerable, easily phagocytosed, arthroconidia to develop into phagocytosis-resistant spherules (Hung et al., 2002; Gonzalez et al., 2011; Nguyen et al., 2013). Arthroconidia are vulnerable to RNS while mature spherules suppress nitric oxide species (NOS) and inducible NOS expression in macrophages (Figure 1) (Gonzalez et al., 2011). Mature spherules are too large for most host phagocytic activity, allowing Coccidiodes to evade early immune detection (Hung et al., 2002). Coccidioides induces host expression of arginase resulting in ornithine and urea production, important components for transition from arthroconidia to spherule (Hung et al., 2007). FGURE 1 www.frontiersin.org Figure 1 Fungal dimorphism presents challenges for immune detection and activation. Early infection: Coccidioides is vulnerable to immune detection during early infection due to the smaller size (2–5 μM) and SOWgp expression which is detected via Dectin-1 and TLR2 on innate immune cells. These interactions mediate clearance via phagocytosis and reactive oxide species production. Later infection: As Coccidioides sporulates, it secretes MEP1 which digests SOWgp from the fungal surface, hampering immune detection. Spherules induce arginase expression in host tissues, suppressing NOS/NO production via an unknown mechanism, contributing to immune suppression. In the spherule state, Coccidioides secretes metalloproteinase 1 (Mep1) which digests an immunodominant antigen spherical outer wall glycoprotein (SOWgp) on the fungal surface (Figure 1) (Hung et al., 2005). Phagocytotic granulocytes rely on pathogen associated molecular patterns such as SOWgp, thus Mep1 secretion prevents detection by innate immune cells (Hung et al., 2005). Coccidioides upregulates nitrate reductase during development, an enzyme that converts nitrate to nitrite, thereby enhancing Coccidioides survival in anoxic conditions, such as those found inside a granuloma (Johannesson et al., 2006). Early detection to inhaled fungus is critical for host response. Macrophages and neutrophils detect Coccidioides arthroconidia and immature spherules via receptors Dectin-1, Dectin-2, and Mincle interacting with SOWgp (Hung et al., 2002; Nguyen et al., 2013). Endothelial lung cells use these same receptors to regulate defensin secretion. Toll-like receptors (TLRs) and c-type lectin receptors (CLRs) interact with major pathogen-associated molecular patterns to detect Coccidioides (Romani, 2004; Viriyakosol et al., 2008; Viriyakosol et al., 2013). Like most fungi, Coccidioides expresses β-glucans, chitins, and mannans in the outer cell wall (Nguyen et al., 2013). These cell components are recognized by a variety of TLRs and CLRs and elicit strong inflammatory responses from local immune cells. Coccidioides interactions with TLR2 and Dectin-1 on macrophages activate production of reactive oxide species (ROS) and inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFα) (Viriyakosol et al., 2008; Viriyakosol et al., 2013). There are no known nucleotide-binding oligomerization domain-like (NOD-like) receptors yet associated with Coccidioides detection. In humans, polymorphisms in IFNγ/IL-12 signaling pathway result in a STAT1 gain of function mutations that associate with increased disease severity in Coccidioides, Histoplasma, and Candida infection (Sampaio et al., 2013). In disseminated Coccidioides, patients with severe disease were found to have a STAT3 mutation (Odio et al., 2015). STAT 3 mediates IL-23 signaling, critical for IFNγ, IL-12, and IL-17 production while STAT1 signaling induces Th1 cell differentiation in response to IL-12 to produce IFNγ; IFNγ, in turn, inhibits Th17 differentiation (Yeh et al., 2014). IL-12β1 receptor deficiency is associated with increased risk of disseminated coccidioidomycosis (Yeh et al., 2014). In chronic mucocutaneous candidiasis, gain of function mutations in STAT1 and STAT3 correlates to more severe disease and poor TH17 responses (Zheng et al., 2015). These observations suggest that STAT1 and STAT3 immune signaling is critical in host control of Th1/Th17 cytokine balance and is required for protection and Coccidioides fungal control. In Blastomyces dermatitidis infection, LECs regulate collaborative killing between alveolar macrophages, dendritic cells (DC), and neutrophils (Hussell and Bell, 2014; Hernández-Santos et al., 2018). Upon LECs ablation, B. dermatitidis phagocytosis is reduced, and viable yeast numbers increase. Other data suggests that IL-1/IL-1R interactions regulate CCL20 expression in LECs. Chemokine CCL20 strongly recruits lymphocytes and weakly recruits neutrophils (Hernández-Santos et al., 2018). IL-1R-deficient mice express less CCL20 and lung Th17 cells are reduced, suggesting that IL-1/IL-1R signaling in LECs could regulate adaptive immune functions (Hernández-Santos et al., 2018). IL-1R is critical for vaccine induced resistance to Coccidioides infection via MyD88 induction of Th17 responses (Hung et al., 2014a; Hung et al., 2016a). Though it has not been explored, LECs could mediate early responses to Coccidioides through IL-1R, suggesting another innate immune cell role in anti-fungal responses within the lung tissues. Alveoli structure likely helps shape local immune responses. Three dominant cell types exist within and around the alveoli structure: Type 1 and Type 2 pneumocytes (also known as alveolar epithelial cells, AECs), and tissue-resident alveolar macrophages (Guillot et al., 2013; Hussell and Bell, 2014). Type 1 pneumocytes (AECI) secrete IL-10 constitutively, which bind to IL-10R on alveolar macrophages to maintain an anti-inflammatory state. Type 2 pneumocytes (or AECII) express CD200 which interacts with CD200R on alveolar macrophage to inhibit pro-inflammatory phenotype (Guillot et al., 2013; Hernández-Santos et al., 2018). Alveolar macrophages express TGFβ-receptors that bind to pneumocyte-expressed αvβ6 integrin, tethering them in the alveolar airspace. In inflammatory conditions, AECIs upregulate TLRs and AECIIs increase SP-A and SP-D production (Guillot et al., 2013). These surfactant proteins are known to enhance pathogen opsonization and phagocytosis, and are capable of binding to Coccidioides antigen (Awasthi et al., 2004). Coccidioides infected mice expressed less SP-A and SP-D protein in their bronchial lavage fluid compared to uninfected and vaccinated controls, demonstrating the pathogen’s capability of altering the lung mucosa (Awasthi et al., 2004). AECII secreted production of surfactant proteins may be influenced by Coccidioides allowing fungal escape of phagocytosis and prolonged survival.

{instruction} ========== In your answer, refer only to the context document. Do not employ any outside knowledge {question} ========== My final research project is on fungal immunity. Read this section from a recent publication and explain the effects of the different interleukins mentioned in the section. Do not give an overview of the molecules, I only want to know their specific functions in fungal immunity. Limit to one sentence per interleukin. {passage 0} ========== Innate Immunity Innate Detection and Immune Evasion The lungs maintain many defense mechanisms to survey and eliminate airborne threats. Lung epithelial cells (LECs) secrete anti-microbial peptides, complement proteins, and defensins which enhance granulocyte activity and create a less hospitable environment for Coccidioides (Hernández-Santos et al., 2018). To survive, Coccidioides must successfully avoid detection from surveying and patrolling innate immune cells. Lung-resident macrophages, also known as alveolar macrophages, comprise up to 95% of pulmonary leukocytes and participate in early immune detection of pathogens and maintain the lung microenvironment (Wynn and Vannella, 2016). In Aspergillus infections, tissue-specific neutrophils are recruited by LECs and enter the lung early after infection due to β-glucan and chitin (Dubey et al., 2014). Innate leukocytes control early pathogen invasion via phagocytosis and production of reactive oxide and reactive nitrogen species (RNS) (Xu and Shinohara, 2017). β-glucan and chitin are conserved across many fungal species, including Coccidioides, so these molecules could interact with epithelial cells and aid in neutrophil recruitment. In cases where host immune responses cannot control infection, disease becomes chronic. Host responses sometimes control infections through granuloma formation in the lung as fungi is walled off instead of destroyed (Nguyen et al., 2013; Johnson et al., 2014; Wynn and Vannella, 2016). To survive lung defenses and evade innate immune responses, Coccidioides expresses virulence factors for immune evasion and survival. Inside the lung, arthroconidia express ornithine decarboxylase, an enzyme implicated during growth from arthroconidia to spherule state (Guevara-Olvera et al., 2000). During transition, the spherule internal cell wall segments bud off into endospores. Lifecycle transition allows vulnerable, easily phagocytosed, arthroconidia to develop into phagocytosis-resistant spherules (Hung et al., 2002; Gonzalez et al., 2011; Nguyen et al., 2013). Arthroconidia are vulnerable to RNS while mature spherules suppress nitric oxide species (NOS) and inducible NOS expression in macrophages (Figure 1) (Gonzalez et al., 2011). Mature spherules are too large for most host phagocytic activity, allowing Coccidiodes to evade early immune detection (Hung et al., 2002). Coccidioides induces host expression of arginase resulting in ornithine and urea production, important components for transition from arthroconidia to spherule (Hung et al., 2007). FGURE 1 www.frontiersin.org Figure 1 Fungal dimorphism presents challenges for immune detection and activation. Early infection: Coccidioides is vulnerable to immune detection during early infection due to the smaller size (2–5 μM) and SOWgp expression which is detected via Dectin-1 and TLR2 on innate immune cells. These interactions mediate clearance via phagocytosis and reactive oxide species production. Later infection: As Coccidioides sporulates, it secretes MEP1 which digests SOWgp from the fungal surface, hampering immune detection. Spherules induce arginase expression in host tissues, suppressing NOS/NO production via an unknown mechanism, contributing to immune suppression. In the spherule state, Coccidioides secretes metalloproteinase 1 (Mep1) which digests an immunodominant antigen spherical outer wall glycoprotein (SOWgp) on the fungal surface (Figure 1) (Hung et al., 2005). Phagocytotic granulocytes rely on pathogen associated molecular patterns such as SOWgp, thus Mep1 secretion prevents detection by innate immune cells (Hung et al., 2005). Coccidioides upregulates nitrate reductase during development, an enzyme that converts nitrate to nitrite, thereby enhancing Coccidioides survival in anoxic conditions, such as those found inside a granuloma (Johannesson et al., 2006). Early detection to inhaled fungus is critical for host response. Macrophages and neutrophils detect Coccidioides arthroconidia and immature spherules via receptors Dectin-1, Dectin-2, and Mincle interacting with SOWgp (Hung et al., 2002; Nguyen et al., 2013). Endothelial lung cells use these same receptors to regulate defensin secretion. Toll-like receptors (TLRs) and c-type lectin receptors (CLRs) interact with major pathogen-associated molecular patterns to detect Coccidioides (Romani, 2004; Viriyakosol et al., 2008; Viriyakosol et al., 2013). Like most fungi, Coccidioides expresses β-glucans, chitins, and mannans in the outer cell wall (Nguyen et al., 2013). These cell components are recognized by a variety of TLRs and CLRs and elicit strong inflammatory responses from local immune cells. Coccidioides interactions with TLR2 and Dectin-1 on macrophages activate production of reactive oxide species (ROS) and inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFα) (Viriyakosol et al., 2008; Viriyakosol et al., 2013). There are no known nucleotide-binding oligomerization domain-like (NOD-like) receptors yet associated with Coccidioides detection. In humans, polymorphisms in IFNγ/IL-12 signaling pathway result in a STAT1 gain of function mutations that associate with increased disease severity in Coccidioides, Histoplasma, and Candida infection (Sampaio et al., 2013). In disseminated Coccidioides, patients with severe disease were found to have a STAT3 mutation (Odio et al., 2015). STAT 3 mediates IL-23 signaling, critical for IFNγ, IL-12, and IL-17 production while STAT1 signaling induces Th1 cell differentiation in response to IL-12 to produce IFNγ; IFNγ, in turn, inhibits Th17 differentiation (Yeh et al., 2014). IL-12β1 receptor deficiency is associated with increased risk of disseminated coccidioidomycosis (Yeh et al., 2014). In chronic mucocutaneous candidiasis, gain of function mutations in STAT1 and STAT3 correlates to more severe disease and poor TH17 responses (Zheng et al., 2015). These observations suggest that STAT1 and STAT3 immune signaling is critical in host control of Th1/Th17 cytokine balance and is required for protection and Coccidioides fungal control. In Blastomyces dermatitidis infection, LECs regulate collaborative killing between alveolar macrophages, dendritic cells (DC), and neutrophils (Hussell and Bell, 2014; Hernández-Santos et al., 2018). Upon LECs ablation, B. dermatitidis phagocytosis is reduced, and viable yeast numbers increase. Other data suggests that IL-1/IL-1R interactions regulate CCL20 expression in LECs. Chemokine CCL20 strongly recruits lymphocytes and weakly recruits neutrophils (Hernández-Santos et al., 2018). IL-1R-deficient mice express less CCL20 and lung Th17 cells are reduced, suggesting that IL-1/IL-1R signaling in LECs could regulate adaptive immune functions (Hernández-Santos et al., 2018). IL-1R is critical for vaccine induced resistance to Coccidioides infection via MyD88 induction of Th17 responses (Hung et al., 2014a; Hung et al., 2016a). Though it has not been explored, LECs could mediate early responses to Coccidioides through IL-1R, suggesting another innate immune cell role in anti-fungal responses within the lung tissues. Alveoli structure likely helps shape local immune responses. Three dominant cell types exist within and around the alveoli structure: Type 1 and Type 2 pneumocytes (also known as alveolar epithelial cells, AECs), and tissue-resident alveolar macrophages (Guillot et al., 2013; Hussell and Bell, 2014). Type 1 pneumocytes (AECI) secrete IL-10 constitutively, which bind to IL-10R on alveolar macrophages to maintain an anti-inflammatory state. Type 2 pneumocytes (or AECII) express CD200 which interacts with CD200R on alveolar macrophage to inhibit pro-inflammatory phenotype (Guillot et al., 2013; Hernández-Santos et al., 2018). Alveolar macrophages express TGFβ-receptors that bind to pneumocyte-expressed αvβ6 integrin, tethering them in the alveolar airspace. In inflammatory conditions, AECIs upregulate TLRs and AECIIs increase SP-A and SP-D production (Guillot et al., 2013). These surfactant proteins are known to enhance pathogen opsonization and phagocytosis, and are capable of binding to Coccidioides antigen (Awasthi et al., 2004). Coccidioides infected mice expressed less SP-A and SP-D protein in their bronchial lavage fluid compared to uninfected and vaccinated controls, demonstrating the pathogen’s capability of altering the lung mucosa (Awasthi et al., 2004). AECII secreted production of surfactant proteins may be influenced by Coccidioides allowing fungal escape of phagocytosis and prolonged survival. https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.581101/full

Write your answer using simple language and do not exceed 120 words. Replace all mention of the word technology with "tech." Please answer using only the information provided below. Do not use any external sources or prior knowledge to support your response.

In well-functioning Standards Developing Organizations, how are ideas selected?

What Standards Are and Why They Matter From computers and smartphones to cars and lightbulbs, societies rely on technology standards for everyday life. In the broadest sense, standards are the common and repeated use of rules, conditions, guidelines, or characteristics for products or related processes, practices, and production methods. They enable technology that is safe, universal, and interoperable. Standards define the requirements that make it possible for mobile phones sold in different countries to communicate across the world, for bank cards issued in one country to be recognized at ATMs in another, and for cars to run on fuel purchased from any gas station. Standards also help manage risk, security, safety, privacy, and quality in the development of new innovations. In short, good standards are good for business, good for consumers, and good for society. Standards Developing Organizations (SDOs) consist of experts from industry, academia, civil society groups, and government, all of whom share a common goal of ensuring safety, interoperability, and competition in a particular technology or technology application. In well functioning SDOs, ideas are selected not on the basis of the nationality, employer, or personality originating them, but instead on the basis of technical merit. Six principles govern the international standards development process: transparency, openness, impartiality and consensus, effectiveness and relevance, coherence, and a commitment to participation by low- and middle-income countries. The private sector has led U.S. engagement with SDOs for more than 100 years. An example of how this system works comes from the communications industry. Qualcomm Technologies provided the proposal in the 1990s that became the basis for all 3G standards, while NTT Docomo, a large mobile phone operator in Japan, provided the proposal that later became LTE, the predominant standard for wireless broadband communication for mobile devices and data terminals. This private sector leadership has come with significant assistance from government and academia. In 1901, the Congress established the National Bureau of Standards—which has since become the National Institute of Standards and Technology (NIST)—as the authoritative domestic measurement science research and standards laboratory. Not long after, five engineering societies and three Federal agencies banded together to establish a national non governmental body now known as the American National Standards Institute (ANSI). ANSI is a private, nonprofit organization that administers and coordinates the U.S. standardization system and is the sole U.S. representative to the International Organization for Standardization (ISO) and the International Electrotechnical Commission. Industry, consortia, and private-sector groups often complement the roles of NIST, ANSI, and ANSI-accredited SDOs, working together to develop standards to solve specific challenges. To date, this approach, supported by U.S. leadership, has fostered an effective and innovative system that has supercharged U.S. and global economic growth. In an era of rapid technological transformation and global scale, standards will continue to define and drive the markets of the future. Standards for CET—advanced technologies that are significant for U.S. competitiveness and national security - carry strategic significance. The United States will work with all nations committed to an open and transparent standards system to lead the way in these new arenas - just as we did with previous internet, wireless communications, and other digital standards. Failing to do so will risk the United States’—and the world’s—innovation, security, and prosperity. Standards for Critical and Emerging Technology The United States will prioritize efforts for standards development for a subset of CET that are essential for U.S. competitiveness and national security, including the following areas: • Communication and Networking Technologies, which are enabling dramatic changes in how consumers, businesses, and governments interact, and which will form the basis of tomorrow’s critical communications networks; • Semiconductors and Microelectronics, including Computing, Memory, and Storage Technologies, which affect every corner of the global economy, society, and government, and which power a panoply of innovations and capabilities; • Artificial Intelligence and Machine Learning, which promise transformative technologies and scientific breakthroughs across industries, but which must be developed in a trustworthy and risk-managed manner; • Biotechnologies, which will affect the health, agricultural, and industrial sectors of all nations, and which will need to be used safely and securely to support the health of our citizens, animals, and environment; • Positioning, Navigation, and Timing Services, which are a largely invisible utility for technology and infrastructure, including the electrical power grid, communications infrastructure and mobile devices, all modes of transportation, precision agriculture, weather forecasting, and emergency response; • Digital Identity Infrastructure and Distributed Ledger Technologies, which increasingly affect a range of key economic sectors; • Clean Energy Generation and Storage, which are critical to the generation, storage, distribution, and climate-friendly and efficient utilization of energy, and to the security of the technologies that support energy-producing plants; and • Quantum Information Technologies, which leverage quantum mechanics for the storage, transmission, manipulation, computing, or measurement of information, with major national security and economic implications. There are also specific applications of CET that departments and agencies have determined will impact our global economy and national security. The United States will focus standards development activities and outreach on these applications, which include: • Automated and Connected Infrastructure, such as smart communities, Internet of Things, and other novel applications; • Biobanking, which involves the collection, storage, and use of biological samples; • Automated, Connected, and Electrified Transportation, including automated and connected surface vehicles of many types and unmanned aircraft systems, many of which may be electric vehicles (EVs), along with the safe and efficient integration into smart communities and the transportation system as a whole, including standards to integrate EVs with the electrical grid and charging infrastructure; • Critical Minerals Supply Chains, where we will promote standards that support increased sustainable extraction of critical minerals necessary to manufacture renewable energy technologies, semiconductors, and EVs; • Cybersecurity and Privacy, which are cross-cutting issues that are critical to enabling the development and deployment of emerging technologies and promote the free flow of data and ideas with trust; and • Carbon Capture, Removal, Utilization and Storage, which can build on evolving standards for CO2 storage, and emerging standards for point source carbon capture, removal, and utilization, especially as those standards relate to monitoring and verification.

In well-functioning Standards Developing Organizations, how are ideas selected? Write your answer using simple language and do not exceed 120 words. Replace all mention of the word technology with "tech." Please answer using only the information provided below. Do not use any external sources or prior knowledge to support your response. What Standards Are and Why They Matter From computers and smartphones to cars and lightbulbs, societies rely on technology standards for everyday life. In the broadest sense, standards are the common and repeated use of rules, conditions, guidelines, or characteristics for products or related processes, practices, and production methods. They enable technology that is safe, universal, and interoperable. Standards define the requirements that make it possible for mobile phones sold in different countries to communicate across the world, for bank cards issued in one country to be recognized at ATMs in another, and for cars to run on fuel purchased from any gas station. Standards also help manage risk, security, safety, privacy, and quality in the development of new innovations. In short, good standards are good for business, good for consumers, and good for society. Standards Developing Organizations (SDOs) consist of experts from industry, academia, civil society groups, and government, all of whom share a common goal of ensuring safety, interoperability, and competition in a particular technology or technology application. In well functioning SDOs, ideas are selected not on the basis of the nationality, employer, or personality originating them, but instead on the basis of technical merit. Six principles govern the international standards development process: transparency, openness, impartiality and consensus, effectiveness and relevance, coherence, and a commitment to participation by low- and middle-income countries. The private sector has led U.S. engagement with SDOs for more than 100 years. An example of how this system works comes from the communications industry. Qualcomm Technologies provided the proposal in the 1990s that became the basis for all 3G standards, while NTT Docomo, a large mobile phone operator in Japan, provided the proposal that later became LTE, the predominant standard for wireless broadband communication for mobile devices and data terminals. This private sector leadership has come with significant assistance from government and academia. In 1901, the Congress established the National Bureau of Standards—which has since become the National Institute of Standards and Technology (NIST)—as the authoritative domestic measurement science research and standards laboratory. Not long after, five engineering societies and three Federal agencies banded together to establish a national non governmental body now known as the American National Standards Institute (ANSI). ANSI is a private, nonprofit organization that administers and coordinates the U.S. standardization system and is the sole U.S. representative to the International Organization for Standardization (ISO) and the International Electrotechnical Commission. Industry, consortia, and private-sector groups often complement the roles of NIST, ANSI, and ANSI-accredited SDOs, working together to develop standards to solve specific challenges. To date, this approach, supported by U.S. leadership, has fostered an effective and innovative system that has supercharged U.S. and global economic growth. In an era of rapid technological transformation and global scale, standards will continue to define and drive the markets of the future. Standards for CET—advanced technologies that are significant for U.S. competitiveness and national security - carry strategic significance. The United States will work with all nations committed to an open and transparent standards system to lead the way in these new arenas - just as we did with previous internet, wireless communications, and other digital standards. Failing to do so will risk the United States’—and the world’s—innovation, security, and prosperity. Standards for Critical and Emerging Technology The United States will prioritize efforts for standards development for a subset of CET that are essential for U.S. competitiveness and national security, including the following areas: • Communication and Networking Technologies, which are enabling dramatic changes in how consumers, businesses, and governments interact, and which will form the basis of tomorrow’s critical communications networks; • Semiconductors and Microelectronics, including Computing, Memory, and Storage Technologies, which affect every corner of the global economy, society, and government, and which power a panoply of innovations and capabilities; • Artificial Intelligence and Machine Learning, which promise transformative technologies and scientific breakthroughs across industries, but which must be developed in a trustworthy and risk-managed manner; • Biotechnologies, which will affect the health, agricultural, and industrial sectors of all nations, and which will need to be used safely and securely to support the health of our citizens, animals, and environment; • Positioning, Navigation, and Timing Services, which are a largely invisible utility for technology and infrastructure, including the electrical power grid, communications infrastructure and mobile devices, all modes of transportation, precision agriculture, weather forecasting, and emergency response; • Digital Identity Infrastructure and Distributed Ledger Technologies, which increasingly affect a range of key economic sectors; • Clean Energy Generation and Storage, which are critical to the generation, storage, distribution, and climate-friendly and efficient utilization of energy, and to the security of the technologies that support energy-producing plants; and • Quantum Information Technologies, which leverage quantum mechanics for the storage, transmission, manipulation, computing, or measurement of information, with major national security and economic implications. There are also specific applications of CET that departments and agencies have determined will impact our global economy and national security. The United States will focus standards development activities and outreach on these applications, which include: • Automated and Connected Infrastructure, such as smart communities, Internet of Things, and other novel applications; • Biobanking, which involves the collection, storage, and use of biological samples; • Automated, Connected, and Electrified Transportation, including automated and connected surface vehicles of many types and unmanned aircraft systems, many of which may be electric vehicles (EVs), along with the safe and efficient integration into smart communities and the transportation system as a whole, including standards to integrate EVs with the electrical grid and charging infrastructure; • Critical Minerals Supply Chains, where we will promote standards that support increased sustainable extraction of critical minerals necessary to manufacture renewable energy technologies, semiconductors, and EVs; • Cybersecurity and Privacy, which are cross-cutting issues that are critical to enabling the development and deployment of emerging technologies and promote the free flow of data and ideas with trust; and • Carbon Capture, Removal, Utilization and Storage, which can build on evolving standards for CO2 storage, and emerging standards for point source carbon capture, removal, and utilization, especially as those standards relate to monitoring and verification.

List five similarities and three differences. Use only the Context block contained in the prompt to respond.

What are the differences between law clerk duties for a district judge and a bankruptcy judge?

G. U.S. Trustees and Private Trustees The U.S. Trustee Program is part of the federal government’s Department of Justice, not a part of the courts. It was established to handle the administrative functions of bankruptcy cases and to ensure the integrity of the bankruptcy system across the nation. The program operates with twenty-one regional offices and ninety-four field offices, which are headed by U.S. trustees and assistant U.S. trustees, respectively. See 28  U.S.C. §§  581–589b. In the six judicial districts in Alabama and North Carolina, the Bankruptcy Administrator Program, rather than the U.S. Trustee Program, handles the administrative functions. See § 302(d) (3)(1) of the Bankruptcy Judges, United States Trustees, and Family Farmer Act of 1986, P.L. 99-554, 100 Stat. 3119, 3123, and § 317(b) of the Federal Courts Study Committee Implementation Act of 1990. The functions of the U.S. trustees are enumerated in 28 U.S.C. § 581(a), and primarily include (1) appointing and supervising the private trustees who collect and disburse funds to creditors in Chapter 7, 12, and 13 cases; (2) ensuring compliance with the Bankruptcy Code with respect to information provided in schedules, disclosure statements, reorganization plans, and other filings; (3) reviewing fee applications of professionals, such as attorneys and accountants, who serve in Chapter 11 reorganization cases; and (4) monitoring bankruptcy cases for fraud and referring criminal matters to the U.S. attorney for prosecution. Trustees do not have independent enforcement powers; rather, they must request the court to rule on matters of administration for which there is no voluntary compliance. The U.S. trustee is responsible for establishing a panel of private trustees to serve in Chapter 7 cases. When a bankruptcy petition is filed under Chapter 7, the U.S. trustee appoints a disinterested person from this panel to serve as interim trustee. At the first meeting of creditors, the creditors may elect another person as trustee, although such elections are rare. The U.S. trustee is also responsible 44 Basic Overview of Litigation in U.S. Courts fjc.dcn • fjc.gov § 3.4.A for appointing one or more “standing” trustees to administer all Chapter 12 and 13 cases filed in a geographic region. In Chapter 11 cases, no trustee is appointed unless the court orders the appointment after notice and a hearing. If the court orders an appointment, the U.S. trustee designates the person who will serve, unless a party-in-interest timely requests that the trustee be elected by the creditors. In Chapter 7, 12, and 13 cases, the U.S. trustee may act as trustee if a private trustee is unavailable, although this is rarely done. The code does not provide for the appointment of a trustee in Chapter 9 cases. 28  U.S.C. §  586, 11 U.S.C. §§ 701–704, 1202, 1104–1106, 1302.    § 3.4 Appeals A. Processing Appeals The steps in an appeal are as follows: 1. Filing a notice of appeal 2. Preparing the record on appeal 3. Docketing the appeal 4. Filing the appellant’s brief 5. Filing the appellee’s brief 6. Filing the appellant’s reply brief 7. Deciding if the court dispenses with oral argument, or scheduling of oral argument 8. Hearing oral argument 9. Deliberating by the court 10. Filing the opinion 11. Filing a petition for rehearing 12. Issuing the mandate (the final stage in the appellate process unless the party applies to the Supreme Court for a writ of certiorari) The Federal Rules of Appellate Procedure establish certain procedural uniformity among the thirteen courts of appeals. However, there are still some differences in the procedures in the various circuits. Each court has local rules and internal operating procedures that describe the precise procedure to be followed 45 Law Clerk Handbook Federal Judicial Center § 3.4.B when there is any variation from the rules and, in some instances, that elaborate on or amplify the rules. See section 4.2. B. Notice of Appeal The timely filing of a notice of appeal is a jurisdictional requirement for any appeal. Appeals may be filed to challenge decisions of the district court, an administrative agency, or a bankruptcy appellate panel. Appeals of agency decisions may be classified as original proceedings in the court of appeals. The notice of appeal is filed in the district court. The purpose of the notice is to inform opposing counsel and the court that an appeal is being taken. The clerk of that court is required by Federal Rule of Appellate Procedure 3(d) to forward a copy of the notice to the clerk of the court of appeals. The time for filing commences when the judgment or order is entered in the district court from which the appeal is taken. The running of that time is tolled by the filing of certain posttrial motions in the district court, and the filing of such motions after a notice of appeal has been filed may vitiate the notice, requiring a new notice of appeal to be filed after the motion is decided. Fed. R. App. P. 4(a). Rule 4 provides the following time periods for filing notices of appeal: • private civil cases: 30 days • civil cases in which the United States is a party: 60 days • criminal cases: 10 days • criminal cases in which appeal by the government is authorized by statute (such as appeals from sentences under the 1984 Sentencing Reform Act): 30 days Upon receipt of the notice of appeal, courts of appeals take steps to ensure that all procedural requirements have been met. The clerk’s office may send counsel a case-opening letter to establish schedules for record preparation and briefing. Circuit mediators may conduct initial mediation/settlement conferences to discuss the issues in the case, with a view to eliminating the briefing of frivolous issues and to discuss the possibility of settlement. See Mediation & Conference Programs in the Federal Courts of Appeals: A Sourcebook for Judges and Lawyers (Federal Judicial Center, 2d ed. 2006). 46 Basic Overview of Litigation in U.S. Courts fjc.dcn • fjc.gov § 3.4.D C. Record Preparation For an appellate court to review the proceedings in a trial court, appellate judges must have a record available of what occurred in the trial court. Local court rules prescribe the requirements for counsel to provide the district court with the record or excerpts of the record (sometimes referred to as a short record), which may include original papers and exhibits filed in the trial court plus a reporter’s transcript of any relevant proceedings. The Sentencing Reform Act requires that the record in a criminal case must also include “(1) that portion of the record . . . that is designated as pertinent by either of the parties; (2) the presentence report; and (3) the information submitted during the sentencing proceeding.” 18 U.S.C. § 3742(d). This information will often be under seal, because it is confidential. The Federal Rules prescribe time limits (deadlines) for providing the record on appeal to the court of appeals. During this time, the appellant must order a transcript of proceedings if one is needed and make arrangements to pay the court reporter for services or, in courts using electronic sound recording for the official record, the clerk of court. The district court clerk assembles the other papers or electronic files that constitute the record on appeal. The district court has the power to extend for an additional fifty days the time for preparing and sending the record on appeal, after which the court of appeals itself may grant extensions. Additional time may be needed if the court reporter has not finished transcribing the proceedings or if counsel has failed to order the transcript in a timely manner. To prevent undue delay, the appellate courts have the discretion to refuse to grant time extensions and may impose sanctions on the appellant or the reporter for unreasonable delays in preparing the record on appeal. D. Docketing the Appeal When the record is completed, or earlier if desired, the appellant must docket the appeal. This is primarily a clerical process and is performed in the office of the clerk of the court of appeals. Unless the appellant is exempt from payment, a docket fee is charged. The clerk of court opens an appropriate file and record and sends a notice to the parties. Frequently, docketing takes place when the record on appeal is filed. The filing of the record provides the base date for most subsequent proceedings in the case. 47 Law Clerk Handbook Federal Judicial Center § 3.4.E E. Briefs and Joint Appendices Because the appellant has the burden of establishing that the trial court erred, it files the opening brief. The appellee then files a brief in response; if the appellant wishes, the appellant may file a reply brief responding to new matters raised in the appellee’s brief. The Federal Rules of Appellate Procedure establish standards for format, color of brief covers, content, methods of reproduction, number of copies, and times for filing of briefs. The local rules for a circuit may impose further requirements. The schedule for filing briefs is as follows: • appellant’s brief: 40 days after filing the record • appellee’s brief: 30 days after service of appellant’s brief • reply brief: 14 days after service of appellee’s brief Some courts of appeals have modified the requirements and standards of the federal rules in certain cases or classes of cases. One of the more common modifications permits parties appealing in forma pauperis to file fewer copies of their briefs. While the briefs are being prepared, the parties are required to determine which portions of the record on appeal are relevant to the issues raised; the appellant is required to reproduce these portions as an appendix to the briefs. There may be only one appendix containing the portions relied on by both the appellant and the appellee, which would be referred to as a joint appendix. If any relevant material is omitted from the appendix, the court is free to refer to the original record. Multiple copies of the appendix may be filed so that each judge and, if needed, each law clerk may have one. Some courts of appeals have eliminated the requirement of an appendix and permit the substitution of photocopies of relatively few parts of the record, usually called record excerpts. The local rules of those courts describe the substitute requirements. Local rules also address procedures for electronic filing. You should become familiar with the rules and procedures in your court. F. Oral Argument If the court does not decide a case exclusively on the basis of the briefs and written record (see section 4.6.B on screening cases to select those appeals to be decided without oral argument), the parties are given an opportunity to present their arguments to the court orally. Federal Rule of Appellate Procedure 34 permits the court to fix the time allowed for oral argument. Courts may allow counsel to file a request in advance for additional time, and the courts have the discretion whether to grant these requests. Generally, not more than two attorneys are 48 Basic Overview of Litigation in U.S. Courts fjc.dcn • fjc.gov § 3.4.G permitted to argue for each side. Some court rules encourage argument by only one attorney for each party. Many appellate judges require their law clerks to prepare a memorandum on each case (called a bench memo) for the judge to review before hearing oral arguments. In some circuits, the law clerk for one judge may prepare a memorandum to be circulated among the three judges on the panel prior to oral argument. The judges will study the briefs before oral argument. The appellant begins the argument. Because the judges have read the briefs and are therefore familiar with the issues, they sometimes begin questioning the attorney shortly after the argument begins. After the appellant’s argument is completed, the appellee responds, followed by any reply by the appellant (if the appellant reserved time for rebuttal). Although the arguments are recorded, so that the judges and their law clerks may later review them, some circuit judges may request one of their law clerks to attend oral argument and take notes of important matters, citations of new authorities, and concessions made during the argument. Most cases are heard by a panel of three judges, but a case may be heard en banc in cases involving a question of exceptional importance or in order to secure or maintain uniformity of decisions. A case heard en banc is heard by all of the active judges on the court and any senior judge of the circuit who sat on the panel that originally heard the case (or, in the Ninth Circuit, by a limited en banc, consisting of the chief judge and ten additional judges selected by lot). En banc hearings are held only when ordered by a majority of the active judges on the court. Some courts hold hearings in only one location, but most hold court in a number of locations within the circuit. G. Deliberation After a case has been argued and submitted to the court, the panel of judges who heard the argument meets to arrive at a decision. In most courts, these meetings are held immediately after the completion of each day’s arguments. Appellate courts perform three distinct functions. First, they decide the controversies before them. Second, they supervise the courts within their jurisdiction. Third, they determine the growth and development of the common law and the interpretation of federal statutory and constitutional law within their jurisdiction. Each of these functions can become important during the decisional phase of an appeal because the court must not only reach the correct result but also explain in its opinion the rationale for its decision. 49 Law Clerk Handbook Federal Judicial Center § 3.4.H In most cases, the court arrives at a tentative decision at the first meeting. At that time, the presiding judge (the senior active circuit judge sitting on the panel) assigns the case to one member of the panel, who later writes an opinion to be submitted to the others for approval. When the judges do not reach agreement so readily, panel members may exchange memoranda about the case and schedule additional meetings or telephone conferences for further discussion. Law clerks for appellate judges should know and follow the court’s internal rules and its customs concerning communications between chambers. H. Opinion and Judgment The final product of the court in most appeals is a written opinion setting forth the decision and the reasoning behind it. The increased number of cases and the burden of writing formal opinions in every case has caused appellate courts to use alternatives to formal opinions (such as memorandum, order, or summary opinions) in many cases, such as those involving only the application of settled principles to a specific fact situation. Local rules or policies may guide the members of the court in deciding which cases deserve full opinions and which opinions should be published. When a panel has agreed on an opinion, the authoring judge electronically transmits it to the clerk of court for public docketing and release. All courts post opinions on the court’s public website. In some courts, before opinions are released, they are circulated to all active judges on the court with a time limit for making suggestions. Sometimes when a judge or a group of judges disagrees with the majority decision reached by their colleagues and they feel strongly enough about it, the judge or judges will write a dissenting opinion explaining what aspects of the decision they disagree with and why. Even though they express opinions that did not prevail, dissents can contribute to the legal debate over the issues at hand and provide judges in similar cases with different perspectives. I. Rehearing The party who loses an appeal may file a petition for rehearing within fourteen days after judgment is entered. That petition attempts to persuade the panel that the decision was erroneous and should be withdrawn or revised. The prevailing party may not file a response to the petition unless one is requested by the court. Most petitions for rehearing are denied. The losing party may also move for a rehearing en banc. That motion is circulated to all members of the original panel and all active judges who did not sit 50 Basic Overview of Litigation in U.S. Courts fjc.dcn • fjc.gov § 3.4.K on the panel. Only the active circuit judges and any senior judge who was a member of the original panel may request a vote on the suggestion to rehear the appeal en banc, and only the active circuit judges may vote on whether the appeal should be reheard en banc; if a rehearing en banc is granted, only active circuit judges and senior circuit judges from the circuit who were members of the original panel may sit on the rehearing. By local rule, a circuit may impose time limitations within which a member of the court may request an answer to a petition for rehearing or rehearing en banc or a vote on such a petition. J. Mandate The mandate is the document by which the court of appeals formally notifies the district court of its decision and by which jurisdiction for any necessary additional proceedings is conferred upon the district court. The mandate is issued by the clerk of court seven calendar days after the time to file a petition for rehearing expires, or seven calendar days after entry of an order denying a timely petition for panel rehearing, petition for rehearing en banc, or motion for stay of mandate, whichever is later. These times may be shortened or lengthened by court order. Fed. R. App. P. 41(b). The losing party may request by motion that the issuance of the mandate be stayed in order to maintain the status quo during the pendency of an application for a writ of certiorari to the Supreme Court. The court of appeals may require that a bond be posted as a condition to staying the issuance of the mandate. K. Motions During the course of an appeal, the parties may file a variety of motions. Most of these are procedural and, to the extent permitted by the Federal Rules of Appellate Procedure, some courts have authorized their clerks of court or other court unit executives to act on motions, for example, motions • for extensions of time to perform any of the acts required by local rules or the Federal Rules of Appellate Procedure • for relief from specific requirements of the local rules or the Federal Rules of Appellate Procedure • for permission to alter the form or content of the record on appeal; • for leave to file amicus curiae briefs • for delay in the issuance of the mandate • for voluntary dismissal of the appeal 51 Law Clerk Handbook Federal Judicial Center § 3.4.L Motions requiring action by a judge or panel of judges are those • on issues relating to criminal cases or suits for postconviction relief such as motions for appointment of counsel, leave to appeal in forma pauperis, certificates of probable cause, and bail pending appeal • for stays or injunctions pending appeal • for leave to file interlocutory appeals • for issues relating to stays granted in the district court • for permission to file a brief containing more pages than the number fixed by the rules • for issues relating to the time allowed for oral argument • to dismiss an appeal filed by the appellee In most courts, the staff attorney’s office is responsible for reviewing motions and referring them to judges for appropriate disposition. L. Emergency Proceedings Both district courts and courts of appeals are frequently asked to make decisions on an emergency basis. In the appellate courts, these occasions usually arise when a litigant or a lower court is about to take some action that may cause irreparable injury. The potentially aggrieved party seeks redress by motion for stay or injunction pending appeal or by petition for writ of mandamus or prohibition. In the district courts, these matters usually arise through a request for a temporary restraining order. Each court has developed internal procedures for handling these matters efficiently, but the procedures vary among courts. Courts have also established special procedures for handling emergency appeals of capital (death penalty) cases. Law clerks should become familiar with the procedures established by the local rules and the judge’s own practices.    § 3.5 Courts of Specialized Jurisdiction You may also encounter litigation from one of the various special courts established by Congress. The term special courts derives from their specialized jurisdiction. 52 Basic Overview of Litigation in U.S. Courts fjc.dcn • fjc.gov § 3.5.D A. Court of Appeals for the Federal Circuit The Court of Appeals for the Federal Circuit, based in Washington, D.C., has jurisdiction over appeals from the following: district courts in cases involving patents and certain claims against the United States; the U.S. Court of Federal Claims; the Court of International Trade; the Court of Veterans Appeals; the Merit Systems Protection Board; the Patent and Trademark Office; the boards that decide government contract issues; and a few other Article I agencies. B. Court of International Trade The Court of International Trade, based in New York City, hears cases concerning the value or classification of imports. Its judges may sit by designation on other Article III courts. C. U.S. Judicial Panel on Multidistrict Litigation This panel was created to consider transferring civil actions involving one or more common questions of fact pending in different districts to a single district for coordinated or consolidated pretrial proceedings. The panel consists of seven district and circuit judges who are appointed by the Chief Justice and sit on the panel in addition to their regular judicial assignments. The panel maintains a roster of transferee judges to whom it assigns the cases it certifies for transfer. For discussion of multidistrict litigation problems, see section 3.1.F. D. Foreign Intelligence Surveillance Court The Foreign Intelligence Surveillance Court (FISC), or the FISA court, as it is popularly called (after the Act that created it), is composed of eleven federal judges, selected by the Chief Justice to a nonrenewable seven-year term. The court’s job is to review applications for governmental surveillance of persons within the United States whom the government suspects of having connections to foreign governments and/or terrorist organizations. A Foreign Intelligence Court of Review was also established to review applications denied by the FISA court. 53 Law Clerk Handbook Federal Judicial Center § 3.6    § 3.6 Article I Courts Congress has created many tribunals to assist it in meeting its legislative responsibilities under Article I of the Constitution. These courts do not exercise judicial power conferred by Article III, and the judges are appointed for fixed terms rather than given life tenure. They include the many administrative law judges serving in the executive agencies who hear disputes over claims and benefits, subject to review by agency officials. A. U.S. Tax Court The U.S. Tax Court has jurisdiction over controversies involving deficiencies determined by the commissioner of internal revenue in income, estate, and gift taxes, as well as other tax-related disputes between taxpayers and the Internal Revenue Service. The principal office of the court is located in Washington, D.C., and it conducts trial sessions in other cities throughout the United States. B. U.S. Court of Federal Claims The U.S. Court of Federal Claims was originally called the U.S. Claims Court. The court has jurisdiction over claims brought against the U.S. government. The court is located in Washington, D.C.; however, its jurisdiction is nationwide, enabling it to conduct trials in locations convenient to the parties involved in the case. C. U.S. Court of Appeals for the Armed Forces Congress established the U.S. Court of Appeals for the Armed Forces as an appellate criminal court, hearing all cases involving military courts-martial. It is located in Washington, D.C. D. U.S. Court of Appeals for Veterans Claims The U.S. Court of Appeals for Veterans Claims has exclusive jurisdiction to review the decisions of the Board of Veterans Appeals. The court’s principal location is in Washington, D.C., but it may hold court anywhere in the United States. 54 fjc.dcn • fjc.gov 4 Chambers and Case Management    § 4.1 Chambers Administration This chapter gives you a broad overview of some of your responsibilities as a law clerk in maintaining a well-run chambers. These responsibilities include helping to ensure chambers security; answering telephones and mail; maintaining the judge’s motion, hearing, and trial calendars; and other miscellaneous matters. Discussing all such duties would, of course, be impossible, and some judges have chambers manuals detailing how they expect their chambers to operate. Understanding and accommodating your judge’s preferences is key to maintaining an efficient chambers, and regardless of the general guidance offered in this chapter, you should always follow the particular policies and practices of your judge. Effective management is essential to the efficient administration of justice. While judicial assistants often have principal responsibility for managing various aspects of chambers administration, as a law clerk you should be familiar with the standard operating procedures in your chambers and be available to pitch in when needed. A. Security The safety and security of federal buildings and the people who work in and visit them are major concerns for the U.S. Marshals Service (USMS). Attorneys and other members of the public must pass through magnetometers and have their briefcases and other items screened by an X-ray machine to enter most courthouses and other federal buildings. In addition, all judges’ chambers are equipped 55 Law Clerk Handbook Federal Judicial Center § 4.1.A with an entry control system that consists of a security camera and monitor and a door release strike. Courthouse employees may be issued keycards enabling them to enter the courthouse without passing through metal detectors and to access secured, nonpublic sectors of the building, including judges’ chambers, depending on the individual court’s access-control security plans. Employees may also have after-hours and weekend access to the building through use of these keycards, which should be kept in a secure place and reported immediately if lost. All courthouse employees should carefully follow security procedures and report potential problems to the USMS. The U.S. Marshals Service is principally responsible for security of the court and its personnel, though most courthouse security functions are performed by court security officers (CSOs), who are funded by the judiciary’s Court Security Program and by the Federal Protective Service on a limited basis. Become familiar with the court’s Occupant Emergency Plan and other related USMS security plans in your courthouse, and help to maintain a secure chambers. Do not let unauthorized strangers into secure areas of the courthouse, and report suspicious mail or threatening phone calls. During security-sensitive proceedings, a judge may request that a deputy from the U.S. Marshals Service or a CSO be present in the courtroom. Because federal judges are occasionally the targets of terrorists or disgruntled litigants, be careful when opening mail. Mail received in the courthouse is routinely screened by the USMS before distribution to chambers and offices. Still, it pays to be alert to suspicious-looking items. Common recognition points for letter and package bombs include the following: • foreign mail, air mail, and special delivery • restrictive markings (e.g., confidential, personal) • excessive postage • handwritten or poorly typed addresses • incorrect titles • titles, but no names • misspelled common words • oily stains or discolorations • no return addresses • rigid envelopes • lopsided or uneven envelopes 56 Chambers and Case Management fjc.dcn • fjc.gov § 4.1.C • protruding wires or tinfoil • excessive securing material such as masking tape or string • drawings, diagrams, or illustrations If a letter or package arouses attention, do not attempt to open it. Instead, immediately notify the marshals’ office or a CSO. B. Telephone Practices for dealing with incoming calls (e.g., how to answer the telephone, how to take messages, and when and if to transfer a call to the judge) will vary from chambers to chambers. In general, however, answer calls promptly, identify the office (e.g., “Judge Smith’s chambers”), and treat all callers courteously. And, of course, hold personal calls to a minimum, both in length and in number. See section 2.2.A.1 on communication with the media. C. Correspondence, Email, and Other Mail In addition to correspondence by U.S. postal and messenger service, many chambers now correspond by email with a wide variety of people, including counsel. While email has in some ways made communicating easier and more efficient, it has also made it even more important to stay on top of organizing and processing the mail. Email also presents serious potential problems relating to the accidental forwarding of messages, either to unintended parties or containing information not intended for the recipient. And bear in mind how easily emails can be broadly disseminated through forwarding and posting on websites and social media. Take special care to avoid sending and forwarding email messages that may result in embarrassment, a breach of confidence, or worse, and review and carefully proofread any outgoing messages (and fight the temptation not to proofread email as carefully as paper correspondence). Most chambers have practices and procedures for handling incoming and outgoing mail, including email (whether and when to delete email messages, how to store important messages for future reference, and other matters of email retention and organization). Quickly become familiar with these practices to help mitigate complications arising from the enormous number of emails that many chambers receive. Depending on office procedure, either a judicial assistant or a law clerk will open and review correspondence and make an initial decision concerning how 57 Law Clerk Handbook Federal Judicial Center § 4.1.C it should be handled. Many judges receive their own emails directly, though some may ask staff to review messages first. Incoming mail and emails should be reviewed as soon as they are received because they may relate to matters scheduled for that day. When correspondence referring to a pending suit is forwarded to any counsel of record over the signature of the judge, law clerk, or judicial assistant, copies should be sent to all other counsel of record to avoid inappropriate ex parte contact. Appellate judges seldom correspond directly with counsel on case-related matters, because appellate judges work on cases as part of a panel or court rather than individually. Instead, appellate judges will send instructions to the clerk of court on how to respond to counsel. Correspondence from the general public that is not related to a case is still important because citizens have a right to courteous treatment. Also, the public’s opinions about the fairness, responsiveness, and effectiveness of the judiciary are influenced by the promptness and appropriateness of the court’s answers. In the district court, some of the correspondence from the public involves requests to be excused from jury service. That subject is dealt with in section 4.3.D.2. Some correspondence contains character references on behalf of an offender who is scheduled for sentencing. Judges differ in their handling of such correspondence. Many simply acknowledge receipt of the letter and refer the letter to the probation office. Other correspondence from the public may express reactions to a judge’s ruling. Whether positive or negative, expressions of opinion by members of the public generally call only for courteous acknowledgment, not for an explanation or justification of the judge’s action. If a letter requests information about a ruling, many judges simply acknowledge receipt of the letter and send a copy of the opinion, if there is one. If more information is requested, many judges refer the writer to the record in the clerk of court’s office. Some judges may wish to respond to a letter that indicates a misunderstanding concerning a significant fact, proceeding, or legal conclusion. Judges who adopt this policy may ask law clerks to prepare a draft of a response for the judge to review. The response should not be argumentative or defensive; it should merely state the relevant facts or legal conclusion as necessary to alleviate the misunderstanding. Prisoners and persons who have been convicted and are awaiting sentence frequently write district and appellate judges. Handle the correspondence of a prisoner represented by counsel the same way as that of any other litigant. Ask your judge how to handle correspondence from prisoners who are proceeding pro se. In some instances, this correspondence may be handled by district court pro se law clerks or, in the appellate courts, either the clerk’s office or staff attor58 Chambers and Case Management fjc.dcn • fjc.gov § 4.1.D ney’s office. In other instances, your judge may have a form letter explaining, for example, that federal law prohibits judges from giving legal advice and suggesting that the prisoner communicate with a lawyer, or a form letter for responding to requests for transfers to another penal institution (which only the Bureau of Prisons can grant). You should never write anything in a letter that would give a prisoner false hope or could compromise the position of the court. D. Internet and Electronic Research New law clerks will receive a Westlaw and/or a LexisNexis password, which may come with additional electronic research training and certain usage guidelines. All computer-assisted legal research (CALR) use via judiciary contracts is to be limited to official judiciary-related research purposes. In addition to these research services, the Internet also offers more informal avenues of research, including access to nearly every newspaper and magazine in the country, as well as to government and law school websites, Internet search engines, and myriad other sources. Contact the circuit library CALR coordinator for assistance with CALR access or training. The CALR coordinators and reference librarians are also available to assist with your research questions. Become familiar with fjc.dcn (http://fjc.dcn), the Federal Judicial Center’s site on the judiciary’s intranet. It provides access to manuals, monographs, desk references, and other publications, as well as to web-based training and orientation programs, streaming media programs, discussion forums, and other resources. JNet (http://jnet.ao.dcn), the intranet site maintained by the Administrative Office of the U.S. Courts, offers information and forms on a range of topics relevant to judicial employees, including benefits, court security, emergency preparedness, human resources, information technology, legal and general research, and travel. The Internet has also posed some serious security and usage challenges for employees and information technology departments in courthouses across the country. The judiciary provides you with a computer and Internet access to help you do your work. Depending on the policy in your court or chambers, you may use it on a limited basis for personal needs if doing so does not interfere with your work and does not cause congestion, delay, or disruption of service to any government system. You should not do anything on your office computer that would embarrass you or the court if it were made public. 59 Law Clerk Handbook Federal Judicial Center § 4.1.E E. Electronic Filing The federal judiciary’s Case Management/Electronic Case Filing (CM/ECF) system allows courts to maintain case documents in electronic form and provides enhanced and updated docket management services. It also gives each court the option to permit case documents—pleadings, motions, petitions—to be filed electronically with the court. CM/ECF uses an Internet connection and a browser and accepts documents in Portable Document Format (PDF). It is easy to use. Filers prepare documents using conventional word-processing software and save them as PDF files. After logging on to the court’s website with a court-issued password, the filer enters basic information about the case and document being filed, attaches the document, and submits it to the court. CM/ECF automatically generates a notice verifying that the court received the filing, and it also sends an email to other parties in the case notifying them of the filing. There are no added fees for filing documents using CM/ECF, but existing document filing fees do apply. Litigants receive one free copy of documents filed electronically in their cases, which they can save or print for their files. Public electronic access to court data is available through the Public Access to Court Electronic Records (PACER) program. Additional copies are available for a small fee to attorneys and the general public for viewing or downloading. The process for receiving and reviewing daily filings in the cases filed before the judge may vary among courts and chambers; you should quickly learn the process in your chambers and your role in implementing and maintaining it. Although familiarity with the workings of the system is helpful, you should refer counsel’s questions to docketing clerks or others in the clerk’s office who deal with the system on a daily basis. F. Judge’s Chambers Calendar The judicial assistant is usually in charge of maintaining the chambers calendar covering the judge’s scheduled court proceedings and other activities. If the calendar is maintained online, other staff on the chambers network may also have limited access to the judge’s schedule. In appellate courts, the clerk of court advises the judge of panel assignments and hearing dates. The judicial assistant, in consultation with the judge, will then schedule all other engagements and commitments around the hearings. In trial courts, the judicial assistant usually confers with the judge and then typically advises the courtroom deputy in charge of scheduling the court calendar of the dates on which trials and hearings are to 60 Chambers and Case Management fjc.dcn • fjc.gov § 4.1.H be set. The judicial assistant then schedules the judge’s remaining commitments around the trials and hearings. Some judges choose not to have a judicial assistant, which allows them to have an additional law clerk. In these instances, a law clerk may maintain the chambers calendar. G. Opening Court In district courts, a law clerk or courtroom deputy usually opens court. One common method is for the clerk or deputy to rap on the door before the judge enters, open the door, then call out, “All rise.” The judge then enters and walks to the bench. The law clerk or deputy walks to the front of the bench and says: “The United States District Court for the ____ District of ____ is now in session. The Honorable ______ presiding.” The judge usually stands during this call, then says, “Please be seated,” and sits. H. Maintaining the Library; Office Supplies, Equipment, and Furniture Many chambers maintain their own libraries, though electronic databases and Internet research reduce the need for access to hard-copy sources and have enabled chambers in the same courthouse to share libraries. In any event, the employee who maintains the library, either a law clerk or a judicial assistant, should regularly file any advance sheets, pocket parts, slip opinions, replacement volumes, and inserts for loose-leaf services that arrive in the mail. File materials daily so that library maintenance does not become burdensome and the materials are current. Procurement and ordering of all law books is done by the circuit library; contact the librarian if you have questions. Promptly rubber-stamp every incoming library book to identify it as U.S. property. Keep track of books borrowed by attorneys for courtroom use and make sure that books are not taken outside the chambers and courtroom. Promptly reshelve books used during the course of research. They will then be easier to find, and the library will be neater. Also be sure that legal pads, book markers, pencils, and pens are always available in the library. Requests for supplies, equipment, and furniture ordinarily are handled in the clerk of court’s office. 61 Law Clerk Handbook Federal Judicial Center § 4.1.I I. Maintaining Office Records and Files You may have to maintain some of the records in your judge’s office, including the following: • case files • trial schedules or calendars • “tickler” records to remind the judge about future case activities • indices to the judge’s prior decisions • indices to slip opinions • work papers relating to cases in progress Such materials may be stored in hard copy, electronically, or both. Some chambers may also maintain office form books, either in hard copy or electronically. The form books may contain office procedure checklists and frequently used forms, such as samples of letters, orders, opinions, jury charges, minute entries, and office or file memoranda written by prior law clerks. The books describe the format and method for written documents issued by the judge or presented to the judge by chambers staff. The form books provide continuity and consistency in office administration and can help educate new law clerks. If case records are being used in the judge’s chambers, make sure that the records are not misplaced and are returned to the office of the clerk of court as soon as the judge or staff member has finished with them. J. Statistical Reporting The JS-10 form, “Monthly Report of Trials and Other Court Activity,” is a report of the trials and nontrial proceedings that a district judge conducted during the month. The clerk of the district court submits a JS-10 form to the Administrative Office for each active or senior district judge, plus any visiting district judges or appellate judges, who conducted trials or proceedings in the district during the month. The form reports both the number and type of trials and proceedings and the amount of time the judge spent conducting them. Some judges fill out the forms themselves, but usually a member of the chambers staff or the courtroom deputy fills out the form for the judge. The CM/ECF systems in some courts can automatically generate the JS-10 reports based on additional information about the trials and proceedings entered during the normal docketing process. Data on magistrate judge workloads and activities are collected through the MJSTAR 62 Chambers and Case Management fjc.dcn • fjc.gov § 4.1.L function in district CM/ECF systems, which stores that data in the NewStats database. This includes not only the number of tasks completed by magistrate judges, but the time burden of many of these duties, including time spent with attorneys and parties. Bankruptcy courts report trials and other court activity on a monthly basis using the B-102 form. Courts of appeals use the JS-30 form to report the number of appellate cases, interlocutory appeals, and petitions for rehearing each month. K. Out-of-Town Trips Some judges must travel to other cities to attend court sessions and may require a chambers staff member to travel with them if the court to which they are traveling does not provide staffing. Judges may also travel on court-related business. Judicial assistants usually arrange travel (although when the judge has chosen to have an additional law clerk in lieu of a judicial assistant, a law clerk may have to make travel arrangements). If your judge is traveling to hold court in another location, prepare for the judge to take along necessary case files and materials; any personal notes or memoranda relating to the cases to be heard; the judge’s robe; paper, pencils, stationery, and other needed supplies (if the site for the out-of-town session is one frequently used by the court, there may be a permanent stock of stationery and supplies); necessary equipment such as a gavel, recording or dictating equipment, and a laptop or tablet computer; the briefs and any other case materials; and mailing labels and envelopes for returning material that the judge does not wish to carry back. Judges and chambers staff who travel on court business will be reimbursed for transportation, food, lodging, and related expenses according to the detailed rules set forth in the Guide to Judiciary Policy. These rules generally reimburse either a flat dollar amount per day, regardless of actual expenses, or itemized actual expenses not in excess of a fixed dollar amount. The judicial assistant should have forms for travel reimbursement—these forms can also be found on JNet. Judges must also report travel not related to cases under regulations found in Volume 19, section 270, of the Guide to Judiciary Policy. L. Assisting with Judges’ Extrajudicial Activities Many judges engage in teaching, writing, lecturing, and other extrajudicial activities. While law clerks may be called on to assist judges in these activities, the Code of Conduct for United States Judges says that judges should not use staff “to any 63 Law Clerk Handbook Federal Judicial Center § 4.1.M substantial degree” to engage in extrajudicial activities to improve the law, the legal system, and the administration of justice; and judges should not use staff to engage in other extrajudicial activities, “except for uses that are de minimis.” M. Preserving Chambers Papers for Historical Purposes The chambers papers of a district or appellate court judge have historical significance as an essential supplement to the official court record. Many papers in judges’ chambers are widely considered valuable, such as correspondence and background material concerning a case, including memoranda between judges and law clerks and judges on an appeals panel; drafts of orders and opinions (particularly draft opinions that have handwritten comments on them, or that have been circulated to other judges and returned with their comments); and correspondence/memoranda concerning court administration, legal activities in the community, and issues of governance, politics, and law. Chambers papers are the personal property of the judge. Each judge has the prerogative to make final decisions about the preservation of chambers papers and the terms of access. Judges can preserve their personal papers and make them available for eventual study by donating them to a manuscript repository. An FJC publication, A Guide to the Preservation of Federal Judges’ Papers (3d ed. 2018), reviews the organization and preservation of historically significant records created by federal judges. The Federal Judicial History Office at the FJC will also provide assistance on issues concerning judges’ papers. N. Rules Regarding the Media in Court Guidelines for allowing cameras and electronic reproduction equipment in the courtroom are published in Volume 10 of the Guide to Judiciary Policy. The guidelines allow the photographing, recording, or broadcasting of appellate arguments. In trial courts, a presiding judge may authorize broadcasting, televising, recording, or taking photographs in the courtroom during ceremonial proceedings. For nonceremonial proceedings, such activities may be allowed for presenting evidence, perpetuating a record of the proceedings, and for security or judicial administration purposes. Federal Rule of Criminal Procedure 53 prohibits photographing and radio broadcasting of criminal proceedings. Some circuit judicial councils have adopted specific instructions for the use of cameras in the courtroom. Although local rules restrict the means by which news may be reported (e.g., no cameras or broadcasting from the trial courtroom 64 Chambers and Case Management fjc.dcn • fjc.gov § 4.2 or environs), “there is nothing that proscribes the press from reporting events that transpire in the courtroom.”    § 4.2Local Court Rules and Administrative Policies Section 2071 of Title 28 of the U.S. Code authorizes federal courts to adopt their own rules, which must be consistent with the national rules and available to the public; it also authorizes the circuit judicial council to abrogate district and bankruptcy courts’ local rules, and authorizes the Judicial Conference to abrogate rules of courts of appeals. Federal Rules of Appellate Procedure 47, Bankruptcy Procedure 9029, Civil Procedure 83, and Criminal Procedure 57 provide additional requirements for local rule adoption and characteristics. The local rules of almost all courts follow the same numbering sequence as the corresponding national rules. These local rules include the procedures for setting cases for trial, scheduling pretrial conferences, setting motions for oral argument, serving memoranda of law, and other details relating to trial. They may also state the procedure for admission of attorneys to practice in the specific district or circuit, the term of the court, the functions of the clerk of court, the rules for filing motions, and more specific data, such as the number of copies required to be filed, limitations on the length of memoranda, the time within which memoranda must be filed, and restrictions on page length, typeface, and margin size. Each court of appeals has local rules concerning procedures for ordering transcripts; filing and docketing the appeal; calendaring; motions; summary disposition of appeals; setting cases for oral argument; time limits on oral argument; petitions for rehearing; petitions for en banc consideration; and stay of mandate. The local rules and internal operating procedures of the courts of appeals are printed in the United States Code Annotated following Title 28 of the Judicial Code, and are available on the courts’ websites. A court’s local rules and any internal operating procedures it adopts establish specific procedures for the court and litigants to follow. You should get these rules and procedures from the court’s website or the clerk’s office and become familiar with them. Keep them available for reference and be on the lookout for any modifications the court may adopt. 65 Law Clerk Handbook Federal Judicial Center § 4.3    § 4.3 Case Management: The Trial Court Many judges believe that the responsibility for moving a case through the trial court is not solely that of the attorneys, and the function of the court is not simply to be available if and when counsel want a hearing. The disposition of all cases as speedily and economically as is consistent with justice is paramount. The Federal Rules of Civil Procedure are to be “construed to secure the just, speedy, and inexpensive determination of every action.” Fed. R. Civ. P. 1. The courts are also required to report semiannually (on April 30 and September 30) for each judge the motions that have been pending and the bench trials that have been submitted for more than six months, and cases that have not been terminated within three years of filing, for publication by the Administrative Office. 28 U.S.C. § 476. Effective docket control means that, early in a case, the judge assumes responsibility for guiding the case to a conclusion. This may include establishing deadlines for filing motions, a time limit for discovery, a date for counsel to take the next step in its prosecution, and a trial date. For specific techniques of case management, consult the Civil Litigation Management Manual. See also Schwarzer & Hirsch, The Elements of Case Management (Federal Judicial Center, 3d ed. 2017). Note that many of the same considerations apply in criminal cases, with the additional complication of computations required by the Speedy Trial Act. 18 U.S.C. §§ 3161–3174. Law clerks should be familiar with the requirements of the Act, since failure to bring a case to trial within the Act’s time limits can have serious repercussions. A. Office Status Sheets Some judges maintain an office status sheet and post it where it is accessible to chambers staff. Its purpose is to keep the judge, the law clerks, and judicial assistants apprised of legal matters under advisement and awaiting disposition. When a matter has been taken under advisement, the assistant or law clerk assigned to the case should indicate it on the status sheet. Keep a personal status list, which can be revised each week, listing all matters for which you are responsible. It will help you make effective use of your time and remember all pending assignments. Some judges require their law clerks to submit personal status lists weekly. Some judges require their judicial assistants to keep a list of all pending matters, the initials or name of the law clerk assigned to work on the matter, and 66 Chambers and Case Management fjc.dcn • fjc.gov § 4.3.C any other pertinent information. If so, keep the assistant advised of all matters assigned, matters completed, and other relevant status information. CM/ECF helps judges use computer technology for docket control and to maintain case inventories and case-status records. Other systems may also be employed. Regardless of which system is used, it is important that it be regularly maintained and continually monitored. B. Calendaring Systems Multijudge trial courts need a system for determining which judge is responsible for each case. In an individual calendar system, each case is randomly assigned to a particular judge at the time it is filed, or soon thereafter, and that judge has complete responsibility for the case until it is terminated. There are also standard procedures for reassigning cases from which the original judge is disqualified, for ensuring that related cases are all assigned to the same judge, and for special assignment of unusual and protracted cases. Local rules usually describe these procedures. C. Trial Scheduling A single trial may be set for a specific date, or the court may set multiple cases for trial on the same day. Some courts use the trailing calendar or trailing docket, in which the court schedules a number of cases for trial beginning on a stated date. The cases are tried in the order reflected by the schedule. Counsel must obtain information from the court and from the attorneys whose cases precede them on the calendar about the progress of those cases, so that they can go to trial whenever the court reaches their case. Most civil cases do not go to trial but are disposed of in some other manner, including dispositive motions and settlement. Judges differ in their approach to encouraging settlement, but the decision whether to settle or proceed to trial is the parties’ alone. If settlement is to be reached, negotiations should be completed in a timely manner. Last-minute settlements may disrupt the court’s schedule, leaving the judges, and sometimes jurors, with unscheduled time. The trailing calendar and other multiple-case-setting devices alleviate some problems caused by last-minute settlement by providing substitute cases to replace those that do not go to trial. Although this resolves the court’s problems, it does not resolve the problems that eve-of-trial settlements cause litigants and counsel. 67 Law Clerk Handbook Federal Judicial Center § 4.3.D Criminal cases take priority on the court’s calendar because they must be tried within the time limits set forth in the Speedy Trial Act. While criminal cases do not settle, the vast majority of them are disposed of by way of plea bargaining and guilty pleas, which again make multiple-case-setting an important calendaring device for the court. D. Jury Management 1. Random Juror Selection The selection of grand and petit jurors in both criminal and civil cases is governed by 28 U.S.C. §§ 1861–1878, under which each district must have a jury selection plan that has been approved by a panel comprising the circuit judicial council and the chief district judge or the chief judge’s designee. The statutory goal of the selection process is to ensure “grand and petit juries selected at random from a fair cross section of the community in the district or division wherein the court convenes” (28 U.S.C. § 1861), and to avoid excluding any citizen “from service as a grand or petit juror . . . on account of race, color, religion, sex, national origin, or economic status” (28 U.S.C. § 1862). The clerk of court usually manages the process of selecting prospective jurors, under the supervision and control of the court. Although the jury selection process may differ slightly in each district, it is generally as follows: 1. The clerk’s office performs a random selection of prospective jurors’ names by computer or manually, using voter registration lists or other sources specified by the court’s plan, and places the names selected in a master jury wheel, which is usually a computer file. The minimum number of names in the master jury wheel must be one-half of 1% of the number on the source lists, or 1,000, whichever is less. 2. As needed by the court, the clerk’s office draws names publicly at random from the master jury wheel and sends jury-qualification questionnaires to those persons whose names are drawn. 3. From the responses to the questionnaires, a determination is made as to which persons are qualified for jury service and which persons are disqualified, exempt, or excused. 4. The names of those determined to be qualified are placed in a second jury wheel consisting of qualified jurors. 5. As needed, the clerk’s office selects names from the qualified jury wheel and prepares lists of the names selected. 68 Chambers and Case Management fjc.dcn • fjc.gov § 4.3.D.2 6. The clerk’s office issues summonses to the necessary number of persons needed for the jury venire several weeks in advance of each trial calendar advising those summoned of the time and place to report for jury service. Some district courts qualify and summons jurors in one step and do not establish a qualified jury wheel. 2. Exemptions, Disqualifications, and Excuses A person is qualified for jury service unless the person • is not a citizen of the United States • is unable to read, write, and understand English with a degree of proficiency sufficient to complete the juror-qualification form satisfactorily • is incapable of rendering satisfactory service because of mental or physical infirmity • is charged with or has been convicted in a state or federal court of record of a crime punishable by imprisonment for more than one year without subsequent restoration of civil rights 28 U.S.C. § 1865. Some district courts have adopted other grounds for exemptions, which are specified in the court’s jury selection plan. Section 1863 of Title 18 requires the plan to provide for the exemption of members of the armed forces in active service; members of state or local fire or police departments; and public officers of the federal, state, and local governments who are actively engaged in the performance of official duties. Jury service is a citizen’s duty as well as a privilege, and courts do not readily grant excuses. A person may, however, be excused from jury service temporarily if the plan states that such service would result in undue hardship or extreme inconvenience. In such a case, the name of an excused juror is placed back in the qualified jury wheel. If a prospective juror approaches you about an excuse, do not express any opinion regarding the request, but simply refer the requester to the clerk’s office or jury administrator for action. Treat persons called for jury service with courtesy; they are providing an important service to the court and the public. Judges in multijudge courthouses often begin jury trials at different hours to obtain maximum use of people summoned for jury service, sending persons examined and not selected to another courtroom so they can be examined for 69 Law Clerk Handbook Federal Judicial Center § 4.3.D.3 selection on another jury, and sometimes using jurors who have served in one trial in a succeeding trial. When prospective jury panels report for possible selection in a case, they should be segregated from other people in the courtroom. Law clerks may be responsible for clearing a portion of the spectator section for the jury panel’s exclusive use. 3. Juror Orientation Most courts conduct a juror orientation program to inform jurors of their responsibilities and to explain the trial process. Orientation videos, including the Federal Judicial Center’s Called to Serve, are available in most courts. 4. Voir Dire In most courts, the judge personally conducts voir dire examination. Federal Rule of Civil Procedure 47 and Federal Rule of Criminal Procedure 24, however, authorize the judge to permit the lawyers to conduct voir dire. If the judge conducts voir dire, the rules authorize counsel to submit specific questions or areas of inquiry that they want the judge to probe. In some courts, magistrate judges conduct voir dire. The law in most circuits permits this in civil cases, though some require consent of the parties. The Supreme Court has held that a magistrate judge may conduct voir dire in a criminal case if the defendant consents (Peretz v. United States, 501 U.S. 923 (1991)), but not if the defendant objects (Gomez v. United States, 490 U.S. 858 (1989)). 5. Jury Supervision In most courts, a deputy clerk is responsible for jury supervision. However, sometimes law clerks have this responsibility. If so, you should be present early enough in the morning to accommodate those members of the jury who arrive before the normal court time. The jury room should be open and available for use by the jurors as they arrive. If the judge permits the jury to take notes, either you or the deputy clerk should provide pads of paper and pencils for distribution to the jurors before the trial begins. Extra pads and pencils should also be placed in the jury room for use during deliberations. If you are responsible for jury supervision, ensure that there is no communication—in the courtroom, jury room, or hallways adjacent to the courtroom and chambers—between jurors and litigants, lawyers, witnesses, or others attending court. 70 Chambers and Case Management fjc.dcn • fjc.gov § 4.3.E Jurors are usually free to go where they wish during recesses, and they may go home at night. Occasionally, however, when there is unusual publicity about the trial or there is reason to believe that someone will attempt to exert improper influence on jurors, the judge may direct that the jury be sequestered. When this occurs, deputy marshals keep the jurors together at all times and supervise them when court is not in session. Jurors in criminal and civil cases are sometimes sequestered from the time they begin deliberating until they reach a verdict. Judges sometimes have law clerks steward the jury during deliberations. Some judges require the law clerk to take a special oath with respect to this duty just before the jury retires. Once the oath is taken, the law clerk assumes primary responsibility for guarding the jury until relieved of this duty by the judge. Remain outside the jury-room door during the entire deliberation process and take every reasonable precaution to ensure that the jurors do not come into contact with other people, especially the litigants, their attorneys, or witnesses. You must never comment on the evidence, the litigants, the attorneys, or the witnesses to any juror (or, for that matter, to anyone else). If a juror has any questions about the trial, at any stage, you should simply state that such questions should be addressed to the judge in writing. Do not answer the question, however simple it may appear. E. Distributing Opinions Federal Rule of Civil Procedure 52(a) requires the judge to make findings of fact and conclusions of law in all actions tried without a jury or with only an advisory jury. The rule permits the judge to do this orally on the record or in writing in an opinion or memorandum. The judge may also write a formal opinion to explain rulings on particular motions. The judicial assistant sends the original of the findings or the opinion and the original of any order for judgment to the docket clerk for filing in the official record. Then the judicial assistant or clerk of court sends a copy of each set of findings or the opinion to each counsel of record, making and distributing other copies in accordance with the judge’s instructions. In most district courts, the clerk of court handles the distribution of opinions, but in a few district courts, this responsibility falls to the law clerk or judicial assistant. The judge decides whether the opinion or findings are to be published. If you are responsible for distributing opinions, check with the judge to determine whether the judge wishes the opinion to be published and make such distribution as the judge directs. In each case, the opinion should be accompanied by a cover letter from the judge; the judge may have a form letter for this purpose. 71 Law Clerk Handbook Federal Judicial Center § 4.4    § 4.4 Special Duties of Law Clerks to Bankruptcy Judges The duties of law clerks to bankruptcy judges are generally similar to the duties of those working for district judges. The volume of cases and proceedings in bankruptcy court is generally greater than in other trial courts, and the chambers must be organized to handle this volume effectively. Bankruptcy judges hold more, and faster, hearings than do district judges. For the chambers staff, that means more scheduling problems, more substantial prehearing preparation of memoranda, and shorter time limits. It also means more pressure from attorneys telephoning to ask for expedited schedules and to ask about procedures, the disposition of motions, and various other matters. Like district judges, bankruptcy judges differ in their attitudes about direct contact between law clerks and attorneys. Some bankruptcy judges hold court in more than one place. Law clerks and judicial assistants to those judges usually have substantial duties in preparing for travel, including assembly of materials (such as appropriate portions of case records necessary for the trip). The judge’s staff will usually have extra duties in the additional places of holding court because the other staff available may not be as complete as in the home court.    § 4.5 U.S. Magistrate Judges The authority of magistrate judges derives primarily from the Federal Magistrates Act of 1968 and as amended numerous times since. 28 U.S.C. §§ 631–639. Significant Supreme Court cases interpreting the Act include Mathews v. Weber, 423 U.S. 261 (1976) (upholding magistrate judge authority to hear Social Security appeals on a report and recommendation basis); United States v. Raddatz, 447 U.S. 667 (1980) (upholding magistrate judge authority to conduct hearings on motions to suppress evidence in felony cases on a report and recommendation basis); Peretz v. United States, 501 U.S. 923 (1991) (upholding magistrate judge authority to conduct felony voir dire proceedings with the parties’ consent); and Roell v. Withrow, 538 U.S. 580 (2003) (holding that parties’ consent to disposition of a civil case by a magistrate judge under 28 U.S.C. § 636(c) could be inferred from the parties’ conduct during the case). A general outline of the duties performed by magistrate judges is described below. 72 Chambers and Case Management fjc.dcn • fjc.gov § 4.5.B A. Initial Proceedings in Criminal Cases Under 28  U.S.C. §  636(a), a magistrate judge may perform various duties and conduct proceedings in criminal cases, including the following: • accept criminal complaints • issue arrest warrants and summonses • issue search warrants • conduct initial appearance proceedings and detention for criminal defendants, informing them of the charges against them and of their rights • set bail or other conditions of release or detention under the Bail Reform Act, 18 U.S.C. §§ 3141–3145 • appoint attorneys for defendants who are unable to afford or obtain counsel • hold preliminary examinations, or “probable cause” hearings • administer oaths and take bail, acknowledgments, affidavits, and depositions • conduct extradition proceedings

G. U.S. Trustees and Private Trustees The U.S. Trustee Program is part of the federal government’s Department of Justice, not a part of the courts. It was established to handle the administrative functions of bankruptcy cases and to ensure the integrity of the bankruptcy system across the nation. The program operates with twenty-one regional offices and ninety-four field offices, which are headed by U.S. trustees and assistant U.S. trustees, respectively. See 28  U.S.C. §§  581–589b. In the six judicial districts in Alabama and North Carolina, the Bankruptcy Administrator Program, rather than the U.S. Trustee Program, handles the administrative functions. See § 302(d) (3)(1) of the Bankruptcy Judges, United States Trustees, and Family Farmer Act of 1986, P.L. 99-554, 100 Stat. 3119, 3123, and § 317(b) of the Federal Courts Study Committee Implementation Act of 1990. The functions of the U.S. trustees are enumerated in 28 U.S.C. § 581(a), and primarily include (1) appointing and supervising the private trustees who collect and disburse funds to creditors in Chapter 7, 12, and 13 cases; (2) ensuring compliance with the Bankruptcy Code with respect to information provided in schedules, disclosure statements, reorganization plans, and other filings; (3) reviewing fee applications of professionals, such as attorneys and accountants, who serve in Chapter 11 reorganization cases; and (4) monitoring bankruptcy cases for fraud and referring criminal matters to the U.S. attorney for prosecution. Trustees do not have independent enforcement powers; rather, they must request the court to rule on matters of administration for which there is no voluntary compliance. The U.S. trustee is responsible for establishing a panel of private trustees to serve in Chapter 7 cases. When a bankruptcy petition is filed under Chapter 7, the U.S. trustee appoints a disinterested person from this panel to serve as interim trustee. At the first meeting of creditors, the creditors may elect another person as trustee, although such elections are rare. The U.S. trustee is also responsible 44 Basic Overview of Litigation in U.S. Courts fjc.dcn • fjc.gov § 3.4.A for appointing one or more “standing” trustees to administer all Chapter 12 and 13 cases filed in a geographic region. In Chapter 11 cases, no trustee is appointed unless the court orders the appointment after notice and a hearing. If the court orders an appointment, the U.S. trustee designates the person who will serve, unless a party-in-interest timely requests that the trustee be elected by the creditors. In Chapter 7, 12, and 13 cases, the U.S. trustee may act as trustee if a private trustee is unavailable, although this is rarely done. The code does not provide for the appointment of a trustee in Chapter 9 cases. 28  U.S.C. §  586, 11 U.S.C. §§ 701–704, 1202, 1104–1106, 1302.    § 3.4 Appeals A. Processing Appeals The steps in an appeal are as follows: 1. Filing a notice of appeal 2. Preparing the record on appeal 3. Docketing the appeal 4. Filing the appellant’s brief 5. Filing the appellee’s brief 6. Filing the appellant’s reply brief 7. Deciding if the court dispenses with oral argument, or scheduling of oral argument 8. Hearing oral argument 9. Deliberating by the court 10. Filing the opinion 11. Filing a petition for rehearing 12. Issuing the mandate (the final stage in the appellate process unless the party applies to the Supreme Court for a writ of certiorari) The Federal Rules of Appellate Procedure establish certain procedural uniformity among the thirteen courts of appeals. However, there are still some differences in the procedures in the various circuits. Each court has local rules and internal operating procedures that describe the precise procedure to be followed 45 Law Clerk Handbook Federal Judicial Center § 3.4.B when there is any variation from the rules and, in some instances, that elaborate on or amplify the rules. See section 4.2. B. Notice of Appeal The timely filing of a notice of appeal is a jurisdictional requirement for any appeal. Appeals may be filed to challenge decisions of the district court, an administrative agency, or a bankruptcy appellate panel. Appeals of agency decisions may be classified as original proceedings in the court of appeals. The notice of appeal is filed in the district court. The purpose of the notice is to inform opposing counsel and the court that an appeal is being taken. The clerk of that court is required by Federal Rule of Appellate Procedure 3(d) to forward a copy of the notice to the clerk of the court of appeals. The time for filing commences when the judgment or order is entered in the district court from which the appeal is taken. The running of that time is tolled by the filing of certain posttrial motions in the district court, and the filing of such motions after a notice of appeal has been filed may vitiate the notice, requiring a new notice of appeal to be filed after the motion is decided. Fed. R. App. P. 4(a). Rule 4 provides the following time periods for filing notices of appeal: • private civil cases: 30 days • civil cases in which the United States is a party: 60 days • criminal cases: 10 days • criminal cases in which appeal by the government is authorized by statute (such as appeals from sentences under the 1984 Sentencing Reform Act): 30 days Upon receipt of the notice of appeal, courts of appeals take steps to ensure that all procedural requirements have been met. The clerk’s office may send counsel a case-opening letter to establish schedules for record preparation and briefing. Circuit mediators may conduct initial mediation/settlement conferences to discuss the issues in the case, with a view to eliminating the briefing of frivolous issues and to discuss the possibility of settlement. See Mediation & Conference Programs in the Federal Courts of Appeals: A Sourcebook for Judges and Lawyers (Federal Judicial Center, 2d ed. 2006). 46 Basic Overview of Litigation in U.S. Courts fjc.dcn • fjc.gov § 3.4.D C. Record Preparation For an appellate court to review the proceedings in a trial court, appellate judges must have a record available of what occurred in the trial court. Local court rules prescribe the requirements for counsel to provide the district court with the record or excerpts of the record (sometimes referred to as a short record), which may include original papers and exhibits filed in the trial court plus a reporter’s transcript of any relevant proceedings. The Sentencing Reform Act requires that the record in a criminal case must also include “(1) that portion of the record . . . that is designated as pertinent by either of the parties; (2) the presentence report; and (3) the information submitted during the sentencing proceeding.” 18 U.S.C. § 3742(d). This information will often be under seal, because it is confidential. The Federal Rules prescribe time limits (deadlines) for providing the record on appeal to the court of appeals. During this time, the appellant must order a transcript of proceedings if one is needed and make arrangements to pay the court reporter for services or, in courts using electronic sound recording for the official record, the clerk of court. The district court clerk assembles the other papers or electronic files that constitute the record on appeal. The district court has the power to extend for an additional fifty days the time for preparing and sending the record on appeal, after which the court of appeals itself may grant extensions. Additional time may be needed if the court reporter has not finished transcribing the proceedings or if counsel has failed to order the transcript in a timely manner. To prevent undue delay, the appellate courts have the discretion to refuse to grant time extensions and may impose sanctions on the appellant or the reporter for unreasonable delays in preparing the record on appeal. D. Docketing the Appeal When the record is completed, or earlier if desired, the appellant must docket the appeal. This is primarily a clerical process and is performed in the office of the clerk of the court of appeals. Unless the appellant is exempt from payment, a docket fee is charged. The clerk of court opens an appropriate file and record and sends a notice to the parties. Frequently, docketing takes place when the record on appeal is filed. The filing of the record provides the base date for most subsequent proceedings in the case. 47 Law Clerk Handbook Federal Judicial Center § 3.4.E E. Briefs and Joint Appendices Because the appellant has the burden of establishing that the trial court erred, it files the opening brief. The appellee then files a brief in response; if the appellant wishes, the appellant may file a reply brief responding to new matters raised in the appellee’s brief. The Federal Rules of Appellate Procedure establish standards for format, color of brief covers, content, methods of reproduction, number of copies, and times for filing of briefs. The local rules for a circuit may impose further requirements. The schedule for filing briefs is as follows: • appellant’s brief: 40 days after filing the record • appellee’s brief: 30 days after service of appellant’s brief • reply brief: 14 days after service of appellee’s brief Some courts of appeals have modified the requirements and standards of the federal rules in certain cases or classes of cases. One of the more common modifications permits parties appealing in forma pauperis to file fewer copies of their briefs. While the briefs are being prepared, the parties are required to determine which portions of the record on appeal are relevant to the issues raised; the appellant is required to reproduce these portions as an appendix to the briefs. There may be only one appendix containing the portions relied on by both the appellant and the appellee, which would be referred to as a joint appendix. If any relevant material is omitted from the appendix, the court is free to refer to the original record. Multiple copies of the appendix may be filed so that each judge and, if needed, each law clerk may have one. Some courts of appeals have eliminated the requirement of an appendix and permit the substitution of photocopies of relatively few parts of the record, usually called record excerpts. The local rules of those courts describe the substitute requirements. Local rules also address procedures for electronic filing. You should become familiar with the rules and procedures in your court. F. Oral Argument If the court does not decide a case exclusively on the basis of the briefs and written record (see section 4.6.B on screening cases to select those appeals to be decided without oral argument), the parties are given an opportunity to present their arguments to the court orally. Federal Rule of Appellate Procedure 34 permits the court to fix the time allowed for oral argument. Courts may allow counsel to file a request in advance for additional time, and the courts have the discretion whether to grant these requests. Generally, not more than two attorneys are 48 Basic Overview of Litigation in U.S. Courts fjc.dcn • fjc.gov § 3.4.G permitted to argue for each side. Some court rules encourage argument by only one attorney for each party. Many appellate judges require their law clerks to prepare a memorandum on each case (called a bench memo) for the judge to review before hearing oral arguments. In some circuits, the law clerk for one judge may prepare a memorandum to be circulated among the three judges on the panel prior to oral argument. The judges will study the briefs before oral argument. The appellant begins the argument. Because the judges have read the briefs and are therefore familiar with the issues, they sometimes begin questioning the attorney shortly after the argument begins. After the appellant’s argument is completed, the appellee responds, followed by any reply by the appellant (if the appellant reserved time for rebuttal). Although the arguments are recorded, so that the judges and their law clerks may later review them, some circuit judges may request one of their law clerks to attend oral argument and take notes of important matters, citations of new authorities, and concessions made during the argument. Most cases are heard by a panel of three judges, but a case may be heard en banc in cases involving a question of exceptional importance or in order to secure or maintain uniformity of decisions. A case heard en banc is heard by all of the active judges on the court and any senior judge of the circuit who sat on the panel that originally heard the case (or, in the Ninth Circuit, by a limited en banc, consisting of the chief judge and ten additional judges selected by lot). En banc hearings are held only when ordered by a majority of the active judges on the court. Some courts hold hearings in only one location, but most hold court in a number of locations within the circuit. G. Deliberation After a case has been argued and submitted to the court, the panel of judges who heard the argument meets to arrive at a decision. In most courts, these meetings are held immediately after the completion of each day’s arguments. Appellate courts perform three distinct functions. First, they decide the controversies before them. Second, they supervise the courts within their jurisdiction. Third, they determine the growth and development of the common law and the interpretation of federal statutory and constitutional law within their jurisdiction. Each of these functions can become important during the decisional phase of an appeal because the court must not only reach the correct result but also explain in its opinion the rationale for its decision. 49 Law Clerk Handbook Federal Judicial Center § 3.4.H In most cases, the court arrives at a tentative decision at the first meeting. At that time, the presiding judge (the senior active circuit judge sitting on the panel) assigns the case to one member of the panel, who later writes an opinion to be submitted to the others for approval. When the judges do not reach agreement so readily, panel members may exchange memoranda about the case and schedule additional meetings or telephone conferences for further discussion. Law clerks for appellate judges should know and follow the court’s internal rules and its customs concerning communications between chambers. H. Opinion and Judgment The final product of the court in most appeals is a written opinion setting forth the decision and the reasoning behind it. The increased number of cases and the burden of writing formal opinions in every case has caused appellate courts to use alternatives to formal opinions (such as memorandum, order, or summary opinions) in many cases, such as those involving only the application of settled principles to a specific fact situation. Local rules or policies may guide the members of the court in deciding which cases deserve full opinions and which opinions should be published. When a panel has agreed on an opinion, the authoring judge electronically transmits it to the clerk of court for public docketing and release. All courts post opinions on the court’s public website. In some courts, before opinions are released, they are circulated to all active judges on the court with a time limit for making suggestions. Sometimes when a judge or a group of judges disagrees with the majority decision reached by their colleagues and they feel strongly enough about it, the judge or judges will write a dissenting opinion explaining what aspects of the decision they disagree with and why. Even though they express opinions that did not prevail, dissents can contribute to the legal debate over the issues at hand and provide judges in similar cases with different perspectives. I. Rehearing The party who loses an appeal may file a petition for rehearing within fourteen days after judgment is entered. That petition attempts to persuade the panel that the decision was erroneous and should be withdrawn or revised. The prevailing party may not file a response to the petition unless one is requested by the court. Most petitions for rehearing are denied. The losing party may also move for a rehearing en banc. That motion is circulated to all members of the original panel and all active judges who did not sit 50 Basic Overview of Litigation in U.S. Courts fjc.dcn • fjc.gov § 3.4.K on the panel. Only the active circuit judges and any senior judge who was a member of the original panel may request a vote on the suggestion to rehear the appeal en banc, and only the active circuit judges may vote on whether the appeal should be reheard en banc; if a rehearing en banc is granted, only active circuit judges and senior circuit judges from the circuit who were members of the original panel may sit on the rehearing. By local rule, a circuit may impose time limitations within which a member of the court may request an answer to a petition for rehearing or rehearing en banc or a vote on such a petition. J. Mandate The mandate is the document by which the court of appeals formally notifies the district court of its decision and by which jurisdiction for any necessary additional proceedings is conferred upon the district court. The mandate is issued by the clerk of court seven calendar days after the time to file a petition for rehearing expires, or seven calendar days after entry of an order denying a timely petition for panel rehearing, petition for rehearing en banc, or motion for stay of mandate, whichever is later. These times may be shortened or lengthened by court order. Fed. R. App. P. 41(b). The losing party may request by motion that the issuance of the mandate be stayed in order to maintain the status quo during the pendency of an application for a writ of certiorari to the Supreme Court. The court of appeals may require that a bond be posted as a condition to staying the issuance of the mandate. K. Motions During the course of an appeal, the parties may file a variety of motions. Most of these are procedural and, to the extent permitted by the Federal Rules of Appellate Procedure, some courts have authorized their clerks of court or other court unit executives to act on motions, for example, motions • for extensions of time to perform any of the acts required by local rules or the Federal Rules of Appellate Procedure • for relief from specific requirements of the local rules or the Federal Rules of Appellate Procedure • for permission to alter the form or content of the record on appeal; • for leave to file amicus curiae briefs • for delay in the issuance of the mandate • for voluntary dismissal of the appeal 51 Law Clerk Handbook Federal Judicial Center § 3.4.L Motions requiring action by a judge or panel of judges are those • on issues relating to criminal cases or suits for postconviction relief such as motions for appointment of counsel, leave to appeal in forma pauperis, certificates of probable cause, and bail pending appeal • for stays or injunctions pending appeal • for leave to file interlocutory appeals • for issues relating to stays granted in the district court • for permission to file a brief containing more pages than the number fixed by the rules • for issues relating to the time allowed for oral argument • to dismiss an appeal filed by the appellee In most courts, the staff attorney’s office is responsible for reviewing motions and referring them to judges for appropriate disposition. L. Emergency Proceedings Both district courts and courts of appeals are frequently asked to make decisions on an emergency basis. In the appellate courts, these occasions usually arise when a litigant or a lower court is about to take some action that may cause irreparable injury. The potentially aggrieved party seeks redress by motion for stay or injunction pending appeal or by petition for writ of mandamus or prohibition. In the district courts, these matters usually arise through a request for a temporary restraining order. Each court has developed internal procedures for handling these matters efficiently, but the procedures vary among courts. Courts have also established special procedures for handling emergency appeals of capital (death penalty) cases. Law clerks should become familiar with the procedures established by the local rules and the judge’s own practices.    § 3.5 Courts of Specialized Jurisdiction You may also encounter litigation from one of the various special courts established by Congress. The term special courts derives from their specialized jurisdiction. 52 Basic Overview of Litigation in U.S. Courts fjc.dcn • fjc.gov § 3.5.D A. Court of Appeals for the Federal Circuit The Court of Appeals for the Federal Circuit, based in Washington, D.C., has jurisdiction over appeals from the following: district courts in cases involving patents and certain claims against the United States; the U.S. Court of Federal Claims; the Court of International Trade; the Court of Veterans Appeals; the Merit Systems Protection Board; the Patent and Trademark Office; the boards that decide government contract issues; and a few other Article I agencies. B. Court of International Trade The Court of International Trade, based in New York City, hears cases concerning the value or classification of imports. Its judges may sit by designation on other Article III courts. C. U.S. Judicial Panel on Multidistrict Litigation This panel was created to consider transferring civil actions involving one or more common questions of fact pending in different districts to a single district for coordinated or consolidated pretrial proceedings. The panel consists of seven district and circuit judges who are appointed by the Chief Justice and sit on the panel in addition to their regular judicial assignments. The panel maintains a roster of transferee judges to whom it assigns the cases it certifies for transfer. For discussion of multidistrict litigation problems, see section 3.1.F. D. Foreign Intelligence Surveillance Court The Foreign Intelligence Surveillance Court (FISC), or the FISA court, as it is popularly called (after the Act that created it), is composed of eleven federal judges, selected by the Chief Justice to a nonrenewable seven-year term. The court’s job is to review applications for governmental surveillance of persons within the United States whom the government suspects of having connections to foreign governments and/or terrorist organizations. A Foreign Intelligence Court of Review was also established to review applications denied by the FISA court. 53 Law Clerk Handbook Federal Judicial Center § 3.6    § 3.6 Article I Courts Congress has created many tribunals to assist it in meeting its legislative responsibilities under Article I of the Constitution. These courts do not exercise judicial power conferred by Article III, and the judges are appointed for fixed terms rather than given life tenure. They include the many administrative law judges serving in the executive agencies who hear disputes over claims and benefits, subject to review by agency officials. A. U.S. Tax Court The U.S. Tax Court has jurisdiction over controversies involving deficiencies determined by the commissioner of internal revenue in income, estate, and gift taxes, as well as other tax-related disputes between taxpayers and the Internal Revenue Service. The principal office of the court is located in Washington, D.C., and it conducts trial sessions in other cities throughout the United States. B. U.S. Court of Federal Claims The U.S. Court of Federal Claims was originally called the U.S. Claims Court. The court has jurisdiction over claims brought against the U.S. government. The court is located in Washington, D.C.; however, its jurisdiction is nationwide, enabling it to conduct trials in locations convenient to the parties involved in the case. C. U.S. Court of Appeals for the Armed Forces Congress established the U.S. Court of Appeals for the Armed Forces as an appellate criminal court, hearing all cases involving military courts-martial. It is located in Washington, D.C. D. U.S. Court of Appeals for Veterans Claims The U.S. Court of Appeals for Veterans Claims has exclusive jurisdiction to review the decisions of the Board of Veterans Appeals. The court’s principal location is in Washington, D.C., but it may hold court anywhere in the United States. 54 fjc.dcn • fjc.gov 4 Chambers and Case Management    § 4.1 Chambers Administration This chapter gives you a broad overview of some of your responsibilities as a law clerk in maintaining a well-run chambers. These responsibilities include helping to ensure chambers security; answering telephones and mail; maintaining the judge’s motion, hearing, and trial calendars; and other miscellaneous matters. Discussing all such duties would, of course, be impossible, and some judges have chambers manuals detailing how they expect their chambers to operate. Understanding and accommodating your judge’s preferences is key to maintaining an efficient chambers, and regardless of the general guidance offered in this chapter, you should always follow the particular policies and practices of your judge. Effective management is essential to the efficient administration of justice. While judicial assistants often have principal responsibility for managing various aspects of chambers administration, as a law clerk you should be familiar with the standard operating procedures in your chambers and be available to pitch in when needed. A. Security The safety and security of federal buildings and the people who work in and visit them are major concerns for the U.S. Marshals Service (USMS). Attorneys and other members of the public must pass through magnetometers and have their briefcases and other items screened by an X-ray machine to enter most courthouses and other federal buildings. In addition, all judges’ chambers are equipped 55 Law Clerk Handbook Federal Judicial Center § 4.1.A with an entry control system that consists of a security camera and monitor and a door release strike. Courthouse employees may be issued keycards enabling them to enter the courthouse without passing through metal detectors and to access secured, nonpublic sectors of the building, including judges’ chambers, depending on the individual court’s access-control security plans. Employees may also have after-hours and weekend access to the building through use of these keycards, which should be kept in a secure place and reported immediately if lost. All courthouse employees should carefully follow security procedures and report potential problems to the USMS. The U.S. Marshals Service is principally responsible for security of the court and its personnel, though most courthouse security functions are performed by court security officers (CSOs), who are funded by the judiciary’s Court Security Program and by the Federal Protective Service on a limited basis. Become familiar with the court’s Occupant Emergency Plan and other related USMS security plans in your courthouse, and help to maintain a secure chambers. Do not let unauthorized strangers into secure areas of the courthouse, and report suspicious mail or threatening phone calls. During security-sensitive proceedings, a judge may request that a deputy from the U.S. Marshals Service or a CSO be present in the courtroom. Because federal judges are occasionally the targets of terrorists or disgruntled litigants, be careful when opening mail. Mail received in the courthouse is routinely screened by the USMS before distribution to chambers and offices. Still, it pays to be alert to suspicious-looking items. Common recognition points for letter and package bombs include the following: • foreign mail, air mail, and special delivery • restrictive markings (e.g., confidential, personal) • excessive postage • handwritten or poorly typed addresses • incorrect titles • titles, but no names • misspelled common words • oily stains or discolorations • no return addresses • rigid envelopes • lopsided or uneven envelopes 56 Chambers and Case Management fjc.dcn • fjc.gov § 4.1.C • protruding wires or tinfoil • excessive securing material such as masking tape or string • drawings, diagrams, or illustrations If a letter or package arouses attention, do not attempt to open it. Instead, immediately notify the marshals’ office or a CSO. B. Telephone Practices for dealing with incoming calls (e.g., how to answer the telephone, how to take messages, and when and if to transfer a call to the judge) will vary from chambers to chambers. In general, however, answer calls promptly, identify the office (e.g., “Judge Smith’s chambers”), and treat all callers courteously. And, of course, hold personal calls to a minimum, both in length and in number. See section 2.2.A.1 on communication with the media. C. Correspondence, Email, and Other Mail In addition to correspondence by U.S. postal and messenger service, many chambers now correspond by email with a wide variety of people, including counsel. While email has in some ways made communicating easier and more efficient, it has also made it even more important to stay on top of organizing and processing the mail. Email also presents serious potential problems relating to the accidental forwarding of messages, either to unintended parties or containing information not intended for the recipient. And bear in mind how easily emails can be broadly disseminated through forwarding and posting on websites and social media. Take special care to avoid sending and forwarding email messages that may result in embarrassment, a breach of confidence, or worse, and review and carefully proofread any outgoing messages (and fight the temptation not to proofread email as carefully as paper correspondence). Most chambers have practices and procedures for handling incoming and outgoing mail, including email (whether and when to delete email messages, how to store important messages for future reference, and other matters of email retention and organization). Quickly become familiar with these practices to help mitigate complications arising from the enormous number of emails that many chambers receive. Depending on office procedure, either a judicial assistant or a law clerk will open and review correspondence and make an initial decision concerning how 57 Law Clerk Handbook Federal Judicial Center § 4.1.C it should be handled. Many judges receive their own emails directly, though some may ask staff to review messages first. Incoming mail and emails should be reviewed as soon as they are received because they may relate to matters scheduled for that day. When correspondence referring to a pending suit is forwarded to any counsel of record over the signature of the judge, law clerk, or judicial assistant, copies should be sent to all other counsel of record to avoid inappropriate ex parte contact. Appellate judges seldom correspond directly with counsel on case-related matters, because appellate judges work on cases as part of a panel or court rather than individually. Instead, appellate judges will send instructions to the clerk of court on how to respond to counsel. Correspondence from the general public that is not related to a case is still important because citizens have a right to courteous treatment. Also, the public’s opinions about the fairness, responsiveness, and effectiveness of the judiciary are influenced by the promptness and appropriateness of the court’s answers. In the district court, some of the correspondence from the public involves requests to be excused from jury service. That subject is dealt with in section 4.3.D.2. Some correspondence contains character references on behalf of an offender who is scheduled for sentencing. Judges differ in their handling of such correspondence. Many simply acknowledge receipt of the letter and refer the letter to the probation office. Other correspondence from the public may express reactions to a judge’s ruling. Whether positive or negative, expressions of opinion by members of the public generally call only for courteous acknowledgment, not for an explanation or justification of the judge’s action. If a letter requests information about a ruling, many judges simply acknowledge receipt of the letter and send a copy of the opinion, if there is one. If more information is requested, many judges refer the writer to the record in the clerk of court’s office. Some judges may wish to respond to a letter that indicates a misunderstanding concerning a significant fact, proceeding, or legal conclusion. Judges who adopt this policy may ask law clerks to prepare a draft of a response for the judge to review. The response should not be argumentative or defensive; it should merely state the relevant facts or legal conclusion as necessary to alleviate the misunderstanding. Prisoners and persons who have been convicted and are awaiting sentence frequently write district and appellate judges. Handle the correspondence of a prisoner represented by counsel the same way as that of any other litigant. Ask your judge how to handle correspondence from prisoners who are proceeding pro se. In some instances, this correspondence may be handled by district court pro se law clerks or, in the appellate courts, either the clerk’s office or staff attor58 Chambers and Case Management fjc.dcn • fjc.gov § 4.1.D ney’s office. In other instances, your judge may have a form letter explaining, for example, that federal law prohibits judges from giving legal advice and suggesting that the prisoner communicate with a lawyer, or a form letter for responding to requests for transfers to another penal institution (which only the Bureau of Prisons can grant). You should never write anything in a letter that would give a prisoner false hope or could compromise the position of the court. D. Internet and Electronic Research New law clerks will receive a Westlaw and/or a LexisNexis password, which may come with additional electronic research training and certain usage guidelines. All computer-assisted legal research (CALR) use via judiciary contracts is to be limited to official judiciary-related research purposes. In addition to these research services, the Internet also offers more informal avenues of research, including access to nearly every newspaper and magazine in the country, as well as to government and law school websites, Internet search engines, and myriad other sources. Contact the circuit library CALR coordinator for assistance with CALR access or training. The CALR coordinators and reference librarians are also available to assist with your research questions. Become familiar with fjc.dcn (http://fjc.dcn), the Federal Judicial Center’s site on the judiciary’s intranet. It provides access to manuals, monographs, desk references, and other publications, as well as to web-based training and orientation programs, streaming media programs, discussion forums, and other resources. JNet (http://jnet.ao.dcn), the intranet site maintained by the Administrative Office of the U.S. Courts, offers information and forms on a range of topics relevant to judicial employees, including benefits, court security, emergency preparedness, human resources, information technology, legal and general research, and travel. The Internet has also posed some serious security and usage challenges for employees and information technology departments in courthouses across the country. The judiciary provides you with a computer and Internet access to help you do your work. Depending on the policy in your court or chambers, you may use it on a limited basis for personal needs if doing so does not interfere with your work and does not cause congestion, delay, or disruption of service to any government system. You should not do anything on your office computer that would embarrass you or the court if it were made public. 59 Law Clerk Handbook Federal Judicial Center § 4.1.E E. Electronic Filing The federal judiciary’s Case Management/Electronic Case Filing (CM/ECF) system allows courts to maintain case documents in electronic form and provides enhanced and updated docket management services. It also gives each court the option to permit case documents—pleadings, motions, petitions—to be filed electronically with the court. CM/ECF uses an Internet connection and a browser and accepts documents in Portable Document Format (PDF). It is easy to use. Filers prepare documents using conventional word-processing software and save them as PDF files. After logging on to the court’s website with a court-issued password, the filer enters basic information about the case and document being filed, attaches the document, and submits it to the court. CM/ECF automatically generates a notice verifying that the court received the filing, and it also sends an email to other parties in the case notifying them of the filing. There are no added fees for filing documents using CM/ECF, but existing document filing fees do apply. Litigants receive one free copy of documents filed electronically in their cases, which they can save or print for their files. Public electronic access to court data is available through the Public Access to Court Electronic Records (PACER) program. Additional copies are available for a small fee to attorneys and the general public for viewing or downloading. The process for receiving and reviewing daily filings in the cases filed before the judge may vary among courts and chambers; you should quickly learn the process in your chambers and your role in implementing and maintaining it. Although familiarity with the workings of the system is helpful, you should refer counsel’s questions to docketing clerks or others in the clerk’s office who deal with the system on a daily basis. F. Judge’s Chambers Calendar The judicial assistant is usually in charge of maintaining the chambers calendar covering the judge’s scheduled court proceedings and other activities. If the calendar is maintained online, other staff on the chambers network may also have limited access to the judge’s schedule. In appellate courts, the clerk of court advises the judge of panel assignments and hearing dates. The judicial assistant, in consultation with the judge, will then schedule all other engagements and commitments around the hearings. In trial courts, the judicial assistant usually confers with the judge and then typically advises the courtroom deputy in charge of scheduling the court calendar of the dates on which trials and hearings are to 60 Chambers and Case Management fjc.dcn • fjc.gov § 4.1.H be set. The judicial assistant then schedules the judge’s remaining commitments around the trials and hearings. Some judges choose not to have a judicial assistant, which allows them to have an additional law clerk. In these instances, a law clerk may maintain the chambers calendar. G. Opening Court In district courts, a law clerk or courtroom deputy usually opens court. One common method is for the clerk or deputy to rap on the door before the judge enters, open the door, then call out, “All rise.” The judge then enters and walks to the bench. The law clerk or deputy walks to the front of the bench and says: “The United States District Court for the ____ District of ____ is now in session. The Honorable ______ presiding.” The judge usually stands during this call, then says, “Please be seated,” and sits. H. Maintaining the Library; Office Supplies, Equipment, and Furniture Many chambers maintain their own libraries, though electronic databases and Internet research reduce the need for access to hard-copy sources and have enabled chambers in the same courthouse to share libraries. In any event, the employee who maintains the library, either a law clerk or a judicial assistant, should regularly file any advance sheets, pocket parts, slip opinions, replacement volumes, and inserts for loose-leaf services that arrive in the mail. File materials daily so that library maintenance does not become burdensome and the materials are current. Procurement and ordering of all law books is done by the circuit library; contact the librarian if you have questions. Promptly rubber-stamp every incoming library book to identify it as U.S. property. Keep track of books borrowed by attorneys for courtroom use and make sure that books are not taken outside the chambers and courtroom. Promptly reshelve books used during the course of research. They will then be easier to find, and the library will be neater. Also be sure that legal pads, book markers, pencils, and pens are always available in the library. Requests for supplies, equipment, and furniture ordinarily are handled in the clerk of court’s office. 61 Law Clerk Handbook Federal Judicial Center § 4.1.I I. Maintaining Office Records and Files You may have to maintain some of the records in your judge’s office, including the following: • case files • trial schedules or calendars • “tickler” records to remind the judge about future case activities • indices to the judge’s prior decisions • indices to slip opinions • work papers relating to cases in progress Such materials may be stored in hard copy, electronically, or both. Some chambers may also maintain office form books, either in hard copy or electronically. The form books may contain office procedure checklists and frequently used forms, such as samples of letters, orders, opinions, jury charges, minute entries, and office or file memoranda written by prior law clerks. The books describe the format and method for written documents issued by the judge or presented to the judge by chambers staff. The form books provide continuity and consistency in office administration and can help educate new law clerks. If case records are being used in the judge’s chambers, make sure that the records are not misplaced and are returned to the office of the clerk of court as soon as the judge or staff member has finished with them. J. Statistical Reporting The JS-10 form, “Monthly Report of Trials and Other Court Activity,” is a report of the trials and nontrial proceedings that a district judge conducted during the month. The clerk of the district court submits a JS-10 form to the Administrative Office for each active or senior district judge, plus any visiting district judges or appellate judges, who conducted trials or proceedings in the district during the month. The form reports both the number and type of trials and proceedings and the amount of time the judge spent conducting them. Some judges fill out the forms themselves, but usually a member of the chambers staff or the courtroom deputy fills out the form for the judge. The CM/ECF systems in some courts can automatically generate the JS-10 reports based on additional information about the trials and proceedings entered during the normal docketing process. Data on magistrate judge workloads and activities are collected through the MJSTAR 62 Chambers and Case Management fjc.dcn • fjc.gov § 4.1.L function in district CM/ECF systems, which stores that data in the NewStats database. This includes not only the number of tasks completed by magistrate judges, but the time burden of many of these duties, including time spent with attorneys and parties. Bankruptcy courts report trials and other court activity on a monthly basis using the B-102 form. Courts of appeals use the JS-30 form to report the number of appellate cases, interlocutory appeals, and petitions for rehearing each month. K. Out-of-Town Trips Some judges must travel to other cities to attend court sessions and may require a chambers staff member to travel with them if the court to which they are traveling does not provide staffing. Judges may also travel on court-related business. Judicial assistants usually arrange travel (although when the judge has chosen to have an additional law clerk in lieu of a judicial assistant, a law clerk may have to make travel arrangements). If your judge is traveling to hold court in another location, prepare for the judge to take along necessary case files and materials; any personal notes or memoranda relating to the cases to be heard; the judge’s robe; paper, pencils, stationery, and other needed supplies (if the site for the out-of-town session is one frequently used by the court, there may be a permanent stock of stationery and supplies); necessary equipment such as a gavel, recording or dictating equipment, and a laptop or tablet computer; the briefs and any other case materials; and mailing labels and envelopes for returning material that the judge does not wish to carry back. Judges and chambers staff who travel on court business will be reimbursed for transportation, food, lodging, and related expenses according to the detailed rules set forth in the Guide to Judiciary Policy. These rules generally reimburse either a flat dollar amount per day, regardless of actual expenses, or itemized actual expenses not in excess of a fixed dollar amount. The judicial assistant should have forms for travel reimbursement—these forms can also be found on JNet. Judges must also report travel not related to cases under regulations found in Volume 19, section 270, of the Guide to Judiciary Policy. L. Assisting with Judges’ Extrajudicial Activities Many judges engage in teaching, writing, lecturing, and other extrajudicial activities. While law clerks may be called on to assist judges in these activities, the Code of Conduct for United States Judges says that judges should not use staff “to any 63 Law Clerk Handbook Federal Judicial Center § 4.1.M substantial degree” to engage in extrajudicial activities to improve the law, the legal system, and the administration of justice; and judges should not use staff to engage in other extrajudicial activities, “except for uses that are de minimis.” M. Preserving Chambers Papers for Historical Purposes The chambers papers of a district or appellate court judge have historical significance as an essential supplement to the official court record. Many papers in judges’ chambers are widely considered valuable, such as correspondence and background material concerning a case, including memoranda between judges and law clerks and judges on an appeals panel; drafts of orders and opinions (particularly draft opinions that have handwritten comments on them, or that have been circulated to other judges and returned with their comments); and correspondence/memoranda concerning court administration, legal activities in the community, and issues of governance, politics, and law. Chambers papers are the personal property of the judge. Each judge has the prerogative to make final decisions about the preservation of chambers papers and the terms of access. Judges can preserve their personal papers and make them available for eventual study by donating them to a manuscript repository. An FJC publication, A Guide to the Preservation of Federal Judges’ Papers (3d ed. 2018), reviews the organization and preservation of historically significant records created by federal judges. The Federal Judicial History Office at the FJC will also provide assistance on issues concerning judges’ papers. N. Rules Regarding the Media in Court Guidelines for allowing cameras and electronic reproduction equipment in the courtroom are published in Volume 10 of the Guide to Judiciary Policy. The guidelines allow the photographing, recording, or broadcasting of appellate arguments. In trial courts, a presiding judge may authorize broadcasting, televising, recording, or taking photographs in the courtroom during ceremonial proceedings. For nonceremonial proceedings, such activities may be allowed for presenting evidence, perpetuating a record of the proceedings, and for security or judicial administration purposes. Federal Rule of Criminal Procedure 53 prohibits photographing and radio broadcasting of criminal proceedings. Some circuit judicial councils have adopted specific instructions for the use of cameras in the courtroom. Although local rules restrict the means by which news may be reported (e.g., no cameras or broadcasting from the trial courtroom 64 Chambers and Case Management fjc.dcn • fjc.gov § 4.2 or environs), “there is nothing that proscribes the press from reporting events that transpire in the courtroom.”    § 4.2Local Court Rules and Administrative Policies Section 2071 of Title 28 of the U.S. Code authorizes federal courts to adopt their own rules, which must be consistent with the national rules and available to the public; it also authorizes the circuit judicial council to abrogate district and bankruptcy courts’ local rules, and authorizes the Judicial Conference to abrogate rules of courts of appeals. Federal Rules of Appellate Procedure 47, Bankruptcy Procedure 9029, Civil Procedure 83, and Criminal Procedure 57 provide additional requirements for local rule adoption and characteristics. The local rules of almost all courts follow the same numbering sequence as the corresponding national rules. These local rules include the procedures for setting cases for trial, scheduling pretrial conferences, setting motions for oral argument, serving memoranda of law, and other details relating to trial. They may also state the procedure for admission of attorneys to practice in the specific district or circuit, the term of the court, the functions of the clerk of court, the rules for filing motions, and more specific data, such as the number of copies required to be filed, limitations on the length of memoranda, the time within which memoranda must be filed, and restrictions on page length, typeface, and margin size. Each court of appeals has local rules concerning procedures for ordering transcripts; filing and docketing the appeal; calendaring; motions; summary disposition of appeals; setting cases for oral argument; time limits on oral argument; petitions for rehearing; petitions for en banc consideration; and stay of mandate. The local rules and internal operating procedures of the courts of appeals are printed in the United States Code Annotated following Title 28 of the Judicial Code, and are available on the courts’ websites. A court’s local rules and any internal operating procedures it adopts establish specific procedures for the court and litigants to follow. You should get these rules and procedures from the court’s website or the clerk’s office and become familiar with them. Keep them available for reference and be on the lookout for any modifications the court may adopt. 65 Law Clerk Handbook Federal Judicial Center § 4.3    § 4.3 Case Management: The Trial Court Many judges believe that the responsibility for moving a case through the trial court is not solely that of the attorneys, and the function of the court is not simply to be available if and when counsel want a hearing. The disposition of all cases as speedily and economically as is consistent with justice is paramount. The Federal Rules of Civil Procedure are to be “construed to secure the just, speedy, and inexpensive determination of every action.” Fed. R. Civ. P. 1. The courts are also required to report semiannually (on April 30 and September 30) for each judge the motions that have been pending and the bench trials that have been submitted for more than six months, and cases that have not been terminated within three years of filing, for publication by the Administrative Office. 28 U.S.C. § 476. Effective docket control means that, early in a case, the judge assumes responsibility for guiding the case to a conclusion. This may include establishing deadlines for filing motions, a time limit for discovery, a date for counsel to take the next step in its prosecution, and a trial date. For specific techniques of case management, consult the Civil Litigation Management Manual. See also Schwarzer & Hirsch, The Elements of Case Management (Federal Judicial Center, 3d ed. 2017). Note that many of the same considerations apply in criminal cases, with the additional complication of computations required by the Speedy Trial Act. 18 U.S.C. §§ 3161–3174. Law clerks should be familiar with the requirements of the Act, since failure to bring a case to trial within the Act’s time limits can have serious repercussions. A. Office Status Sheets Some judges maintain an office status sheet and post it where it is accessible to chambers staff. Its purpose is to keep the judge, the law clerks, and judicial assistants apprised of legal matters under advisement and awaiting disposition. When a matter has been taken under advisement, the assistant or law clerk assigned to the case should indicate it on the status sheet. Keep a personal status list, which can be revised each week, listing all matters for which you are responsible. It will help you make effective use of your time and remember all pending assignments. Some judges require their law clerks to submit personal status lists weekly. Some judges require their judicial assistants to keep a list of all pending matters, the initials or name of the law clerk assigned to work on the matter, and 66 Chambers and Case Management fjc.dcn • fjc.gov § 4.3.C any other pertinent information. If so, keep the assistant advised of all matters assigned, matters completed, and other relevant status information. CM/ECF helps judges use computer technology for docket control and to maintain case inventories and case-status records. Other systems may also be employed. Regardless of which system is used, it is important that it be regularly maintained and continually monitored. B. Calendaring Systems Multijudge trial courts need a system for determining which judge is responsible for each case. In an individual calendar system, each case is randomly assigned to a particular judge at the time it is filed, or soon thereafter, and that judge has complete responsibility for the case until it is terminated. There are also standard procedures for reassigning cases from which the original judge is disqualified, for ensuring that related cases are all assigned to the same judge, and for special assignment of unusual and protracted cases. Local rules usually describe these procedures. C. Trial Scheduling A single trial may be set for a specific date, or the court may set multiple cases for trial on the same day. Some courts use the trailing calendar or trailing docket, in which the court schedules a number of cases for trial beginning on a stated date. The cases are tried in the order reflected by the schedule. Counsel must obtain information from the court and from the attorneys whose cases precede them on the calendar about the progress of those cases, so that they can go to trial whenever the court reaches their case. Most civil cases do not go to trial but are disposed of in some other manner, including dispositive motions and settlement. Judges differ in their approach to encouraging settlement, but the decision whether to settle or proceed to trial is the parties’ alone. If settlement is to be reached, negotiations should be completed in a timely manner. Last-minute settlements may disrupt the court’s schedule, leaving the judges, and sometimes jurors, with unscheduled time. The trailing calendar and other multiple-case-setting devices alleviate some problems caused by last-minute settlement by providing substitute cases to replace those that do not go to trial. Although this resolves the court’s problems, it does not resolve the problems that eve-of-trial settlements cause litigants and counsel. 67 Law Clerk Handbook Federal Judicial Center § 4.3.D Criminal cases take priority on the court’s calendar because they must be tried within the time limits set forth in the Speedy Trial Act. While criminal cases do not settle, the vast majority of them are disposed of by way of plea bargaining and guilty pleas, which again make multiple-case-setting an important calendaring device for the court. D. Jury Management 1. Random Juror Selection The selection of grand and petit jurors in both criminal and civil cases is governed by 28 U.S.C. §§ 1861–1878, under which each district must have a jury selection plan that has been approved by a panel comprising the circuit judicial council and the chief district judge or the chief judge’s designee. The statutory goal of the selection process is to ensure “grand and petit juries selected at random from a fair cross section of the community in the district or division wherein the court convenes” (28 U.S.C. § 1861), and to avoid excluding any citizen “from service as a grand or petit juror . . . on account of race, color, religion, sex, national origin, or economic status” (28 U.S.C. § 1862). The clerk of court usually manages the process of selecting prospective jurors, under the supervision and control of the court. Although the jury selection process may differ slightly in each district, it is generally as follows: 1. The clerk’s office performs a random selection of prospective jurors’ names by computer or manually, using voter registration lists or other sources specified by the court’s plan, and places the names selected in a master jury wheel, which is usually a computer file. The minimum number of names in the master jury wheel must be one-half of 1% of the number on the source lists, or 1,000, whichever is less. 2. As needed by the court, the clerk’s office draws names publicly at random from the master jury wheel and sends jury-qualification questionnaires to those persons whose names are drawn. 3. From the responses to the questionnaires, a determination is made as to which persons are qualified for jury service and which persons are disqualified, exempt, or excused. 4. The names of those determined to be qualified are placed in a second jury wheel consisting of qualified jurors. 5. As needed, the clerk’s office selects names from the qualified jury wheel and prepares lists of the names selected. 68 Chambers and Case Management fjc.dcn • fjc.gov § 4.3.D.2 6. The clerk’s office issues summonses to the necessary number of persons needed for the jury venire several weeks in advance of each trial calendar advising those summoned of the time and place to report for jury service. Some district courts qualify and summons jurors in one step and do not establish a qualified jury wheel. 2. Exemptions, Disqualifications, and Excuses A person is qualified for jury service unless the person • is not a citizen of the United States • is unable to read, write, and understand English with a degree of proficiency sufficient to complete the juror-qualification form satisfactorily • is incapable of rendering satisfactory service because of mental or physical infirmity • is charged with or has been convicted in a state or federal court of record of a crime punishable by imprisonment for more than one year without subsequent restoration of civil rights 28 U.S.C. § 1865. Some district courts have adopted other grounds for exemptions, which are specified in the court’s jury selection plan. Section 1863 of Title 18 requires the plan to provide for the exemption of members of the armed forces in active service; members of state or local fire or police departments; and public officers of the federal, state, and local governments who are actively engaged in the performance of official duties. Jury service is a citizen’s duty as well as a privilege, and courts do not readily grant excuses. A person may, however, be excused from jury service temporarily if the plan states that such service would result in undue hardship or extreme inconvenience. In such a case, the name of an excused juror is placed back in the qualified jury wheel. If a prospective juror approaches you about an excuse, do not express any opinion regarding the request, but simply refer the requester to the clerk’s office or jury administrator for action. Treat persons called for jury service with courtesy; they are providing an important service to the court and the public. Judges in multijudge courthouses often begin jury trials at different hours to obtain maximum use of people summoned for jury service, sending persons examined and not selected to another courtroom so they can be examined for 69 Law Clerk Handbook Federal Judicial Center § 4.3.D.3 selection on another jury, and sometimes using jurors who have served in one trial in a succeeding trial. When prospective jury panels report for possible selection in a case, they should be segregated from other people in the courtroom. Law clerks may be responsible for clearing a portion of the spectator section for the jury panel’s exclusive use. 3. Juror Orientation Most courts conduct a juror orientation program to inform jurors of their responsibilities and to explain the trial process. Orientation videos, including the Federal Judicial Center’s Called to Serve, are available in most courts. 4. Voir Dire In most courts, the judge personally conducts voir dire examination. Federal Rule of Civil Procedure 47 and Federal Rule of Criminal Procedure 24, however, authorize the judge to permit the lawyers to conduct voir dire. If the judge conducts voir dire, the rules authorize counsel to submit specific questions or areas of inquiry that they want the judge to probe. In some courts, magistrate judges conduct voir dire. The law in most circuits permits this in civil cases, though some require consent of the parties. The Supreme Court has held that a magistrate judge may conduct voir dire in a criminal case if the defendant consents (Peretz v. United States, 501 U.S. 923 (1991)), but not if the defendant objects (Gomez v. United States, 490 U.S. 858 (1989)). 5. Jury Supervision In most courts, a deputy clerk is responsible for jury supervision. However, sometimes law clerks have this responsibility. If so, you should be present early enough in the morning to accommodate those members of the jury who arrive before the normal court time. The jury room should be open and available for use by the jurors as they arrive. If the judge permits the jury to take notes, either you or the deputy clerk should provide pads of paper and pencils for distribution to the jurors before the trial begins. Extra pads and pencils should also be placed in the jury room for use during deliberations. If you are responsible for jury supervision, ensure that there is no communication—in the courtroom, jury room, or hallways adjacent to the courtroom and chambers—between jurors and litigants, lawyers, witnesses, or others attending court. 70 Chambers and Case Management fjc.dcn • fjc.gov § 4.3.E Jurors are usually free to go where they wish during recesses, and they may go home at night. Occasionally, however, when there is unusual publicity about the trial or there is reason to believe that someone will attempt to exert improper influence on jurors, the judge may direct that the jury be sequestered. When this occurs, deputy marshals keep the jurors together at all times and supervise them when court is not in session. Jurors in criminal and civil cases are sometimes sequestered from the time they begin deliberating until they reach a verdict. Judges sometimes have law clerks steward the jury during deliberations. Some judges require the law clerk to take a special oath with respect to this duty just before the jury retires. Once the oath is taken, the law clerk assumes primary responsibility for guarding the jury until relieved of this duty by the judge. Remain outside the jury-room door during the entire deliberation process and take every reasonable precaution to ensure that the jurors do not come into contact with other people, especially the litigants, their attorneys, or witnesses. You must never comment on the evidence, the litigants, the attorneys, or the witnesses to any juror (or, for that matter, to anyone else). If a juror has any questions about the trial, at any stage, you should simply state that such questions should be addressed to the judge in writing. Do not answer the question, however simple it may appear. E. Distributing Opinions Federal Rule of Civil Procedure 52(a) requires the judge to make findings of fact and conclusions of law in all actions tried without a jury or with only an advisory jury. The rule permits the judge to do this orally on the record or in writing in an opinion or memorandum. The judge may also write a formal opinion to explain rulings on particular motions. The judicial assistant sends the original of the findings or the opinion and the original of any order for judgment to the docket clerk for filing in the official record. Then the judicial assistant or clerk of court sends a copy of each set of findings or the opinion to each counsel of record, making and distributing other copies in accordance with the judge’s instructions. In most district courts, the clerk of court handles the distribution of opinions, but in a few district courts, this responsibility falls to the law clerk or judicial assistant. The judge decides whether the opinion or findings are to be published. If you are responsible for distributing opinions, check with the judge to determine whether the judge wishes the opinion to be published and make such distribution as the judge directs. In each case, the opinion should be accompanied by a cover letter from the judge; the judge may have a form letter for this purpose. 71 Law Clerk Handbook Federal Judicial Center § 4.4    § 4.4 Special Duties of Law Clerks to Bankruptcy Judges The duties of law clerks to bankruptcy judges are generally similar to the duties of those working for district judges. The volume of cases and proceedings in bankruptcy court is generally greater than in other trial courts, and the chambers must be organized to handle this volume effectively. Bankruptcy judges hold more, and faster, hearings than do district judges. For the chambers staff, that means more scheduling problems, more substantial prehearing preparation of memoranda, and shorter time limits. It also means more pressure from attorneys telephoning to ask for expedited schedules and to ask about procedures, the disposition of motions, and various other matters. Like district judges, bankruptcy judges differ in their attitudes about direct contact between law clerks and attorneys. Some bankruptcy judges hold court in more than one place. Law clerks and judicial assistants to those judges usually have substantial duties in preparing for travel, including assembly of materials (such as appropriate portions of case records necessary for the trip). The judge’s staff will usually have extra duties in the additional places of holding court because the other staff available may not be as complete as in the home court.    § 4.5 U.S. Magistrate Judges The authority of magistrate judges derives primarily from the Federal Magistrates Act of 1968 and as amended numerous times since. 28 U.S.C. §§ 631–639. Significant Supreme Court cases interpreting the Act include Mathews v. Weber, 423 U.S. 261 (1976) (upholding magistrate judge authority to hear Social Security appeals on a report and recommendation basis); United States v. Raddatz, 447 U.S. 667 (1980) (upholding magistrate judge authority to conduct hearings on motions to suppress evidence in felony cases on a report and recommendation basis); Peretz v. United States, 501 U.S. 923 (1991) (upholding magistrate judge authority to conduct felony voir dire proceedings with the parties’ consent); and Roell v. Withrow, 538 U.S. 580 (2003) (holding that parties’ consent to disposition of a civil case by a magistrate judge under 28 U.S.C. § 636(c) could be inferred from the parties’ conduct during the case). A general outline of the duties performed by magistrate judges is described below. 72 Chambers and Case Management fjc.dcn • fjc.gov § 4.5.B A. Initial Proceedings in Criminal Cases Under 28  U.S.C. §  636(a), a magistrate judge may perform various duties and conduct proceedings in criminal cases, including the following: • accept criminal complaints • issue arrest warrants and summonses • issue search warrants • conduct initial appearance proceedings and detention for criminal defendants, informing them of the charges against them and of their rights • set bail or other conditions of release or detention under the Bail Reform Act, 18 U.S.C. §§ 3141–3145 • appoint attorneys for defendants who are unable to afford or obtain counsel • hold preliminary examinations, or “probable cause” hearings • administer oaths and take bail, acknowledgments, affidavits, and depositions • conduct extradition proceedings List five similarities and three differences. Use only the Context block contained in the prompt to respond. What are the differences between law clerk duties for a district judge and a bankruptcy judge?

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. [user request] [context document]

I just found out I am pregnant and my doctor's office gave me a long list of things I cannot eat or partake in. Using this article as a reference, please explain what those items are and why they are not acceptable for pregnancy. Use at least 500 words.

Pregnancy nutrition: Foods to avoid during pregnancy More foods can affect your health or your baby's health than you might realize. Learn what not to eat when you're pregnant. By Mayo Clinic Staff You want what's best for your baby. That's why you might do things like add sliced fruit to your fortified breakfast cereal, top your salads with chickpeas or snack on almonds. But do you know what foods not to eat during pregnancy? Here's some basic information about eating during pregnancy. Don't eat seafood high in mercury Seafood can be a great source of protein. And the omega-3 fatty acids in many fish can help your baby's brain and eye development. But some fish and shellfish have levels of mercury that could be harmful. Too much mercury could damage your baby's growing nervous system. The bigger and older the fish, the more mercury it's likely to contain. The U.S. Food and Drug Administration (FDA) says not to eat the following while pregnant: Bigeye tuna. King mackerel. Marlin. Orange roughy. Swordfish. Shark. Tilefish. So what's safe? Some types of seafood have little mercury. The Dietary Guidelines for Americans advises pregnant people to eat 8 to 12 ounces (224 to 336 grams) of seafood a week. That's 2 to 3 servings. Here are some options: Anchovies. Black sea bass. Catfish. Cod. Freshwater trout. Herring. Light canned tuna. Oysters. Pollock. Salmon. Sardines. Shad. Shrimp. Sole. Tilapia. Whitefish. Don't eat raw, undercooked or tainted seafood To avoid harmful bacteria or viruses in seafood: Don't eat raw fish and shellfish. Examples of raw or undercooked foods to avoid include sushi, sashimi, ceviche and raw oysters, scallops or clams. Don't eat uncooked seafood that's refrigerated. Examples include seafood labeled nova style, lox, kippered, smoked or jerky. It's OK to eat smoked seafood if it's in a casserole or other cooked dish. Canned and shelf-stable versions also are safe. Watch for local fish advisories. If you eat fish from local waters, check for fish advisories to see how often you can safely eat those fish. Make sure to do this when water pollution is a concern. If you're not sure about the safety of fish you have already eaten, don't eat any more fish that week. Cook seafood well. Cook fish to an inside temperature of 145 F (63 C). Fish is done when it flakes with a fork and looks milky white throughout. Cook shrimp, lobster and scallops until they're milky white. Cook clams, mussels and oysters until their shells open. Throw away any that don't open. Don't eat undercooked meat, poultry or eggs During pregnancy, you're at a higher risk of food poisoning from bacteria. This is called foodborne illness. How your body reacts to food poisoning when you're pregnant might be worse than if you weren't pregnant. Although it's rare, food poisoning may affect the baby, too. To prevent foodborne illness: Fully cook all meats and poultry before eating. Use a meat thermometer to make sure. Cook hot dogs and lunch meats until they're steaming hot. Or don't eat them at all. They can be sources of a rare but serious foodborne illness known as a listeria infection. Don't eat pates and meat spreads that are stored in a refrigerator. Canned and shelf-stable versions are OK. Cook eggs until the egg yolks and whites are firm. Raw eggs can have harmful bacteria. Don't eat foods that may be made with raw or partly cooked eggs. Examples include homemade eggnog, raw batter and dough, tiramisu, freshly made or homemade hollandaise sauce, homemade Caesar salad dressing and homemade ice cream. Don't eat ready-made meat salads or seafood salads. These include ham salad, tuna salad and chicken salad. Don't eat unpasteurized foods Many low-fat dairy products can be a healthy part of your diet. These include skim milk, mozzarella cheese and cottage cheese. But don't eat or drink anything that contains milk that hasn't gone through a process called pasteurization. Products that have unpasteurized milk could cause foodborne illness. Avoid soft cheeses, such as brie, feta and blue cheese, unless the label says they're pasteurized or made with pasteurized milk. Don't drink juice or cider that isn't pasteurized. Don't eat unwashed fruits and vegetables To get rid of harmful bacteria, wash all raw fruits and vegetables well. Don't eat any raw sprouts, including alfalfa, clover, radish and mung bean. They might have harmful bacteria. Be sure to fully cook sprouts. Don't have too much caffeine Caffeine can cross to the baby, but the effects on the baby aren't clear. To be safe, your health care professional might tell you not to have caffeine while pregnant. Or you may be told to limit caffeine to less than 200 milligrams (mg) a day. An 8-ounce (240-milliliters, or mL) cup of brewed coffee has about 95 mg of caffeine. An 8-ounce (240-mL) cup of brewed tea has about 47 mg. And a 12-ounce (360-mL) cola with caffeine has about 33 mg. Don't drink herbal tea Not much is known about the effects of certain herbs on fetuses. As a result, don't drink herbal tea unless your health care professional says it's OK. That includes the types of herbal tea made for pregnancy. Don't drink alcohol No amount of alcohol has been proved safe during pregnancy. To be safe, don't drink any alcohol. Consider the risks. Drinking alcohol during pregnancy leads to a higher risk of miscarriage and stillbirth. Drinking alcohol also may result in fetal alcohol syndrome. The syndrome can cause the face to form oddly and cause lower intelligence. If you're worried about alcohol you drank before you knew you were pregnant, or if you think you need help to stop drinking, talk to your health care professional.

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. I just found out I am pregnant and my doctor's office gave me a long list of things I cannot eat or partake in. Using this article as a reference, please explain what those items are and why they are not acceptable for pregnancy. Use at least 500 words. Pregnancy nutrition: Foods to avoid during pregnancy More foods can affect your health or your baby's health than you might realize. Learn what not to eat when you're pregnant. By Mayo Clinic Staff You want what's best for your baby. That's why you might do things like add sliced fruit to your fortified breakfast cereal, top your salads with chickpeas or snack on almonds. But do you know what foods not to eat during pregnancy? Here's some basic information about eating during pregnancy. Don't eat seafood high in mercury Seafood can be a great source of protein. And the omega-3 fatty acids in many fish can help your baby's brain and eye development. But some fish and shellfish have levels of mercury that could be harmful. Too much mercury could damage your baby's growing nervous system. The bigger and older the fish, the more mercury it's likely to contain. The U.S. Food and Drug Administration (FDA) says not to eat the following while pregnant: Bigeye tuna. King mackerel. Marlin. Orange roughy. Swordfish. Shark. Tilefish. So what's safe? Some types of seafood have little mercury. The Dietary Guidelines for Americans advises pregnant people to eat 8 to 12 ounces (224 to 336 grams) of seafood a week. That's 2 to 3 servings. Here are some options: Anchovies. Black sea bass. Catfish. Cod. Freshwater trout. Herring. Light canned tuna. Oysters. Pollock. Salmon. Sardines. Shad. Shrimp. Sole. Tilapia. Whitefish. Don't eat raw, undercooked or tainted seafood To avoid harmful bacteria or viruses in seafood: Don't eat raw fish and shellfish. Examples of raw or undercooked foods to avoid include sushi, sashimi, ceviche and raw oysters, scallops or clams. Don't eat uncooked seafood that's refrigerated. Examples include seafood labeled nova style, lox, kippered, smoked or jerky. It's OK to eat smoked seafood if it's in a casserole or other cooked dish. Canned and shelf-stable versions also are safe. Watch for local fish advisories. If you eat fish from local waters, check for fish advisories to see how often you can safely eat those fish. Make sure to do this when water pollution is a concern. If you're not sure about the safety of fish you have already eaten, don't eat any more fish that week. Cook seafood well. Cook fish to an inside temperature of 145 F (63 C). Fish is done when it flakes with a fork and looks milky white throughout. Cook shrimp, lobster and scallops until they're milky white. Cook clams, mussels and oysters until their shells open. Throw away any that don't open. Don't eat undercooked meat, poultry or eggs During pregnancy, you're at a higher risk of food poisoning from bacteria. This is called foodborne illness. How your body reacts to food poisoning when you're pregnant might be worse than if you weren't pregnant. Although it's rare, food poisoning may affect the baby, too. To prevent foodborne illness: Fully cook all meats and poultry before eating. Use a meat thermometer to make sure. Cook hot dogs and lunch meats until they're steaming hot. Or don't eat them at all. They can be sources of a rare but serious foodborne illness known as a listeria infection. Don't eat pates and meat spreads that are stored in a refrigerator. Canned and shelf-stable versions are OK. Cook eggs until the egg yolks and whites are firm. Raw eggs can have harmful bacteria. Don't eat foods that may be made with raw or partly cooked eggs. Examples include homemade eggnog, raw batter and dough, tiramisu, freshly made or homemade hollandaise sauce, homemade Caesar salad dressing and homemade ice cream. Don't eat ready-made meat salads or seafood salads. These include ham salad, tuna salad and chicken salad. Don't eat unpasteurized foods Many low-fat dairy products can be a healthy part of your diet. These include skim milk, mozzarella cheese and cottage cheese. But don't eat or drink anything that contains milk that hasn't gone through a process called pasteurization. Products that have unpasteurized milk could cause foodborne illness. Avoid soft cheeses, such as brie, feta and blue cheese, unless the label says they're pasteurized or made with pasteurized milk. Don't drink juice or cider that isn't pasteurized. Don't eat unwashed fruits and vegetables To get rid of harmful bacteria, wash all raw fruits and vegetables well. Don't eat any raw sprouts, including alfalfa, clover, radish and mung bean. They might have harmful bacteria. Be sure to fully cook sprouts. Don't have too much caffeine Caffeine can cross to the baby, but the effects on the baby aren't clear. To be safe, your health care professional might tell you not to have caffeine while pregnant. Or you may be told to limit caffeine to less than 200 milligrams (mg) a day. An 8-ounce (240-milliliters, or mL) cup of brewed coffee has about 95 mg of caffeine. An 8-ounce (240-mL) cup of brewed tea has about 47 mg. And a 12-ounce (360-mL) cola with caffeine has about 33 mg. Don't drink herbal tea Not much is known about the effects of certain herbs on fetuses. As a result, don't drink herbal tea unless your health care professional says it's OK. That includes the types of herbal tea made for pregnancy. Don't drink alcohol No amount of alcohol has been proved safe during pregnancy. To be safe, don't drink any alcohol. Consider the risks. Drinking alcohol during pregnancy leads to a higher risk of miscarriage and stillbirth. Drinking alcohol also may result in fetal alcohol syndrome. The syndrome can cause the face to form oddly and cause lower intelligence. If you're worried about alcohol you drank before you knew you were pregnant, or if you think you need help to stop drinking, talk to your health care professional. https://www.mayoclinic.org/healthy-lifestyle/pregnancy-week-by-week/in-depth/pregnancy-nutrition/art-20043844

You must respond using only information provided in the prompt. Explain your reasoning with at least 3 supporting points.

What is the probable date range for this document

The main challenges are, if such divergence simply reflects differences in financial market structures and regulatory/supervisory tools and instruments as well as with a principles-based approach, or a IPOL | Policy Department for Economic, Scientific and Quality of Life Policies PE 740.067 46 more fundamental shift towards a less regulated financial system that focuses on growth and ‘competitiveness’ of the sector and less on its stability. It is important to stress, however, that not all observers, and none of our interviewees, see necessarily a contradiction between growth/competitiveness and stability, even though economic research has shown that rapid growth of the financial sector can result in financial fragility and crisis. 3.2.1. Low, medium and high divergence Low divergence: Under this scenario, there will be adjustments to regulations such as Solvency II as well as other initiatives in line with increasing the ‘competitiveness’ of the UK as financial centre. However, there will not be major divergence, especially in areas with international standards, such as bank capital regulation. There might be informal consultations between UK and EU regulatory and possibly legislative authorities to converge on rules in new areas such as crypto and the decentralised financial system more generally. Even under the politically most positive developments (as described below in 3.2.2), however, there will be divergence between the UK and EU, also as EU Law is significantly amended with the UK not following it (in other words, passive divergence). Regulatory cooperation, however, will allow for such divergence not to turn into beggar-thy-neighbour policies. Apart from resolving the political conflict around the Northern Ireland Protocol (NIP), a reconfirmation of the stability focus of the prudential policies and regulation in the UK is necessary in our opinion. In terms of specific segments of the financial system, we would expect least divergence in areas where international standards play an important role, such as capital and liquidity regulation of banks. Interestingly, it seems that the EU is diverging more from the initial global standards than the UK (see discussion above in 3.1). Similarly, given the early initiative that EU authorities have taken with the green taxonomy and the joint participation in many global fora and other cooperation initiatives, we would also expect the UK to follow the lead in this area, as already discussed above, even though there might be a certain degree of divergence. It is important to stress that many of the legislative initiatives in sustainable finance in the UK are still in the early stages and one has to look beyond political headlines to details once they are spelled out. Medium divergence: Under this scenario, there will be more significant divergence and fewer attempts to converge on new rules such as in the area of green finance or crypto asset developments. Divergence will be more likely and more prominent in areas where international standards are less important and where the UK has not inherited any EU regulations such as in the two areas already mentioned, green finance and crypto. While supervisory cooperation between EU and UK authorities might continue (and will be necessary in areas of regulatory equivalence), regulatory cooperation even if formalised will be less strong and there will not necessarily be any voluntary attempt by UK authorities to follow adjustments and changes in EU regulation and supervision. On the other hand, both the UK and the EU are members of global regulatory bodies across different segments of the financial system (FSB, Basel Committee) and this will effectively be a constraint on too much positive or negative divergence. High divergence: Under this final scenario, there would be a rather aggressive legislative and regulatory drive in the UK to diverge from EU rules. This would involve both replacing existing EU rules with new regulation and adopting divergent rules where such rules were not inherited, such as in green finance and crypto/digital finance more broadly. It can also include not following changes in EU legislation to thus mark differences between the two regulatory jurisdictions. We would expect such aggressive divergence especially in areas where UK authorities see growth opportunities and they feel less constrained by international fora and cooperation initiatives. Crypto is certainly an area where one could envision such aggressive divergence. Such high divergence, however, seems more likely under Recent trends in UK financial sector regulation and possible implications for the EU 47 PE 740.067 an institutional architecture in the UK where the independence of regulatory authorities has been significantly weakened (though not necessarily in a formal, i.e., legislative manner) and growth/competitiveness objectives are clearly prioritised over stability concerns. As we will discuss in section 3.2.2, which of the three scenarios will develop depends very much on how the overall political relationship between the EU and the UK will develop over the next years, with the Northern Ireland Protocol being the major hurdle in this relationship. 3.2.2. Disentangling the Northern Ireland Protocol situation to unblock/reactivate UKEU regulatory cooperation Resolving the dispute between the UK and the EU on the implementation of the Northern Ireland Protocol (NIP) seems key to rebuild trust and unblock UK-EU regulatory cooperation across a number of policy areas including the financial sector. Resolving this dispute requires political leadership from the UK Prime Minister taking office in October 2022, Rishi Sunak, and bringing on board both the European Research Group (ERG) of hardcore Brexiters in the British Parliament and Northern Ireland’s Unionists, not an easy feat. While immediate conflicts can be avoided by delaying the legislative process of the NIP Bill (which would override and breach the NIP and the Withdrawal Agreement), cooperation between UK and EU authorities on trade data provision from the UK to the EU, and not taking unilateral steps, the resolution of the ‘stand-off’ cannot be delayed forever. Namely, the Northern Ireland Executive has not been established since the 2022 May elections and new elections to the Legislative Assembly will have to be called in spring 2023, which raise the political temperature in the region. The upcoming 25th anniversary of the Good Friday Agreement in 2023 increases both internal and external (especially from the US) pressures. Finally, in case of increasing divergence in goods standards between the UK and the EU, there will be increasing pressure from the EU on properly monitoring trade between Great Britain and Northern Ireland. In case the conflict around the Northern Ireland Protocol can be resolved to the satisfaction of both sides, there should be few if any barriers for future cooperation between UK and EU authorities on financial sector issues. Addressing the stand-off around the NIP is thus a necessary though not sufficient condition. At the end of November 2022, the Council Presidency and the European Parliament actually reached a provisional agreement on a Regulation on ‘autonomous measures’ potentially taken as a retaliation and that would allow the EU to ensure ‘timely and effective exercise of its rights in enforcing and implementing’ the Withdrawal Agreement and the TCA162. At the same time, not long after, the European Commission Vice President Maroš Šefčovič stressed the ‘window of opportunity for a positive outcome’163 in the context of the extension of practical arrangements for veterinary medicines until December 2025. This positive ‘mood music’ has been echoed by Leo Varadkar, the Taoiseach in Ireland, who stressed the increased trust and flexibility between the UK and the EU – notwithstanding remaining differences164. There will certainly be competing interests (similar to what we could observe during the UK’s EU membership) and no expectations of complete convergence, but an institutional framework for regulatory dialogue could be put in place. 162 Council of the EU, ‘EU-UK Relations: Council Presidency and European Parliament Reach Provisional Agreement on a Regulation on Autonomous Measures’ (30 November 2022) https://www.consilium.europa.eu/en/press/press-releases/2022/11/30/eu-uk-relationscouncil-presidency-and-european-parliament-reach-provisional-agreement-on-a-regulation-on-autonomous-measures/, accessed 5 January 2023. 163 ‘Statement by Vice-President Maroš Šefčovič’ (European Commission, 19 December 2022) https://ec.europa.eu/commission/presscorner/detail/en/statement_22_7831, accessed 5 January 2023. 164 “Much Better Mood Music” in EU-UK Relations than at Any Period since Brexit Referendum - Taoiseach’ (n 22). IPOL | Policy Department for Economic, Scientific and Quality of Life Policies PE 740.067 48 Before the resolution of this conflict, it is difficult to see any progress happening in terms of regulatory cooperation. Similar, if the conflict around the NIP escalates again, it is hard to envision any progress towards trade partnership of the UK with third countries such as the US.

You must respond using only information provided in the prompt. Explain your reasoning with at least 3 supporting points. The main challenges are, if such divergence simply reflects differences in financial market structures and regulatory/supervisory tools and instruments as well as with a principles-based approach, or a IPOL | Policy Department for Economic, Scientific and Quality of Life Policies PE 740.067 46 more fundamental shift towards a less regulated financial system that focuses on growth and ‘competitiveness’ of the sector and less on its stability. It is important to stress, however, that not all observers, and none of our interviewees, see necessarily a contradiction between growth/competitiveness and stability, even though economic research has shown that rapid growth of the financial sector can result in financial fragility and crisis. 3.2.1. Low, medium and high divergence Low divergence: Under this scenario, there will be adjustments to regulations such as Solvency II as well as other initiatives in line with increasing the ‘competitiveness’ of the UK as financial centre. However, there will not be major divergence, especially in areas with international standards, such as bank capital regulation. There might be informal consultations between UK and EU regulatory and possibly legislative authorities to converge on rules in new areas such as crypto and the decentralised financial system more generally. Even under the politically most positive developments (as described below in 3.2.2), however, there will be divergence between the UK and EU, also as EU Law is significantly amended with the UK not following it (in other words, passive divergence). Regulatory cooperation, however, will allow for such divergence not to turn into beggar-thy-neighbour policies. Apart from resolving the political conflict around the Northern Ireland Protocol (NIP), a reconfirmation of the stability focus of the prudential policies and regulation in the UK is necessary in our opinion. In terms of specific segments of the financial system, we would expect least divergence in areas where international standards play an important role, such as capital and liquidity regulation of banks. Interestingly, it seems that the EU is diverging more from the initial global standards than the UK (see discussion above in 3.1). Similarly, given the early initiative that EU authorities have taken with the green taxonomy and the joint participation in many global fora and other cooperation initiatives, we would also expect the UK to follow the lead in this area, as already discussed above, even though there might be a certain degree of divergence. It is important to stress that many of the legislative initiatives in sustainable finance in the UK are still in the early stages and one has to look beyond political headlines to details once they are spelled out. Medium divergence: Under this scenario, there will be more significant divergence and fewer attempts to converge on new rules such as in the area of green finance or crypto asset developments. Divergence will be more likely and more prominent in areas where international standards are less important and where the UK has not inherited any EU regulations such as in the two areas already mentioned, green finance and crypto. While supervisory cooperation between EU and UK authorities might continue (and will be necessary in areas of regulatory equivalence), regulatory cooperation even if formalised will be less strong and there will not necessarily be any voluntary attempt by UK authorities to follow adjustments and changes in EU regulation and supervision. On the other hand, both the UK and the EU are members of global regulatory bodies across different segments of the financial system (FSB, Basel Committee) and this will effectively be a constraint on too much positive or negative divergence. High divergence: Under this final scenario, there would be a rather aggressive legislative and regulatory drive in the UK to diverge from EU rules. This would involve both replacing existing EU rules with new regulation and adopting divergent rules where such rules were not inherited, such as in green finance and crypto/digital finance more broadly. It can also include not following changes in EU legislation to thus mark differences between the two regulatory jurisdictions. We would expect such aggressive divergence especially in areas where UK authorities see growth opportunities and they feel less constrained by international fora and cooperation initiatives. Crypto is certainly an area where one could envision such aggressive divergence. Such high divergence, however, seems more likely under Recent trends in UK financial sector regulation and possible implications for the EU 47 PE 740.067 an institutional architecture in the UK where the independence of regulatory authorities has been significantly weakened (though not necessarily in a formal, i.e., legislative manner) and growth/competitiveness objectives are clearly prioritised over stability concerns. As we will discuss in section 3.2.2, which of the three scenarios will develop depends very much on how the overall political relationship between the EU and the UK will develop over the next years, with the Northern Ireland Protocol being the major hurdle in this relationship. 3.2.2. Disentangling the Northern Ireland Protocol situation to unblock/reactivate UKEU regulatory cooperation Resolving the dispute between the UK and the EU on the implementation of the Northern Ireland Protocol (NIP) seems key to rebuild trust and unblock UK-EU regulatory cooperation across a number of policy areas including the financial sector. Resolving this dispute requires political leadership from the UK Prime Minister taking office in October 2022, Rishi Sunak, and bringing on board both the European Research Group (ERG) of hardcore Brexiters in the British Parliament and Northern Ireland’s Unionists, not an easy feat. While immediate conflicts can be avoided by delaying the legislative process of the NIP Bill (which would override and breach the NIP and the Withdrawal Agreement), cooperation between UK and EU authorities on trade data provision from the UK to the EU, and not taking unilateral steps, the resolution of the ‘stand-off’ cannot be delayed forever. Namely, the Northern Ireland Executive has not been established since the 2022 May elections and new elections to the Legislative Assembly will have to be called in spring 2023, which raise the political temperature in the region. The upcoming 25th anniversary of the Good Friday Agreement in 2023 increases both internal and external (especially from the US) pressures. Finally, in case of increasing divergence in goods standards between the UK and the EU, there will be increasing pressure from the EU on properly monitoring trade between Great Britain and Northern Ireland. In case the conflict around the Northern Ireland Protocol can be resolved to the satisfaction of both sides, there should be few if any barriers for future cooperation between UK and EU authorities on financial sector issues. Addressing the stand-off around the NIP is thus a necessary though not sufficient condition. At the end of November 2022, the Council Presidency and the European Parliament actually reached a provisional agreement on a Regulation on ‘autonomous measures’ potentially taken as a retaliation and that would allow the EU to ensure ‘timely and effective exercise of its rights in enforcing and implementing’ the Withdrawal Agreement and the TCA162. At the same time, not long after, the European Commission Vice President Maroš Šefčovič stressed the ‘window of opportunity for a positive outcome’163 in the context of the extension of practical arrangements for veterinary medicines until December 2025. This positive ‘mood music’ has been echoed by Leo Varadkar, the Taoiseach in Ireland, who stressed the increased trust and flexibility between the UK and the EU – notwithstanding remaining differences164. There will certainly be competing interests (similar to what we could observe during the UK’s EU membership) and no expectations of complete convergence, but an institutional framework for regulatory dialogue could be put in place. 162 Council of the EU, ‘EU-UK Relations: Council Presidency and European Parliament Reach Provisional Agreement on a Regulation on Autonomous Measures’ (30 November 2022) https://www.consilium.europa.eu/en/press/press-releases/2022/11/30/eu-uk-relationscouncil-presidency-and-european-parliament-reach-provisional-agreement-on-a-regulation-on-autonomous-measures/, accessed 5 January 2023. 163 ‘Statement by Vice-President Maroš Šefčovič’ (European Commission, 19 December 2022) https://ec.europa.eu/commission/presscorner/detail/en/statement_22_7831, accessed 5 January 2023. 164 “Much Better Mood Music” in EU-UK Relations than at Any Period since Brexit Referendum - Taoiseach’ (n 22). IPOL | Policy Department for Economic, Scientific and Quality of Life Policies PE 740.067 48 Before the resolution of this conflict, it is difficult to see any progress happening in terms of regulatory cooperation. Similar, if the conflict around the NIP escalates again, it is hard to envision any progress towards trade partnership of the UK with third countries such as the US. What is the probable date range for this document

Please only use the provided information to answer the question. Do not use any external knowledge or prior knowledge. The answer should be extracted based on the text only.

Based on the provided text, can you provide the steps taken when leave is needed for FMLA?

Employees must provide a 30-day advance notice to employers when the need for leave is foreseeable based on an expected birth or a scheduled medical treatment.52 When the need for leave is not foreseeable (e.g., hospitalization resulting from an automobile accident) or when leave is needed to address a qualifying military exigency, notice must be given “as soon as practicable.”53 In some cases, an employer may delay approval of FMLA leave when advance notice requirements are not met. Compliance with Employers’ Policy for Requesting Leave In general, employers may condition FMLA leave approval upon an employee’s adherence to the employer’s policy for requesting leave.54 For example, if established in employer policy, an employer may require written request for leave, or require the employee to call-in prior to an absence when using intermittent leave. There are limits, however, on when employer policy can be used to deny or delay FMLA leave. Employers may not apply a longer notice period than the 30-day notice provided in the act (e.g., the employer cannot require a 45-day notice). An FMLA leave request that does not meet employer policy may not be denied if unusual circumstances prevent the employee from following employer policy (e.g., emergency medical treatment is required). Scheduling Planned Medical Treatment and Leave When the need for FMLA leave is based on a planned medical treatment and is foreseeable, the employee must make a reasonable effort to schedule the treatment so as not to disrupt unduly the business operations.55 Plans made between the employer and employee regarding scheduling of leave and the timing of planned medical treatment are subject to the approval of the employee’s health care provider. Employer Rights to Require Certification In some instances, employers may require that an employee’s request for FMLA leave be supported by medical certification (e.g., that a serious health condition exists) or other certification (e.g., to determine active duty status of a military member).56 Employers must notify employees each time certification is required, and inform employees of the anticipated consequences should the employee fail to provide certification (e.g., denial of leave). Medical Certification of a Serious Health Condition An employer may require an employee requesting leave for a serious health condition—his or her own, or that of a family member—to provide medical certification verifying that such a condition exists, and related information.57 A new certification of a serious health condition can be required every 12 months.

System Instruction: Please only use the provided information to answer the question. Do not use any external knowledge or prior knowledge. The answer should be extracted based on the text only. Question: Based on the provided text, can you provide the steps taken when leave is needed for FMLA? Context block: Employees must provide a 30-day advance notice to employers when the need for leave is foreseeable based on an expected birth or a scheduled medical treatment.52 When the need for leave is not foreseeable (e.g., hospitalization resulting from an automobile accident) or when leave is needed to address a qualifying military exigency, notice must be given “as soon as practicable.”53 In some cases, an employer may delay approval of FMLA leave when advance notice requirements are not met. Compliance with Employers’ Policy for Requesting Leave In general, employers may condition FMLA leave approval upon an employee’s adherence to the employer’s policy for requesting leave.54 For example, if established in employer policy, an employer may require written request for leave, or require the employee to call-in prior to an absence when using intermittent leave. There are limits, however, on when employer policy can be used to deny or delay FMLA leave. Employers may not apply a longer notice period than the 30-day notice provided in the act (e.g., the employer cannot require a 45-day notice). An FMLA leave request that does not meet employer policy may not be denied if unusual circumstances prevent the employee from following employer policy (e.g., emergency medical treatment is required). Scheduling Planned Medical Treatment and Leave When the need for FMLA leave is based on a planned medical treatment and is foreseeable, the employee must make a reasonable effort to schedule the treatment so as not to disrupt unduly the business operations.55 Plans made between the employer and employee regarding scheduling of leave and the timing of planned medical treatment are subject to the approval of the employee’s health care provider. Employer Rights to Require Certification In some instances, employers may require that an employee’s request for FMLA leave be supported by medical certification (e.g., that a serious health condition exists) or other certification (e.g., to determine active duty status of a military member).56 Employers must notify employees each time certification is required, and inform employees of the anticipated consequences should the employee fail to provide certification (e.g., denial of leave). Medical Certification of a Serious Health Condition An employer may require an employee requesting leave for a serious health condition—his or her own, or that of a family member—to provide medical certification verifying that such a condition exists, and related information.57 A new certification of a serious health condition can be required every 12 months.

{instruction} ========== In your answer, refer only to the context document. Do not employ any outside knowledge {question} ========== [user request] {passage 0} ========== [context document]

What is the purpose of the medication Amlodipine and what are some of the potential side effects of its usage? Make your response no less than 150 words.

Why is this medication prescribed? Amlodipine is used alone or in combination with other medications to treat high blood pressure in adults and children 6 years and older. It is also used to treat certain types of angina (chest pain) and coronary artery disease (narrowing of the blood vessels that supply blood to the heart). Amlodipine is in a class of medications called calcium channel blockers. It lowers blood pressure by relaxing the blood vessels so the heart does not have to pump as hard. It controls chest pain by increasing the supply of blood to the heart. If taken regularly, amlodipine controls chest pain, but it does not stop chest pain once it starts. Your doctor may prescribe a different medication to take when you have chest pain. High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation. How should this medicine be used? Amlodipine comes as a tablet, an oral solution (liquid), and a suspension (liquid) to take by mouth. It is usually taken once a day with or without food. Take amlodipine around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take amlodipine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor. Shake the suspension well before each use to mix the medication evenly. Your doctor will probably start you on a low dose of amlodipine and gradually increase your dose. Amlodipine helps to control high blood pressure, angina, and coronary artery disease, but does not cure these conditions. Continue to take amlodipine even if you feel well. Do not stop taking amlodipine without talking to your doctor. Other uses for this medicine This medication may be prescribed for other uses; ask your doctor or pharmacist for more information. What special precautions should I follow? Before taking amlodipine, tell your doctor and pharmacist if you are allergic to amlodipine, any other medications, or any ingredients in amlodipine tablets, oral solution, or suspension. Ask your pharmacist for a list of the ingredients. tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you carefully for side effects. tell your doctor if you have or have ever had heart failure or heart or liver disease. tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking amlodipine, call your doctor. What special dietary instructions should I follow? If your doctor prescribes a low-salt or low-sodium diet, follow these directions carefully. What should I do if I forget a dose? Take the missed dose as soon as you remember it. However, if it is less than 12 hours until your next scheduled dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one. What side effects can this medication cause? Amlodipine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: swelling of the hands, feet, ankles, or lower legs nausea stomach pain dizziness or lightheadedness muscle stiffness or tremors Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately or get emergency medical treatment: more frequent or more severe chest pain rapid, pounding, or irregular heartbeat If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (https://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

{instruction} ========== In your answer, refer only to the context document. Do not employ any outside knowledge {question} ========== What is the purpose of the medication Amlodipine and what are some of the potential side effects of its usage? Make your response no less than 150 words. {passage 0} ========== Why is this medication prescribed? Amlodipine is used alone or in combination with other medications to treat high blood pressure in adults and children 6 years and older. It is also used to treat certain types of angina (chest pain) and coronary artery disease (narrowing of the blood vessels that supply blood to the heart). Amlodipine is in a class of medications called calcium channel blockers. It lowers blood pressure by relaxing the blood vessels so the heart does not have to pump as hard. It controls chest pain by increasing the supply of blood to the heart. If taken regularly, amlodipine controls chest pain, but it does not stop chest pain once it starts. Your doctor may prescribe a different medication to take when you have chest pain. High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation. How should this medicine be used? Amlodipine comes as a tablet, an oral solution (liquid), and a suspension (liquid) to take by mouth. It is usually taken once a day with or without food. Take amlodipine around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take amlodipine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor. Shake the suspension well before each use to mix the medication evenly. Your doctor will probably start you on a low dose of amlodipine and gradually increase your dose. Amlodipine helps to control high blood pressure, angina, and coronary artery disease, but does not cure these conditions. Continue to take amlodipine even if you feel well. Do not stop taking amlodipine without talking to your doctor. Other uses for this medicine This medication may be prescribed for other uses; ask your doctor or pharmacist for more information. What special precautions should I follow? Before taking amlodipine, tell your doctor and pharmacist if you are allergic to amlodipine, any other medications, or any ingredients in amlodipine tablets, oral solution, or suspension. Ask your pharmacist for a list of the ingredients. tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you carefully for side effects. tell your doctor if you have or have ever had heart failure or heart or liver disease. tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking amlodipine, call your doctor. What special dietary instructions should I follow? If your doctor prescribes a low-salt or low-sodium diet, follow these directions carefully. What should I do if I forget a dose? Take the missed dose as soon as you remember it. However, if it is less than 12 hours until your next scheduled dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one. What side effects can this medication cause? Amlodipine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: swelling of the hands, feet, ankles, or lower legs nausea stomach pain dizziness or lightheadedness muscle stiffness or tremors Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately or get emergency medical treatment: more frequent or more severe chest pain rapid, pounding, or irregular heartbeat If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (https://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088). https://medlineplus.gov/druginfo/meds/a692044.html

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. [user request] [context document]

My son has severe eczema. I want to understand more about it and how to treat it at home. Using this article, please explain what eczema is and how to treat it. Use at least 400 words.

Eczema, a.k.a., atopic dermatitis, is a chronic skin condition that causes patches of red, dry, and flaky skin that can trigger maddening itching and sometimes soreness and pain, too—the result of a rogue inflammatory response attacking your skin, which happens to be the largest organ in your body. Its symptoms can vary in both appearance and severity among different people and ethnic groups, per the National Eczema Association(NEA). And sometimes, the way people with eczema describe their condition varies, too. Take the term “papular” eczema. Some info-seekers out there who rely too much on Dr. Google might think this is a legit (and unique) type of atopic dermatitis—but our expert dermatologists are here to set the record straight. Papular Eczema What Is Papular Eczema? “Papular eczema really doesn’t mean something specific but when I imagine it, I imagine bumps rather than plaques,” says Scott Elman, M.D., a dermatologist and assistant professor of clinical dermatology and cutaneous surgery at University of Miami Health in Florida. These bumps, rather than flat, inflamed plaques, may be what eczema more often looks like on darker skin tones, adds Jeff Yu, M.D., a dermatologist at Massachusetts General Hospital and assistant professor of dermatology at Harvard Medical School in Boston. “We use that term but only for certain ethnic groups. We tend to see eczema that’s a little bit bumpier in African Americans and other people of color,” explains Dr. Yu. Meanwhile, Amy Paller, M.D., the chair of the Department of Dermatology at Northwestern Medicine in Evanston, IL, questions the term entirely. “I’ve never heard [of] ‘papular’ eczema,” she says. “We call it atopic dermatitis.” Meaning, people who say they have papular eczema likely mean their eczema is more bumpy than patchy. And those bumps may be more common in darker skin. But at the end of the day, it’s all just atopic dermatitis. Symptoms What Are the Symptoms of Papular Eczema? If your eczema is of the papular variety, you’ll likely see small, raised bumps on your skin rather than large, flat rashes. This symptom is more often seen on the skin of Black and brown people, say our experts. Beyond that, the majority of atopic dermatitis symptoms are the same. Here’s what you might experience, and it can happen anywhere on your body: Darkening of the skin around your eyes Dry, cracked skin Itching Oozing and crusting on the inflamed skin Raw, sensitive skin from scratching Swollen skin with a rash Thickened skin According to Dr. Elman, bumps, rashes, and irritated and inflamed skin can all look different on different people. On lighter skin, these skin symptoms look pink or red. On darker skin, areas affected by eczema may look more purple, burgundy, or brown. “That inflammation is absolutely seen differently on different skin tones,” adds Dr. Elman. “The redness may be more subtle. It could be a bit more purple. And it might be harder to discern on darker skin.” Causes What Causes Eczema? Your skin, when it’s acting like it’s supposed to, serves as a barrier between the inside of your body and the outside world. But, in eczema, “the skin barrier just stops working as well, so the body is exposed to things that it isn’t used to seeing, and that can trigger flares,” says Dr. Elman. A few things might cause that dysfunction in your skin barrier. For starters, your genes. Some people are born with a gene variant that interferes with the skin's ability to protect as it should, acording to Mayo Clinic. Bacteria is another possible culprit, per Mayo. Too much of the bacteria Staphylococcus aureus (or just “staph” for short) on the skin can crowd out the good bacteria and keep your skin barrier from doing its job. Either way, it’s that defective skin barrier that leads to all the problems in eczema. When you have a weak skin barrier, your skin can’t hold in moisture as well. And it’s unable to keep out bacteria, irritants, allergens, and potential environmental triggers like cigarette smoke. That faulty skin barrier—or all the germs and other stuff that creep in as a result—can set off an immune system reaction that leads to that itchy, inflamed, and irritated skin that you probably know all too well, Dr. Elman says. Diagnosis How Is Papular Eczema Diagnosed? There is no blood test, biopsy, or X-ray for atopic dermatitis. Instead, your dermatologist or primary care physician will likely look at your skin to check for the physical signs and symptoms of atopic dermatitis, Dr. Yu explains. Then they might ask whether you have family members with eczema. They may also want to know if you or a family member has food allergies, seasonal allergies or asthma since those can be risk factors for eczema, per the NEA. If your doctor does order some testing for you, these are usually done to rule out other problems, like a specific allergy for which you’d need what’s called a patch test. Home Remedies Home Remedies for Eczema If you’ve got mild eczema, chances are you can get it under control on your own. “Most people who have very mild eczema probably don't end up seeing a dermatologist,” Dr. Yu confirms. According to Dr. Yu, you might be able to keep your symptoms at bay with some of the following DIY and OTC solutions: Moisturize Your Skin It’s critical to moisturize as soon as you get out of the tub or the shower. “It’s important that you’re using moisturizing ointments, something that has the consistency of Vaseline or Aquaphor,” Dr. Yu advises. There’s a specific protocol for moisturizing when you have eczema: After bathing in lukewarm water, pat your skin dry, and never rub it. Apply any topical medications that you use. Then, within three minutes of patting dry, while the skin is still damp, slather on your moisturizer. This “soak and seal” method locks moisture in and reseals that broken skin barrier. Add Some Oatmeal Studies show that colloidal oatmeal can help bring moisture back to eczema skin. You can: Add it to your lukewarm bath Make it into a paste and press it directly into the affected area Use eczema products containing it Soak in a Bleach Bath “When you do a diluted bleach bath, similar to the concentration you find in a swimming pool, it has actually shown to be very anti-inflammatory,” says Dr. Yu. The NEA recommends a 10-minute bleach bath two to three times each week. Add a half-cup of household bleach to a full tub of lukewarm water. Soak for 10 minutes. Rinse off with clean water. Then, pat dry. P.S.: A 10-minute dip in the swimming pool gets the job done, too! Moisturizing Oils Some—but not all—oils can bring relief to eczema-inflamed skin. There’s evidence that sunflower oil, coconut oil, and shea butter have benefits for this type of irritation. But you can’t just grab any old oil from your kitchen. “Stay away from olive oil, advises Dr. Yu. “The fatty acids found in olive oil actually promote the growth of yeast on your skin.” You apply coconut or other oils to the skin twice a day, just as you would any moisturizer. Ideally, one application per day is right after you bathe when your skin is still damp. If coconut oil is your pick, go for “virgin” or “cold-pressed.” Any other extraction method uses chemicals that could irritate your skin even more, say the NEA. Anti-Itch Cream Use OTC Anti-Itch Cream Try an anti-itch cream containing 1% hydrocortisone no more than twice a day on the irritated areas. Apply it after your bath and before you moisturize. This steroid calms down itching, swelling and irritation by quelling the body’s inflammatory response.

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. My son has severe eczema. I want to understand more about it and how to treat it at home. Using this article, please explain what eczema is and how to treat it. Use at least 400 words. Eczema, a.k.a., atopic dermatitis, is a chronic skin condition that causes patches of red, dry, and flaky skin that can trigger maddening itching and sometimes soreness and pain, too—the result of a rogue inflammatory response attacking your skin, which happens to be the largest organ in your body. Its symptoms can vary in both appearance and severity among different people and ethnic groups, per the National Eczema Association(NEA). And sometimes, the way people with eczema describe their condition varies, too. Take the term “papular” eczema. Some info-seekers out there who rely too much on Dr. Google might think this is a legit (and unique) type of atopic dermatitis—but our expert dermatologists are here to set the record straight. Papular Eczema What Is Papular Eczema? “Papular eczema really doesn’t mean something specific but when I imagine it, I imagine bumps rather than plaques,” says Scott Elman, M.D., a dermatologist and assistant professor of clinical dermatology and cutaneous surgery at University of Miami Health in Florida. These bumps, rather than flat, inflamed plaques, may be what eczema more often looks like on darker skin tones, adds Jeff Yu, M.D., a dermatologist at Massachusetts General Hospital and assistant professor of dermatology at Harvard Medical School in Boston. “We use that term but only for certain ethnic groups. We tend to see eczema that’s a little bit bumpier in African Americans and other people of color,” explains Dr. Yu. Meanwhile, Amy Paller, M.D., the chair of the Department of Dermatology at Northwestern Medicine in Evanston, IL, questions the term entirely. “I’ve never heard [of] ‘papular’ eczema,” she says. “We call it atopic dermatitis.” Meaning, people who say they have papular eczema likely mean their eczema is more bumpy than patchy. And those bumps may be more common in darker skin. But at the end of the day, it’s all just atopic dermatitis. Symptoms What Are the Symptoms of Papular Eczema? If your eczema is of the papular variety, you’ll likely see small, raised bumps on your skin rather than large, flat rashes. This symptom is more often seen on the skin of Black and brown people, say our experts. Beyond that, the majority of atopic dermatitis symptoms are the same. Here’s what you might experience, and it can happen anywhere on your body: Darkening of the skin around your eyes Dry, cracked skin Itching Oozing and crusting on the inflamed skin Raw, sensitive skin from scratching Swollen skin with a rash Thickened skin According to Dr. Elman, bumps, rashes, and irritated and inflamed skin can all look different on different people. On lighter skin, these skin symptoms look pink or red. On darker skin, areas affected by eczema may look more purple, burgundy, or brown. “That inflammation is absolutely seen differently on different skin tones,” adds Dr. Elman. “The redness may be more subtle. It could be a bit more purple. And it might be harder to discern on darker skin.” Causes What Causes Eczema? Your skin, when it’s acting like it’s supposed to, serves as a barrier between the inside of your body and the outside world. But, in eczema, “the skin barrier just stops working as well, so the body is exposed to things that it isn’t used to seeing, and that can trigger flares,” says Dr. Elman. A few things might cause that dysfunction in your skin barrier. For starters, your genes. Some people are born with a gene variant that interferes with the skin's ability to protect as it should, acording to Mayo Clinic. Bacteria is another possible culprit, per Mayo. Too much of the bacteria Staphylococcus aureus (or just “staph” for short) on the skin can crowd out the good bacteria and keep your skin barrier from doing its job. Either way, it’s that defective skin barrier that leads to all the problems in eczema. When you have a weak skin barrier, your skin can’t hold in moisture as well. And it’s unable to keep out bacteria, irritants, allergens, and potential environmental triggers like cigarette smoke. That faulty skin barrier—or all the germs and other stuff that creep in as a result—can set off an immune system reaction that leads to that itchy, inflamed, and irritated skin that you probably know all too well, Dr. Elman says. Diagnosis How Is Papular Eczema Diagnosed? There is no blood test, biopsy, or X-ray for atopic dermatitis. Instead, your dermatologist or primary care physician will likely look at your skin to check for the physical signs and symptoms of atopic dermatitis, Dr. Yu explains. Then they might ask whether you have family members with eczema. They may also want to know if you or a family member has food allergies, seasonal allergies or asthma since those can be risk factors for eczema, per the NEA. If your doctor does order some testing for you, these are usually done to rule out other problems, like a specific allergy for which you’d need what’s called a patch test. Home Remedies Home Remedies for Eczema If you’ve got mild eczema, chances are you can get it under control on your own. “Most people who have very mild eczema probably don't end up seeing a dermatologist,” Dr. Yu confirms. According to Dr. Yu, you might be able to keep your symptoms at bay with some of the following DIY and OTC solutions: Moisturize Your Skin It’s critical to moisturize as soon as you get out of the tub or the shower. “It’s important that you’re using moisturizing ointments, something that has the consistency of Vaseline or Aquaphor,” Dr. Yu advises. There’s a specific protocol for moisturizing when you have eczema: After bathing in lukewarm water, pat your skin dry, and never rub it. Apply any topical medications that you use. Then, within three minutes of patting dry, while the skin is still damp, slather on your moisturizer. This “soak and seal” method locks moisture in and reseals that broken skin barrier. Add Some Oatmeal Studies show that colloidal oatmeal can help bring moisture back to eczema skin. You can: Add it to your lukewarm bath Make it into a paste and press it directly into the affected area Use eczema products containing it Soak in a Bleach Bath “When you do a diluted bleach bath, similar to the concentration you find in a swimming pool, it has actually shown to be very anti-inflammatory,” says Dr. Yu. The NEA recommends a 10-minute bleach bath two to three times each week. Add a half-cup of household bleach to a full tub of lukewarm water. Soak for 10 minutes. Rinse off with clean water. Then, pat dry. P.S.: A 10-minute dip in the swimming pool gets the job done, too! Moisturizing Oils Some—but not all—oils can bring relief to eczema-inflamed skin. There’s evidence that sunflower oil, coconut oil, and shea butter have benefits for this type of irritation. But you can’t just grab any old oil from your kitchen. “Stay away from olive oil, advises Dr. Yu. “The fatty acids found in olive oil actually promote the growth of yeast on your skin.” You apply coconut or other oils to the skin twice a day, just as you would any moisturizer. Ideally, one application per day is right after you bathe when your skin is still damp. If coconut oil is your pick, go for “virgin” or “cold-pressed.” Any other extraction method uses chemicals that could irritate your skin even more, say the NEA. Anti-Itch Cream Use OTC Anti-Itch Cream Try an anti-itch cream containing 1% hydrocortisone no more than twice a day on the irritated areas. Apply it after your bath and before you moisturize. This steroid calms down itching, swelling and irritation by quelling the body’s inflammatory response. https://www.healthcentral.com/condition/eczema/papular-eczema

Use only information from the provided context

how does rop apply to photographs?

State Right of Publicity Laws The ROP is protected in some form by the laws of most U.S. states, and the number of states that recognize this right has expanded over the past several decades. One study found that 35 states recognized the ROP as of 2020. ROP laws generally create a private right of action for the unauthorized commercial use of another person’s NIL. For example, if a manufacturer uses a famous athlete’s name or face in a TV commercial without her permission, the athlete could sue the manufacturer for violating her ROP, and a court could order the manufacturer to pay damages and stop showing the commercial. What constitutes an unauthorized commercial use of NIL can vary from state to state. Some states’ ROP laws may apply only to advertising, while others more broadly apply to any use that commercially benefits the user, such as video game or comic book characters based on real people. Other notable differences between the ROP laws of various states concern questions such as: • Is the ROP protected by statute, common law, or both? Twenty-five states have enacted statutes protecting the ROP. In some of these states, including California, the ROP is protected by both statutes and common law (law derived from court opinions). In Congressional Research Service https://crsreports.congress.gov LSB11052 Congressional Research Service 2 other states, including Delaware, the ROP is protected by common law only, sometimes as an application of a common law “right of privacy.” • What parts of a person’s identity does the ROP protect? The ROP often only protects a person’s NIL, voice, and signature. In some states, the ROP also includes someone’s “distinctive appearance, gestures, or mannerisms.” Courts have construed certain states’ ROP laws to protect more abstract aspects of personal identity, finding defendants liable for using an image of a famous driver’s race car, a blonde robot performing Vanna White’s role on a game show, or the catch phrase “here’s Johnny.” • Do all individuals enjoy the ROP? State laws vary as to whether all persons or only those with “commercially valuable” NIL (such as celebrities) may assert ROP claims. • Does the ROP survive a person’s death? In some states, the ROP is descendible, meaning it can be asserted by one’s heirs after a person dies. States that recognize a descendible (or postmortem) ROP differ as to their duration, with postmortem rights lasting 20 years in Virginia, 70 years in California, and 100 years in Oklahoma, for instance. Under Tennessee law, postmortem ROP may last indefinitely. In other states, the ROP is not descendible, or else courts have not resolved the issue. Often, the law of the state in which a person is domiciled—or, where they were domiciled when they died—governs their ROP. Indiana’s ROP statute, however, allows suit “regardless of a personality’s domicile” for infringing materials “disseminated within Indiana.” This law may allow non-Indiana plaintiffs to sue for infringing materials that are made available in Indiana via television or the internet. Intersection of Right of Publicity and Federal IP Laws Although the ROP is distinct from the forms of IP already protected by federal law, it is related in some ways to trademarks and copyrights. If Congress chooses to regulate the ROP via federal law, it may consider how best to harmonize the ROP with existing trademark and copyright laws. Trademarks While the ROP generally protects commercial uses of a person’s identity, trademarks protect commercial uses of words, names, and other symbols that distinguish one person’s goods from others. The ROP may overlap with trademarks in cases where aspects of a person’s NIL can be trademarked. A person’s name, for instance, may be trademarked if it acquires a distinctive meaning and is used commercially to identify goods or services (e.g., McDonald’s). The ROP may be seen as serving a similar function to trademarks, although some scholars have criticized the theoretical foundations and expansion of the ROP. Trademark infringement occurs when someone without authorization uses a trademark in a way that creates a likelihood of confusion for consumers. The Lanham Act—the federal trademark law—also establishes a cause of action for “false endorsement,” which provides additional protection that overlaps with the ROP. False endorsement occurs when a person’s identity is used in a way that is likely to confuse consumers into believing that the person recommends a product. In 2023, for instance, actor Tom Hanks alerted fans that an AI-generated replica of him was being used to advertise a dental plan without his permission; such scenarios might give rise to both state ROP and Lanham Act false endorsement claims. State ROP laws can provide broader protection than the Lanham Act, however, as they often prohibit unauthorized commercial uses of NIL regardless of whether they imply any sponsorship or confuse consumers. In addition, some courts have held only individuals with “recognizability” (such as Hanks) may sue for false endorsement, whereas many state laws allow all individuals to sue for ROP violations. Congressional Research Service 3 Copyrights Copyrights protect original works of authorship that are “fixed” (i.e., recorded) in a “tangible medium,” including books, paintings, music recordings, and films. The Copyright Act gives copyright owners the “exclusive right” to reproduce (copy), perform, display, and distribute copyrighted works and to make derivative works (adaptations) from them. Generally, a work’s author automatically owns the copyright but may sell or license it to others. In short, whereas ROP laws prohibit unauthorized uses of another person’s identity, copyright law prohibits unauthorized uses of another’s creative works. As one illustration, in January 2024, the estate of comedian George Carlin filed a lawsuit based on an unauthorized comedy program delivered in an AI-generated imitation of Carlin’s voice. The complaint claims defendants infringed their copyrights by making copies of Carlin’s works to train the AI model— similar to other AI-related copyright lawsuits noted in a separate Legal Sidebar—and that defendants violated Carlin’s ROP under California law by using his NIL to promote the comedy program and other media. The ROP intersects with copyright law inasmuch as both fictional and nonfictional copyrighted works often include the NIL of real people, including descriptions, portrayals, recordings, or performances of those people. For example, people depicted in photographs often do not hold the copyright, since the photographer is usually considered the author, but they may have ROP interests implicated by how those photos are used. These rights may come into conflict, such as when a copyright owner displays photographs in a way that commercially exploits the NIL of people shown in the photographs. Section 301 of the Copyright Act provides that the Copyright Act preempts (supersedes) any state law rights that are “equivalent to” a copyright holder’s exclusive rights. Some commentators argue courts have inconsistently applied Section 301 in cases where copyrights conflict with the ROP. Some courts have dismissed lawsuits that allege copyright holders violated the ROP by exercising their exclusive rights under the Copyright Act. For instance, in 2017, one court held that Section 301 preempted a suit claiming the sale of photographs of NCAA athletes violated the athletes’ ROP. Other courts have held that Section 301 does not preempt ROP claims based on advertising. For example, one court held that a sports announcer’s ROP claim was not preempted where an excerpt of his voice from a copyrighted broadcast was used in a commercial for a video game. Congress could clarify the scope of copyright preemption of ROP claims by amending Section 301. In addition, if Congress enacts any new protections for ROP at the federal level, it may specify under what circumstances copyright would preempt such protections. ROP laws can protect commercial interests in live performances, which cannot be copyrighted unless they are “fixed” (e.g., filmed). In the Supreme Court’s only ROP case to date, for instance, a performer sued a television company for broadcasting his “human cannonball” act, undermining ticket sales for the act. The Supreme Court held that the First Amendment did not prevent the performer from asserting a ROP claim against the company. As an exception to the rule that live performances have no copyright protection, in 1994 Congress provided criminal and civil liability for recording and distributing live music performances without permission, although some courts have questioned these laws’ constitutionality.

Use only information from the provided context how does rop apply to photographs? State Right of Publicity Laws The ROP is protected in some form by the laws of most U.S. states, and the number of states that recognize this right has expanded over the past several decades. One study found that 35 states recognized the ROP as of 2020. ROP laws generally create a private right of action for the unauthorized commercial use of another person’s NIL. For example, if a manufacturer uses a famous athlete’s name or face in a TV commercial without her permission, the athlete could sue the manufacturer for violating her ROP, and a court could order the manufacturer to pay damages and stop showing the commercial. What constitutes an unauthorized commercial use of NIL can vary from state to state. Some states’ ROP laws may apply only to advertising, while others more broadly apply to any use that commercially benefits the user, such as video game or comic book characters based on real people. Other notable differences between the ROP laws of various states concern questions such as: • Is the ROP protected by statute, common law, or both? Twenty-five states have enacted statutes protecting the ROP. In some of these states, including California, the ROP is protected by both statutes and common law (law derived from court opinions). In Congressional Research Service https://crsreports.congress.gov LSB11052 Congressional Research Service 2 other states, including Delaware, the ROP is protected by common law only, sometimes as an application of a common law “right of privacy.” • What parts of a person’s identity does the ROP protect? The ROP often only protects a person’s NIL, voice, and signature. In some states, the ROP also includes someone’s “distinctive appearance, gestures, or mannerisms.” Courts have construed certain states’ ROP laws to protect more abstract aspects of personal identity, finding defendants liable for using an image of a famous driver’s race car, a blonde robot performing Vanna White’s role on a game show, or the catch phrase “here’s Johnny.” • Do all individuals enjoy the ROP? State laws vary as to whether all persons or only those with “commercially valuable” NIL (such as celebrities) may assert ROP claims. • Does the ROP survive a person’s death? In some states, the ROP is descendible, meaning it can be asserted by one’s heirs after a person dies. States that recognize a descendible (or postmortem) ROP differ as to their duration, with postmortem rights lasting 20 years in Virginia, 70 years in California, and 100 years in Oklahoma, for instance. Under Tennessee law, postmortem ROP may last indefinitely. In other states, the ROP is not descendible, or else courts have not resolved the issue. Often, the law of the state in which a person is domiciled—or, where they were domiciled when they died—governs their ROP. Indiana’s ROP statute, however, allows suit “regardless of a personality’s domicile” for infringing materials “disseminated within Indiana.” This law may allow non-Indiana plaintiffs to sue for infringing materials that are made available in Indiana via television or the internet. Intersection of Right of Publicity and Federal IP Laws Although the ROP is distinct from the forms of IP already protected by federal law, it is related in some ways to trademarks and copyrights. If Congress chooses to regulate the ROP via federal law, it may consider how best to harmonize the ROP with existing trademark and copyright laws. Trademarks While the ROP generally protects commercial uses of a person’s identity, trademarks protect commercial uses of words, names, and other symbols that distinguish one person’s goods from others. The ROP may overlap with trademarks in cases where aspects of a person’s NIL can be trademarked. A person’s name, for instance, may be trademarked if it acquires a distinctive meaning and is used commercially to identify goods or services (e.g., McDonald’s). The ROP may be seen as serving a similar function to trademarks, although some scholars have criticized the theoretical foundations and expansion of the ROP. Trademark infringement occurs when someone without authorization uses a trademark in a way that creates a likelihood of confusion for consumers. The Lanham Act—the federal trademark law—also establishes a cause of action for “false endorsement,” which provides additional protection that overlaps with the ROP. False endorsement occurs when a person’s identity is used in a way that is likely to confuse consumers into believing that the person recommends a product. In 2023, for instance, actor Tom Hanks alerted fans that an AI-generated replica of him was being used to advertise a dental plan without his permission; such scenarios might give rise to both state ROP and Lanham Act false endorsement claims. State ROP laws can provide broader protection than the Lanham Act, however, as they often prohibit unauthorized commercial uses of NIL regardless of whether they imply any sponsorship or confuse consumers. In addition, some courts have held only individuals with “recognizability” (such as Hanks) may sue for false endorsement, whereas many state laws allow all individuals to sue for ROP violations. Congressional Research Service 3 Copyrights Copyrights protect original works of authorship that are “fixed” (i.e., recorded) in a “tangible medium,” including books, paintings, music recordings, and films. The Copyright Act gives copyright owners the “exclusive right” to reproduce (copy), perform, display, and distribute copyrighted works and to make derivative works (adaptations) from them. Generally, a work’s author automatically owns the copyright but may sell or license it to others. In short, whereas ROP laws prohibit unauthorized uses of another person’s identity, copyright law prohibits unauthorized uses of another’s creative works. As one illustration, in January 2024, the estate of comedian George Carlin filed a lawsuit based on an unauthorized comedy program delivered in an AI-generated imitation of Carlin’s voice. The complaint claims defendants infringed their copyrights by making copies of Carlin’s works to train the AI model— similar to other AI-related copyright lawsuits noted in a separate Legal Sidebar—and that defendants violated Carlin’s ROP under California law by using his NIL to promote the comedy program and other media. The ROP intersects with copyright law inasmuch as both fictional and nonfictional copyrighted works often include the NIL of real people, including descriptions, portrayals, recordings, or performances of those people. For example, people depicted in photographs often do not hold the copyright, since the photographer is usually considered the author, but they may have ROP interests implicated by how those photos are used. These rights may come into conflict, such as when a copyright owner displays photographs in a way that commercially exploits the NIL of people shown in the photographs. Section 301 of the Copyright Act provides that the Copyright Act preempts (supersedes) any state law rights that are “equivalent to” a copyright holder’s exclusive rights. Some commentators argue courts have inconsistently applied Section 301 in cases where copyrights conflict with the ROP. Some courts have dismissed lawsuits that allege copyright holders violated the ROP by exercising their exclusive rights under the Copyright Act. For instance, in 2017, one court held that Section 301 preempted a suit claiming the sale of photographs of NCAA athletes violated the athletes’ ROP. Other courts have held that Section 301 does not preempt ROP claims based on advertising. For example, one court held that a sports announcer’s ROP claim was not preempted where an excerpt of his voice from a copyrighted broadcast was used in a commercial for a video game. Congress could clarify the scope of copyright preemption of ROP claims by amending Section 301. In addition, if Congress enacts any new protections for ROP at the federal level, it may specify under what circumstances copyright would preempt such protections. ROP laws can protect commercial interests in live performances, which cannot be copyrighted unless they are “fixed” (e.g., filmed). In the Supreme Court’s only ROP case to date, for instance, a performer sued a television company for broadcasting his “human cannonball” act, undermining ticket sales for the act. The Supreme Court held that the First Amendment did not prevent the performer from asserting a ROP claim against the company. As an exception to the rule that live performances have no copyright protection, in 1994 Congress provided criminal and civil liability for recording and distributing live music performances without permission, although some courts have questioned these laws’ constitutionality.

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> [user request] <TEXT> [context document]

My daughter just turned 16 and we are looking at buying her her first car. We want to make sure that she's safe, especially during winter as we live in Montana where it gets very snowy. She likes to listen to her music from her iPhone while driving. Which car would be our best option?

Best New Cars for Teens Under $30,000 2024 Toyota Prius Starting Price: $29,045 | Rating: 4.8 2024 Toyota Prius Limited The Toyota Prius is the car that made “hybrid” a household word. Toyota redesigned the Prius for 2023, molding it into the sleek shape of a speedster. Well, it’s not that. However, it still manages an impressive combined driving fuel economy of 57 mpg. Students heading for the snow belt can add all-wheel drive (AWD). Its rear-seat legroom is about average for the segment. The IIHS named the Prius to its Top Safety Pick+ list. Every Prius comes with automatic emergency braking with pedestrian detection, lane-departure warning with steering assist, adaptive cruise control, lane-keeping assist, and high-beam assist. Blind-spot monitoring and rear cross-traffic alert come standard as well. If the new models are out of your price range, the previous-generation Prius is also an excellent choice. See Toyota Prius models for sale near you Compare dealer offers 2024 Honda Civic Starting Price: $25,045 | Rating: 4.7 2024 Honda Civic Sedan in red driving on a road. The Civic made our list of picks for several reasons, including the fact that it’s a frequent Kelley Blue Book Best Buy Award winner. In addition, the all-new Civic retook the throne as our Compact Car Best Buy for 2022 and repeated for 2023 and 2024. The IIHS named it a Top Safety Pick, and it earned a 5-Star safety rating from NHTSA. It also gets a government-estimated 36 mpg in combined driving. Every 2024 Civic arrives with the Honda Sensing suite of driver aids, including forward collision warning, auto emergency braking, lane-departure warning, lane-keeping assist, and adaptive cruise control. Connectivity technology includes Apple CarPlay and Android Auto, one USB port, and Bluetooth connectivity. Honda typically doesn’t offer option packages. To gain more content, you must move up in trim level. And look to the hatchback model ($26,045) for more cargo space. See Honda Civic models for sale near you Compare dealer offers 2024 Toyota Corolla Starting Price: $23,145 | Rating: 4.4 2023 Toyota Corolla in white near a lake. The carryover Toyota Corolla was an IIHS Top Safety Pick for 2023. It also boasts low cost-to-own figures and historically good reliability. The Corolla’s starting price reflects the entry-level LE model. It offers standard equipment like automatic climate control, remote keyless entry, and a rear-seat center armrest. Every 2024 Corolla comes with Toyota’s Safety Sense 3.0. This advanced driver assistance technology suite includes pre-collision with pedestrian detection, automatic emergency braking, adaptive cruise control, lane-departure warning, lane-keeping assist, traffic sign recognition, and automatic high beams. The optional Premium Package offers a blind-spot monitor with a rear cross-traffic alert system, which is great for teen drivers. Connectivity features include Bluetooth, voice recognition, four USB ports, Amazon Alexa, Apple CarPlay, Android Auto, and Wi-Fi capability. The Environmental Protection Agency’s (EPA) government-certified combined fuel economy is 35 mpg. See Toyota Corolla models for sale near you Compare dealer offers 2024 Kia Seltos Starting Price: $25,865 | Rating: 4.8 2024 Kia Seltos SX in white near Palm Springs at sunset. Every version of the surprisingly roomy Kia Seltos subcompact SUV comes with a full suite of safety features, including forward collision warning with emergency braking, driver attention warning, lane-departure warning, lane-keeping assist, lane centering, and high-beam assist. To add blind-spot monitoring and rear cross-traffic alert, you must move up to the S grade, adding $600 to the bottom line. Connectivity features include Bluetooth with voice recognition, Apple CarPlay, Android Auto, and one USB port. With a second-row seat large enough to accommodate adults, Seltos also provides class-leading cargo space. See Kia Seltos models for sale near you Compare dealer offers 2024 Subaru Crosstrek Starting Price: $26,540 | Rating: 4.6 2024 Subaru Crosstrek in blue near white fence. Redesigned for 2024, Subaru’s go-anywhere Crosstrek is an IIHS Top Safety Pick. It comes standard with AWD backed by a continuously variable automatic transmission (CVT). Fuel economy is a respectable 29 mpg combined or 27 in Wilderness trim. Every Crosstrek comes standard with Subaru’s EyeSight Driver Assist Technology. It also boasts forward collision warning with automatic emergency braking, lane-keeping assist, and adaptive cruise control. A blind-spot monitor with rear cross-traffic alert is optional or standard on upper trim levels. Connectivity includes dual 7-inch touchscreens, Apple CarPlay, Android Auto (wireless is an option), Bluetooth connectivity, and hands-free phone integration. See Subaru Crosstrek models for sale near you Compare dealer offers 2024 Hyundai Kona Starting Price: $25,625 | Rating: 4.8 2024 Hyundai Kona Limited in Mirage Green with hills in the background. Totally redesigned for 2024, the Hyundai Kona offers tremendous value as a subcompact SUV with eye-catching exterior styling. Its small size makes parking easy, a big plus for teens. The rear cargo area is well suited to carry gear. In addition, Apple CarPlay and Android Auto connectivity come standard. Fuel economy is as good as 35 mpg on the highway with the gas engine. An all-electric version (EV) is also available. The IIHS named the Kona to the TSP+ list. There is plenty of value here, as even the base SE model comes standard with blind-spot monitoring, lane-keeping assist, forward collision-avoidance assist, lane-change assist, and rear cross-traffic collision warning. A 12.3-inch touchscreen and wireless Apple CarPlay and Android Auto are also included. See Hyundai Kona models for sale near you Compare dealer offers 2024 Chevrolet Trailblazer Starting Price: $24,395 | Rating: 4.2 2024 Chevrolet Trailblazer ACTIV in white near a cabin. Being one of Chevy’s smaller SUVs doesn’t stop the Trailblazer from being a considerable value. Some exterior restyling for 2024 dramatically improves its curb appeal. Moreover, the increased number of standard features for 2024 makes it more fetching than ever. Its standard advanced safety features include automatic forward emergency braking with pedestrian detection, lane-keeping assist, and lane departure warning. High-beam assist is also standard. We recommend opting for the $345 Driver Confidence Package that adds blind-spot monitoring and rear cross-traffic alert. It’s a bargain. Fundamentally unchanged since the IIHS named it a TSP+ winner in 2022, the Trailblazer remains a safe pick for teens. With the most rear-seat legroom in its class and a little better than average cargo space, the Trailblazer is an impressive hauler. At 30 mpg, its combined fuel economy is above average among rivals. You can add AWD for $2,000. See Chevrolet Trailblazer models for sale near you Compare dealer offers 2024 Nissan Sentra Starting Price: $22,320 | Rating: 4.0 2024 Nissan Sentra SR in blue near a directional sign. The most affordable new car on this list, the Nissan Sentra offers a bit of sportiness for teens, plus practicality and upscale styling. This compact car has “zero gravity” seats designed to be comfortable when driving to school or a job. The Sentra delivers fuel economy as good as 40 mpg on the highway (34 mpg in mixed city/highway driving), so trips to the gas station won’t be too frequent. Apple CarPlay and Android Auto are standard on all models. In addition to 10 airbags, even the base grade comes with the full suite of SafetyShield 360 driver aids, including auto emergency braking with pedestrian detection, rear cross-traffic alert, rear automatic braking, blind-spot warning, lane-departure warning, and high-beam assist. Essentially unchanged since it was added to the IIHS 2022 TSP+ list, the Sentra is still a solid safety pick for teens.

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> My daughter just turned 16 and we are looking at buying her her first car. We want to make sure that she's safe, especially during winter as we live in Montana where it gets very snowy. She likes to listen to her music from her iPhone while driving. Which car would be our best option? <TEXT> Best New Cars for Teens Under $30,000 2024 Toyota Prius Starting Price: $29,045 | Rating: 4.8 2024 Toyota Prius Limited The Toyota Prius is the car that made “hybrid” a household word. Toyota redesigned the Prius for 2023, molding it into the sleek shape of a speedster. Well, it’s not that. However, it still manages an impressive combined driving fuel economy of 57 mpg. Students heading for the snow belt can add all-wheel drive (AWD). Its rear-seat legroom is about average for the segment. The IIHS named the Prius to its Top Safety Pick+ list. Every Prius comes with automatic emergency braking with pedestrian detection, lane-departure warning with steering assist, adaptive cruise control, lane-keeping assist, and high-beam assist. Blind-spot monitoring and rear cross-traffic alert come standard as well. If the new models are out of your price range, the previous-generation Prius is also an excellent choice. See Toyota Prius models for sale near you Compare dealer offers 2024 Honda Civic Starting Price: $25,045 | Rating: 4.7 2024 Honda Civic Sedan in red driving on a road. The Civic made our list of picks for several reasons, including the fact that it’s a frequent Kelley Blue Book Best Buy Award winner. In addition, the all-new Civic retook the throne as our Compact Car Best Buy for 2022 and repeated for 2023 and 2024. The IIHS named it a Top Safety Pick, and it earned a 5-Star safety rating from NHTSA. It also gets a government-estimated 36 mpg in combined driving. Every 2024 Civic arrives with the Honda Sensing suite of driver aids, including forward collision warning, auto emergency braking, lane-departure warning, lane-keeping assist, and adaptive cruise control. Connectivity technology includes Apple CarPlay and Android Auto, one USB port, and Bluetooth connectivity. Honda typically doesn’t offer option packages. To gain more content, you must move up in trim level. And look to the hatchback model ($26,045) for more cargo space. See Honda Civic models for sale near you Compare dealer offers 2024 Toyota Corolla Starting Price: $23,145 | Rating: 4.4 2023 Toyota Corolla in white near a lake. The carryover Toyota Corolla was an IIHS Top Safety Pick for 2023. It also boasts low cost-to-own figures and historically good reliability. The Corolla’s starting price reflects the entry-level LE model. It offers standard equipment like automatic climate control, remote keyless entry, and a rear-seat center armrest. Every 2024 Corolla comes with Toyota’s Safety Sense 3.0. This advanced driver assistance technology suite includes pre-collision with pedestrian detection, automatic emergency braking, adaptive cruise control, lane-departure warning, lane-keeping assist, traffic sign recognition, and automatic high beams. The optional Premium Package offers a blind-spot monitor with a rear cross-traffic alert system, which is great for teen drivers. Connectivity features include Bluetooth, voice recognition, four USB ports, Amazon Alexa, Apple CarPlay, Android Auto, and Wi-Fi capability. The Environmental Protection Agency’s (EPA) government-certified combined fuel economy is 35 mpg. See Toyota Corolla models for sale near you Compare dealer offers 2024 Kia Seltos Starting Price: $25,865 | Rating: 4.8 2024 Kia Seltos SX in white near Palm Springs at sunset. Every version of the surprisingly roomy Kia Seltos subcompact SUV comes with a full suite of safety features, including forward collision warning with emergency braking, driver attention warning, lane-departure warning, lane-keeping assist, lane centering, and high-beam assist. To add blind-spot monitoring and rear cross-traffic alert, you must move up to the S grade, adding $600 to the bottom line. Connectivity features include Bluetooth with voice recognition, Apple CarPlay, Android Auto, and one USB port. With a second-row seat large enough to accommodate adults, Seltos also provides class-leading cargo space. See Kia Seltos models for sale near you Compare dealer offers 2024 Subaru Crosstrek Starting Price: $26,540 | Rating: 4.6 2024 Subaru Crosstrek in blue near white fence. Redesigned for 2024, Subaru’s go-anywhere Crosstrek is an IIHS Top Safety Pick. It comes standard with AWD backed by a continuously variable automatic transmission (CVT). Fuel economy is a respectable 29 mpg combined or 27 in Wilderness trim. Every Crosstrek comes standard with Subaru’s EyeSight Driver Assist Technology. It also boasts forward collision warning with automatic emergency braking, lane-keeping assist, and adaptive cruise control. A blind-spot monitor with rear cross-traffic alert is optional or standard on upper trim levels. Connectivity includes dual 7-inch touchscreens, Apple CarPlay, Android Auto (wireless is an option), Bluetooth connectivity, and hands-free phone integration. See Subaru Crosstrek models for sale near you Compare dealer offers 2024 Hyundai Kona Starting Price: $25,625 | Rating: 4.8 2024 Hyundai Kona Limited in Mirage Green with hills in the background. Totally redesigned for 2024, the Hyundai Kona offers tremendous value as a subcompact SUV with eye-catching exterior styling. Its small size makes parking easy, a big plus for teens. The rear cargo area is well suited to carry gear. In addition, Apple CarPlay and Android Auto connectivity come standard. Fuel economy is as good as 35 mpg on the highway with the gas engine. An all-electric version (EV) is also available. The IIHS named the Kona to the TSP+ list. There is plenty of value here, as even the base SE model comes standard with blind-spot monitoring, lane-keeping assist, forward collision-avoidance assist, lane-change assist, and rear cross-traffic collision warning. A 12.3-inch touchscreen and wireless Apple CarPlay and Android Auto are also included. See Hyundai Kona models for sale near you Compare dealer offers 2024 Chevrolet Trailblazer Starting Price: $24,395 | Rating: 4.2 2024 Chevrolet Trailblazer ACTIV in white near a cabin. Being one of Chevy’s smaller SUVs doesn’t stop the Trailblazer from being a considerable value. Some exterior restyling for 2024 dramatically improves its curb appeal. Moreover, the increased number of standard features for 2024 makes it more fetching than ever. Its standard advanced safety features include automatic forward emergency braking with pedestrian detection, lane-keeping assist, and lane departure warning. High-beam assist is also standard. We recommend opting for the $345 Driver Confidence Package that adds blind-spot monitoring and rear cross-traffic alert. It’s a bargain. Fundamentally unchanged since the IIHS named it a TSP+ winner in 2022, the Trailblazer remains a safe pick for teens. With the most rear-seat legroom in its class and a little better than average cargo space, the Trailblazer is an impressive hauler. At 30 mpg, its combined fuel economy is above average among rivals. You can add AWD for $2,000. See Chevrolet Trailblazer models for sale near you Compare dealer offers 2024 Nissan Sentra Starting Price: $22,320 | Rating: 4.0 2024 Nissan Sentra SR in blue near a directional sign. The most affordable new car on this list, the Nissan Sentra offers a bit of sportiness for teens, plus practicality and upscale styling. This compact car has “zero gravity” seats designed to be comfortable when driving to school or a job. The Sentra delivers fuel economy as good as 40 mpg on the highway (34 mpg in mixed city/highway driving), so trips to the gas station won’t be too frequent. Apple CarPlay and Android Auto are standard on all models. In addition to 10 airbags, even the base grade comes with the full suite of SafetyShield 360 driver aids, including auto emergency braking with pedestrian detection, rear cross-traffic alert, rear automatic braking, blind-spot warning, lane-departure warning, and high-beam assist. Essentially unchanged since it was added to the IIHS 2022 TSP+ list, the Sentra is still a solid safety pick for teens. https://www.kbb.com/best-cars/teens/

This task requires you to answer questions based solely on the information provided in the prompt. You are not allowed to use any external resources or prior knowledge. Give your answer in bullet points and follow each one with an explanation.

Please summarize this text for a layperson.

Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressants. SSRIs are called selective because they affect serotonin rather than other chemicals in the brain. These drugs block the reuptake (removal) of serotonin, which keeps the level of serotonin balanced and helps regulate mood. SSRIs Affect Serotonin Levels in the Brain There are currently seven SSRI drugs on the market in the United States (TABLE 1). These medications are generally safer than older antidepressants, with fewer side effects and drug interactions. In general, SSRIs have received approval from the FDA as safe and effective in the treatment of major depressive disorder. Many are also approved for anxiety disorders such as panic disorder, generalized anxiety disorder, and social anxiety disorder. Certain drugs in this category are also approved for use in obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD), and bulimia. SSRIs are slightly different in how quickly they work and how long they stay in the body. Their side effects also differ somewhat. Common side effects include nervousness, problems sleeping, headache, dry mouth, nausea, changes in sexual desire, and erectile dysfunction. Nausea can be reduced by taking the medicine with food. Nervousness and insomnia can be reduced by taking the drug just before bedtime. Most adverse effects of SSRIs gradually disappear after a few weeks of therapy. SSRIs show an effect after 4 to 6 weeks of daily use. If one drug in this category does not work in a particular person, another drug may work. SSRIs can interact with other medications that also cause increased serotonin levels in the brain. These include other antidepressants, prescription opioids, migraine medications, cocaine, and St. John’s wort (a medicinal herb used to treat depression). If one or more of these drugs are used with an SSRI, a high level of serotonin in the brain can result in serotonin syndrome. Symptoms such as extreme anxiety, tremors, fast heartbeat, sweating, and confusion require emergency care. Although SSRIs are not addictive, stopping them abruptly can cause symptoms that mimic withdrawal. A doctor should provide guidelines for slowly tapering off an SSRI to avoid symptoms of nausea, dizziness, and fatigue. Warnings and Precautions Generally, SSRIs are safe and carry few risks. All antidepressants, including SSRIs, can cause an increase in suicidal thoughts or actions, especially in young adults beginning therapy or changing dosages. SSRIs can increase the risk of gastrointestinal bleeding when taken with nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen, or with drugs with a side effect of bleeding, such as warfarin. Taking a drug that lowers stomach acid may be helpful. Women who are considering pregnancy, who are pregnant, or who are breastfeeding should discuss the potential effects of SSRIs on the fetus or infant and consider a break in therapy to avoid exposure. Several SSRIs are being studied for diseases other than those specified in their FDA labeling. Some of the uses that have shown promise include prevention of migraine, pain of diabetic neuropathy, fibromyalgia, vasovagal syncope (fainting), and premature ejaculation.

This task requires you to answer questions based solely on the information provided in the prompt. You are not allowed to use any external resources or prior knowledge. Give your answer in bullet points and follow each one with an explanation. Please summarize this text for a layperson. Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressants. SSRIs are called selective because they affect serotonin rather than other chemicals in the brain. These drugs block the reuptake (removal) of serotonin, which keeps the level of serotonin balanced and helps regulate mood. SSRIs Affect Serotonin Levels in the Brain There are currently seven SSRI drugs on the market in the United States (TABLE 1). These medications are generally safer than older antidepressants, with fewer side effects and drug interactions. In general, SSRIs have received approval from the FDA as safe and effective in the treatment of major depressive disorder. Many are also approved for anxiety disorders such as panic disorder, generalized anxiety disorder, and social anxiety disorder. Certain drugs in this category are also approved for use in obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD), and bulimia. SSRIs are slightly different in how quickly they work and how long they stay in the body. Their side effects also differ somewhat. Common side effects include nervousness, problems sleeping, headache, dry mouth, nausea, changes in sexual desire, and erectile dysfunction. Nausea can be reduced by taking the medicine with food. Nervousness and insomnia can be reduced by taking the drug just before bedtime. Most adverse effects of SSRIs gradually disappear after a few weeks of therapy. SSRIs show an effect after 4 to 6 weeks of daily use. If one drug in this category does not work in a particular person, another drug may work. SSRIs can interact with other medications that also cause increased serotonin levels in the brain. These include other antidepressants, prescription opioids, migraine medications, cocaine, and St. John’s wort (a medicinal herb used to treat depression). If one or more of these drugs are used with an SSRI, a high level of serotonin in the brain can result in serotonin syndrome. Symptoms such as extreme anxiety, tremors, fast heartbeat, sweating, and confusion require emergency care. Although SSRIs are not addictive, stopping them abruptly can cause symptoms that mimic withdrawal. A doctor should provide guidelines for slowly tapering off an SSRI to avoid symptoms of nausea, dizziness, and fatigue. Warnings and Precautions Generally, SSRIs are safe and carry few risks. All antidepressants, including SSRIs, can cause an increase in suicidal thoughts or actions, especially in young adults beginning therapy or changing dosages. SSRIs can increase the risk of gastrointestinal bleeding when taken with nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen, or with drugs with a side effect of bleeding, such as warfarin. Taking a drug that lowers stomach acid may be helpful. Women who are considering pregnancy, who are pregnant, or who are breastfeeding should discuss the potential effects of SSRIs on the fetus or infant and consider a break in therapy to avoid exposure. Several SSRIs are being studied for diseases other than those specified in their FDA labeling. Some of the uses that have shown promise include prevention of migraine, pain of diabetic neuropathy, fibromyalgia, vasovagal syncope (fainting), and premature ejaculation.

You can only respond using the information in the context block. You will focus on explaining programming concepts while avoiding the use of specific code lines.

What is the difference between a method and a function?

Strings Are Immutable To wrap this section up, let’s discuss an important property of string objects. Strings are immutable, which means that you can’t change them once you’ve created them. For instance, see what happens when you try to assign a new letter to one particular character of a string: >>> word = "goal" >>> word[0] = "f" Traceback (most recent call last): File "<pyshell#16>", line 1, in <module> word[0] = "f" TypeError: 'str' object does not support item assignment Python throws a TypeError and tells you that str objects don’t support item assignment. If you want to alter a string, then you must create an entirely new string. To change the string "goal" to the string "foal", you can use a string slice to concatenate the letter "f" with everything but the first letter of the word "goal": >>> word = "goal" >>> word = "f" + word[1:] >>> word 'foal' First, you assign the string "goal" to the variable word. Then you concatenate the slice word[1:], which is the string "oal", with the letter "f" to get the string "foal". If you’re getting a different result here, then make sure you’re including the colon character (:) as part of the string slice. 4.3 Manipulate Strings With Methods Strings come bundled with special functions called string methods that you can use to work with and manipulate strings. There are numerous string methods available, but we’ll focus on some of the most commonly used ones. In this section, you’ll learn how to: • Convert a string to uppercase or lowercase • Remove whitespace from a string • Determine if a string begins or ends with certain characters Let’s go! Converting String Case To convert a string to all lowercase letters, you use the string’s .lower() method. This is done by tacking .lower() onto the end of the string itself: >>> "Jean-Luc Picard".lower() 'jean-luc picard' The dot (.) tells Python that what follows is the name of a method— the lower() method in this case. Note We’ll refer to string methods with a dot (.) at the beginning of their names. For example, .lower() is written with a leading dot instead of as lower(). This makes it easier to differentiate functions that are string methods from built-in functions like print() and type(). String methods don’t just work on string literals. You can also use .lower() on a string assigned to a variable: >>> name = "Jean-Luc Picard" >>> name.lower() 'jean-luc picard' The opposite of .lower() is .upper(), which converts every character in a string to uppercase: >>> name.upper() 'JEAN-LUC PICARD' Compare the .upper() and .lower() string methods to the len() function you saw in the last section. Aside from the different results of these functions, the important distinction here is how they’re used. len() is a stand-alone function. If you want to determine the length of the name string, then you call the len() function directly: >>> len(name) 15 On the other hand, .upper() and .lower() must be used in conjunction with a string. They do not exist independently. String Methods and Immutability Recall from the previous section that strings are immutable—they can’t be changed once they’ve been created. Most string methods that alter a string, like .upper() and .lower(), actually return copies of the original string with the appropriate modifications. If you aren’t careful, this can introduce subtle bugs into your program. Try this out in IDLE’s interactive window: >>> name = "Picard" >>> name.upper() 'PICARD' >>> name 'Picard' When you call name.upper(), nothing about name actually changes. If you need to keep the result, then you need to assign it to a variable: >>> name = "Picard" >>> name = name.upper() >>> name 'PICARD' name.upper() returns a new string "PICARD", which is reassigned to the name variable. This overrides the original string "Picard" that you first assigned to name.

system instruction: [You can only respond using the information in the context block. You will focus on explaining programming concepts while avoiding the use of specific code lines.] question: [What is the difference between a method and a function?] context block: [Strings Are Immutable To wrap this section up, let’s discuss an important property of string objects. Strings are immutable, which means that you can’t change them once you’ve created them. For instance, see what happens when you try to assign a new letter to one particular character of a string: >>> word = "goal" >>> word[0] = "f" Traceback (most recent call last): File "<pyshell#16>", line 1, in <module> word[0] = "f" TypeError: 'str' object does not support item assignment Python throws a TypeError and tells you that str objects don’t support item assignment. If you want to alter a string, then you must create an entirely new string. To change the string "goal" to the string "foal", you can use a string slice to concatenate the letter "f" with everything but the first letter of the word "goal": >>> word = "goal" >>> word = "f" + word[1:] >>> word 'foal' First, you assign the string "goal" to the variable word. Then you concatenate the slice word[1:], which is the string "oal", with the letter "f" to get the string "foal". If you’re getting a different result here, then make sure you’re including the colon character (:) as part of the string slice. 4.3 Manipulate Strings With Methods Strings come bundled with special functions called string methods that you can use to work with and manipulate strings. There are numerous string methods available, but we’ll focus on some of the most commonly used ones. In this section, you’ll learn how to: • Convert a string to uppercase or lowercase • Remove whitespace from a string • Determine if a string begins or ends with certain characters Let’s go! Converting String Case To convert a string to all lowercase letters, you use the string’s .lower() method. This is done by tacking .lower() onto the end of the string itself: >>> "Jean-Luc Picard".lower() 'jean-luc picard' The dot (.) tells Python that what follows is the name of a method— the lower() method in this case. Note We’ll refer to string methods with a dot (.) at the beginning of their names. For example, .lower() is written with a leading dot instead of as lower(). This makes it easier to differentiate functions that are string methods from built-in functions like print() and type(). String methods don’t just work on string literals. You can also use .lower() on a string assigned to a variable: >>> name = "Jean-Luc Picard" >>> name.lower() 'jean-luc picard' The opposite of .lower() is .upper(), which converts every character in a string to uppercase: >>> name.upper() 'JEAN-LUC PICARD' Compare the .upper() and .lower() string methods to the len() function you saw in the last section. Aside from the different results of these functions, the important distinction here is how they’re used. len() is a stand-alone function. If you want to determine the length of the name string, then you call the len() function directly: >>> len(name) 15 On the other hand, .upper() and .lower() must be used in conjunction with a string. They do not exist independently. String Methods and Immutability Recall from the previous section that strings are immutable—they can’t be changed once they’ve been created. Most string methods that alter a string, like .upper() and .lower(), actually return copies of the original string with the appropriate modifications. If you aren’t careful, this can introduce subtle bugs into your program. Try this out in IDLE’s interactive window: >>> name = "Picard" >>> name.upper() 'PICARD' >>> name 'Picard' When you call name.upper(), nothing about name actually changes. If you need to keep the result, then you need to assign it to a variable: >>> name = "Picard" >>> name = name.upper() >>> name 'PICARD' name.upper() returns a new string "PICARD", which is reassigned to the name variable. This overrides the original string "Picard" that you first assigned to name.]

Only provide commentary from the context included.

How, if at all, does the owner of this business respond to negative reviews?

&Pizza Google Reviews Josh Local Guide·316 reviews·113 photos a month ago Ordered online and my receipt had no details confirming my items. I text them like they said and they never responded. Then they have Uber do the order delivery but I didn't know that before putting the tip in and then the driver said he … More Photo 1 in review by Josh Photo 2 in review by Josh &pizza - Dupont (Owner) a month ago We regret to hear about your experience with the online ordering and delivery process. Your response is important to us as we strive to improve our services. We will address the issues you've mentioned with our team to ensure a better experience for all our customers. Thank you for bringing this to our attention. Gine “Gine The Mae Nai's Winery” MaeNaiWinery Local Guide·369 reviews·5043 photos 3 months ago Dine in | Dinner | $10–20 Such a lovely freshly made pizza with various options, really hard time to decide which one to order lol. Very fast and nice service. Pizza just got ready in 8mins. Have two long tables to enjoy, or take away. … More Photo 1 in review by Gine “Gine The Mae Nai's Winery” MaeNaiWinery Photo 2 in review by Gine “Gine The Mae Nai's Winery” MaeNaiWinery Photo 3 in review by Gine “Gine The Mae Nai's Winery” MaeNaiWinery Photo 4 in review by Gine “Gine The Mae Nai's Winery” MaeNaiWinery Photo 5 in review by Gine “Gine The Mae Nai's Winery” MaeNaiWinery Photo 6 in review by Gine “Gine The Mae Nai's Winery” MaeNaiWinery Photo 7 in review by Gine “Gine The Mae Nai's Winery” MaeNaiWinery Photo 8 in review by Gine “Gine The Mae Nai's Winery” MaeNaiWinery Photo 9 in review by Gine “Gine The Mae Nai's Winery” MaeNaiWinery &pizza - Dupont (Owner) a month ago Thank you for your 5-star rating! We're thrilled to hear that you enjoyed our freshly made pizza and fast service. Your response is important to us as we strive to improve our services. We hope to see you again soon for another delicious experience! Torianna Todd 3 reviews·2 photos a week ago NEW Take out | Dinner | $10–20 Super friendly staff and the food was really good! We got 2 pizzas- one cheese and one margarita with some extra toppings, and garlic knots. … More Photo 1 in review by Torianna Todd Photo 2 in review by Torianna Todd Addison Hosner Local Guide·100 reviews·141 photos a month ago Never had pizza from here before but ordered online for pickup during lunch. Showed up on time and the order was ready without delay. The pizza is a great serving size and depending on your appetite and what you get this could be two meals … More &pizza - Dupont (Owner) a month ago Thank you for taking the time to share your experience with us! We are thrilled to hear that you enjoyed our pizza and that your order was ready on time. Your response is important to us as we strive to improve our services. We look forward to serving you again soon! Allen Nuccio Local Guide·297 reviews·380 photos a week ago NEW Dine in | Lunch | $10–20 If you're not familiar, &pizza is like Fancy Pizza Hut in flatbread form. Their pies are pretty good and their garlic knots are delicious. This location has fantastic customer service, but also smells heavily of a bathroom for whatever reason. Anyway, pretty good all-in-all. … More Alma Local Guide·147 reviews·278 photos 7 months ago Take out | Dinner | $10–20 Pizza is good and doesn't take long from ordering to paying so it's fast and convenient. Staff is super friendly and nice … More Photo 1 in review by Alma Photo 2 in review by Alma Photo 3 in review by Alma Photo 4 in review by Alma Photo 5 in review by Alma Lizzy Amirana Local Guide·146 reviews·224 photos 4 months ago Smells like mold in the place but wonderful pizza! Their gluten free pizza with vegan cheese and meat substitute is 💣 … More Photo 1 in review by Lizzy Amirana 1 &pizza - Dupont (Owner) a month ago We regret to hear about the issue you encountered during your visit. Your response is important to us as we strive to improve our services. We're glad you enjoyed the gluten free pizza with vegan cheese and meat substitute. Thank you for sharing your experience. Emma Fan Local Guide·28 reviews·20 photos a month ago We ordered 8 pizzas (menu items) and 4 of them was made incorrectly - missing all the meat, missing veggies & pineapple, wrong sauce, missing spices. They weren’t just missing one or two ingredients, they were made into something completely … More &pizza - Dupont (Owner) a month ago We regret to hear about your experience and the incorrect pizza orders. Your response is important to us as we strive to improve our services. We will address this with our kitchen staff to ensure such mistakes are not repeated. Thank you for bringing this to our attention. Aban Koprulu 74 reviews·3 photos 3 weeks ago NEW The pizza is good but omg the sewage smell was unbearable. I tried to hold my breath and breathe through my mouth. I almost passed out. I don’t think this place is safe according USDA food and safety inspection. I will have to report it … More 1 &pizza - Dupont (Owner) 3 weeks ago We regret to hear about your experience. Your response is important to us as we strive to improve our services. We will investigate the issue immediately to ensure a safe and pleasant dining experience for all our customers. Thank you for bringing this to our attention. Jacob Fix Local Guide·22 reviews·12 photos 4 months ago Take out | Lunch | $10–20 Very fast, affordable, and huge portions. Great deal and great pizza. … More Photo 1 in review by Jacob Fix Jason A 4 reviews·2 photos 2 years ago Take out | Lunch | $10–20 Great pizza in Dupont! Walking distance from the Mayflower hotel. Fast friendly service. The Maverick is my favorite and garlic knots are a nice add on. Photo 1 in review by Jason A Photo 2 in review by Jason A Mehrnoosh Kh Local Guide·245 reviews·1644 photos 6 months ago Take out | Dinner It is a good pizza place for late night bites. … More Photo 1 in review by Mehrnoosh Kh Photo 2 in review by Mehrnoosh Kh Photo 3 in review by Mehrnoosh Kh Photo 4 in review by Mehrnoosh Kh Photo 5 in review by Mehrnoosh Kh Photo 6 in review by Mehrnoosh Kh Photo 7 in review by Mehrnoosh Kh Photo 8 in review by Mehrnoosh Kh Ryan Griffith 11 reviews 4 months ago Don't bother ordering Uber Eats here because they won't make the food and you'll have to cancel the order. And if you dine in apparently it smells like piss. … More Samuel Davie 37 reviews·102 photos a year ago Take out | Dinner | $10–20 Delicious pizza and the perfect serving for 1 person. I always get the pineapple jacked and take my Tour de Pizza cutter for a ride. Going for a pizza ride #tourdepizzacutter 🚴🏼🍕😊 Photo 2 in review by Samuel Davie 3 Alan Marrero Local Guide·215 reviews·2873 photos 5 months ago Nasty piss smell, we had to leave in an instant. No wonder the place was empty. The pizzas looked great in the pictures, if you want to eat a pizza in smelly atmosphere THIS IS IT! … More 2 Henry Kloepper Local Guide·121 reviews·77 photos 7 years ago Was quite decent. Fast, reasonable price, good taste. Though I just had Pizza Paradiso and if you have some extra time it's well worth it over &pizza, especially if you are interested in having an alcoholic drink with your pizza. If you're in a rush this works better. Photo 1 in review by Henry Kloepper Damien Shaner Local Guide·30 reviews·140 photos 3 weeks ago NEW They are so ghetto they have a security guard that locks the door and doesn't let people inside after the place fills full of "dangerous people"...well before the actual closing time. &pizza - Dupont (Owner) 2 weeks ago We regret to hear about your experience at our restaurant. Your response is important to us as we strive to improve our services. We take the safety of our customers seriously and will address this issue with our security team. Thank you for bringing this to our attention. Diana Marquez 2 reviews 9 months ago Dine in | $10–20 My sister and I came in to grab some food after a night out it was very busy but the team was very efficient and Luis definitely made sure we had a great experience. He has exceptional customer service skills, very out going and just great at what he does and overall takes great care of guests. Will definitely be coming back soon ! Matthew Rice Local Guide·14 reviews·54 photos 4 months ago Take out | Dinner | $10–20 Pizza was decent, but as other reviews have noted, the restaurant had an unbearable stench. The owner needs to call a plumber or an exterminator (or both). … More Elizabeth Dapper 8 reviews·4 photos 3 months ago Dine in | Dinner | $10–20 Good place, good service, loud music which is always a little hard when talking with friends... but the food and the employees never disappoint! … More &pizza - Dupont (Owner) a month ago Thank you for taking the time to share your experience with us. We're glad to hear that you enjoyed the food and service, but we understand that the loud music can be a challenge. Your response is important to us as we strive to improve our services. We hope to have the opportunity to serve you again in the future. D C 8 reviews·2 photos 6 months ago Take out | Dinner I just have to add to the other reviews about the absolutely putrid horrifying smell in here, which hits you upon entering. I had ordered Uber Eats, otherwise I would have immediately left. This place most likely has an ongoing sewage issue that is not being addressed properly. No place that sells food should smell like this. … More 2 Andy Jovel 11 reviews·1 photo a year ago Take out | Lunch | $10–20 Sorry, but the pizza was cold and there was little to none chicken mostly just blue cheese crumbles. There were none jalapenos at all either. Photo 1 in review by Andy Jovel Brei Evans 4 reviews·11 photos 3 days ago NEW This locations stinks so bad. The people are nice here though. … More Cedar Baltz 7 reviews 7 months ago Take out | Dinner | $30–50 I got take out and the guy gave me 1 correct pizza I ordered and gave me a completely different order for the 2nd pizza. He showed me the first pizza with the correct toppings on it. I assumed the 2nd pizza he handed me was the right order … More Nathan Sellers Local Guide·90 reviews·323 photos 4 years ago This is really good pizza. The manager was super friendly and helpful too. My son begged to go back the whole trip and said it was the best pizza he'd ever had. Photo 1 in review by Nathan Sellers Kelli Roberts Local Guide·349 reviews·305 photos 6 years ago Second &pizza today. This location is even bigger! Food was delicious, but I would advise going light on the toppings if you choose a gluten free pizza. Too many toppings can make the pizza heavy and messy. Photo 1 in review by Kelli Roberts Photo 2 in review by Kelli Roberts 2 Jahanna Reese 13 reviews·1 photo 11 months ago This is My favorite & pizza Location, great service and they don’t rush you . 5 stars out of 5 Photo 1 in review by Jahanna Reese Josh Griswell Local Guide·26 reviews·21 photos 5 years ago Great food, good price, friendly staff! I ordered the vegan pizza and it was awesome! Their craft soda fountain has some great selections as well. Food was cooked quickly and tasted great! Photo 1 in review by Josh Griswell 1 David Zaga Local Guide·48 reviews·83 photos 6 months ago I mean the price was ok. The place smelled, clearly not very well maintained. And the pizza was ok. The guys working the counter, although dealing with a lot of customers were working hard and gave good service … More 2 Samim zamiri 1 review a month ago You gotta taste their pizza and you’ll definitely like it … More &pizza - Dupont (Owner) a month ago Thank you for your 5-star rating! We're thrilled to hear that you enjoyed our pizza. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Sabrina Lisenby 3 reviews·1 photo 2 years ago Amazing staff, great service, and was so fast. Oh by the way they have amazing pizza and garlic knots. If this isn’t enough to make you try them out, do it anyway lol 😂🤣 Photo 1 in review by Sabrina Lisenby &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We're thrilled to hear that you had an amazing experience with our staff and enjoyed our pizza and garlic knots. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Ashllyn Silva Local Guide·64 reviews·63 photos a year ago Dine in | Lunch | $10–20 Actually so obsessed with this pizza. So glad to find out they have multiple locations in my home city. Photo 1 in review by Ashllyn Silva Zhuoran Li 7 reviews·6 photos a year ago The guy is super nice. He is friendly. The pizza is so good. It is really a top place for some pizza quick bite Photo 1 in review by Zhuoran Li J Foodgeek Local Guide·715 reviews·732 photos 2 years ago So earlier today I got I texted coupon for a $5 pizza, so I walk in to dupont S location and I figure I'll just make the order in the place, and I look at the places where the ingredients are, and see slimy rod and spinach and black basil, … More Photo 1 in review by J Foodgeek 1 HoneyD 11 reviews 6 months ago Why does this place stink? Walked up expecting smell of fresh pizza but smells like dirty sewage, smells better outside. Couldn't imagine sitting down in here to eat. … More 2 Sarah Jackson Local Guide·81 reviews·2 photos 4 years ago Pizza flavor is good & could have been a 5 star. Delivery wAs about 30 mins on Fri Evening. ..but it was delivered COLD,,,,!.to order is difficult, forget calling you will only get voicemail tell you they only text or order online. They … More Photo 1 in review by Sarah Jackson 1 &pizza - Dupont (Owner) 4 years ago Hey Sarah, thanks for the review and sorry your pies didnt arrive to you in a state we're proud of. If you're up for it, feel free to reach back out and we'd be happy to make it up to you Daniel Ruiz Local Guide·49 reviews·200 photos 4 years ago Great place to eat pizza, fast service, prices are okay, each style is around $10, not so crowed and staff is friendly, very reccomended if you are hungry and looking for something quick. Photo 1 in review by Daniel Ruiz John Yeung Local Guide·130 reviews·151 photos 7 years ago How can you not like &pizza? I come here all the time. Overall it is really good but sometimes the quality is inconsistent. The pizza might be slightly burnt on the edges. The few times I want to buy soda, their machine does not have all the flavors. Photo 1 in review by John Yeung Liam Amiri Local Guide·377 reviews·2368 photos a year ago Decent pizza but don't expect some authentic NYC style pizza. … More Photo 1 in review by Liam Amiri Eddie Hoss Local Guide·268 reviews·74 photos a year ago Dine in | Dinner Oddly enough, some of the best pizza I've had in some time. Visited during the Halloween bar crawl and the three employees were overwhelmed but kept at it. Waited around 45 min for my pizza, but it was worth it. Decent prices and when … More David Dotson Local Guide·146 reviews·574 photos 2 years ago Dine in | Dinner | $10–20 Great pizza & excellent service Both Gluten Free crust & Vegan protein options available (vegan cheese, vegan sausage & chickpeas) … More Photo 1 in review by David Dotson 1 &pizza - Dupont (Owner) 2 years ago Thank you so much for the review David! We're so glad you were able to use our loyalty coupon as well! Ishmael Kamara Local Guide·117 reviews·649 photos a year ago Take out | Dinner | $20–30 &pizza is always great. Went there late on Friday for something to eat. With the crowd from the clubs be prepared to wait and they don't have any indoor seating at that time. Overall you can't go wrong with a personalized pizza from here. … More tshirt tae 7 reviews·6 photos a year ago Pizza was banging line was fast great place custom Pizza Photo 1 in review by tshirt tae Niggle W 14 reviews 6 months ago The store is quiet but the staff is very polite, clean and the pizza came out good. … More Anthony Ayo 4 reviews·1 photo a year ago Lunch | $30–50 Pizza was great! Service was just as awesome! We brought a group of 13 people and Terrence and the crew were happy and helpful. Can’t wait to come back when I’m back in town. … More williampiedra100 3 reviews·1 photo 3 weeks ago NEW Dine in | $10–20 Bryan attended us with great care. … More &pizza - Dupont (Owner) 2 weeks ago Thank you for the 5-star rating! We're thrilled to hear that Bryan took great care of you. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Vannessa Rodello Local Guide·129 reviews·103 photos 4 years ago All the toppings you want and so many options! My only criticism is the crust wasn't as crispy as I'd like. Photo 1 in review by Vannessa Rodello Photo 2 in review by Vannessa Rodello R Bakshi Local Guide·65 reviews·166 photos 6 years ago Excellent pizza and super friendly staff! Photo 1 in review by R Bakshi Photo 2 in review by R Bakshi Krystle Local Guide·107 reviews·224 photos 4 years ago It was really good. But it was sooooo hot in there and took foreverrrrrrr. Pepperoni and bacon. I'm basic lol Photo 1 in review by Krystle Leah Trunsky (raindropAuxilitrix) 1 review 11 months ago Went here with my friends—the pizza was great and the server Chris was super cool! Super friendly. Whoever made the pizza was patient with our orders too. :) Destine Jones 5 reviews 11 months ago Take out | Dinner | $10–20 I came into &Pizza today for lunch and the the staffAndre and Terrace was very helpful polite service was great clean environment fast service I was surprise to see no line so the pizza came out quick and I was able to enjoy it and get … More 1 &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We're thrilled to hear that Andre and Terrace provided helpful and polite service, and that you enjoyed a quick and delicious lunch. Your response is important to us as we strive to improve our services. We appreciate your kind words and hope to see you again soon! Roberts Brian 1 review a year ago I went through this pizza shop last night the service was amazing they were really on point, making sure the customers got everything they needed and more this will definitely be my go to pizza place yours truly Mr.Roberts.. James Drosin 2 reviews 9 months ago Dine in Luis the Manager gave me the best guest experience! Food was amazing definitely recommend. S/O to them! I will definitely be back! Heather Dorsey Local Guide·130 reviews·393 photos 4 years ago The American honey pizza is really good. And the cereal milk soda tastes exactly like cereal milk. So. Service with a snarl. Photo 1 in review by Heather Dorsey &pizza - Dupont (Owner) 4 years ago Thanks for the review Heather! :) Kate Farrell Stanford 4 reviews·2 photos 11 months ago When I walked in, no one was in there and it smelled terrible, as if the floor had been mopped with dirty toilet water. We couldn't imagine staying in there long enough to order, let alone eat. … More 2 &pizza - Dupont (Owner) 11 months ago We apologize that our service did not satisfy your expectations. We set a high standard for ourselves and are truly sorry to hear that standard was not met in your interaction with our business. Your happiness is our number one priority. We well take your feedback into consideration. Jason Miller Local Guide·401 reviews·14 photos 2 years ago Take out | Lunch | $30–50 I love &pizza and usually get awesome service however, this visit to this location was lagging. The 2 staff were seemingly working against each other and they burnt mine and my other 2 family members pizzas. I … More Michael Green Local Guide·113 reviews·665 photos a year ago Dine in | Dinner | $10–20 Flat bread pizza made your way. Staff was fun and engaging. Food was great and was more than enough. Large enough to share but on a hungry day good enough to keep it for yourself. … More Nadia M 8 reviews·4 photos a year ago Normally I’m a huge fan of &Pizza, but this location is so severely understaffed during rush hours that it has proven actually impossible to get the pizzas we ordered. The &pizza website said our order would be ready within 15-20 minutes, … More 1 Chandrell Christopher 7 reviews·3 photos 2 years ago Service was great! Really nice employees, loved syncere and lavell were amazing! Photo 1 in review by Chandrell Christopher Jlyne B Local Guide·63 reviews·14 photos 4 years ago Got a gluten free American honey and oh my goodness I wish there was one closer to where I live. Incredible tasting food and the soda was really good as well. I gave it four because a few of the toppings didn't look very fresh (wilted … More 1 &pizza - Dupont (Owner) 4 years ago Thanks for the review! :) Jamon Pulliam 2 reviews 2 years ago This location is hands down the best! I was visiting from Los Angeles and the service here was impeccable! And don’t get me started on the pizza! They took their time and put nothing but ingredients and love in that one. Would definitely recommend Dean Albrecht 3 reviews a year ago Take out | Dinner | $10–20 Excellent food with great service. Andre helped me make the right choice. Would recommend to anyone who’s in DC and wants something quick to eat. 1 Esse Darden Local Guide·287 reviews·551 photos 2 years ago Take out | Dinner | $10–20 Ordered the Manhattan, while waiting for my personalized order being made - which I received after noticing a distinctive stinginess with every topping that was applied before it was put in the oven, an excessive prolonged period of time; … More 1 &pizza - Dupont (Owner) 2 years ago Thank you for taking the time to share your feedback. We set a high standard for ourselves, and we’re so sorry to hear that this was not displayed during your visit at our location. Your feedback is important to us and we’ll make sure to make the proper adjustments for next time. I’m also going to send this feedback to the shop and district leader to address with the team there because this isn’t what we want our guests to experience at all. We hope that your next visit with us is nothing like what you experienced recently! Scott C Local Guide·33 reviews·9 photos 3 years ago Great pizza and garlic knots! Not your typical style but still quite special and worth trying...over and over again! The dough and toppings are always on point! I also appreciated their program to help frontline workers. Highly highly recommended! 1 &pizza - Dupont (Owner) 3 years ago Thanks for the review Scott! We had to try something different this time. We hope you enjoyed it though! Sean Local Guide·61 reviews·42 photos 2 years ago Take out | Dinner | $30–50 We got delivery. Late night. Pizzas were not good. Got It for a party and we all laughed at how bad it was, and how small they were in the box. (And they forgot one of our items.) all that and only a 1.5 hour wait. Haha. Only reason for the extra star (instead of just 1) was the cookies were really good! … More 1 Kiran Singh Local Guide·70 reviews·66 photos 4 years ago The pizza here is so delicious! The crust is flavorful and tasty and the tomato sauce is so deliciously tangy. I was really blown away by the quality & taste of the pizza! Their ingredients taste fresh and you can add as many toppings as … More &pizza - Dupont (Owner) 4 years ago Thank you so much!🖤🍕🖤 Michael Cupertino Local Guide·106 reviews·163 photos 4 years ago I don't know if it was an "off day" here, but service was so slow we had to leave. There were 3 people in front of us and we waited 20 minutes before we left. The employee was more concerned about cutting a 1/4 of an inch of crust off of … More Jessica Peters 12 reviews·6 photos 5 years ago The pizza at & pizza is great. That’s why I have been coming back for years. However beware of the customer service. Recently at the DuPont location, I enjoyed a great pizza and needed to use the restroom. When I asked an employee who was … More 2 Alok Sinha Local Guide·58 reviews a year ago Stopped by here and this is a great place for pizza. I ordered the new G and added some spicy honey and it was delicious. Would definitely recommend stopping by here if you have a chance. &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We're thrilled to hear that you enjoyed the new G pizza with added spicy honey. Your response is important to us as we strive to improve our services. We appreciate your recommendation and look forward to serving you again soon! S G Local Guide·12 reviews a year ago Amazing pizza and unique experience. Build your own pizza to a new level. Fresh toppings and an amazing taste. The place is small but the tastw is huge. Loved the food and the service. A definite must. Claire Mizutani Local Guide·54 reviews·374 photos a year ago Take out I got four pizzas to take back to my family:The Maverick, CBR, Billie, and Kalamata Harris. Two of them were on gluten-free crust. Ordering was pretty hectic because there were many young people coming to eat between going to different bars … More 2 Wanda Murphy 33 reviews 2 years ago This was the worst pizza I have ever purchased from & Pizza. The person in front of me, ordered four pizzas. They should have removed my pizza promptly. Instead, the crust is burnt, the spinach dry and the other vegetables dried out. … More &pizza - Dupont (Owner) 2 years ago Terribly sorry to hear about your experience Wanda! We have reported this information to our senior management to resolve and to take the proper measure for quality control. You can send us an additional message at 200-03 or send us an email at [email protected]. Thank you again for bringing this to our attention. Robyn J Local Guide·54 reviews 5 years ago Absolutely the best pizza I have every eaten. The bread was amazingly light and doughy. I didn't have the disgustingly full feeling after eating an entire pizza. The toppings were fresh and delicious and unlimited. Love the healthy choices and sauce variety. 1 &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We're thrilled to hear that you enjoyed our pizza, especially the light and doughy crust and fresh, unlimited toppings. We're glad you appreciate our healthy choices and sauce variety. Your response is important to us as we strive to improve our services. A G 10 reviews a year ago I’m literally in this place as of 06/06/22 and it just took me a whole hour to get a pizza which is ridiculous! Low staff and no sense if urgency. Felt bad for the employee up front who seemed suer overwhelmed, pizza is good usually but won’t be back at this location. &pizza - Dupont (Owner) a year ago Hey Andy! Thanks for you review. We are sorry to hear that we did not provide the best experience! Please reach out to us at 200-03 so we can make this right. 🍕 Timur Plavan Local Guide·97 reviews·278 photos a year ago Dine in | $20–30 The most inefficient &pizza I've ever tried in my life. Ordered online, came 30 mins later and waited for another 50 minutes. Order was missing things in both pizzas. &pizza is great but I would avoid this location. … More Natalia Diaz Torres 1 review·1 photo 2 years ago If I could give 0 stars, I would. This review is based on an UberEats order. I ordered 4 pizzas and an order of … More Photo 1 in review by Natalia Diaz Torres Rishi M Local Guide·9 reviews·22 photos 2 years ago Visited late September 2021 for an online pickup order. Waited 2 hours for my order. … More 1 Michel Louis Local Guide·16 reviews·2 photos 2 years ago Take out | Dinner | $10–20 One of the best pizza I ever tried Photo 1 in review by Michel Louis Rachel Wortmann Local Guide·61 reviews·173 photos 2 years ago Ordered online and waited 45 min for my pizza. App had said it would take 10 min so was quite frustrating … More Kristen Eggleston Local Guide·50 reviews·8 photos 4 years ago The pizza is great but the service here could be a bit better. I went at a time where it wasn't busy at all. The woman who made my order was friendly and helpful and while my order was cooking, I sat at a table nearby. The woman who was at … More Jéssica Bittencourt 1 review·1 photo 2 years ago Lavelle great service, thank you! Photo 1 in review by Jéssica Bittencourt 1 Matt Ramey 3 reviews 11 months ago Dine in | Dinner | $1–10 We went in to have wholesome family dinner experience but quickly exited upon my initial smell test which returned a result consisting of bathroom juices/putrid garbage. 2 Matthew Cantisani 2 reviews a year ago Dine in | Dinner | $10–20 Excellent service!! Food was delicious and made quickly. I will definitely come back to this &pizza location! De Wheeler-Chopan 10 reviews 7 months ago Worst experience ever! Pizza wasn't ready to order. The servers states they didn't care that we waited! … More Stefan Hovy 5 reviews 6 years ago Incredible! Was in DC for a long weekend and ended up going to &pizza 3 times! Twice at this location where the staff and manager were very friendly and open for a chat. Not to mention the delicious pizza with equally delicious vegan options. Would recommend this to anyone visiting DC! 1 Joey Norris 4 reviews a year ago Take out | Dinner | $10–20 Andre was such a great help and made sure to treat us right with amazing pizza. Appreciate the amazing service and will gladly go again. S. T. Grandy 19 reviews·6 photos 4 years ago The pizza is good but I was a bit disappointed to see that the employee who made my pizza only put a racing stripe of sauce right down the middle of the dough. Literally a line down...not spread at all. Also, they may need to turn the ovens … More 1 Monte' Kent 2 reviews a year ago Andre at &pizza DuPont south was amazing.. helped me with my gift card at this location. He service and attention to detail was great. Must go location. Thanks Andre! Sameer Singhal Local Guide·41 reviews·8 photos 7 years ago Great at any time of day. This is a unique pizza experience, and I love the fact that you can customize your pizza to your liking for one flat price. Definitely a place to try, and you'll most likely want to keep coming back Cecilia Demoski 1 review 11 months ago Take out | Dinner | $10–20 This is a great place to grab some great pizza! Amazing service and good quality pizza. Miracle Parish Local Guide·75 reviews·6 photos a year ago I will be filing a police report against the fair skinned man with dreads. He put his hands on me multiple times when I was trying to exit the building. The entire line saw it and they were appalled. I was trying to get to my Uber and he … More Ali A Local Guide·691 reviews·435 photos 4 years ago Delicious, but higher prices than their quality. Crowded around noon time, my experience of course. Employees are ok, but they can be much better. … More Brie Morgan 5 reviews 2 years ago I been coming to this pizza spot for a few months and their always respectful and clean They have awesome pizza and the best customer service the manager always takes care of me and makes sure my pizza is hot and ready to go no complaints will continue to send friends and family India Marshall 28 reviews 2 years ago Employees are nice but mangers need to do a better job with organizing during rush hour. Bathrooms are never available for customers. This has been the case for over 5 years. Luis Miron 3 reviews 11 months ago Dine in | Dinner | $10–20 Amazing service by Andre! and delicious pizza. Definitely the place to eat before a night out of drinking. Breanna Duff 9 reviews·1 photo a year ago the security card told me I could not sit down even though I have a disability. There is no rule to this. He was being very rude for no reason. 1 Katie Kennedy 21 reviews 6 years ago The service was terrible here. We were there for the first time and clearly confused but rather than offering help to us, the staff ignored us. They offered no help when we had questions about some dietary restrictions either. And you can't … More 2 Evan Farrara 12 reviews·1 photo 7 years ago Incredibly loud inside to the point that the employees couldn't hear me correctly when ordering. As a result, when asked if I wanted spicy or non-spicy sauce, I replied "non-spicy" and got spicy anyways. That being said, it ended up being … More Mohammed Yahia Local Guide·384 reviews·1524 photos 5 years ago &pizza is a good, simple pizza place. They don't have many choices, just pizzas, but they are awesome. They have a few set pizzas you can order or a make-your-own-pizza option. They also have the option for gluten-free dough which is $3 … More 1 Jobina Beale 3 reviews a year ago Went in there today for lunch and Tay was awesome. Amazing, courteous and good customer service. I walk from Farragut West Metro to get my pizza all because of him. Gideon Tong Local Guide·155 reviews·233 photos 4 years ago Great pizza! Fast service, would go again. As someone from the west coast we also have build your own pizza places like Pieology and Blaze Pizza but this style of "shoebox pizza" is pretty unique and you can definitely eat a whole pizza on your own even if you don't usually eat that much. &pizza - Dupont (Owner) 4 years ago Great to hear. Thanks! Sara R. Local Guide·144 reviews·305 photos a year ago Dine in | Dinner | $10–20 Vegan-friendly, they even gave vegan pizza. I would like to see more filling vegan toppings options like some Beyond Meat or something. The service was quick and friendly. … More 1 cy mcfadgion 3 reviews 3 months ago Quan, cam and bre were amazing … More &pizza - Dupont (Owner) a month ago Thank you for your 5-star rating! We're thrilled to hear that Quan, Cam, and Bre provided amazing service. Your response is important to us as we strive to improve our services. We look forward to serving you again soon! Khaleel Johns-Watts 58 reviews 10 months ago Best late night dc spot call ahead after 3am if ur with a group and just order all the pizza Emma C Local Guide·83 reviews·85 photos 5 years ago Of all the made-to-order personalized pizza places out there, &pizza has my heart. They offer several delicious dough options including gluten free. All of the toppings are very high quality (get the meatballs!!). After topping, they put it … More 2 A “2Freckles” Oz Local Guide·15 reviews·2 photos 5 years ago I really liked this place, however my second experience here was not like my first. Took me 30 mins to get my order. The cashier was very stressed maybe it was his first day on the job because he did not know how to run the register. The … More Ada Rebecca Smith Local Guide·447 reviews·165 photos a year ago Dine in | Dinner | $10–20 The service was not great, the guy making the pizzas was very slow and wasn't able to find items that should have been easily located(the spinach was empty, he took several minutes looking for it and they were out of spinach). … More Ian Winbrock Local Guide·131 reviews·14 photos 7 years ago I love &pizza. I'm from the West Coast and we have "cook as you wait" pizza places, but nothing on the same level as &pizza. This place is superb. Always greeted by some friendly folks behind the counter and then I either complete one of … More Bill Hipsher Local Guide·41 reviews·987 photos 7 years ago Staff was very nice and pizza we got as ordered was great. The fountain machine was broken so your drink options were limited to can/bottle options for tea/lemonade that they had in a fridge. Ordered a Hawaiian style pizza that was supposed … More 1 Scott Dwyer 12 reviews·1 photo a year ago Great place to get a bite when you out drinking in depot circle. The pizza is awesome, and the prices are better than at the bar. … More Justin Andersen Local Guide·15 reviews a year ago Take out This was the most frustrating experience I've ever been in. Our take out order was over an hour late. And that's the least frustrating part of the night... I don't know if I have the energy to explain everything. Andrea M Local Guide·69 reviews·46 photos a year ago They gave me the wrong pizza. I texted customer service and they said they needed a picture in order to issue a refund. I told them my camera was broken and was not able to take a picture. They told me I couldn't get a full refund without a photograph but they could offer me $5 for a new pizza. Josh Higham Local Guide·148 reviews·84 photos 6 years ago Co-workers had talked this place up, but I found it only decent. I definitely enjoyed the unique soda fountain more than the pizza. Great variety of unique flavors. Pizza was fine but unremarkable. Ariel Holmes 2 reviews 4 years ago James and Deon made my night. I would have been left hungry if it was for the girl up front. But thank you 2 for the lovely service much appreciated. I will remember it & I will be back (during opening hours) thanks again! &pizza - Dupont (Owner) 4 years ago Glad to hear our team solidified your evening (and future visits) with great service. We will be sure share with both James and Deon your kind words! Thanks for stopping by, Ariel! Leanne Quinn 1 review·1 photo 2 years ago Great service and fantastic pizza! Photo 1 in review by Leanne Quinn &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We are thrilled to hear that you enjoyed our fantastic pizza and great service. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Tracey N Local Guide·87 reviews·70 photos 5 years ago Pizza would have been better if it was warmer, but their service was shorthanded..... they had one person taking out the pizza from the oven, boxing it, putting on the finishing garnishes AND ringing up the customers...... that's too … More Theresa Kemp 5 reviews a year ago Dine in | Dinner | $1–10 Andre was fantastic! He served our party fresh, hot, pizza. Thank you for the great customer service. Diana Martinez 3 reviews·2 photos 2 years ago I work nearby and I appreciate that my orders are always done right away and I can quickly just pick up. Great customer service. Very strict on covid regulations. Key 2 reviews 2 years ago Customer service was excellent upon arrival. Store was clean and needs were met in a timely fashion. Very friendly and patient staff. 5 Stars to Terence!! Greg Smith 14 reviews·2 photos 10 months ago Delivery | Lunch | $10–20 Did carry out. Pizza was good, but not great. Strange beverage options … More Bali Adawal Local Guide·203 reviews·1637 photos 4 years ago I have always liked the concept of a highly customized pizza and the overall product turns out to be quite appealing. … More 2 Aleks Nekrasov 91 reviews·67 photos 11 months ago As far as GOOD pizza goes, this place completed my order in 8 minutes. &pizza - Dupont (Owner) 11 months ago Thanks for the awesome review! Hope to see you soon. Gnelossi Hamadou Local Guide·6 reviews·7 photos a year ago Visited this place yesterday for my first time , just wanna say thank you for the entire team that work yesterday night. They were patient and friendly specially the manager Andre Cecilia Local Guide·80 reviews·2 photos 5 years ago We had a pleasant experience at a different branch of &pizza so we tried this branch. This branch was stingy on the toppings and the dining area was not wiped down after customers have eaten there. All 3 of us felt queasy after eating here... Josh Eid-Ries 10 reviews·3 photos 6 years ago Delish, super affordable and very easy to customize your order with no upcharges. The staff are a delight and the food is superb. The drink offerings are also wonderful. I'd recommend the 11 grain crust(ask for it) the mango passion fruit soda and root beer. Vegan cheese and veggie based protein options were a lovely bonus! Pradipto Banerjee Local Guide·29 reviews·96 photos 7 years ago Their pizzas are the best value for money. Unlimited toppings on a big flat bread for just $10. And they're open till 4 am, which is great when you're leaving the bars at 2 and want to get some food. NAI- NAI 3 reviews 2 years ago Dupont is awesome. The place is clean and the pizza is great! One of the workers Decostia provided excellent customer service! I definitely recommend this store! Jaqueline Veltri 2 reviews 4 years ago The pizza here is delicious but it is the second time in a row that I find a long black hair in my pizza. It’s so frustrating and disgusting! I hope management finds a way to keep the employees hair out of the food. F.A. B Local Guide·39 reviews·15 photos 4 years ago James was an amazing manager. My card wasn't working for some reason and he still made my pizza and gave it to me for free. Absolutely amazing customer service! Thank you James! &pizza - Dupont (Owner) 4 years ago Hey there! Thanks so much for the love. We always appreciate our loyal fans. Sunil Singh Local Guide·183 reviews·134 photos 5 years ago &Pizza is something like Blaze Pizza. You pick your dough, then the sauces, and then all your toppings. It's unlimited sauces, and unlimited toppings. And after the pizza is baked, you can add any other sauces, or other toppings. And … More breathemusic94 2 reviews a year ago I love coming to this &pizza, Tay is always a welcome face at this establishment, he is extremely helpful and all around fun to talk to. The food is always amazing here. Crystal 1 review·1 photo 2 years ago &pizza Great good and atmosphere, staff was friendly Photo 1 in review by Crystal Thomas Scheurich Local Guide·33 reviews·1 photo 6 years ago I really like the new fast casual trend. Others may complain about it, but it matches my lifestyle and sets a good middle ground on price. &pizza is the best example of fast casual in this region. Really awesome and ultra customizable food … More Oliver Borg 11 reviews a year ago Andre was super helpful! Fantastic late night spot, quick service, friendly staff, and good food. What more could you want. Dale L. Roberts Local Guide·52 reviews·118 photos 6 years ago This is the second &pizza I've gone to today and wow! This place is even better. There's more seating and it's not even busy. Well worth it! And the staff was friendly and attentive. 5+ stars Nibha Rastogi 7 reviews·2 photos 5 years ago ordered a craft your own... SO GOOD!!! The tribe were super courteous and I got what I wanted. Got a traditional with mushrooms, spicy Italian sausage, onions, pesto finish. Jordi Segura Local Guide·115 reviews·366 photos 7 years ago We ate in this pizza shop during our trip to Washington, and we found the pizza and drinks tasty and original. You can make your own pizza or order one of the existing recipes. I would recommend it for take out or a quick bite. Brandon Boone Local Guide·377 reviews·1050 photos 4 years ago Quick and delicious lunch, very filling and I'm a big guy. Definitely mix it up don't settle for cheese and pepperoni... Never thought I'd have honey on a pizza. &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We're thrilled to hear that you enjoyed our unique pizza options. Your response is important to us as we strive to improve our services. We hope to serve you again soon with more delicious and filling options! ROBIN THOMPSON Local Guide·94 reviews·221 photos 6 years ago I love this place! They have a great pizza selection . I love their specialty sodas. Try the cream soda. There is a wait though due to their being only one person to ring up your order and box your pizza. T Williams 9 reviews 4 years ago Best way to order a to go pizza is on their website. After a long day of sightseeing, a couple of their "oblong" pizzas was just right. Thin crust was great, toppings good. Prepared quickly. &pizza - Dupont (Owner) 4 years ago Thanks for the review and for stopping by, T! Ashley Craft 4 reviews 2 years ago I love The Dupont Team everyone is so nice Tay always goes above and beyond for the customers amazing customer service!! DuPont Team keep up the great work!! Jelani Phipps 8 reviews 2 years ago Food is so delicious. The manager Delonta gave me supervisor service. I would definitely go back again. You won't be disappointed!!! Nely Hernández 2 reviews·1 photo 10 months ago Love this late location . Super busy They are still very patient with customers. Lance Porciuncula 1 review 2 years ago The workers there are super friendly and nice. The service was also pretty great. Got my pizza with little wait. Ismail Gomaa Local Guide·364 reviews·1240 photos 7 years ago Some of the best pizza I've ever had. Any combination worked because their ingredients are absolutely perfect. I enjoyed everything I've tried there, even the stuff I don't usually like. Sarah Semlear Local Guide·154 reviews·1292 photos 5 years ago The gluten free crust is pretty good! It's not a completely gf environment so they can't guarantee there is no cross contamination, but they are careful and change gloves when handling the gf crust. The options are fun and there is a good amount of toping choices for build your own. 1 &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We understand the importance of providing a safe environment for our gluten-free customers and we're glad to hear that you appreciated our efforts. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Michael williamson 9 reviews a year ago Take out | Lunch | $10–20 Pizzas are not that good and one of the workers not that friendly pizza crust had sir burnt from dirty oven … More Jennifer Telfort 4 reviews 2 years ago The service is great! Thank you so much for making my pizza just the way I like it!! I will be back again!!! Hailey Gruch 7 reviews a year ago Take out Wonderful experience... it was busy but they made me feel at ease... wonderful service... thanks to Quan, Malik, Justin and faith William Minter Local Guide·85 reviews·79 photos 7 years ago Thin crunchy crust that isn't overcooked. Awesome fresh toppings and sauce. Perfect for lunch or later night special. Not the best place to sit and eat as space is limited inside(20-25 at best) Cameron Asgharpour 1 review 2 years ago Great customer service and staff is very attentive. Pizza was awesome LadyLewis 2u Local Guide·17 reviews·15 photos 5 years ago &pizza is my fav pizza, but unfortunately, I experienced the WORST, not just customer service, but attitudes EVER! When I asked for assistance, I was only given the 202 number they have taped on the glass display. It was weird bc 2 … More Angel Aguiluz 1 review a year ago Tay is a hell of a entrepreneur! A lovely lad, Marcia also made an astonishing pizza with Nikko. 10/10 if you’re near Faragut North Rakia Pinkney 3 reviews 2 years ago The staff are very friendly and the food came out great and in a timely manner. I will be back, this is the best &pizza location! Dante Gardner 1 review 2 years ago I had an amazing experience. Antonio, and Roshan were very accommodating to my child who is particular about his pizza topping’s . 1 Scott Jason Local Guide·38 reviews·46 photos 4 years ago Thin crust pizza was very tasty and filling. I had red sauce with fresh mozzarella, tomatoes and onions. They do have a gluten free crust for $3 extra. 1 Chris Morris Local Guide·49 reviews·25 photos 4 years ago Pizza was way better than expected. Really nice staff. They were able to get people in and out quickly. I will definitely be returning. 1 &pizza - Dupont (Owner) 4 years ago Thanks for the review :) Raynell Jackson 26 reviews·26 photos 4 years ago I pizza and staff are wonderful Photo 1 in review by Raynell Jackson Photo 2 in review by Raynell Jackson Killian Devitt Local Guide·128 reviews·541 photos 8 years ago What's not to like about this place? It's just great, simple pizza. Tried the Maverick the first time I went and I haven't ordered anything else since. Perfect for lunch if you can avoid the rush. &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We're thrilled to hear that you enjoyed our Maverick pizza and that it's become your go-to choice. We appreciate your support and hope to serve you again soon. Your response is important to us as we strive to improve our services. taliyah hughes 4 reviews 2 years ago Great customer service, quick service! FOOD IS AMAZING! My favorite spot to come after a drunk night 🤪. Highly recommended Mo Love 38 reviews 3 years ago I went in there for the first time a couple of weeks ago. The restaurant had a really foul odor and I could smell it through my mask. Although, I ordered a pizza online and picked it up, I did not eat it and I will never go back to that pizzeria. 1 &pizza - Dupont (Owner) 3 years ago Thank you for taking the time to share your feedback Mo. Our management team will be looking into the odor that you are referring to for the Dupont location. I'm sorry to hear that the experience did not meet your expectations and I would like to apologize for this. Chris Oliver Local Guide·17 reviews·1 photo 8 years ago Great customisable pizza in a relaxed atmosphere. Their home made cola is to die for and so much tastier than coke or Pepsi. Only criticism is that the music was way too loud. Amanda Neilson 6 reviews 2 years ago Great experience! We had a large group and they were fast and efficient. Love the pizza! Breasia Lawson 5 reviews·1 photo 2 years ago Labella made my pizza so good and had the best costumer service ever, he was very bubbly and pleasant and Met all of my demands because I’m a very picky eater lol he’s the best Adriana Lopez 5 reviews 11 months ago Great service! Everything was on point! Andrew was very attentive and polite! Thank you 😃 Merlin Tondji 2 reviews 2 years ago This place is great . Unfortunately last night we couldn't custom the pizza however the team still amazing Briana McKellery 9 reviews·5 photos 2 years ago Beat servers best pizzas and my fav location but all are great. Definitely suggest stopping here for a late night craving after a night out! Tiffany Dendy 3 reviews a year ago Dine in | Dinner | $20–30 Wave and Twan provided excellent customer service on my visit. Gloves were changed prior to assisting us Thanks guys ! Micheal Stone 2 reviews 2 years ago Team was friendly with great service. Pizza came out great! Will continue to come back Forrice Brunson 1 review a year ago Courteous and professional staff members. My order was completed without issues. It was fresh, hot, and the toppings were 🤌🏽. Saee’Rozay 1 review a year ago Take out | Dinner | $10–20 First Time At &Pizza . Great Service By Andre ! Respectful & Kind . Will Definitely Be Back Especially At This Location Medachi 509 16 reviews 4 years ago This is the worst & pizza that I’ve ever been they don’t change their gloves. They got nasty attitude they should reconsider on hiring people there. If I’m paying $11 for pizza I should be treated with respect the customer service is terrible I can’t even tell them how I want my pizza to get done. 1 &pizza - Dupont (Owner) 4 years ago Hi Questa, thanks for the feedback. We'll be sure to address this promptly with the shop. Angel Angelov Local Guide·159 reviews·920 photos 4 years ago A bit dodgy place but pizza was perfect. They offer you to choose from anything you want to add to it and can make it as you like. Was really delicious. Not beer or any liquor though 1 Nataliya Kostiw 2 reviews a year ago Alonzo was amazing, he helped us with everything and was very polite and informative! Would definitely recommend! Simply, Tasha. Local Guide·130 reviews·244 photos 5 years ago Idk what the rating I'm assuming it must be great for I'm too drunk to realize food but let me tell you...today I walked in and walked out....the stench was crazy...it smelled like a dirty barn...or zoo...sewage...idk but I couldn't even order to go and I was just dissappointed... it is a super rainy day today.... 2 Kylie Gilbert Local Guide·19 reviews 7 years ago Could eat this every day for the rest of my life. Not a lot of seating inside though. Also check out ordering ahead, it's much faster. The sodas are good too! Josh Robichaud Local Guide·93 reviews·123 photos 8 years ago Great custom pizza at a reasonable price. Either the preset menu or build your own, can't go wrong. Plenty of seating and fast service. Andrew Isett Local Guide·185 reviews·230 photos 7 years ago Good pizza custom made the way you like. Similar to Chipotle with a burrito, &pizza allows for any toppings they have and different sauces. Always some left over too!! Ethan Granetz 3 reviews a year ago Take out | Dinner | $10–20 Andre got us food real late. He made an awesome pizza. 10/10 service J 4 Local Guide·131 reviews·64 photos 7 years ago Oh yes lawd. This pizza is so good and u dictate the toppings. Yum. Decent price for DC and a food serving size. Not glutinous but more than sufficient. Arely Castro 1 review 2 years ago Amazing service ! & the pizza was so delicious that I will come back again! Jimmy DeVault 15 reviews·1 photo 5 years ago Great food, concept and atmosphere. First time at this location and this may just be this location but service was super slow! The team here also seemed very disorganized, there was no designated cashier which caused a bottleneck at the register where everyone just stood. Maybe they were short staffed? 1 Destiny Cruz 3 reviews 2 years ago GREAT service! And even better pizza! This is my regular location Bc they never disappoint 😉 Punky Banks 1 review 4 years ago I had a great experience. Our cashier Diamond was kind, courteous, and offered great recommendations. I’ll be back soon. Overall great food and great service! &pizza - Dupont (Owner) 4 years ago Thank you so much for the great review Punky! We look forward to seeing you agin soon. Kevin S 3 reviews 2 years ago This is specifically for the website ordering experience. I typically pick up but I needed delivery and my nearby &pizza store was temporarily closed. The problem is that it is impossible to switch the store you're getting delivery from, or … More 1 &pizza - Dupont (Owner) 2 years ago Thank you for your feedback Kevin! I'm sorry to hear that this was your experience trying to order online. We'll flag this information over to our development team to fix. Najm Aldin 9 reviews 9 months ago Luis is very professional and he took care of me. Very nice guy Samantha Zarrilli Local Guide·25 reviews·2 photos 2 years ago Amazing service! So great. Lavelle went above and beyond to make us feel welcome. Promote him!! . Jeremy R. Stinson Local Guide·178 reviews·293 photos 4 years ago &Pizza is one of my favorite pizza joints in DC. Not all locations are created equal, but this particular location is always clean, the staff is friendly and helpful, and I never have to wait too long. &pizza - Dupont (Owner) 4 years ago Hey, Jeremy. Thanks so much for review! руня 11 reviews 7 years ago Great vegan options, (they have mozzarella daiya and veg meat crumbles)! Lots of fresh veggies, good unique gourmet choices of sauce too. The pesto is delicious. The price is reasonable for a vegan pizza, compared to zpizza which recently … More 1 Fabian Meneses 5 reviews a year ago Staying at a hotel close by this place has been our stop daily! From the friendly staff to the delicious food, you have to try this pizza! Mouhamadou Thioune 4 reviews a year ago I like eating at &pizza Dupont. The pizza is always on point. The place is always clean and Tay always provides good customer service. Reilly Sheehy 1 review a year ago They were so lovely - they gave me free water when my friend and I needed it most. 10/10 Ryan Norton 7 reviews 7 years ago I tried calling multiple times to have a question about their menu answered. Each time it automatically goes to a recording and it gives you the option to press "2" to speak to an employee. However when you choose that option the phone … More Geneva Kropper 4 reviews 4 years ago The pizza here is fine, but the staff is very rude and will let you stand at the counter without asking how they can help you. Very poor standard of hospitality and out of place in DC. nate porter 2 reviews a year ago Tay is the best. I love the customer service. He should be promoted. Nikko & Marciara are amazing and should also be promoted!! Isaiah Benjamin 3 reviews 2 years ago I always have a great experience, I work in the area the workers are always fantastic to chat with. Food is always delicious, my go to spot for lunch. Angelica Martinez Local Guide·54 reviews·115 photos 4 years ago Stopped by this place when in the area. Design your own pizza from scratch, and then customize it. The staff assemble your pizza as you watch ... you get to decide everything which goes on the pizza as you follow it down the line. We … More 1 Ariana Brown 3 reviews 2 years ago Very professional clean and made my pizza in a timely manner. Staff was perfect Levon Akopian 8 reviews a year ago Dine in | Other | $10–20 It was amazing and tasty Perfect pizzas, friendly crew … More Jamie Sneed 1 review 2 years ago Outstanding place, great service, Terrence was a huge help and help me build the perfect pizza for my first time!! Teezy Teez 2 reviews a year ago The establishment was amazing, Tay was very kind and ensured we were okay during our time at the restaurant. &pizza - Dupont (Owner) 2 months ago We're thrilled to hear that you had an amazing experience at our restaurant and that Tay took great care of you. Your response is important to us as we strive to improve our services. Thank you for the 5-star rating! We hope to welcome you back soon. kiara cooper 1 review 2 years ago I experience the best customer service with an employee name Lavelle! Definitely would recommend. The pizza was amazing !! Lisa Smith 5 reviews 2 years ago They have an excellent menu selection and you can add anything else you desire... or you can build your pizza from scratch... all at one reasonable price! Delightfully Delicious 👍 2 &pizza - Dupont (Owner) 4 years ago Thanks for the review! :) M A Local Guide·31 reviews·16 photos a year ago The vegan mozzarella and vegan sausage are amazing. To &pizza: please bring back the vegan chicken. Chris Anderson Local Guide·36 reviews·182 photos a year ago Not extremely friendly but excellent excellent pizza. The dough is the best part. 1 Sachin Bhattiprolu 2 reviews a year ago They take orders beyond 10pm but you cannot eat there because they close at 10pm. People here were incredibly rude and forcibly removed chairs WHILE 10+ people were trying to sit and eat. Incredibly rude place. Blue Moon 4 reviews 7 years ago literally the best pizza i've ever eaten. i had the vegan options. they were incredible.staff was really nice. would recommend to everyone. It’s Me Local Guide·381 reviews·169 photos 7 years ago As usual, friendly staff. First time at Dupont location, but just as good as the H St one. … More &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We regret that we no longer offer San Pellegrino and apologize for any inconvenience caused. Your response is important to us as we strive to improve our services. We appreciate your feedback and hope to see you again soon! Quennitta Winzor 1 review 2 years ago The manager is wonderful and fast. But I feel like they were catering to the white people. I almost felt invisible. Darlene Craft 4 reviews 2 years ago I love coming here the manager Tay always knows exactly what the customer service at DuPont is beyond amazing :) Sinceree Stewart 2 reviews·1 photo 2 years ago Great customer service and very patient. Photo 1 in review by Sinceree Stewart lizzle thrvxxx 2 reviews a year ago Andre was very helpful I been goin here for about and year and the customer service is great 10/10 Jas 3 reviews 2 years ago Best pizza I’ve ever had and the workers are the nicest people ever!!!! Come here for a quick bite! &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We're thrilled to hear that you enjoyed our pizza and had a great experience with our staff. Your response is important to us as we strive to improve our services. We hope to see you again soon for another quick bite! Jalen Dixon 1 review a year ago Great service and very reasonable prices! The pizza is also prepared very quickly! Candice Mulholland 4 reviews 2 years ago Terence was awesome! They are always quick and so friendly when I’m in there. 10/10 on the pizza too 😊 Tim Larkin Local Guide·72 reviews·226 photos 5 years ago Damn, this is good pizza Photo 1 in review by Tim Larkin Ron Hagage Local Guide·87 reviews·83 photos 5 years ago Subpar and overpriced pizza place. Compared to u street pizza joints, this place is trendy, hipster and serves mediocre pizza at best. … More 1 Dj Teck Entertainment 1 review 2 years ago Quick and easy. Best pizza I’ve every had. Especially after the club. Will be back Adam Christensen Local Guide·71 reviews·326 photos 8 months ago No way to reach the store and UberEats never delivered my food. … More Erika R. Local Guide·50 reviews·18 photos 5 years ago Reminds me if Blaze. Make your own pizza and craft soda, but some of those toppings should. DEFINITELY go on the pizza as it's being cooked not at the end. Beyond the Clubhouse 1 review a year ago The staff here did a great job, very attentive and engaging. Especially Antonio. A wonferful customer experience! Ryan Local Guide·12 reviews 2 years ago Take out | Dinner | $10–20 Made a mistake when placing my order online and Antonio was awesome helping me get it corrected quickly and courteously. Will Return! … More Alfredo Schonborn 3 reviews a year ago Dine in | Dinner | $10–20 This place was a fantastic establishment to eat with quality food. A recommendation to everyone Ryan Dudrow 1 review 2 years ago Great service for an amazing price for a whole pizza awesome employees 10/10 would recommend Briana Jones 1 review 2 years ago I go to this location all the time! Great customer service and the pizza is always perfect! Haylee Smith 1 review a year ago Awesome pizza & employees. Has original drinks that all taste good! Justin Adams 8 reviews 4 years ago 1st time here. The food was great and the price was right. No complaints. Wish I had found this place sooner. Trip Taker 117 reviews·58 photos 2 years ago I'd like to give it a .5 star. Says that it's open but door is locked, lights are on and you can see employees inside working. Stephen Oliver Local Guide·13 reviews·17 photos 6 years ago Greeted by smells of rancid food or trash when entering. Smell intensifies as you walk further in. Trash everywhere and dirty tables. Bathrooms out of order. … More William Nelson 2 reviews 2 years ago great location! everyone here had great service and the pizza was good! 🙌🏽 Clementina Fernandez Valle 4 reviews·7 photos 2 years ago Great service and really quick. The pizza was delicious and the place is really nice. Jade Boone 2 reviews 2 years ago Staff was very friendly and efficient with taking customers orders in a timely manner! Will definitely visit again Quita11 2 reviews a year ago Terrence was awesome!!! He answered any question I had and did it with a great sense of humor. Marcus Smith Local Guide·115 reviews·5 photos 3 years ago The staff was polite, and efficient this staff is prepared for lunch rush, I even got a bottle of water Since I do a lot of delivery work, I really appreciate these things. 1 &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating and positive feedback! We're glad to hear that you had a great experience with our staff and that the service was efficient. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Marissa Amore Local Guide·57 reviews·13 photos 5 years ago It’s pizza & it’s good. Need I say more? Great location by clubs and night life. Great place to grab a bite on the late night Michael Smalls 2 reviews 2 years ago Fantastic experience! The service was excellent and I love their pizza. &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We're thrilled to hear about your fantastic experience and love for our pizza. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Hycent Nwaneri 1 review 2 years ago Great service!! Antonio really helped me and made sure everything was taken care of for me! Definitely will be back. &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We're thrilled to hear that Antonio provided great service and made sure everything was taken care of for you. Your response is important to us as we strive to improve our services. We look forward to welcoming you back soon! Alan Harris Local Guide·151 reviews·259 photos 6 years ago It was late when I went but it was still a great pizza. I could tell the associates were ready to go but appreciated the pizza. Will come again. Isaiah “Zay” West 1 review 2 years ago We came on Christmas Eve and the service was phenomenal! Antonio and Brian were great! Thank you &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We're thrilled to hear that Antonio and Brian provided phenomenal service on Christmas Eve. Your response is important to us as we strive to improve our services. We hope to have the pleasure of serving you again soon. Ryan Stevens 10 reviews 4 years ago Truly the worst experience . The all male staff associated with the shift on December 6th, at 12:22 am was extremely rude. Customer service was just extremely poor. &pizza - Dupont (Owner) 4 years ago Hey Ryan, I'm really sorry about your experience. We'd love to hear some more details about it if you can reach out to us on our text line, 200-03. Aja Clark 11 reviews 2 years ago Service was excellent! Came to this one because the one in Georgetown was closed. Brian and Antonio were really helpful and pleasant. Beverly Barber 4 reviews·2 photos 2 years ago The staff was very helpful with everything I needed and also made sure I was safe by giving me a mask to protect myself❤️ Patricia Babb 7 reviews 2 years ago Staff was very friendly and accommodating and the pizza was exceptional. Great location :) stefanie riggins 5 reviews 7 years ago Amazingly friendly staff! Our first dining experience in DC and we plan to hit them up again!!! Fresh deliciousness! LynDale Lewis Local Guide·159 reviews·358 photos 4 years ago Good pizza... one size, so be prepared to share if you don't easy a small pizza yourself. Simple menu. &pizza - Dupont (Owner) 4 years ago Hey there! Thanks so much for the love. We always appreciate our loyal fans. Renuka Joshi 3 reviews a year ago Dine in | Dinner | $10–20 Great pizza made quickly. The team working here is super nice. tomas moser 2 reviews 2 years ago Wonderful pizza great especially after a night out. Definitely recommend. &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We're glad to hear that you enjoyed the pizza, especially after a night out. Your response is important to us as we strive to improve our services. We hope to serve you again soon. Vanessa Jimenez Local Guide·49 reviews·8 photos 7 years ago Add your favorite toppings to an amazing crust with eclectic soda flavors for a good price. Comfortable, casual atmosphere. Nista Bob-Grey 1 review 2 years ago This &pizza location is great , the staff was super friendly and I got helped really quick! Stephanie Becker Local Guide·70 reviews·76 photos 5 years ago Different pizza place. Still liked it, one pie can feed 2 people if your not real hungry. Unique combinations. 1 Richo Local Guide·18 reviews·24 photos 4 years ago Delicious pizza, Maverick with extra cheese wont dissapoint any meat lover. Open until late is very helpful. &pizza - Dupont (Owner) 4 years ago Good choice with the Maverick Ricardo! Definitely a fan favorite. Thanks for the great review too! Chris Meaclem 4 reviews·1 photo 7 years ago Only $10 for any pizza, custom made. Basically the subway of pizza - choose your base and any toppings. They charge a flat rate, not per topping. Alex B. Local Guide·190 reviews·277 photos 7 years ago Love &pizza. This place stays open late on the weekends but is pretty full of drunk club goers. Still, it hits the spot after some dancing. robert brown 1 review 2 years ago Service at this location was the best I’ve had at any in the DMV area! Definitely will be going again. Amir Ghasdi 11 reviews·15 photos 5 years ago I built my own Pizza: pesto and spicy tomato, mushroom and Tomato, whole mozzarella, Italian sausages, beef, and finishing with goat cheese and arugula and for sure garlic oil!!! Tenija Livingston 1 review 11 months ago Dine in | Lunch | $1–10 Amazing!!! The workers were welcoming and very cheerful. 10/10 Kalaa 3 reviews 2 years ago Very fast pace store love how my pizza tastes perfect every single time. Brendan M. Local Guide·95 reviews·31 photos 5 years ago The pizza is fantastic. the employees are not. I got the feeling they didn't not care about the job or product they were giving customers. Allen Local Guide·288 reviews·819 photos a year ago Very poor service here. I was the only person in line and the employees did not even acknowledge me. They were having a conversation amongst themselves. Dog Matic 1 review a year ago Fast Great service from the two brother working feb 4 at 6pm Danielle Carr 2 reviews 2 years ago The guy who made my pizza made sure it was done right like forreal lol didn’t skimp me and it looks delicious Halio J 16 reviews 5 years ago Terrible customer service. Staf will rush you and slap together a terrible job of a pizza. Management no better. No wonder employees are terrible, management is even worse. Nadeen Siddiqui 6 reviews 5 years ago Terrible service. They just threw toppings without caring about making it tasty. Don’t waste your time and money here. Chose a place that actually tries. 1 Cory Simmons 1 review 2 years ago I got food poisoning. No disrespect to the workers, but my stomach hurts so much and I’m so mad lol. Thompson Hangen Local Guide·36 reviews·9 photos 4 years ago Fast and great pizza! What's not to love about &pizza? The staff here are friendly and accommodating! Christy McCann Local Guide·48 reviews·18 photos 2 years ago Food was not made correctly and a bit late, the secjrry staff is super rude, but employees were nice. Cavin Ward-Caviness Local Guide·319 reviews·769 photos 6 years ago Fresh, quick, tons of toppings, and most importantly tasty. If you have the chance definitely go to one of the many locations and see why all the hype is deserved Esprit Cha 2 reviews a year ago Amazing pizza, amazing service, awesome experience as a whole m g 11 reviews a year ago We bought a pizza and we’re immediately screamed at and tossed out for eating it inside. Like what? The moment I hand you cash you throw me out. I can’t eat my pizza inside? &pizza - Dupont (Owner) a year ago Hi Max. Sorry to read about your experience. Can you text us at 200-03 to provide more detail. Edwin Lopez 5 reviews·2 photos a year ago &pizza is my all-time favorite for a fast casual -- and delicious -- pizza. This location is a mainstay, too! R. T. Local Guide·16 reviews 7 years ago This place was gross!!! Trash everywhere and it smelled pretty bad. There's definitely better &pizza's to go to in DC. I went in and came right back out! 1 Rebecca Schick 32 reviews a year ago Take out | Dinner | $10–20 Very tasty pizza. Staff were great JED CREEK 8 reviews 7 years ago Do not ever go here it's terrible. My friend got food poisoning, so it's not safe to go here. And the management and the staff are terrible and refuse to take responsibility. Avoid this place at all costs! Monae' Bailey 4 reviews 2 years ago Antonio was very helpful, assisted me with ordering my meal. 10/10 would recommend! Kelli Smith 3 reviews 2 years ago I always get the best service here. I live &Pizza and Terrence is great!!! Emily Nelson 1 review 4 years ago Amazing, charismatic staff and even better pizza!! Very creative and innovative pizza and drink choices :-) Josiah Tomes 4 reviews·2 photos a year ago Staff is very nice! Photo 1 in review by Josiah Tomes GLENN EVANS Local Guide·41 reviews 4 years ago DONT WAIST YOUR TIME.OR.MONEY. PLACE WOULDN'T LAST A WEEK IN JERSEY. FIRST I TRIED TO CALL AND THEY DONT TAKE CALLS U HAVE TO ORDER ONLINE OR … More 2 Gucci simon Local Guide·64 reviews·4 photos 4 years ago Food was great. The service was horrible. Only 2 ppl in the store had some manners. The REST HORRIBLE. &pizza - Dupont (Owner) 4 years ago Hi Gucci. Thanks for the feedback. We're sorry that your experience was below expectation. We'll be sure to relay this message to the Shop Lead so that improvements can be made asap. Alyse Edwards 2 reviews 2 years ago Friendly, polite and helpful staff. Pizza is good too duh! C Michele 1 review a year ago Staff is dope. Pizza is delicious. Big fan! Lauren Prather 2 reviews 2 years ago Friendly and helpful! Quick service and the food is 🔥🔥! Lavelle was amazing and super helpful! Amazing customer service! Austin Zielman Local Guide·437 reviews·1539 photos 7 years ago Great pizza served super fast! Downside is that it's directly next to/under sa club, and the constant thumping is quite disturbing. Billy Local Guide·207 reviews·404 photos 7 years ago Cool spot for a flat bread pizza. You make your own pizza which is pretty cool. The price is reasonable one pizza is good for 2ppl. Kenny Culver Local Guide·14 reviews·1 photo 4 years ago pizza was so spicy I couldn't eat it I took it back in I said hey I need a new one I don't know why it's spicy they said tough s*** bounce &pizza - Dupont (Owner) 4 years ago Hey there! I'm so sorry to hear about your bad experience. If you get a chance, please text us on our customer service line at 200-03 and we will make this right. Priya Patel 2 reviews 2 years ago Loved it! Everyone was so accommodating and understanding! Great pizza! Emir Yılkıcı 5 reviews·3 photos 7 years ago They simply blend some cheap ingredients. The food tasted not that good. I don't recommend unless everywhere else is closed. Johnny Neilson 2 reviews 2 years ago Dine in my family loves this place! very good food and friendly staff! Luis Medina (COACHMETONY) Local Guide·97 reviews·324 photos 6 years ago Great food! I'm vegetarian and I had a lot of options here. Only thing is that serving sizes are really small. Chiquita Jackson 1 review 2 years ago Great food and quick service! Loved the garlic knots too. mike epps 3 reviews 2 years ago Great quality pizza, fast and friendly customer service. Dylan McDowell Local Guide·138 reviews·79 photos 7 years ago Best option for a pizza lunch in D.C. This location has more indoor seating, but during prime times be prepared to walk to a nearby park. Kay Tunez 1 review 2 years ago Quey was great and very helpful since it was my first time she made my experience 10 times better. Derrick A. Morton 2 reviews 2 years ago The coolest & Pizza in the DMV everyone in there will make you laugh ! Thank you for my good 🍕 DK Walker 7 reviews 6 years ago Best pizza ever! Far from traditional tasting pizza, leaves a funky delicacy in your mouth that leaves you beyond satisfied! Renee S. Local Guide·55 reviews·4 photos 7 years ago Pretty good! The prices are reasonable (listed at the top of the menu) and pizza is delicious! I ordered the gnaric... good choice! Tray Smith 4 reviews a year ago Great place. Jainyn was great cook. She was nice and quick. Music for every ocation Local Guide·6 reviews·334 photos 5 years ago I love these pizzas Photo 1 in review by Music for every ocation Christopher Edwards 2 reviews 2 years ago I had the best experience. Customer service was A1 and the food was awesome Pauline Abah 1 review a year ago When back to this place after my Last visit and the service is always amazing Nicholas Mildebrath 1 review 2 years ago Go-to lunch spot in DuPont. Pizzas are great and filling - quick service and always good music. Tustin Neilson 6 reviews 2 years ago Dine in | Lunch | $10–20 Quick service and tasty pizza! I recommend adding the hot honey. … More helene h 1 review a year ago Delivery | Dinner Super good pizza, delicious drinks, love it <3 &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We're thrilled to hear that you enjoyed our pizza and drinks. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Jimmy Sambuo 6 reviews·7 photos 2 years ago Fast and friendly service! &pizza is my goto pizza place. Marquis Savant 1 review a year ago Delivery | Lunch Waited over 30 min for a delivery while the employees traded food with shake shack Gabriel Marín 7 reviews·1 photo a year ago Lovely place and pizza is great!! Tay was a complete gentleman. &pizza - Dupont (Owner) 2 months ago We appreciate your 5-star rating! We're glad you enjoyed the pizza and the service provided by Tay. Your response is important to us as we strive to improve our services. Thank you for taking the time to share your experience with us. Messaijah Shillingford 2 reviews a year ago The food was great! Tae gave wonderful customer service! &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We're thrilled to hear that you enjoyed the food and received wonderful customer service from Tae. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Donald Jackson 7 reviews a year ago Dine in | Lunch | $10–20 Love how the pizza is made on the spot, fresh ingredients and creative mixes Talisha Harris 4 reviews 2 years ago Terence was great! Ever want great pizza and good vibes, come to Dupont location! Corey DeAngelis Local Guide·204 reviews·623 photos 7 years ago Best custom pizza ever Photo 1 in review by Corey DeAngelis Frankie B 1 review 2 years ago Absolutely love this place. Service is quick and food is great Kaylah B Local Guide·48 reviews·18 photos a year ago Take out | Dinner | $10–20 Super fresh, super quick service even though it was very busy! Anna zakharchishin 1 review a year ago Other | $10–20 Alonzo was the absolute best. Should definitely be running the place! Baylee Childress 2 reviews 5 years ago Love this place. Always delicious. Staff is always friendly. Tyler is a bit of a Chav. Tsvetelina Petkova Local Guide·99 reviews·147 photos 4 years ago Really kice and tasty pizza. Affordable price and you choose your topics. Basically you choose your pizza from scratch. Yummy. &pizza - Dupont (Owner) 4 years ago Glad you enjoy the concept Tsvetelina! And thanks for dropping a review! Steve Murphy Local Guide·43 reviews·417 photos 5 years ago Good, quick pizza while you wait. Not as good as wood burning oven etc, but satisfies... James Papanestor Local Guide·88 reviews·574 photos 2 years ago Thin crust and the choices for the toppings are not like any other! Went three times in one week. Tarikah Omar 3 reviews 6 years ago Pizza was fantastic, service was awesome, there was an unpleasant odor when entering that definitely needs to be addressed 1 Javier Borja Local Guide·19 reviews·1 photo 5 years ago Love the food, large space with plenty of seating. It's not a warm place but in great location G Local Guide·116 reviews a year ago Food was good staff was friendly and helpful. … More Amar-Jyrel Mott 2 reviews 2 years ago I love it! Staff is nice & I've never had a bad experience! N K Local Guide·98 reviews·38 photos 6 years ago The best build to suit pizza joint I've tried. Light years ahead of blaze on quality of ingredients. Gahana Dahiya 6 reviews·1 photo 3 years ago I go to this place all the time! Food is great and the staff is always nice. &pizza - Dupont (Owner) 3 years ago Thank you so much for the review and thank you for being a returning guest! Can't wait to see you again next time! Patrice Mobitang 1 review 2 years ago Great pizza. My familly and I love this location Yuting (Nychii) Local Guide·114 reviews·1683 photos 7 years ago Really enjoy the way this chain makes pizza! This location doesn't have a lot of seating though... Sakina Allen 2 reviews 11 months ago great customer service!!!! definitely recommend. George A 1 review 2 years ago Ordered waited for 2 hours and then my order was canceled. They asked me to reorder. It was my first time ordering from them and my last time. TEAM SHERBOURNE Local Guide·405 reviews·284 photos a year ago I'm from NY and Always have to visit a &pizza while in DC! &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We are thrilled to hear that you always enjoy visiting &pizza while in DC. Your response is important to us as we strive to improve our services. We hope to continue exceeding your expectations on your future visits. Carlos Patiño Local Guide·168 reviews·431 photos 4 years ago Really, good pizza! Just pick what you want with it and enjoy. Friendly people. &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We're delighted to hear that you enjoyed our pizza and found our staff friendly. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Erica Burwell 4 reviews 6 years ago The service was good food is normal. If u r n the mood for pizza good place to go. Aris Preston 2 reviews 2 years ago Pizza is great Antoni and Bron were very helpful and lead to a great lunch. Weiyan Zhang 2 reviews 2 years ago I quite like the pizza here! Self designed pizza is always the best big boi rj 1 review a year ago Take out | Dinner Awesome establishment, good service, tasty pizza Bryan Moises Hernandez Benitez 1 review a year ago the crust is the best and the staff are great, down to earth people. Courtney Metcalfe 5 reviews 2 years ago Lavelle was awesome and gave us great service! awesome pizza Jennifer Morgan 6 reviews a year ago Take out | Dinner | $10–20 Great option for a quick / delicious late night dinner. … More James Gregory 2 reviews a year ago Good pizza great people!! Great late night fix &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We're thrilled to hear that you enjoyed our pizza and our service. We're always here to satisfy those late-night cravings. Your response is important to us as we strive to improve our services. Ms Lola 2 reviews 2 years ago Antonio was the best I love how he makes my pizza, I absolutely love this location. Adeola A 11 reviews 4 years ago The pizza is fine, they don't allow you to sit down and eat late nights on the weekend, although they are open, and the security is very rude about it. Joni Hurley 3 reviews·1 photo 5 years ago Pizza was amazing!!!! One of my best GF pizza crust (order well done) Tat hazelton 4 reviews 2 years ago Good Customer Service, Fast Paced & Loaded Pizza Up. Joseph Rhinehart 11 reviews·1 photo 2 years ago Friendly staff. Great food . Will definitely come back. AHMED RABANE 2 reviews a year ago Always great customer service. Terence is definitely a great asset for this location Kendi Johnson 1 review 2 years ago Lavelle was very professional. He put love into my pizza Justin Wang Local Guide·92 reviews 7 years ago Make your own pizza for $9? As many toppings/sauces/garnishes as you want?? I love &pizza. Tahlia Stangherlin 8 reviews·4 photos a year ago Tay was very helpful when i checked out today. very polite and friendly ! Nisha P 6 reviews·1 photo 2 years ago Great experience! Quick and convent! It’s a must try if you are in D.C. Pooja Rastogi 5 reviews·2 photos 2 years ago Love the pizza and employees!!!!!! So so nice especially lavelle Jake Backers 3 reviews a year ago This place is the best!! also the pizza??? smashing!!! Chanel Beaudoin 1 review 2 years ago Great pizza love it here. Loved the service! Allen Cardenas Local Guide·42 reviews·10 photos 5 years ago So glad there is an &pizza in Dupont. It's quick, easy, and delicious. Awesome value for your money Chanelle Combs 1 review 2 years ago Antonio the best I love this location best pizza and they close at 4am Clifton McEachin 3 reviews 2 years ago Great service!!!! The best pizza I’ve ever head!!! Lucas Orjales 2 reviews a year ago Tay was the best supervisor! Absolutely delicious pizza! Antwane Wrenn 1 review a year ago I love this location .employee are fun and patient Kristin Fillingim 1 review 2 years ago Là elle was the best!! Great service. 5 out of 5 every time!!!! &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We are thrilled to hear that you had a great experience with us. Your response is important to us as we strive to improve our services. We look forward to serving you again soon! Jackie Warner 2 reviews 2 years ago Great service and pizza! Antonio, Brianna and Jalen are the best. Veronica Sarai Melara Cornejo 1 review a year ago Good customer service! Friendly people and always willing to help. Lifeasevon 6 reviews 2 years ago The pizza is always great ! Extra crispy too David Oliveira 4 reviews 2 years ago Take out | Dinner | $10–20 Love their pizza, clean and nice location miles vondra Local Guide·10 reviews·12 photos a year ago Great pizza, even better people. JP was great! Yousif M Local Guide·26 reviews·3 photos 5 years ago Lots of crust on the pizza because of how it's made. Super fresh and feels almost healthy! Lauren Hastings 1 review 2 years ago Take out | Dinner Service was great and the vibe even better! Lavelle’s assistance was top notch Precious Johnson Local Guide·25 reviews 2 years ago Service was great at this location! Food was delicious 😋 Kannan Ramanathan Local Guide·73 reviews·27 photos 4 years ago You can just add all the ingredients you want and the dough of the pizza is thin and delicious &pizza - Dupont (Owner) 4 years ago Hey Kannan, glad you loved it! Come again soon! Al S. 1 review 2 years ago Outstanding service and made one hell of a pizza Delonte Briggs, MBA Local Guide·48 reviews·18 photos 4 years ago Staff was not welcoming and had the dude had an attitude when clarifying build your own versus a classic adding a few extra toppings...it didn't master i was willing to pay the difference.. 1 &pizza - Dupont (Owner) 4 years ago Sorry to hear that your pizza experience wasn't the best. Thank you for your feedback. I will forward this information to the appropriate people. Please reach out to us so that we can make this right. A'Jae Boyd 2 reviews 2 years ago Great customer service. Order done in a timely fashion. &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We're thrilled to hear that your order was delivered in a timely fashion. Your response is important to us as we strive to improve our services. We hope to serve you again soon! John Benson Local Guide·23 reviews·183 photos 4 years ago Customer service at this location is atrocious. The crew working the evening shift on 2/28/20 were very rude. Stay away! Dallas S. Local Guide·101 reviews·89 photos 5 years ago My first pizza in DC. Quick service and great good at a decent price. Jordhon Horelien 2 reviews 2 years ago Lavelle was an excellent help to getting the pizza of my choice. Very helpful &pizza - Dupont (Owner) 2 months ago Thank you for taking the time to leave a review. We are thrilled to hear that Lavelle was able to assist you in getting the pizza of your choice. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Courtney Wade 4 reviews 2 years ago Labella is awesome. He goes the extra mile. Thank you! Dusan Vasiljevic Local Guide·50 reviews·25 photos 4 years ago Excellent suggested choices of toppings, quick service, good enough interior. Mig Local Guide·581 reviews·590 photos 6 years ago Love this pizza: Favorite go to - Red sauce with pepporoni and sausage drizzled with pesto on top. Mercedes White 3 reviews 2 years ago Phenomenal experience with Antonio and the rest of the staff. The place was very clean! Kate Neilson 3 reviews 2 years ago Dine in | Lunch | $10–20 love & pizza! come here often and always enjoy it. … More KDASH201 14 reviews·1 photo 7 years ago Best pizza I ever had. You just have to go and try it yourself Debbie James 8 reviews 2 years ago Ran efficiently under pressure during Halloween eve and Lavelle was very helpful Bosh Gobran Local Guide·304 reviews·695 photos 7 years ago Great Pizza, fast and they have a vegan/vegetarian options:) fund staff Smash Diddy 5 reviews 6 years ago Service was good and food great who dnt love pizza lol &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We're glad to hear that you enjoyed our service and food, especially the pizza. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Heidi Wiles Local Guide·25 reviews·2 photos 7 years ago I just love the the atmosphere the people are great and the pizza is delicious. Need one in Hagerstown MD. hector paredes Local Guide·51 reviews·712 photos 2 months ago I love this Pizza … More &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We're thrilled to hear that you love our pizza. Your response is important to us as we strive to improve our services. We look forward to serving you again soon. Justin Bozeman 3 reviews 5 years ago Ordered via Uber Eats, Pizza came completely wrong from what was ordered, and added whatever they wanted to the pizza and when called , no one answers the phone and call was looped, no one ever responded to my e-mails regarding the wrong order 1 Alana Peery 6 reviews·13 photos a year ago Great pizza and better service! Kunal Vijan Local Guide·117 reviews·505 photos 4 years ago Very nice n tasty. Much better than DC Pizza James Plain Local Guide·9 reviews 5 years ago i tried the american honey pizza, and was great! The craft sodas are also really interesting! danelle hankins 8 reviews 2 years ago Antonio made me a great pizza today and answered all my questions. Fly Gurl Local Guide·193 reviews·271 photos 4 years ago The staff was great they are very customer service driven , fast , and very clean Rodolfo Diaz 1 review a year ago Great Place! Awesome customer service! Dean Naps 2 reviews a year ago Awesome pizza, great service, thank you &pizza! EBEMBI Alain 3 reviews 2 years ago Great location. Staff are really friendly and patient Robin Young 5 reviews 5 years ago Fantastic pizza and an AMAZING staff!! I could eat there everyday!!’ Javid Pourkia Local Guide·128 reviews·1295 photos 5 years ago It's not just food, is love Photo 1 in review by Javid Pourkia Petra Sosa 2 reviews·1 photo a year ago Best pizza in town , customer service is A1 ! Photo 1 in review by Petra Sosa khairy jones 3 reviews 2 years ago This was a great place to go late at night and it handled the long line well Alvaro Dalessandro Local Guide·44 reviews·3 photos 4 years ago Tasty pizza, only downside is the place didn't have Coca-Cola Money Monkey 1 review 2 years ago lavelle was extremely helpful and made sure i was set and provided good service Living the life of lele Vibing 12 reviews·2 photos a year ago Great customer service made me feel welcome &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We're thrilled to hear that our customer service made you feel welcome. Your response is important to us as we strive to improve our services. We hope to continue providing a great experience for you in the future. Abish Anklesaria Local Guide·94 reviews·53 photos 7 years ago Fresh pizza. Good toppings selection. Kid friendly as well. Great place for a fast custom pizza. Rob G Local Guide·151 reviews·301 photos 2 years ago First visit. Fast service, excellent pizza! Matt Peterson 2 reviews 2 years ago an icon, a legend, showstopping beautiful amazing never the same the best &pizza in DC Eric Midder Local Guide·146 reviews 4 years ago Could be a little quicker but very friendly staff and great pizza! Sandra Gaillardetz 4 reviews 5 years ago This Pizza was phenomenal ! Loved it and would definitely go back!!

Only provide commentary from the context included. How, if at all, does the owner of this business respond to negative reviews? &Pizza Google Reviews Josh Local Guide·316 reviews·113 photos a month ago Ordered online and my receipt had no details confirming my items. I text them like they said and they never responded. Then they have Uber do the order delivery but I didn't know that before putting the tip in and then the driver said he … More Photo 1 in review by Josh Photo 2 in review by Josh &pizza - Dupont (Owner) a month ago We regret to hear about your experience with the online ordering and delivery process. Your response is important to us as we strive to improve our services. We will address the issues you've mentioned with our team to ensure a better experience for all our customers. Thank you for bringing this to our attention. Gine “Gine The Mae Nai's Winery” MaeNaiWinery Local Guide·369 reviews·5043 photos 3 months ago Dine in | Dinner | $10–20 Such a lovely freshly made pizza with various options, really hard time to decide which one to order lol. Very fast and nice service. Pizza just got ready in 8mins. Have two long tables to enjoy, or take away. … More Photo 1 in review by Gine “Gine The Mae Nai's Winery” MaeNaiWinery Photo 2 in review by Gine “Gine The Mae Nai's Winery” MaeNaiWinery Photo 3 in review by Gine “Gine The Mae Nai's Winery” MaeNaiWinery Photo 4 in review by Gine “Gine The Mae Nai's Winery” MaeNaiWinery Photo 5 in review by Gine “Gine The Mae Nai's Winery” MaeNaiWinery Photo 6 in review by Gine “Gine The Mae Nai's Winery” MaeNaiWinery Photo 7 in review by Gine “Gine The Mae Nai's Winery” MaeNaiWinery Photo 8 in review by Gine “Gine The Mae Nai's Winery” MaeNaiWinery Photo 9 in review by Gine “Gine The Mae Nai's Winery” MaeNaiWinery &pizza - Dupont (Owner) a month ago Thank you for your 5-star rating! We're thrilled to hear that you enjoyed our freshly made pizza and fast service. Your response is important to us as we strive to improve our services. We hope to see you again soon for another delicious experience! Torianna Todd 3 reviews·2 photos a week ago NEW Take out | Dinner | $10–20 Super friendly staff and the food was really good! We got 2 pizzas- one cheese and one margarita with some extra toppings, and garlic knots. … More Photo 1 in review by Torianna Todd Photo 2 in review by Torianna Todd Addison Hosner Local Guide·100 reviews·141 photos a month ago Never had pizza from here before but ordered online for pickup during lunch. Showed up on time and the order was ready without delay. The pizza is a great serving size and depending on your appetite and what you get this could be two meals … More &pizza - Dupont (Owner) a month ago Thank you for taking the time to share your experience with us! We are thrilled to hear that you enjoyed our pizza and that your order was ready on time. Your response is important to us as we strive to improve our services. We look forward to serving you again soon! Allen Nuccio Local Guide·297 reviews·380 photos a week ago NEW Dine in | Lunch | $10–20 If you're not familiar, &pizza is like Fancy Pizza Hut in flatbread form. Their pies are pretty good and their garlic knots are delicious. This location has fantastic customer service, but also smells heavily of a bathroom for whatever reason. Anyway, pretty good all-in-all. … More Alma Local Guide·147 reviews·278 photos 7 months ago Take out | Dinner | $10–20 Pizza is good and doesn't take long from ordering to paying so it's fast and convenient. Staff is super friendly and nice … More Photo 1 in review by Alma Photo 2 in review by Alma Photo 3 in review by Alma Photo 4 in review by Alma Photo 5 in review by Alma Lizzy Amirana Local Guide·146 reviews·224 photos 4 months ago Smells like mold in the place but wonderful pizza! Their gluten free pizza with vegan cheese and meat substitute is 💣 … More Photo 1 in review by Lizzy Amirana 1 &pizza - Dupont (Owner) a month ago We regret to hear about the issue you encountered during your visit. Your response is important to us as we strive to improve our services. We're glad you enjoyed the gluten free pizza with vegan cheese and meat substitute. Thank you for sharing your experience. Emma Fan Local Guide·28 reviews·20 photos a month ago We ordered 8 pizzas (menu items) and 4 of them was made incorrectly - missing all the meat, missing veggies & pineapple, wrong sauce, missing spices. They weren’t just missing one or two ingredients, they were made into something completely … More &pizza - Dupont (Owner) a month ago We regret to hear about your experience and the incorrect pizza orders. Your response is important to us as we strive to improve our services. We will address this with our kitchen staff to ensure such mistakes are not repeated. Thank you for bringing this to our attention. Aban Koprulu 74 reviews·3 photos 3 weeks ago NEW The pizza is good but omg the sewage smell was unbearable. I tried to hold my breath and breathe through my mouth. I almost passed out. I don’t think this place is safe according USDA food and safety inspection. I will have to report it … More 1 &pizza - Dupont (Owner) 3 weeks ago We regret to hear about your experience. Your response is important to us as we strive to improve our services. We will investigate the issue immediately to ensure a safe and pleasant dining experience for all our customers. Thank you for bringing this to our attention. Jacob Fix Local Guide·22 reviews·12 photos 4 months ago Take out | Lunch | $10–20 Very fast, affordable, and huge portions. Great deal and great pizza. … More Photo 1 in review by Jacob Fix Jason A 4 reviews·2 photos 2 years ago Take out | Lunch | $10–20 Great pizza in Dupont! Walking distance from the Mayflower hotel. Fast friendly service. The Maverick is my favorite and garlic knots are a nice add on. Photo 1 in review by Jason A Photo 2 in review by Jason A Mehrnoosh Kh Local Guide·245 reviews·1644 photos 6 months ago Take out | Dinner It is a good pizza place for late night bites. … More Photo 1 in review by Mehrnoosh Kh Photo 2 in review by Mehrnoosh Kh Photo 3 in review by Mehrnoosh Kh Photo 4 in review by Mehrnoosh Kh Photo 5 in review by Mehrnoosh Kh Photo 6 in review by Mehrnoosh Kh Photo 7 in review by Mehrnoosh Kh Photo 8 in review by Mehrnoosh Kh Ryan Griffith 11 reviews 4 months ago Don't bother ordering Uber Eats here because they won't make the food and you'll have to cancel the order. And if you dine in apparently it smells like piss. … More Samuel Davie 37 reviews·102 photos a year ago Take out | Dinner | $10–20 Delicious pizza and the perfect serving for 1 person. I always get the pineapple jacked and take my Tour de Pizza cutter for a ride. Going for a pizza ride #tourdepizzacutter 🚴🏼🍕😊 Photo 2 in review by Samuel Davie 3 Alan Marrero Local Guide·215 reviews·2873 photos 5 months ago Nasty piss smell, we had to leave in an instant. No wonder the place was empty. The pizzas looked great in the pictures, if you want to eat a pizza in smelly atmosphere THIS IS IT! … More 2 Henry Kloepper Local Guide·121 reviews·77 photos 7 years ago Was quite decent. Fast, reasonable price, good taste. Though I just had Pizza Paradiso and if you have some extra time it's well worth it over &pizza, especially if you are interested in having an alcoholic drink with your pizza. If you're in a rush this works better. Photo 1 in review by Henry Kloepper Damien Shaner Local Guide·30 reviews·140 photos 3 weeks ago NEW They are so ghetto they have a security guard that locks the door and doesn't let people inside after the place fills full of "dangerous people"...well before the actual closing time. &pizza - Dupont (Owner) 2 weeks ago We regret to hear about your experience at our restaurant. Your response is important to us as we strive to improve our services. We take the safety of our customers seriously and will address this issue with our security team. Thank you for bringing this to our attention. Diana Marquez 2 reviews 9 months ago Dine in | $10–20 My sister and I came in to grab some food after a night out it was very busy but the team was very efficient and Luis definitely made sure we had a great experience. He has exceptional customer service skills, very out going and just great at what he does and overall takes great care of guests. Will definitely be coming back soon ! Matthew Rice Local Guide·14 reviews·54 photos 4 months ago Take out | Dinner | $10–20 Pizza was decent, but as other reviews have noted, the restaurant had an unbearable stench. The owner needs to call a plumber or an exterminator (or both). … More Elizabeth Dapper 8 reviews·4 photos 3 months ago Dine in | Dinner | $10–20 Good place, good service, loud music which is always a little hard when talking with friends... but the food and the employees never disappoint! … More &pizza - Dupont (Owner) a month ago Thank you for taking the time to share your experience with us. We're glad to hear that you enjoyed the food and service, but we understand that the loud music can be a challenge. Your response is important to us as we strive to improve our services. We hope to have the opportunity to serve you again in the future. D C 8 reviews·2 photos 6 months ago Take out | Dinner I just have to add to the other reviews about the absolutely putrid horrifying smell in here, which hits you upon entering. I had ordered Uber Eats, otherwise I would have immediately left. This place most likely has an ongoing sewage issue that is not being addressed properly. No place that sells food should smell like this. … More 2 Andy Jovel 11 reviews·1 photo a year ago Take out | Lunch | $10–20 Sorry, but the pizza was cold and there was little to none chicken mostly just blue cheese crumbles. There were none jalapenos at all either. Photo 1 in review by Andy Jovel Brei Evans 4 reviews·11 photos 3 days ago NEW This locations stinks so bad. The people are nice here though. … More Cedar Baltz 7 reviews 7 months ago Take out | Dinner | $30–50 I got take out and the guy gave me 1 correct pizza I ordered and gave me a completely different order for the 2nd pizza. He showed me the first pizza with the correct toppings on it. I assumed the 2nd pizza he handed me was the right order … More Nathan Sellers Local Guide·90 reviews·323 photos 4 years ago This is really good pizza. The manager was super friendly and helpful too. My son begged to go back the whole trip and said it was the best pizza he'd ever had. Photo 1 in review by Nathan Sellers Kelli Roberts Local Guide·349 reviews·305 photos 6 years ago Second &pizza today. This location is even bigger! Food was delicious, but I would advise going light on the toppings if you choose a gluten free pizza. Too many toppings can make the pizza heavy and messy. Photo 1 in review by Kelli Roberts Photo 2 in review by Kelli Roberts 2 Jahanna Reese 13 reviews·1 photo 11 months ago This is My favorite & pizza Location, great service and they don’t rush you . 5 stars out of 5 Photo 1 in review by Jahanna Reese Josh Griswell Local Guide·26 reviews·21 photos 5 years ago Great food, good price, friendly staff! I ordered the vegan pizza and it was awesome! Their craft soda fountain has some great selections as well. Food was cooked quickly and tasted great! Photo 1 in review by Josh Griswell 1 David Zaga Local Guide·48 reviews·83 photos 6 months ago I mean the price was ok. The place smelled, clearly not very well maintained. And the pizza was ok. The guys working the counter, although dealing with a lot of customers were working hard and gave good service … More 2 Samim zamiri 1 review a month ago You gotta taste their pizza and you’ll definitely like it … More &pizza - Dupont (Owner) a month ago Thank you for your 5-star rating! We're thrilled to hear that you enjoyed our pizza. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Sabrina Lisenby 3 reviews·1 photo 2 years ago Amazing staff, great service, and was so fast. Oh by the way they have amazing pizza and garlic knots. If this isn’t enough to make you try them out, do it anyway lol 😂🤣 Photo 1 in review by Sabrina Lisenby &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We're thrilled to hear that you had an amazing experience with our staff and enjoyed our pizza and garlic knots. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Ashllyn Silva Local Guide·64 reviews·63 photos a year ago Dine in | Lunch | $10–20 Actually so obsessed with this pizza. So glad to find out they have multiple locations in my home city. Photo 1 in review by Ashllyn Silva Zhuoran Li 7 reviews·6 photos a year ago The guy is super nice. He is friendly. The pizza is so good. It is really a top place for some pizza quick bite Photo 1 in review by Zhuoran Li J Foodgeek Local Guide·715 reviews·732 photos 2 years ago So earlier today I got I texted coupon for a $5 pizza, so I walk in to dupont S location and I figure I'll just make the order in the place, and I look at the places where the ingredients are, and see slimy rod and spinach and black basil, … More Photo 1 in review by J Foodgeek 1 HoneyD 11 reviews 6 months ago Why does this place stink? Walked up expecting smell of fresh pizza but smells like dirty sewage, smells better outside. Couldn't imagine sitting down in here to eat. … More 2 Sarah Jackson Local Guide·81 reviews·2 photos 4 years ago Pizza flavor is good & could have been a 5 star. Delivery wAs about 30 mins on Fri Evening. ..but it was delivered COLD,,,,!.to order is difficult, forget calling you will only get voicemail tell you they only text or order online. They … More Photo 1 in review by Sarah Jackson 1 &pizza - Dupont (Owner) 4 years ago Hey Sarah, thanks for the review and sorry your pies didnt arrive to you in a state we're proud of. If you're up for it, feel free to reach back out and we'd be happy to make it up to you Daniel Ruiz Local Guide·49 reviews·200 photos 4 years ago Great place to eat pizza, fast service, prices are okay, each style is around $10, not so crowed and staff is friendly, very reccomended if you are hungry and looking for something quick. Photo 1 in review by Daniel Ruiz John Yeung Local Guide·130 reviews·151 photos 7 years ago How can you not like &pizza? I come here all the time. Overall it is really good but sometimes the quality is inconsistent. The pizza might be slightly burnt on the edges. The few times I want to buy soda, their machine does not have all the flavors. Photo 1 in review by John Yeung Liam Amiri Local Guide·377 reviews·2368 photos a year ago Decent pizza but don't expect some authentic NYC style pizza. … More Photo 1 in review by Liam Amiri Eddie Hoss Local Guide·268 reviews·74 photos a year ago Dine in | Dinner Oddly enough, some of the best pizza I've had in some time. Visited during the Halloween bar crawl and the three employees were overwhelmed but kept at it. Waited around 45 min for my pizza, but it was worth it. Decent prices and when … More David Dotson Local Guide·146 reviews·574 photos 2 years ago Dine in | Dinner | $10–20 Great pizza & excellent service Both Gluten Free crust & Vegan protein options available (vegan cheese, vegan sausage & chickpeas) … More Photo 1 in review by David Dotson 1 &pizza - Dupont (Owner) 2 years ago Thank you so much for the review David! We're so glad you were able to use our loyalty coupon as well! Ishmael Kamara Local Guide·117 reviews·649 photos a year ago Take out | Dinner | $20–30 &pizza is always great. Went there late on Friday for something to eat. With the crowd from the clubs be prepared to wait and they don't have any indoor seating at that time. Overall you can't go wrong with a personalized pizza from here. … More tshirt tae 7 reviews·6 photos a year ago Pizza was banging line was fast great place custom Pizza Photo 1 in review by tshirt tae Niggle W 14 reviews 6 months ago The store is quiet but the staff is very polite, clean and the pizza came out good. … More Anthony Ayo 4 reviews·1 photo a year ago Lunch | $30–50 Pizza was great! Service was just as awesome! We brought a group of 13 people and Terrence and the crew were happy and helpful. Can’t wait to come back when I’m back in town. … More williampiedra100 3 reviews·1 photo 3 weeks ago NEW Dine in | $10–20 Bryan attended us with great care. … More &pizza - Dupont (Owner) 2 weeks ago Thank you for the 5-star rating! We're thrilled to hear that Bryan took great care of you. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Vannessa Rodello Local Guide·129 reviews·103 photos 4 years ago All the toppings you want and so many options! My only criticism is the crust wasn't as crispy as I'd like. Photo 1 in review by Vannessa Rodello Photo 2 in review by Vannessa Rodello R Bakshi Local Guide·65 reviews·166 photos 6 years ago Excellent pizza and super friendly staff! Photo 1 in review by R Bakshi Photo 2 in review by R Bakshi Krystle Local Guide·107 reviews·224 photos 4 years ago It was really good. But it was sooooo hot in there and took foreverrrrrrr. Pepperoni and bacon. I'm basic lol Photo 1 in review by Krystle Leah Trunsky (raindropAuxilitrix) 1 review 11 months ago Went here with my friends—the pizza was great and the server Chris was super cool! Super friendly. Whoever made the pizza was patient with our orders too. :) Destine Jones 5 reviews 11 months ago Take out | Dinner | $10–20 I came into &Pizza today for lunch and the the staffAndre and Terrace was very helpful polite service was great clean environment fast service I was surprise to see no line so the pizza came out quick and I was able to enjoy it and get … More 1 &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We're thrilled to hear that Andre and Terrace provided helpful and polite service, and that you enjoyed a quick and delicious lunch. Your response is important to us as we strive to improve our services. We appreciate your kind words and hope to see you again soon! Roberts Brian 1 review a year ago I went through this pizza shop last night the service was amazing they were really on point, making sure the customers got everything they needed and more this will definitely be my go to pizza place yours truly Mr.Roberts.. James Drosin 2 reviews 9 months ago Dine in Luis the Manager gave me the best guest experience! Food was amazing definitely recommend. S/O to them! I will definitely be back! Heather Dorsey Local Guide·130 reviews·393 photos 4 years ago The American honey pizza is really good. And the cereal milk soda tastes exactly like cereal milk. So. Service with a snarl. Photo 1 in review by Heather Dorsey &pizza - Dupont (Owner) 4 years ago Thanks for the review Heather! :) Kate Farrell Stanford 4 reviews·2 photos 11 months ago When I walked in, no one was in there and it smelled terrible, as if the floor had been mopped with dirty toilet water. We couldn't imagine staying in there long enough to order, let alone eat. … More 2 &pizza - Dupont (Owner) 11 months ago We apologize that our service did not satisfy your expectations. We set a high standard for ourselves and are truly sorry to hear that standard was not met in your interaction with our business. Your happiness is our number one priority. We well take your feedback into consideration. Jason Miller Local Guide·401 reviews·14 photos 2 years ago Take out | Lunch | $30–50 I love &pizza and usually get awesome service however, this visit to this location was lagging. The 2 staff were seemingly working against each other and they burnt mine and my other 2 family members pizzas. I … More Michael Green Local Guide·113 reviews·665 photos a year ago Dine in | Dinner | $10–20 Flat bread pizza made your way. Staff was fun and engaging. Food was great and was more than enough. Large enough to share but on a hungry day good enough to keep it for yourself. … More Nadia M 8 reviews·4 photos a year ago Normally I’m a huge fan of &Pizza, but this location is so severely understaffed during rush hours that it has proven actually impossible to get the pizzas we ordered. The &pizza website said our order would be ready within 15-20 minutes, … More 1 Chandrell Christopher 7 reviews·3 photos 2 years ago Service was great! Really nice employees, loved syncere and lavell were amazing! Photo 1 in review by Chandrell Christopher Jlyne B Local Guide·63 reviews·14 photos 4 years ago Got a gluten free American honey and oh my goodness I wish there was one closer to where I live. Incredible tasting food and the soda was really good as well. I gave it four because a few of the toppings didn't look very fresh (wilted … More 1 &pizza - Dupont (Owner) 4 years ago Thanks for the review! :) Jamon Pulliam 2 reviews 2 years ago This location is hands down the best! I was visiting from Los Angeles and the service here was impeccable! And don’t get me started on the pizza! They took their time and put nothing but ingredients and love in that one. Would definitely recommend Dean Albrecht 3 reviews a year ago Take out | Dinner | $10–20 Excellent food with great service. Andre helped me make the right choice. Would recommend to anyone who’s in DC and wants something quick to eat. 1 Esse Darden Local Guide·287 reviews·551 photos 2 years ago Take out | Dinner | $10–20 Ordered the Manhattan, while waiting for my personalized order being made - which I received after noticing a distinctive stinginess with every topping that was applied before it was put in the oven, an excessive prolonged period of time; … More 1 &pizza - Dupont (Owner) 2 years ago Thank you for taking the time to share your feedback. We set a high standard for ourselves, and we’re so sorry to hear that this was not displayed during your visit at our location. Your feedback is important to us and we’ll make sure to make the proper adjustments for next time. I’m also going to send this feedback to the shop and district leader to address with the team there because this isn’t what we want our guests to experience at all. We hope that your next visit with us is nothing like what you experienced recently! Scott C Local Guide·33 reviews·9 photos 3 years ago Great pizza and garlic knots! Not your typical style but still quite special and worth trying...over and over again! The dough and toppings are always on point! I also appreciated their program to help frontline workers. Highly highly recommended! 1 &pizza - Dupont (Owner) 3 years ago Thanks for the review Scott! We had to try something different this time. We hope you enjoyed it though! Sean Local Guide·61 reviews·42 photos 2 years ago Take out | Dinner | $30–50 We got delivery. Late night. Pizzas were not good. Got It for a party and we all laughed at how bad it was, and how small they were in the box. (And they forgot one of our items.) all that and only a 1.5 hour wait. Haha. Only reason for the extra star (instead of just 1) was the cookies were really good! … More 1 Kiran Singh Local Guide·70 reviews·66 photos 4 years ago The pizza here is so delicious! The crust is flavorful and tasty and the tomato sauce is so deliciously tangy. I was really blown away by the quality & taste of the pizza! Their ingredients taste fresh and you can add as many toppings as … More &pizza - Dupont (Owner) 4 years ago Thank you so much!🖤🍕🖤 Michael Cupertino Local Guide·106 reviews·163 photos 4 years ago I don't know if it was an "off day" here, but service was so slow we had to leave. There were 3 people in front of us and we waited 20 minutes before we left. The employee was more concerned about cutting a 1/4 of an inch of crust off of … More Jessica Peters 12 reviews·6 photos 5 years ago The pizza at & pizza is great. That’s why I have been coming back for years. However beware of the customer service. Recently at the DuPont location, I enjoyed a great pizza and needed to use the restroom. When I asked an employee who was … More 2 Alok Sinha Local Guide·58 reviews a year ago Stopped by here and this is a great place for pizza. I ordered the new G and added some spicy honey and it was delicious. Would definitely recommend stopping by here if you have a chance. &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We're thrilled to hear that you enjoyed the new G pizza with added spicy honey. Your response is important to us as we strive to improve our services. We appreciate your recommendation and look forward to serving you again soon! S G Local Guide·12 reviews a year ago Amazing pizza and unique experience. Build your own pizza to a new level. Fresh toppings and an amazing taste. The place is small but the tastw is huge. Loved the food and the service. A definite must. Claire Mizutani Local Guide·54 reviews·374 photos a year ago Take out I got four pizzas to take back to my family:The Maverick, CBR, Billie, and Kalamata Harris. Two of them were on gluten-free crust. Ordering was pretty hectic because there were many young people coming to eat between going to different bars … More 2 Wanda Murphy 33 reviews 2 years ago This was the worst pizza I have ever purchased from & Pizza. The person in front of me, ordered four pizzas. They should have removed my pizza promptly. Instead, the crust is burnt, the spinach dry and the other vegetables dried out. … More &pizza - Dupont (Owner) 2 years ago Terribly sorry to hear about your experience Wanda! We have reported this information to our senior management to resolve and to take the proper measure for quality control. You can send us an additional message at 200-03 or send us an email at [email protected]. Thank you again for bringing this to our attention. Robyn J Local Guide·54 reviews 5 years ago Absolutely the best pizza I have every eaten. The bread was amazingly light and doughy. I didn't have the disgustingly full feeling after eating an entire pizza. The toppings were fresh and delicious and unlimited. Love the healthy choices and sauce variety. 1 &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We're thrilled to hear that you enjoyed our pizza, especially the light and doughy crust and fresh, unlimited toppings. We're glad you appreciate our healthy choices and sauce variety. Your response is important to us as we strive to improve our services. A G 10 reviews a year ago I’m literally in this place as of 06/06/22 and it just took me a whole hour to get a pizza which is ridiculous! Low staff and no sense if urgency. Felt bad for the employee up front who seemed suer overwhelmed, pizza is good usually but won’t be back at this location. &pizza - Dupont (Owner) a year ago Hey Andy! Thanks for you review. We are sorry to hear that we did not provide the best experience! Please reach out to us at 200-03 so we can make this right. 🍕 Timur Plavan Local Guide·97 reviews·278 photos a year ago Dine in | $20–30 The most inefficient &pizza I've ever tried in my life. Ordered online, came 30 mins later and waited for another 50 minutes. Order was missing things in both pizzas. &pizza is great but I would avoid this location. … More Natalia Diaz Torres 1 review·1 photo 2 years ago If I could give 0 stars, I would. This review is based on an UberEats order. I ordered 4 pizzas and an order of … More Photo 1 in review by Natalia Diaz Torres Rishi M Local Guide·9 reviews·22 photos 2 years ago Visited late September 2021 for an online pickup order. Waited 2 hours for my order. … More 1 Michel Louis Local Guide·16 reviews·2 photos 2 years ago Take out | Dinner | $10–20 One of the best pizza I ever tried Photo 1 in review by Michel Louis Rachel Wortmann Local Guide·61 reviews·173 photos 2 years ago Ordered online and waited 45 min for my pizza. App had said it would take 10 min so was quite frustrating … More Kristen Eggleston Local Guide·50 reviews·8 photos 4 years ago The pizza is great but the service here could be a bit better. I went at a time where it wasn't busy at all. The woman who made my order was friendly and helpful and while my order was cooking, I sat at a table nearby. The woman who was at … More Jéssica Bittencourt 1 review·1 photo 2 years ago Lavelle great service, thank you! Photo 1 in review by Jéssica Bittencourt 1 Matt Ramey 3 reviews 11 months ago Dine in | Dinner | $1–10 We went in to have wholesome family dinner experience but quickly exited upon my initial smell test which returned a result consisting of bathroom juices/putrid garbage. 2 Matthew Cantisani 2 reviews a year ago Dine in | Dinner | $10–20 Excellent service!! Food was delicious and made quickly. I will definitely come back to this &pizza location! De Wheeler-Chopan 10 reviews 7 months ago Worst experience ever! Pizza wasn't ready to order. The servers states they didn't care that we waited! … More Stefan Hovy 5 reviews 6 years ago Incredible! Was in DC for a long weekend and ended up going to &pizza 3 times! Twice at this location where the staff and manager were very friendly and open for a chat. Not to mention the delicious pizza with equally delicious vegan options. Would recommend this to anyone visiting DC! 1 Joey Norris 4 reviews a year ago Take out | Dinner | $10–20 Andre was such a great help and made sure to treat us right with amazing pizza. Appreciate the amazing service and will gladly go again. S. T. Grandy 19 reviews·6 photos 4 years ago The pizza is good but I was a bit disappointed to see that the employee who made my pizza only put a racing stripe of sauce right down the middle of the dough. Literally a line down...not spread at all. Also, they may need to turn the ovens … More 1 Monte' Kent 2 reviews a year ago Andre at &pizza DuPont south was amazing.. helped me with my gift card at this location. He service and attention to detail was great. Must go location. Thanks Andre! Sameer Singhal Local Guide·41 reviews·8 photos 7 years ago Great at any time of day. This is a unique pizza experience, and I love the fact that you can customize your pizza to your liking for one flat price. Definitely a place to try, and you'll most likely want to keep coming back Cecilia Demoski 1 review 11 months ago Take out | Dinner | $10–20 This is a great place to grab some great pizza! Amazing service and good quality pizza. Miracle Parish Local Guide·75 reviews·6 photos a year ago I will be filing a police report against the fair skinned man with dreads. He put his hands on me multiple times when I was trying to exit the building. The entire line saw it and they were appalled. I was trying to get to my Uber and he … More Ali A Local Guide·691 reviews·435 photos 4 years ago Delicious, but higher prices than their quality. Crowded around noon time, my experience of course. Employees are ok, but they can be much better. … More Brie Morgan 5 reviews 2 years ago I been coming to this pizza spot for a few months and their always respectful and clean They have awesome pizza and the best customer service the manager always takes care of me and makes sure my pizza is hot and ready to go no complaints will continue to send friends and family India Marshall 28 reviews 2 years ago Employees are nice but mangers need to do a better job with organizing during rush hour. Bathrooms are never available for customers. This has been the case for over 5 years. Luis Miron 3 reviews 11 months ago Dine in | Dinner | $10–20 Amazing service by Andre! and delicious pizza. Definitely the place to eat before a night out of drinking. Breanna Duff 9 reviews·1 photo a year ago the security card told me I could not sit down even though I have a disability. There is no rule to this. He was being very rude for no reason. 1 Katie Kennedy 21 reviews 6 years ago The service was terrible here. We were there for the first time and clearly confused but rather than offering help to us, the staff ignored us. They offered no help when we had questions about some dietary restrictions either. And you can't … More 2 Evan Farrara 12 reviews·1 photo 7 years ago Incredibly loud inside to the point that the employees couldn't hear me correctly when ordering. As a result, when asked if I wanted spicy or non-spicy sauce, I replied "non-spicy" and got spicy anyways. That being said, it ended up being … More Mohammed Yahia Local Guide·384 reviews·1524 photos 5 years ago &pizza is a good, simple pizza place. They don't have many choices, just pizzas, but they are awesome. They have a few set pizzas you can order or a make-your-own-pizza option. They also have the option for gluten-free dough which is $3 … More 1 Jobina Beale 3 reviews a year ago Went in there today for lunch and Tay was awesome. Amazing, courteous and good customer service. I walk from Farragut West Metro to get my pizza all because of him. Gideon Tong Local Guide·155 reviews·233 photos 4 years ago Great pizza! Fast service, would go again. As someone from the west coast we also have build your own pizza places like Pieology and Blaze Pizza but this style of "shoebox pizza" is pretty unique and you can definitely eat a whole pizza on your own even if you don't usually eat that much. &pizza - Dupont (Owner) 4 years ago Great to hear. Thanks! Sara R. Local Guide·144 reviews·305 photos a year ago Dine in | Dinner | $10–20 Vegan-friendly, they even gave vegan pizza. I would like to see more filling vegan toppings options like some Beyond Meat or something. The service was quick and friendly. … More 1 cy mcfadgion 3 reviews 3 months ago Quan, cam and bre were amazing … More &pizza - Dupont (Owner) a month ago Thank you for your 5-star rating! We're thrilled to hear that Quan, Cam, and Bre provided amazing service. Your response is important to us as we strive to improve our services. We look forward to serving you again soon! Khaleel Johns-Watts 58 reviews 10 months ago Best late night dc spot call ahead after 3am if ur with a group and just order all the pizza Emma C Local Guide·83 reviews·85 photos 5 years ago Of all the made-to-order personalized pizza places out there, &pizza has my heart. They offer several delicious dough options including gluten free. All of the toppings are very high quality (get the meatballs!!). After topping, they put it … More 2 A “2Freckles” Oz Local Guide·15 reviews·2 photos 5 years ago I really liked this place, however my second experience here was not like my first. Took me 30 mins to get my order. The cashier was very stressed maybe it was his first day on the job because he did not know how to run the register. The … More Ada Rebecca Smith Local Guide·447 reviews·165 photos a year ago Dine in | Dinner | $10–20 The service was not great, the guy making the pizzas was very slow and wasn't able to find items that should have been easily located(the spinach was empty, he took several minutes looking for it and they were out of spinach). … More Ian Winbrock Local Guide·131 reviews·14 photos 7 years ago I love &pizza. I'm from the West Coast and we have "cook as you wait" pizza places, but nothing on the same level as &pizza. This place is superb. Always greeted by some friendly folks behind the counter and then I either complete one of … More Bill Hipsher Local Guide·41 reviews·987 photos 7 years ago Staff was very nice and pizza we got as ordered was great. The fountain machine was broken so your drink options were limited to can/bottle options for tea/lemonade that they had in a fridge. Ordered a Hawaiian style pizza that was supposed … More 1 Scott Dwyer 12 reviews·1 photo a year ago Great place to get a bite when you out drinking in depot circle. The pizza is awesome, and the prices are better than at the bar. … More Justin Andersen Local Guide·15 reviews a year ago Take out This was the most frustrating experience I've ever been in. Our take out order was over an hour late. And that's the least frustrating part of the night... I don't know if I have the energy to explain everything. Andrea M Local Guide·69 reviews·46 photos a year ago They gave me the wrong pizza. I texted customer service and they said they needed a picture in order to issue a refund. I told them my camera was broken and was not able to take a picture. They told me I couldn't get a full refund without a photograph but they could offer me $5 for a new pizza. Josh Higham Local Guide·148 reviews·84 photos 6 years ago Co-workers had talked this place up, but I found it only decent. I definitely enjoyed the unique soda fountain more than the pizza. Great variety of unique flavors. Pizza was fine but unremarkable. Ariel Holmes 2 reviews 4 years ago James and Deon made my night. I would have been left hungry if it was for the girl up front. But thank you 2 for the lovely service much appreciated. I will remember it & I will be back (during opening hours) thanks again! &pizza - Dupont (Owner) 4 years ago Glad to hear our team solidified your evening (and future visits) with great service. We will be sure share with both James and Deon your kind words! Thanks for stopping by, Ariel! Leanne Quinn 1 review·1 photo 2 years ago Great service and fantastic pizza! Photo 1 in review by Leanne Quinn &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We are thrilled to hear that you enjoyed our fantastic pizza and great service. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Tracey N Local Guide·87 reviews·70 photos 5 years ago Pizza would have been better if it was warmer, but their service was shorthanded..... they had one person taking out the pizza from the oven, boxing it, putting on the finishing garnishes AND ringing up the customers...... that's too … More Theresa Kemp 5 reviews a year ago Dine in | Dinner | $1–10 Andre was fantastic! He served our party fresh, hot, pizza. Thank you for the great customer service. Diana Martinez 3 reviews·2 photos 2 years ago I work nearby and I appreciate that my orders are always done right away and I can quickly just pick up. Great customer service. Very strict on covid regulations. Key 2 reviews 2 years ago Customer service was excellent upon arrival. Store was clean and needs were met in a timely fashion. Very friendly and patient staff. 5 Stars to Terence!! Greg Smith 14 reviews·2 photos 10 months ago Delivery | Lunch | $10–20 Did carry out. Pizza was good, but not great. Strange beverage options … More Bali Adawal Local Guide·203 reviews·1637 photos 4 years ago I have always liked the concept of a highly customized pizza and the overall product turns out to be quite appealing. … More 2 Aleks Nekrasov 91 reviews·67 photos 11 months ago As far as GOOD pizza goes, this place completed my order in 8 minutes. &pizza - Dupont (Owner) 11 months ago Thanks for the awesome review! Hope to see you soon. Gnelossi Hamadou Local Guide·6 reviews·7 photos a year ago Visited this place yesterday for my first time , just wanna say thank you for the entire team that work yesterday night. They were patient and friendly specially the manager Andre Cecilia Local Guide·80 reviews·2 photos 5 years ago We had a pleasant experience at a different branch of &pizza so we tried this branch. This branch was stingy on the toppings and the dining area was not wiped down after customers have eaten there. All 3 of us felt queasy after eating here... Josh Eid-Ries 10 reviews·3 photos 6 years ago Delish, super affordable and very easy to customize your order with no upcharges. The staff are a delight and the food is superb. The drink offerings are also wonderful. I'd recommend the 11 grain crust(ask for it) the mango passion fruit soda and root beer. Vegan cheese and veggie based protein options were a lovely bonus! Pradipto Banerjee Local Guide·29 reviews·96 photos 7 years ago Their pizzas are the best value for money. Unlimited toppings on a big flat bread for just $10. And they're open till 4 am, which is great when you're leaving the bars at 2 and want to get some food. NAI- NAI 3 reviews 2 years ago Dupont is awesome. The place is clean and the pizza is great! One of the workers Decostia provided excellent customer service! I definitely recommend this store! Jaqueline Veltri 2 reviews 4 years ago The pizza here is delicious but it is the second time in a row that I find a long black hair in my pizza. It’s so frustrating and disgusting! I hope management finds a way to keep the employees hair out of the food. F.A. B Local Guide·39 reviews·15 photos 4 years ago James was an amazing manager. My card wasn't working for some reason and he still made my pizza and gave it to me for free. Absolutely amazing customer service! Thank you James! &pizza - Dupont (Owner) 4 years ago Hey there! Thanks so much for the love. We always appreciate our loyal fans. Sunil Singh Local Guide·183 reviews·134 photos 5 years ago &Pizza is something like Blaze Pizza. You pick your dough, then the sauces, and then all your toppings. It's unlimited sauces, and unlimited toppings. And after the pizza is baked, you can add any other sauces, or other toppings. And … More breathemusic94 2 reviews a year ago I love coming to this &pizza, Tay is always a welcome face at this establishment, he is extremely helpful and all around fun to talk to. The food is always amazing here. Crystal 1 review·1 photo 2 years ago &pizza Great good and atmosphere, staff was friendly Photo 1 in review by Crystal Thomas Scheurich Local Guide·33 reviews·1 photo 6 years ago I really like the new fast casual trend. Others may complain about it, but it matches my lifestyle and sets a good middle ground on price. &pizza is the best example of fast casual in this region. Really awesome and ultra customizable food … More Oliver Borg 11 reviews a year ago Andre was super helpful! Fantastic late night spot, quick service, friendly staff, and good food. What more could you want. Dale L. Roberts Local Guide·52 reviews·118 photos 6 years ago This is the second &pizza I've gone to today and wow! This place is even better. There's more seating and it's not even busy. Well worth it! And the staff was friendly and attentive. 5+ stars Nibha Rastogi 7 reviews·2 photos 5 years ago ordered a craft your own... SO GOOD!!! The tribe were super courteous and I got what I wanted. Got a traditional with mushrooms, spicy Italian sausage, onions, pesto finish. Jordi Segura Local Guide·115 reviews·366 photos 7 years ago We ate in this pizza shop during our trip to Washington, and we found the pizza and drinks tasty and original. You can make your own pizza or order one of the existing recipes. I would recommend it for take out or a quick bite. Brandon Boone Local Guide·377 reviews·1050 photos 4 years ago Quick and delicious lunch, very filling and I'm a big guy. Definitely mix it up don't settle for cheese and pepperoni... Never thought I'd have honey on a pizza. &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We're thrilled to hear that you enjoyed our unique pizza options. Your response is important to us as we strive to improve our services. We hope to serve you again soon with more delicious and filling options! ROBIN THOMPSON Local Guide·94 reviews·221 photos 6 years ago I love this place! They have a great pizza selection . I love their specialty sodas. Try the cream soda. There is a wait though due to their being only one person to ring up your order and box your pizza. T Williams 9 reviews 4 years ago Best way to order a to go pizza is on their website. After a long day of sightseeing, a couple of their "oblong" pizzas was just right. Thin crust was great, toppings good. Prepared quickly. &pizza - Dupont (Owner) 4 years ago Thanks for the review and for stopping by, T! Ashley Craft 4 reviews 2 years ago I love The Dupont Team everyone is so nice Tay always goes above and beyond for the customers amazing customer service!! DuPont Team keep up the great work!! Jelani Phipps 8 reviews 2 years ago Food is so delicious. The manager Delonta gave me supervisor service. I would definitely go back again. You won't be disappointed!!! Nely Hernández 2 reviews·1 photo 10 months ago Love this late location . Super busy They are still very patient with customers. Lance Porciuncula 1 review 2 years ago The workers there are super friendly and nice. The service was also pretty great. Got my pizza with little wait. Ismail Gomaa Local Guide·364 reviews·1240 photos 7 years ago Some of the best pizza I've ever had. Any combination worked because their ingredients are absolutely perfect. I enjoyed everything I've tried there, even the stuff I don't usually like. Sarah Semlear Local Guide·154 reviews·1292 photos 5 years ago The gluten free crust is pretty good! It's not a completely gf environment so they can't guarantee there is no cross contamination, but they are careful and change gloves when handling the gf crust. The options are fun and there is a good amount of toping choices for build your own. 1 &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We understand the importance of providing a safe environment for our gluten-free customers and we're glad to hear that you appreciated our efforts. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Michael williamson 9 reviews a year ago Take out | Lunch | $10–20 Pizzas are not that good and one of the workers not that friendly pizza crust had sir burnt from dirty oven … More Jennifer Telfort 4 reviews 2 years ago The service is great! Thank you so much for making my pizza just the way I like it!! I will be back again!!! Hailey Gruch 7 reviews a year ago Take out Wonderful experience... it was busy but they made me feel at ease... wonderful service... thanks to Quan, Malik, Justin and faith William Minter Local Guide·85 reviews·79 photos 7 years ago Thin crunchy crust that isn't overcooked. Awesome fresh toppings and sauce. Perfect for lunch or later night special. Not the best place to sit and eat as space is limited inside(20-25 at best) Cameron Asgharpour 1 review 2 years ago Great customer service and staff is very attentive. Pizza was awesome LadyLewis 2u Local Guide·17 reviews·15 photos 5 years ago &pizza is my fav pizza, but unfortunately, I experienced the WORST, not just customer service, but attitudes EVER! When I asked for assistance, I was only given the 202 number they have taped on the glass display. It was weird bc 2 … More Angel Aguiluz 1 review a year ago Tay is a hell of a entrepreneur! A lovely lad, Marcia also made an astonishing pizza with Nikko. 10/10 if you’re near Faragut North Rakia Pinkney 3 reviews 2 years ago The staff are very friendly and the food came out great and in a timely manner. I will be back, this is the best &pizza location! Dante Gardner 1 review 2 years ago I had an amazing experience. Antonio, and Roshan were very accommodating to my child who is particular about his pizza topping’s . 1 Scott Jason Local Guide·38 reviews·46 photos 4 years ago Thin crust pizza was very tasty and filling. I had red sauce with fresh mozzarella, tomatoes and onions. They do have a gluten free crust for $3 extra. 1 Chris Morris Local Guide·49 reviews·25 photos 4 years ago Pizza was way better than expected. Really nice staff. They were able to get people in and out quickly. I will definitely be returning. 1 &pizza - Dupont (Owner) 4 years ago Thanks for the review :) Raynell Jackson 26 reviews·26 photos 4 years ago I pizza and staff are wonderful Photo 1 in review by Raynell Jackson Photo 2 in review by Raynell Jackson Killian Devitt Local Guide·128 reviews·541 photos 8 years ago What's not to like about this place? It's just great, simple pizza. Tried the Maverick the first time I went and I haven't ordered anything else since. Perfect for lunch if you can avoid the rush. &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We're thrilled to hear that you enjoyed our Maverick pizza and that it's become your go-to choice. We appreciate your support and hope to serve you again soon. Your response is important to us as we strive to improve our services. taliyah hughes 4 reviews 2 years ago Great customer service, quick service! FOOD IS AMAZING! My favorite spot to come after a drunk night 🤪. Highly recommended Mo Love 38 reviews 3 years ago I went in there for the first time a couple of weeks ago. The restaurant had a really foul odor and I could smell it through my mask. Although, I ordered a pizza online and picked it up, I did not eat it and I will never go back to that pizzeria. 1 &pizza - Dupont (Owner) 3 years ago Thank you for taking the time to share your feedback Mo. Our management team will be looking into the odor that you are referring to for the Dupont location. I'm sorry to hear that the experience did not meet your expectations and I would like to apologize for this. Chris Oliver Local Guide·17 reviews·1 photo 8 years ago Great customisable pizza in a relaxed atmosphere. Their home made cola is to die for and so much tastier than coke or Pepsi. Only criticism is that the music was way too loud. Amanda Neilson 6 reviews 2 years ago Great experience! We had a large group and they were fast and efficient. Love the pizza! Breasia Lawson 5 reviews·1 photo 2 years ago Labella made my pizza so good and had the best costumer service ever, he was very bubbly and pleasant and Met all of my demands because I’m a very picky eater lol he’s the best Adriana Lopez 5 reviews 11 months ago Great service! Everything was on point! Andrew was very attentive and polite! Thank you 😃 Merlin Tondji 2 reviews 2 years ago This place is great . Unfortunately last night we couldn't custom the pizza however the team still amazing Briana McKellery 9 reviews·5 photos 2 years ago Beat servers best pizzas and my fav location but all are great. Definitely suggest stopping here for a late night craving after a night out! Tiffany Dendy 3 reviews a year ago Dine in | Dinner | $20–30 Wave and Twan provided excellent customer service on my visit. Gloves were changed prior to assisting us Thanks guys ! Micheal Stone 2 reviews 2 years ago Team was friendly with great service. Pizza came out great! Will continue to come back Forrice Brunson 1 review a year ago Courteous and professional staff members. My order was completed without issues. It was fresh, hot, and the toppings were 🤌🏽. Saee’Rozay 1 review a year ago Take out | Dinner | $10–20 First Time At &Pizza . Great Service By Andre ! Respectful & Kind . Will Definitely Be Back Especially At This Location Medachi 509 16 reviews 4 years ago This is the worst & pizza that I’ve ever been they don’t change their gloves. They got nasty attitude they should reconsider on hiring people there. If I’m paying $11 for pizza I should be treated with respect the customer service is terrible I can’t even tell them how I want my pizza to get done. 1 &pizza - Dupont (Owner) 4 years ago Hi Questa, thanks for the feedback. We'll be sure to address this promptly with the shop. Angel Angelov Local Guide·159 reviews·920 photos 4 years ago A bit dodgy place but pizza was perfect. They offer you to choose from anything you want to add to it and can make it as you like. Was really delicious. Not beer or any liquor though 1 Nataliya Kostiw 2 reviews a year ago Alonzo was amazing, he helped us with everything and was very polite and informative! Would definitely recommend! Simply, Tasha. Local Guide·130 reviews·244 photos 5 years ago Idk what the rating I'm assuming it must be great for I'm too drunk to realize food but let me tell you...today I walked in and walked out....the stench was crazy...it smelled like a dirty barn...or zoo...sewage...idk but I couldn't even order to go and I was just dissappointed... it is a super rainy day today.... 2 Kylie Gilbert Local Guide·19 reviews 7 years ago Could eat this every day for the rest of my life. Not a lot of seating inside though. Also check out ordering ahead, it's much faster. The sodas are good too! Josh Robichaud Local Guide·93 reviews·123 photos 8 years ago Great custom pizza at a reasonable price. Either the preset menu or build your own, can't go wrong. Plenty of seating and fast service. Andrew Isett Local Guide·185 reviews·230 photos 7 years ago Good pizza custom made the way you like. Similar to Chipotle with a burrito, &pizza allows for any toppings they have and different sauces. Always some left over too!! Ethan Granetz 3 reviews a year ago Take out | Dinner | $10–20 Andre got us food real late. He made an awesome pizza. 10/10 service J 4 Local Guide·131 reviews·64 photos 7 years ago Oh yes lawd. This pizza is so good and u dictate the toppings. Yum. Decent price for DC and a food serving size. Not glutinous but more than sufficient. Arely Castro 1 review 2 years ago Amazing service ! & the pizza was so delicious that I will come back again! Jimmy DeVault 15 reviews·1 photo 5 years ago Great food, concept and atmosphere. First time at this location and this may just be this location but service was super slow! The team here also seemed very disorganized, there was no designated cashier which caused a bottleneck at the register where everyone just stood. Maybe they were short staffed? 1 Destiny Cruz 3 reviews 2 years ago GREAT service! And even better pizza! This is my regular location Bc they never disappoint 😉 Punky Banks 1 review 4 years ago I had a great experience. Our cashier Diamond was kind, courteous, and offered great recommendations. I’ll be back soon. Overall great food and great service! &pizza - Dupont (Owner) 4 years ago Thank you so much for the great review Punky! We look forward to seeing you agin soon. Kevin S 3 reviews 2 years ago This is specifically for the website ordering experience. I typically pick up but I needed delivery and my nearby &pizza store was temporarily closed. The problem is that it is impossible to switch the store you're getting delivery from, or … More 1 &pizza - Dupont (Owner) 2 years ago Thank you for your feedback Kevin! I'm sorry to hear that this was your experience trying to order online. We'll flag this information over to our development team to fix. Najm Aldin 9 reviews 9 months ago Luis is very professional and he took care of me. Very nice guy Samantha Zarrilli Local Guide·25 reviews·2 photos 2 years ago Amazing service! So great. Lavelle went above and beyond to make us feel welcome. Promote him!! . Jeremy R. Stinson Local Guide·178 reviews·293 photos 4 years ago &Pizza is one of my favorite pizza joints in DC. Not all locations are created equal, but this particular location is always clean, the staff is friendly and helpful, and I never have to wait too long. &pizza - Dupont (Owner) 4 years ago Hey, Jeremy. Thanks so much for review! руня 11 reviews 7 years ago Great vegan options, (they have mozzarella daiya and veg meat crumbles)! Lots of fresh veggies, good unique gourmet choices of sauce too. The pesto is delicious. The price is reasonable for a vegan pizza, compared to zpizza which recently … More 1 Fabian Meneses 5 reviews a year ago Staying at a hotel close by this place has been our stop daily! From the friendly staff to the delicious food, you have to try this pizza! Mouhamadou Thioune 4 reviews a year ago I like eating at &pizza Dupont. The pizza is always on point. The place is always clean and Tay always provides good customer service. Reilly Sheehy 1 review a year ago They were so lovely - they gave me free water when my friend and I needed it most. 10/10 Ryan Norton 7 reviews 7 years ago I tried calling multiple times to have a question about their menu answered. Each time it automatically goes to a recording and it gives you the option to press "2" to speak to an employee. However when you choose that option the phone … More Geneva Kropper 4 reviews 4 years ago The pizza here is fine, but the staff is very rude and will let you stand at the counter without asking how they can help you. Very poor standard of hospitality and out of place in DC. nate porter 2 reviews a year ago Tay is the best. I love the customer service. He should be promoted. Nikko & Marciara are amazing and should also be promoted!! Isaiah Benjamin 3 reviews 2 years ago I always have a great experience, I work in the area the workers are always fantastic to chat with. Food is always delicious, my go to spot for lunch. Angelica Martinez Local Guide·54 reviews·115 photos 4 years ago Stopped by this place when in the area. Design your own pizza from scratch, and then customize it. The staff assemble your pizza as you watch ... you get to decide everything which goes on the pizza as you follow it down the line. We … More 1 Ariana Brown 3 reviews 2 years ago Very professional clean and made my pizza in a timely manner. Staff was perfect Levon Akopian 8 reviews a year ago Dine in | Other | $10–20 It was amazing and tasty Perfect pizzas, friendly crew … More Jamie Sneed 1 review 2 years ago Outstanding place, great service, Terrence was a huge help and help me build the perfect pizza for my first time!! Teezy Teez 2 reviews a year ago The establishment was amazing, Tay was very kind and ensured we were okay during our time at the restaurant. &pizza - Dupont (Owner) 2 months ago We're thrilled to hear that you had an amazing experience at our restaurant and that Tay took great care of you. Your response is important to us as we strive to improve our services. Thank you for the 5-star rating! We hope to welcome you back soon. kiara cooper 1 review 2 years ago I experience the best customer service with an employee name Lavelle! Definitely would recommend. The pizza was amazing !! Lisa Smith 5 reviews 2 years ago They have an excellent menu selection and you can add anything else you desire... or you can build your pizza from scratch... all at one reasonable price! Delightfully Delicious 👍 2 &pizza - Dupont (Owner) 4 years ago Thanks for the review! :) M A Local Guide·31 reviews·16 photos a year ago The vegan mozzarella and vegan sausage are amazing. To &pizza: please bring back the vegan chicken. Chris Anderson Local Guide·36 reviews·182 photos a year ago Not extremely friendly but excellent excellent pizza. The dough is the best part. 1 Sachin Bhattiprolu 2 reviews a year ago They take orders beyond 10pm but you cannot eat there because they close at 10pm. People here were incredibly rude and forcibly removed chairs WHILE 10+ people were trying to sit and eat. Incredibly rude place. Blue Moon 4 reviews 7 years ago literally the best pizza i've ever eaten. i had the vegan options. they were incredible.staff was really nice. would recommend to everyone. It’s Me Local Guide·381 reviews·169 photos 7 years ago As usual, friendly staff. First time at Dupont location, but just as good as the H St one. … More &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We regret that we no longer offer San Pellegrino and apologize for any inconvenience caused. Your response is important to us as we strive to improve our services. We appreciate your feedback and hope to see you again soon! Quennitta Winzor 1 review 2 years ago The manager is wonderful and fast. But I feel like they were catering to the white people. I almost felt invisible. Darlene Craft 4 reviews 2 years ago I love coming here the manager Tay always knows exactly what the customer service at DuPont is beyond amazing :) Sinceree Stewart 2 reviews·1 photo 2 years ago Great customer service and very patient. Photo 1 in review by Sinceree Stewart lizzle thrvxxx 2 reviews a year ago Andre was very helpful I been goin here for about and year and the customer service is great 10/10 Jas 3 reviews 2 years ago Best pizza I’ve ever had and the workers are the nicest people ever!!!! Come here for a quick bite! &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We're thrilled to hear that you enjoyed our pizza and had a great experience with our staff. Your response is important to us as we strive to improve our services. We hope to see you again soon for another quick bite! Jalen Dixon 1 review a year ago Great service and very reasonable prices! The pizza is also prepared very quickly! Candice Mulholland 4 reviews 2 years ago Terence was awesome! They are always quick and so friendly when I’m in there. 10/10 on the pizza too 😊 Tim Larkin Local Guide·72 reviews·226 photos 5 years ago Damn, this is good pizza Photo 1 in review by Tim Larkin Ron Hagage Local Guide·87 reviews·83 photos 5 years ago Subpar and overpriced pizza place. Compared to u street pizza joints, this place is trendy, hipster and serves mediocre pizza at best. … More 1 Dj Teck Entertainment 1 review 2 years ago Quick and easy. Best pizza I’ve every had. Especially after the club. Will be back Adam Christensen Local Guide·71 reviews·326 photos 8 months ago No way to reach the store and UberEats never delivered my food. … More Erika R. Local Guide·50 reviews·18 photos 5 years ago Reminds me if Blaze. Make your own pizza and craft soda, but some of those toppings should. DEFINITELY go on the pizza as it's being cooked not at the end. Beyond the Clubhouse 1 review a year ago The staff here did a great job, very attentive and engaging. Especially Antonio. A wonferful customer experience! Ryan Local Guide·12 reviews 2 years ago Take out | Dinner | $10–20 Made a mistake when placing my order online and Antonio was awesome helping me get it corrected quickly and courteously. Will Return! … More Alfredo Schonborn 3 reviews a year ago Dine in | Dinner | $10–20 This place was a fantastic establishment to eat with quality food. A recommendation to everyone Ryan Dudrow 1 review 2 years ago Great service for an amazing price for a whole pizza awesome employees 10/10 would recommend Briana Jones 1 review 2 years ago I go to this location all the time! Great customer service and the pizza is always perfect! Haylee Smith 1 review a year ago Awesome pizza & employees. Has original drinks that all taste good! Justin Adams 8 reviews 4 years ago 1st time here. The food was great and the price was right. No complaints. Wish I had found this place sooner. Trip Taker 117 reviews·58 photos 2 years ago I'd like to give it a .5 star. Says that it's open but door is locked, lights are on and you can see employees inside working. Stephen Oliver Local Guide·13 reviews·17 photos 6 years ago Greeted by smells of rancid food or trash when entering. Smell intensifies as you walk further in. Trash everywhere and dirty tables. Bathrooms out of order. … More William Nelson 2 reviews 2 years ago great location! everyone here had great service and the pizza was good! 🙌🏽 Clementina Fernandez Valle 4 reviews·7 photos 2 years ago Great service and really quick. The pizza was delicious and the place is really nice. Jade Boone 2 reviews 2 years ago Staff was very friendly and efficient with taking customers orders in a timely manner! Will definitely visit again Quita11 2 reviews a year ago Terrence was awesome!!! He answered any question I had and did it with a great sense of humor. Marcus Smith Local Guide·115 reviews·5 photos 3 years ago The staff was polite, and efficient this staff is prepared for lunch rush, I even got a bottle of water Since I do a lot of delivery work, I really appreciate these things. 1 &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating and positive feedback! We're glad to hear that you had a great experience with our staff and that the service was efficient. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Marissa Amore Local Guide·57 reviews·13 photos 5 years ago It’s pizza & it’s good. Need I say more? Great location by clubs and night life. Great place to grab a bite on the late night Michael Smalls 2 reviews 2 years ago Fantastic experience! The service was excellent and I love their pizza. &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We're thrilled to hear about your fantastic experience and love for our pizza. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Hycent Nwaneri 1 review 2 years ago Great service!! Antonio really helped me and made sure everything was taken care of for me! Definitely will be back. &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We're thrilled to hear that Antonio provided great service and made sure everything was taken care of for you. Your response is important to us as we strive to improve our services. We look forward to welcoming you back soon! Alan Harris Local Guide·151 reviews·259 photos 6 years ago It was late when I went but it was still a great pizza. I could tell the associates were ready to go but appreciated the pizza. Will come again. Isaiah “Zay” West 1 review 2 years ago We came on Christmas Eve and the service was phenomenal! Antonio and Brian were great! Thank you &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We're thrilled to hear that Antonio and Brian provided phenomenal service on Christmas Eve. Your response is important to us as we strive to improve our services. We hope to have the pleasure of serving you again soon. Ryan Stevens 10 reviews 4 years ago Truly the worst experience . The all male staff associated with the shift on December 6th, at 12:22 am was extremely rude. Customer service was just extremely poor. &pizza - Dupont (Owner) 4 years ago Hey Ryan, I'm really sorry about your experience. We'd love to hear some more details about it if you can reach out to us on our text line, 200-03. Aja Clark 11 reviews 2 years ago Service was excellent! Came to this one because the one in Georgetown was closed. Brian and Antonio were really helpful and pleasant. Beverly Barber 4 reviews·2 photos 2 years ago The staff was very helpful with everything I needed and also made sure I was safe by giving me a mask to protect myself❤️ Patricia Babb 7 reviews 2 years ago Staff was very friendly and accommodating and the pizza was exceptional. Great location :) stefanie riggins 5 reviews 7 years ago Amazingly friendly staff! Our first dining experience in DC and we plan to hit them up again!!! Fresh deliciousness! LynDale Lewis Local Guide·159 reviews·358 photos 4 years ago Good pizza... one size, so be prepared to share if you don't easy a small pizza yourself. Simple menu. &pizza - Dupont (Owner) 4 years ago Hey there! Thanks so much for the love. We always appreciate our loyal fans. Renuka Joshi 3 reviews a year ago Dine in | Dinner | $10–20 Great pizza made quickly. The team working here is super nice. tomas moser 2 reviews 2 years ago Wonderful pizza great especially after a night out. Definitely recommend. &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We're glad to hear that you enjoyed the pizza, especially after a night out. Your response is important to us as we strive to improve our services. We hope to serve you again soon. Vanessa Jimenez Local Guide·49 reviews·8 photos 7 years ago Add your favorite toppings to an amazing crust with eclectic soda flavors for a good price. Comfortable, casual atmosphere. Nista Bob-Grey 1 review 2 years ago This &pizza location is great , the staff was super friendly and I got helped really quick! Stephanie Becker Local Guide·70 reviews·76 photos 5 years ago Different pizza place. Still liked it, one pie can feed 2 people if your not real hungry. Unique combinations. 1 Richo Local Guide·18 reviews·24 photos 4 years ago Delicious pizza, Maverick with extra cheese wont dissapoint any meat lover. Open until late is very helpful. &pizza - Dupont (Owner) 4 years ago Good choice with the Maverick Ricardo! Definitely a fan favorite. Thanks for the great review too! Chris Meaclem 4 reviews·1 photo 7 years ago Only $10 for any pizza, custom made. Basically the subway of pizza - choose your base and any toppings. They charge a flat rate, not per topping. Alex B. Local Guide·190 reviews·277 photos 7 years ago Love &pizza. This place stays open late on the weekends but is pretty full of drunk club goers. Still, it hits the spot after some dancing. robert brown 1 review 2 years ago Service at this location was the best I’ve had at any in the DMV area! Definitely will be going again. Amir Ghasdi 11 reviews·15 photos 5 years ago I built my own Pizza: pesto and spicy tomato, mushroom and Tomato, whole mozzarella, Italian sausages, beef, and finishing with goat cheese and arugula and for sure garlic oil!!! Tenija Livingston 1 review 11 months ago Dine in | Lunch | $1–10 Amazing!!! The workers were welcoming and very cheerful. 10/10 Kalaa 3 reviews 2 years ago Very fast pace store love how my pizza tastes perfect every single time. Brendan M. Local Guide·95 reviews·31 photos 5 years ago The pizza is fantastic. the employees are not. I got the feeling they didn't not care about the job or product they were giving customers. Allen Local Guide·288 reviews·819 photos a year ago Very poor service here. I was the only person in line and the employees did not even acknowledge me. They were having a conversation amongst themselves. Dog Matic 1 review a year ago Fast Great service from the two brother working feb 4 at 6pm Danielle Carr 2 reviews 2 years ago The guy who made my pizza made sure it was done right like forreal lol didn’t skimp me and it looks delicious Halio J 16 reviews 5 years ago Terrible customer service. Staf will rush you and slap together a terrible job of a pizza. Management no better. No wonder employees are terrible, management is even worse. Nadeen Siddiqui 6 reviews 5 years ago Terrible service. They just threw toppings without caring about making it tasty. Don’t waste your time and money here. Chose a place that actually tries. 1 Cory Simmons 1 review 2 years ago I got food poisoning. No disrespect to the workers, but my stomach hurts so much and I’m so mad lol. Thompson Hangen Local Guide·36 reviews·9 photos 4 years ago Fast and great pizza! What's not to love about &pizza? The staff here are friendly and accommodating! Christy McCann Local Guide·48 reviews·18 photos 2 years ago Food was not made correctly and a bit late, the secjrry staff is super rude, but employees were nice. Cavin Ward-Caviness Local Guide·319 reviews·769 photos 6 years ago Fresh, quick, tons of toppings, and most importantly tasty. If you have the chance definitely go to one of the many locations and see why all the hype is deserved Esprit Cha 2 reviews a year ago Amazing pizza, amazing service, awesome experience as a whole m g 11 reviews a year ago We bought a pizza and we’re immediately screamed at and tossed out for eating it inside. Like what? The moment I hand you cash you throw me out. I can’t eat my pizza inside? &pizza - Dupont (Owner) a year ago Hi Max. Sorry to read about your experience. Can you text us at 200-03 to provide more detail. Edwin Lopez 5 reviews·2 photos a year ago &pizza is my all-time favorite for a fast casual -- and delicious -- pizza. This location is a mainstay, too! R. T. Local Guide·16 reviews 7 years ago This place was gross!!! Trash everywhere and it smelled pretty bad. There's definitely better &pizza's to go to in DC. I went in and came right back out! 1 Rebecca Schick 32 reviews a year ago Take out | Dinner | $10–20 Very tasty pizza. Staff were great JED CREEK 8 reviews 7 years ago Do not ever go here it's terrible. My friend got food poisoning, so it's not safe to go here. And the management and the staff are terrible and refuse to take responsibility. Avoid this place at all costs! Monae' Bailey 4 reviews 2 years ago Antonio was very helpful, assisted me with ordering my meal. 10/10 would recommend! Kelli Smith 3 reviews 2 years ago I always get the best service here. I live &Pizza and Terrence is great!!! Emily Nelson 1 review 4 years ago Amazing, charismatic staff and even better pizza!! Very creative and innovative pizza and drink choices :-) Josiah Tomes 4 reviews·2 photos a year ago Staff is very nice! Photo 1 in review by Josiah Tomes GLENN EVANS Local Guide·41 reviews 4 years ago DONT WAIST YOUR TIME.OR.MONEY. PLACE WOULDN'T LAST A WEEK IN JERSEY. FIRST I TRIED TO CALL AND THEY DONT TAKE CALLS U HAVE TO ORDER ONLINE OR … More 2 Gucci simon Local Guide·64 reviews·4 photos 4 years ago Food was great. The service was horrible. Only 2 ppl in the store had some manners. The REST HORRIBLE. &pizza - Dupont (Owner) 4 years ago Hi Gucci. Thanks for the feedback. We're sorry that your experience was below expectation. We'll be sure to relay this message to the Shop Lead so that improvements can be made asap. Alyse Edwards 2 reviews 2 years ago Friendly, polite and helpful staff. Pizza is good too duh! C Michele 1 review a year ago Staff is dope. Pizza is delicious. Big fan! Lauren Prather 2 reviews 2 years ago Friendly and helpful! Quick service and the food is 🔥🔥! Lavelle was amazing and super helpful! Amazing customer service! Austin Zielman Local Guide·437 reviews·1539 photos 7 years ago Great pizza served super fast! Downside is that it's directly next to/under sa club, and the constant thumping is quite disturbing. Billy Local Guide·207 reviews·404 photos 7 years ago Cool spot for a flat bread pizza. You make your own pizza which is pretty cool. The price is reasonable one pizza is good for 2ppl. Kenny Culver Local Guide·14 reviews·1 photo 4 years ago pizza was so spicy I couldn't eat it I took it back in I said hey I need a new one I don't know why it's spicy they said tough s*** bounce &pizza - Dupont (Owner) 4 years ago Hey there! I'm so sorry to hear about your bad experience. If you get a chance, please text us on our customer service line at 200-03 and we will make this right. Priya Patel 2 reviews 2 years ago Loved it! Everyone was so accommodating and understanding! Great pizza! Emir Yılkıcı 5 reviews·3 photos 7 years ago They simply blend some cheap ingredients. The food tasted not that good. I don't recommend unless everywhere else is closed. Johnny Neilson 2 reviews 2 years ago Dine in my family loves this place! very good food and friendly staff! Luis Medina (COACHMETONY) Local Guide·97 reviews·324 photos 6 years ago Great food! I'm vegetarian and I had a lot of options here. Only thing is that serving sizes are really small. Chiquita Jackson 1 review 2 years ago Great food and quick service! Loved the garlic knots too. mike epps 3 reviews 2 years ago Great quality pizza, fast and friendly customer service. Dylan McDowell Local Guide·138 reviews·79 photos 7 years ago Best option for a pizza lunch in D.C. This location has more indoor seating, but during prime times be prepared to walk to a nearby park. Kay Tunez 1 review 2 years ago Quey was great and very helpful since it was my first time she made my experience 10 times better. Derrick A. Morton 2 reviews 2 years ago The coolest & Pizza in the DMV everyone in there will make you laugh ! Thank you for my good 🍕 DK Walker 7 reviews 6 years ago Best pizza ever! Far from traditional tasting pizza, leaves a funky delicacy in your mouth that leaves you beyond satisfied! Renee S. Local Guide·55 reviews·4 photos 7 years ago Pretty good! The prices are reasonable (listed at the top of the menu) and pizza is delicious! I ordered the gnaric... good choice! Tray Smith 4 reviews a year ago Great place. Jainyn was great cook. She was nice and quick. Music for every ocation Local Guide·6 reviews·334 photos 5 years ago I love these pizzas Photo 1 in review by Music for every ocation Christopher Edwards 2 reviews 2 years ago I had the best experience. Customer service was A1 and the food was awesome Pauline Abah 1 review a year ago When back to this place after my Last visit and the service is always amazing Nicholas Mildebrath 1 review 2 years ago Go-to lunch spot in DuPont. Pizzas are great and filling - quick service and always good music. Tustin Neilson 6 reviews 2 years ago Dine in | Lunch | $10–20 Quick service and tasty pizza! I recommend adding the hot honey. … More helene h 1 review a year ago Delivery | Dinner Super good pizza, delicious drinks, love it <3 &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We're thrilled to hear that you enjoyed our pizza and drinks. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Jimmy Sambuo 6 reviews·7 photos 2 years ago Fast and friendly service! &pizza is my goto pizza place. Marquis Savant 1 review a year ago Delivery | Lunch Waited over 30 min for a delivery while the employees traded food with shake shack Gabriel Marín 7 reviews·1 photo a year ago Lovely place and pizza is great!! Tay was a complete gentleman. &pizza - Dupont (Owner) 2 months ago We appreciate your 5-star rating! We're glad you enjoyed the pizza and the service provided by Tay. Your response is important to us as we strive to improve our services. Thank you for taking the time to share your experience with us. Messaijah Shillingford 2 reviews a year ago The food was great! Tae gave wonderful customer service! &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We're thrilled to hear that you enjoyed the food and received wonderful customer service from Tae. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Donald Jackson 7 reviews a year ago Dine in | Lunch | $10–20 Love how the pizza is made on the spot, fresh ingredients and creative mixes Talisha Harris 4 reviews 2 years ago Terence was great! Ever want great pizza and good vibes, come to Dupont location! Corey DeAngelis Local Guide·204 reviews·623 photos 7 years ago Best custom pizza ever Photo 1 in review by Corey DeAngelis Frankie B 1 review 2 years ago Absolutely love this place. Service is quick and food is great Kaylah B Local Guide·48 reviews·18 photos a year ago Take out | Dinner | $10–20 Super fresh, super quick service even though it was very busy! Anna zakharchishin 1 review a year ago Other | $10–20 Alonzo was the absolute best. Should definitely be running the place! Baylee Childress 2 reviews 5 years ago Love this place. Always delicious. Staff is always friendly. Tyler is a bit of a Chav. Tsvetelina Petkova Local Guide·99 reviews·147 photos 4 years ago Really kice and tasty pizza. Affordable price and you choose your topics. Basically you choose your pizza from scratch. Yummy. &pizza - Dupont (Owner) 4 years ago Glad you enjoy the concept Tsvetelina! And thanks for dropping a review! Steve Murphy Local Guide·43 reviews·417 photos 5 years ago Good, quick pizza while you wait. Not as good as wood burning oven etc, but satisfies... James Papanestor Local Guide·88 reviews·574 photos 2 years ago Thin crust and the choices for the toppings are not like any other! Went three times in one week. Tarikah Omar 3 reviews 6 years ago Pizza was fantastic, service was awesome, there was an unpleasant odor when entering that definitely needs to be addressed 1 Javier Borja Local Guide·19 reviews·1 photo 5 years ago Love the food, large space with plenty of seating. It's not a warm place but in great location G Local Guide·116 reviews a year ago Food was good staff was friendly and helpful. … More Amar-Jyrel Mott 2 reviews 2 years ago I love it! Staff is nice & I've never had a bad experience! N K Local Guide·98 reviews·38 photos 6 years ago The best build to suit pizza joint I've tried. Light years ahead of blaze on quality of ingredients. Gahana Dahiya 6 reviews·1 photo 3 years ago I go to this place all the time! Food is great and the staff is always nice. &pizza - Dupont (Owner) 3 years ago Thank you so much for the review and thank you for being a returning guest! Can't wait to see you again next time! Patrice Mobitang 1 review 2 years ago Great pizza. My familly and I love this location Yuting (Nychii) Local Guide·114 reviews·1683 photos 7 years ago Really enjoy the way this chain makes pizza! This location doesn't have a lot of seating though... Sakina Allen 2 reviews 11 months ago great customer service!!!! definitely recommend. George A 1 review 2 years ago Ordered waited for 2 hours and then my order was canceled. They asked me to reorder. It was my first time ordering from them and my last time. TEAM SHERBOURNE Local Guide·405 reviews·284 photos a year ago I'm from NY and Always have to visit a &pizza while in DC! &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We are thrilled to hear that you always enjoy visiting &pizza while in DC. Your response is important to us as we strive to improve our services. We hope to continue exceeding your expectations on your future visits. Carlos Patiño Local Guide·168 reviews·431 photos 4 years ago Really, good pizza! Just pick what you want with it and enjoy. Friendly people. &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We're delighted to hear that you enjoyed our pizza and found our staff friendly. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Erica Burwell 4 reviews 6 years ago The service was good food is normal. If u r n the mood for pizza good place to go. Aris Preston 2 reviews 2 years ago Pizza is great Antoni and Bron were very helpful and lead to a great lunch. Weiyan Zhang 2 reviews 2 years ago I quite like the pizza here! Self designed pizza is always the best big boi rj 1 review a year ago Take out | Dinner Awesome establishment, good service, tasty pizza Bryan Moises Hernandez Benitez 1 review a year ago the crust is the best and the staff are great, down to earth people. Courtney Metcalfe 5 reviews 2 years ago Lavelle was awesome and gave us great service! awesome pizza Jennifer Morgan 6 reviews a year ago Take out | Dinner | $10–20 Great option for a quick / delicious late night dinner. … More James Gregory 2 reviews a year ago Good pizza great people!! Great late night fix &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We're thrilled to hear that you enjoyed our pizza and our service. We're always here to satisfy those late-night cravings. Your response is important to us as we strive to improve our services. Ms Lola 2 reviews 2 years ago Antonio was the best I love how he makes my pizza, I absolutely love this location. Adeola A 11 reviews 4 years ago The pizza is fine, they don't allow you to sit down and eat late nights on the weekend, although they are open, and the security is very rude about it. Joni Hurley 3 reviews·1 photo 5 years ago Pizza was amazing!!!! One of my best GF pizza crust (order well done) Tat hazelton 4 reviews 2 years ago Good Customer Service, Fast Paced & Loaded Pizza Up. Joseph Rhinehart 11 reviews·1 photo 2 years ago Friendly staff. Great food . Will definitely come back. AHMED RABANE 2 reviews a year ago Always great customer service. Terence is definitely a great asset for this location Kendi Johnson 1 review 2 years ago Lavelle was very professional. He put love into my pizza Justin Wang Local Guide·92 reviews 7 years ago Make your own pizza for $9? As many toppings/sauces/garnishes as you want?? I love &pizza. Tahlia Stangherlin 8 reviews·4 photos a year ago Tay was very helpful when i checked out today. very polite and friendly ! Nisha P 6 reviews·1 photo 2 years ago Great experience! Quick and convent! It’s a must try if you are in D.C. Pooja Rastogi 5 reviews·2 photos 2 years ago Love the pizza and employees!!!!!! So so nice especially lavelle Jake Backers 3 reviews a year ago This place is the best!! also the pizza??? smashing!!! Chanel Beaudoin 1 review 2 years ago Great pizza love it here. Loved the service! Allen Cardenas Local Guide·42 reviews·10 photos 5 years ago So glad there is an &pizza in Dupont. It's quick, easy, and delicious. Awesome value for your money Chanelle Combs 1 review 2 years ago Antonio the best I love this location best pizza and they close at 4am Clifton McEachin 3 reviews 2 years ago Great service!!!! The best pizza I’ve ever head!!! Lucas Orjales 2 reviews a year ago Tay was the best supervisor! Absolutely delicious pizza! Antwane Wrenn 1 review a year ago I love this location .employee are fun and patient Kristin Fillingim 1 review 2 years ago Là elle was the best!! Great service. 5 out of 5 every time!!!! &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We are thrilled to hear that you had a great experience with us. Your response is important to us as we strive to improve our services. We look forward to serving you again soon! Jackie Warner 2 reviews 2 years ago Great service and pizza! Antonio, Brianna and Jalen are the best. Veronica Sarai Melara Cornejo 1 review a year ago Good customer service! Friendly people and always willing to help. Lifeasevon 6 reviews 2 years ago The pizza is always great ! Extra crispy too David Oliveira 4 reviews 2 years ago Take out | Dinner | $10–20 Love their pizza, clean and nice location miles vondra Local Guide·10 reviews·12 photos a year ago Great pizza, even better people. JP was great! Yousif M Local Guide·26 reviews·3 photos 5 years ago Lots of crust on the pizza because of how it's made. Super fresh and feels almost healthy! Lauren Hastings 1 review 2 years ago Take out | Dinner Service was great and the vibe even better! Lavelle’s assistance was top notch Precious Johnson Local Guide·25 reviews 2 years ago Service was great at this location! Food was delicious 😋 Kannan Ramanathan Local Guide·73 reviews·27 photos 4 years ago You can just add all the ingredients you want and the dough of the pizza is thin and delicious &pizza - Dupont (Owner) 4 years ago Hey Kannan, glad you loved it! Come again soon! Al S. 1 review 2 years ago Outstanding service and made one hell of a pizza Delonte Briggs, MBA Local Guide·48 reviews·18 photos 4 years ago Staff was not welcoming and had the dude had an attitude when clarifying build your own versus a classic adding a few extra toppings...it didn't master i was willing to pay the difference.. 1 &pizza - Dupont (Owner) 4 years ago Sorry to hear that your pizza experience wasn't the best. Thank you for your feedback. I will forward this information to the appropriate people. Please reach out to us so that we can make this right. A'Jae Boyd 2 reviews 2 years ago Great customer service. Order done in a timely fashion. &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We're thrilled to hear that your order was delivered in a timely fashion. Your response is important to us as we strive to improve our services. We hope to serve you again soon! John Benson Local Guide·23 reviews·183 photos 4 years ago Customer service at this location is atrocious. The crew working the evening shift on 2/28/20 were very rude. Stay away! Dallas S. Local Guide·101 reviews·89 photos 5 years ago My first pizza in DC. Quick service and great good at a decent price. Jordhon Horelien 2 reviews 2 years ago Lavelle was an excellent help to getting the pizza of my choice. Very helpful &pizza - Dupont (Owner) 2 months ago Thank you for taking the time to leave a review. We are thrilled to hear that Lavelle was able to assist you in getting the pizza of your choice. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Courtney Wade 4 reviews 2 years ago Labella is awesome. He goes the extra mile. Thank you! Dusan Vasiljevic Local Guide·50 reviews·25 photos 4 years ago Excellent suggested choices of toppings, quick service, good enough interior. Mig Local Guide·581 reviews·590 photos 6 years ago Love this pizza: Favorite go to - Red sauce with pepporoni and sausage drizzled with pesto on top. Mercedes White 3 reviews 2 years ago Phenomenal experience with Antonio and the rest of the staff. The place was very clean! Kate Neilson 3 reviews 2 years ago Dine in | Lunch | $10–20 love & pizza! come here often and always enjoy it. … More KDASH201 14 reviews·1 photo 7 years ago Best pizza I ever had. You just have to go and try it yourself Debbie James 8 reviews 2 years ago Ran efficiently under pressure during Halloween eve and Lavelle was very helpful Bosh Gobran Local Guide·304 reviews·695 photos 7 years ago Great Pizza, fast and they have a vegan/vegetarian options:) fund staff Smash Diddy 5 reviews 6 years ago Service was good and food great who dnt love pizza lol &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We're glad to hear that you enjoyed our service and food, especially the pizza. Your response is important to us as we strive to improve our services. We hope to serve you again soon! Heidi Wiles Local Guide·25 reviews·2 photos 7 years ago I just love the the atmosphere the people are great and the pizza is delicious. Need one in Hagerstown MD. hector paredes Local Guide·51 reviews·712 photos 2 months ago I love this Pizza … More &pizza - Dupont (Owner) 2 months ago Thank you for your 5-star rating! We're thrilled to hear that you love our pizza. Your response is important to us as we strive to improve our services. We look forward to serving you again soon. Justin Bozeman 3 reviews 5 years ago Ordered via Uber Eats, Pizza came completely wrong from what was ordered, and added whatever they wanted to the pizza and when called , no one answers the phone and call was looped, no one ever responded to my e-mails regarding the wrong order 1 Alana Peery 6 reviews·13 photos a year ago Great pizza and better service! Kunal Vijan Local Guide·117 reviews·505 photos 4 years ago Very nice n tasty. Much better than DC Pizza James Plain Local Guide·9 reviews 5 years ago i tried the american honey pizza, and was great! The craft sodas are also really interesting! danelle hankins 8 reviews 2 years ago Antonio made me a great pizza today and answered all my questions. Fly Gurl Local Guide·193 reviews·271 photos 4 years ago The staff was great they are very customer service driven , fast , and very clean Rodolfo Diaz 1 review a year ago Great Place! Awesome customer service! Dean Naps 2 reviews a year ago Awesome pizza, great service, thank you &pizza! EBEMBI Alain 3 reviews 2 years ago Great location. Staff are really friendly and patient Robin Young 5 reviews 5 years ago Fantastic pizza and an AMAZING staff!! I could eat there everyday!!’ Javid Pourkia Local Guide·128 reviews·1295 photos 5 years ago It's not just food, is love Photo 1 in review by Javid Pourkia Petra Sosa 2 reviews·1 photo a year ago Best pizza in town , customer service is A1 ! Photo 1 in review by Petra Sosa khairy jones 3 reviews 2 years ago This was a great place to go late at night and it handled the long line well Alvaro Dalessandro Local Guide·44 reviews·3 photos 4 years ago Tasty pizza, only downside is the place didn't have Coca-Cola Money Monkey 1 review 2 years ago lavelle was extremely helpful and made sure i was set and provided good service Living the life of lele Vibing 12 reviews·2 photos a year ago Great customer service made me feel welcome &pizza - Dupont (Owner) 2 months ago Thank you for the 5-star rating! We're thrilled to hear that our customer service made you feel welcome. Your response is important to us as we strive to improve our services. We hope to continue providing a great experience for you in the future. Abish Anklesaria Local Guide·94 reviews·53 photos 7 years ago Fresh pizza. Good toppings selection. Kid friendly as well. Great place for a fast custom pizza. Rob G Local Guide·151 reviews·301 photos 2 years ago First visit. Fast service, excellent pizza! Matt Peterson 2 reviews 2 years ago an icon, a legend, showstopping beautiful amazing never the same the best &pizza in DC Eric Midder Local Guide·146 reviews 4 years ago Could be a little quicker but very friendly staff and great pizza! Sandra Gaillardetz 4 reviews 5 years ago This Pizza was phenomenal ! Loved it and would definitely go back!!

Write the answer in one paragraph, using full sentences. Use only the document provided. Use language that is easy to understand.

What purpose does the OSINT serve? Is there a potential for abuse if the OSINT is utilized?

Title: Fugitive Tracking using Open Source Intelligence ( OSINT) Author: Pranav Waghmare Abstract: The fugitive tracking has been a challenging topic for various law enforcement agencies across the world. The use of technology, social media, and other social media platforms, etc offers unique opportunities to track the digital footprint left by Fugutives. In this research paper, we will explore the methodologies, Legal as well as Ethical Considerations, OSINT mapping, and cyber forensic technologies that can be helpful in tracking fugitives. Introduction : Fugitive tracking has evolved over a period of time but also now has a global framework. Interpol created a global framework and classification of fugitives based on their crime and threat level. They have also created a color-coded system. The local government agencies also have their own classification system for fugitives. Methodologies : OSINT Framework Mapping : The Interpole’s framework for data classification can be incorporated with OSINT. The Interpole classifies fugitives with color codes and also updates the data every hour. This is really for mapping it to OSINT Framework for real-time monitoring and cross-referencing the searches. OSINT comparatively accesses vast resources but the Interpol framework provides the necessary filter to refine the searches. Electronic copy available at: https://ssrn.com/abstract=4719968 Here is the overview of the Color code System used by Interpol : ● Red Notice: Red is the highest level of importance and also states the individual wanted by Law enforcement and governments for arrest and extradition For Example: The person who is found guilty of murder and on the run falls under Red Notice ● Blue Notice: The Blue Notice is mainly concerned with gathering enough information about the person of Interest by Law Enforcement. For Example, The people under blue notices are suspects and wanted for questioning by authorities. The gang members whom law enforcement may suspect connected with crime and needed for questioning will fall under Blue Notice ● Green Notice: The green notice fugitive is considered a public safety threat. For Example, Sex Offenders and Drug traffickers will fall under “ Green Notice”. Here the country is making Interpol aware this person is a threat to public safety ● Yellow Notice: Yellow Notice is more about the Identity of the missing individuals or person who is incapable of identifying themselves For Example, a Missing Child who is underage or an individual with mental incapability will be under a Yellow Notice Electronic copy available at: https://ssrn.com/abstract=4719968 ● Black Notice: The black notice is issued about unidentified bodies. For Example, If a war crime is committed and mass graves of unidentified bodies are found they come under black notice ● Purple Notice: The purple notice is mainly used to gather information about the operational details of the crime such as devices used or methods used by them to hide. For Example, Drug Tunnels will come under purple notice Cyber Forensics and OSINT : The Digital Footprint creation will be very efficient with the use of OSINT. The geolocation tags, social media posts, and publicly available information about fugitives will help to create a digital footprint and help investigators understand the patterns in fugitive behavior. This also helps to reconstruct the timeline as shown in Figure 1 which can help the investigator understand the events and suspects. Geolocation Tracking: With OSINT we can build geotags of the places an individual has been and cross-check with Interpol notices as they get updated every hour. OSINT also provides information about individuals known associated that can be also valuable in terms of building Geolocation Tracking. For example, One can search the fugitive's location and past history of residential addresses can help to pinpoint their possible location and understand the pattern in their movements Electronic copy available at: https://ssrn.com/abstract=4719968 Social Media Monitoring: The social media accounts of fugitives provide essential details about their likes or dislikes, the images and videos posted by them, and the metadata associated with them. Social media also give understanding to their known friends or associates. This can be further matched with witness and journalist statements. The metadata search and social media monitoring can help create a digital footprint and also be searched for further updated information posted by Interpol every hour. Legal and Ethical Consideration : While implementing as well as using OSINT framework it is really essential to keep track of local laws and jurisdiction. There is the possibility that this system can be abused if it falls into the wrong hands, It can be used to track dissidents, political and religious minorities, or opponents. Hence there need to be awareness of local laws as well ethical consideration must be taken into consideration. There have been instances where the Interpol framework was abused in the past but over the period of time, Interpol is evolving. For Example, China issued red notices for Uyghurs. The Interpol latter made firm in their policy that they will not issue notices for individuals who have refugee status in another country and they firmly believe that an individual is innocent until proven guilty. Hence, The Interpol framework mapping into OSINT is essential as Interpol holds the highest standards of Ethical approach in terms of tracking Fugutatives. Conclusion : To Conclude, The OSINT is a highly efficient framework, and mapping into the Interpoles framework makes it a very effective tool with legal and ethical considerations Electronic copy available at: https://ssrn.com/abstract=4719968 References: 1. Interpol (2011) Interpole’s Rules on Processing Data: Interpol https://www.interpol.int/en/Who-we-are/Legal-framework/Data-protection 2 C. Rafailă, F. Gurzău, C. Grumăzescu, and I. Bica, "MTAFinder - Unified OSINT platform for efficient data gathering," 2023 15th International Conference on Electronics, Computers and Artificial Intelligence (ECAI), Bucharest, Romania, 2023 3 HOROS, ANDREW J.(2023) 21st Century Open-Source Intelligence and Law Enforcement Utilization 4 Lakomy, Miron. (2023). Open-source intelligence and research on online terrorist communication: Identifying ethical and security dilemmas. 5 Daragh Murray, Yvonne McDermott, K Alexa Koenig, Mapping the Use of Open Source Research in UN Human Rights Investigations, Journal of Human Rights Practice, Volume 14, Issue 2, July 2022, Pages 554–581 ( Figure 1) 6 J. W. Johnsen and K. Franke, "The impact of preprocessing in natural language for open source intelligence and criminal investigation," 2019 IEEE International Conference on Big Data (Big Data), Los Angeles, CA, USA, 2019 Electronic copy available at: https://ssrn.com/abstract=4719968

Write the answer in one paragraph, using full sentences. Use only the document provided. Use language that is easy to understand. What purpose does the OSINT serve? Is there a potential for abuse if the OSINT is utilized? Title: Fugitive Tracking using Open Source Intelligence ( OSINT) Author: Pranav Waghmare Abstract: The fugitive tracking has been a challenging topic for various law enforcement agencies across the world. The use of technology, social media, and other social media platforms, etc offers unique opportunities to track the digital footprint left by Fugutives. In this research paper, we will explore the methodologies, Legal as well as Ethical Considerations, OSINT mapping, and cyber forensic technologies that can be helpful in tracking fugitives. Introduction : Fugitive tracking has evolved over a period of time but also now has a global framework. Interpol created a global framework and classification of fugitives based on their crime and threat level. They have also created a color-coded system. The local government agencies also have their own classification system for fugitives. Methodologies : OSINT Framework Mapping : The Interpole’s framework for data classification can be incorporated with OSINT. The Interpole classifies fugitives with color codes and also updates the data every hour. This is really for mapping it to OSINT Framework for real-time monitoring and cross-referencing the searches. OSINT comparatively accesses vast resources but the Interpol framework provides the necessary filter to refine the searches. Electronic copy available at: https://ssrn.com/abstract=4719968 Here is the overview of the Color code System used by Interpol : ● Red Notice: Red is the highest level of importance and also states the individual wanted by Law enforcement and governments for arrest and extradition For Example: The person who is found guilty of murder and on the run falls under Red Notice ● Blue Notice: The Blue Notice is mainly concerned with gathering enough information about the person of Interest by Law Enforcement. For Example, The people under blue notices are suspects and wanted for questioning by authorities. The gang members whom law enforcement may suspect connected with crime and needed for questioning will fall under Blue Notice ● Green Notice: The green notice fugitive is considered a public safety threat. For Example, Sex Offenders and Drug traffickers will fall under “ Green Notice”. Here the country is making Interpol aware this person is a threat to public safety ● Yellow Notice: Yellow Notice is more about the Identity of the missing individuals or person who is incapable of identifying themselves For Example, a Missing Child who is underage or an individual with mental incapability will be under a Yellow Notice Electronic copy available at: https://ssrn.com/abstract=4719968 ● Black Notice: The black notice is issued about unidentified bodies. For Example, If a war crime is committed and mass graves of unidentified bodies are found they come under black notice ● Purple Notice: The purple notice is mainly used to gather information about the operational details of the crime such as devices used or methods used by them to hide. For Example, Drug Tunnels will come under purple notice Cyber Forensics and OSINT : The Digital Footprint creation will be very efficient with the use of OSINT. The geolocation tags, social media posts, and publicly available information about fugitives will help to create a digital footprint and help investigators understand the patterns in fugitive behavior. This also helps to reconstruct the timeline as shown in Figure 1 which can help the investigator understand the events and suspects. Geolocation Tracking: With OSINT we can build geotags of the places an individual has been and cross-check with Interpol notices as they get updated every hour. OSINT also provides information about individuals known associated that can be also valuable in terms of building Geolocation Tracking. For example, One can search the fugitive's location and past history of residential addresses can help to pinpoint their possible location and understand the pattern in their movements Electronic copy available at: https://ssrn.com/abstract=4719968 Social Media Monitoring: The social media accounts of fugitives provide essential details about their likes or dislikes, the images and videos posted by them, and the metadata associated with them. Social media also give understanding to their known friends or associates. This can be further matched with witness and journalist statements. The metadata search and social media monitoring can help create a digital footprint and also be searched for further updated information posted by Interpol every hour. Legal and Ethical Consideration : While implementing as well as using OSINT framework it is really essential to keep track of local laws and jurisdiction. There is the possibility that this system can be abused if it falls into the wrong hands, It can be used to track dissidents, political and religious minorities, or opponents. Hence there need to be awareness of local laws as well ethical consideration must be taken into consideration. There have been instances where the Interpol framework was abused in the past but over the period of time, Interpol is evolving. For Example, China issued red notices for Uyghurs. The Interpol latter made firm in their policy that they will not issue notices for individuals who have refugee status in another country and they firmly believe that an individual is innocent until proven guilty. Hence, The Interpol framework mapping into OSINT is essential as Interpol holds the highest standards of Ethical approach in terms of tracking Fugutatives. Conclusion : To Conclude, The OSINT is a highly efficient framework, and mapping into the Interpoles framework makes it a very effective tool with legal and ethical considerations Electronic copy available at: https://ssrn.com/abstract=4719968 References: 1. Interpol (2011) Interpole’s Rules on Processing Data: Interpol https://www.interpol.int/en/Who-we-are/Legal-framework/Data-protection 2 C. Rafailă, F. Gurzău, C. Grumăzescu, and I. Bica, "MTAFinder - Unified OSINT platform for efficient data gathering," 2023 15th International Conference on Electronics, Computers and Artificial Intelligence (ECAI), Bucharest, Romania, 2023 3 HOROS, ANDREW J.(2023) 21st Century Open-Source Intelligence and Law Enforcement Utilization 4 Lakomy, Miron. (2023). Open-source intelligence and research on online terrorist communication: Identifying ethical and security dilemmas. 5 Daragh Murray, Yvonne McDermott, K Alexa Koenig, Mapping the Use of Open Source Research in UN Human Rights Investigations, Journal of Human Rights Practice, Volume 14, Issue 2, July 2022, Pages 554–581 ( Figure 1) 6 J. W. Johnsen and K. Franke, "The impact of preprocessing in natural language for open source intelligence and criminal investigation," 2019 IEEE International Conference on Big Data (Big Data), Los Angeles, CA, USA, 2019 Electronic copy available at: https://ssrn.com/abstract=4719968

{instruction} ========== In your answer, refer only to the context document. Do not employ any outside knowledge {question} ========== [user request] {passage 0} ========== [context document]

Summarize the information about periorbital hyperchromia in about 600 words. In bold at the end of the response, tell me what type of individuals are most affected by it.

INTRODUCTION Although periorbital hyperpigmentation (also called peri- palpebral hyperpigmentation, dark eyelids, dark eye circles, dark circles, or simply under-eye circles) is a mere color difference between the palpebral skin and the remaining facial skin, it makes people look tired or older, which negatively affects their quality of life. 1,-4 It has a higher prevalence in individuals with darker skin, hair and eyes, and affects age groups and genders equally. Nevertheless, there are a higher number of complaints from women, especially senior women. There are few studies about the etiology of this condition, however dark eye circles with a vascular component are known to present a dominant autoso- mal family inheritance pattern. 2,3 Periorbital hyperpigmentation seems to have multifactori- al causes that involve intrinsic factors (determined by the indi- vidual''''''''s genetics), and extrinsic factors (sun exposure, smoking, alcoholism and sleep deprivation, for instance). However, the presence of melanic pigment and hemosiderotic pigment in the affected sites is a distinctive feature in its etiopathogeny. 2-4 Melanic hyperpigmentation is more frequent in brunet adults, as a consequence of excessive and cumulative exposure to the sun, which increases the production of melanin, reduces the skin''''''''s thickness and increases the dilatation of blood vessels. 2,4,5 Intense vascularization is mainly found in people belong- ing to certain ethnic groups such as Arabs, Turks, Hindus, inhab- itants of the Iberian Peninsula and their respective descendants. In these ethnicities, its manifestation tends to take place earlier, often during childhood. In those individuals there is no change in the color of the skin; the eyelid appears darkened because the dilated vessels are visible due to the transparency of the skin. 2 In those cases, therefore, the problem is often aggravated when the lower eyelid''''''''s vessels are more dilated (e.g., from fatigue, insom- nia, oral breathing, crying), causing dermal blood extravasation. The liberation of ferric ions takes place locally, entailing the for- mation of free radicals that stimulate the melanocytes, which generates melanic pigmentation. 2, 4-6 Other causes noted as being responsible for the appearance of dark eye circles are post-inflammatory hyperpigmentation secondary to atopic and contact dermatitis, sleep deprivation, oral breathing, alcoholism, smoking, use of certain medications (contraceptives, chemotherapy, antipsychotic and some types of eye drops), the presence of palpebral sagging (due to aging) and of disorders that develop with hydric retention and palpebral edema (thyroid disorders, nephropathies, cardiopathies and pneumopathies) – all of which worsen the unattractive appear- ance of dark eye circles. 2-4,7 Various treatments have been proposed for periorbital hyperchromia, however there are few studies on their long-term efficacy. The main types of treatment are: topical application of depigmenting products, chemical peelings, dermabrasion, cryosurgery, fillings with hyaluronic acid, intense pulsed light, CO2, argon, ruby and excimer lasers. 2-4, 6, 8-12 PALPEBRAL ANATOMY The eyelids are tegumentary pleats that participate in facial expression and aesthetics, however their main function is to pro- tect the eyeballs through sensorial filtration actions carried out by the palpebral cilia, and the Meibomian and lachrymal glands'''''''' secretions. In this manner, the cornea remains hydrated and the closing movements of the eyes function as a barrier to external traumas and prevent the cornea from drying out. 13-17 The upper eyelid reaches upwards to the eyebrow, which separates it from the forehead. The lower eyelid extends down- wards up to the lower border of the orbit, and is delimited by the genian region. 15 The palpebral fissure, which measures 9-10 mm in adults, is determined by the interaction of the muscles that open and close the eyelids. To open the eyelid, the palpebral elevator mus- cle is assisted by two other accessory muscles (Muller''''''''s and frontalis muscles). 18 The aging process decreases the palpebral fis- sure''''''''s vertical opening, due to the progressive lowering of the upper eyelid, 14 which is caused by a decrease in the upper eye- lid lifter muscle''''''''s aponeurosis action. 15 The skin becomes more flaccid, less elastic and has a greater propensity to wrinkle 16. The orbicular and tarsal muscles, the orbital septum and the conjunctival mucous membrane also go through transforma- tions in the elderly. In addition, gravity and facial expressions influence the mechanical deformation of those structures. 17 A cohort study with 320 patients (aged 10-89) evaluated participants'''''''' eyelids frontally and laterally and found that there is a correlation between a decrease in the palpebral fissure and an increase in the age of patients. 19 PALPEBRAL REGION''''''''S SKIN AND SUBCUTANEOUS TISSUE Palpebral skin is the thinnest in the human body (< 1 mm). Its epidermis is constituted of stratified epithelium, which is very thin (0.4 mm) compared to that of the palmoplantar region (the thickness of which is approximately 1.6 mm). 13 The nasal portion of the palpebral skin has thinner hair and more sebaceous glands (i.e., it is softer and oilier) than its tem- poral portion. The transition between the eyelids'''''''' thin skin and the remaining facial skin is clinically observable. 13 The palpebral dermis is composed of loose conjunctive tissue, and is extremely thin in that region. It is absent in the pre-tarsal skin, in the medial and lateral ligaments of the eyelid, where the skin adheres to the underlying fibrous tissue. The thinness of the skin, combined with the lack of fatty tissue, gives that region its characteristic translucency. As a result, the accu- mulation of melanin and/or vessel dilatation in that region can be easily seen, through transparency, as bilateral homogeneous hyperpigmentation. 2,4,5,13 PALPEBRAL REGION''''''''S VENOUS AND LYMPH VASCULARIZATION The eyelids'''''''' arterial irrigation comes through many vessels: the supratrochlear, supraorbital, lachrymal and dorsum of the nose arteries (all originating in the facial artery); the angular artery (originating in the facial artery); the transverse artery (originating in the facial artery); the transverse facial artery (originating in the superficial temporal artery) and the branch- es of the superficial temporal artery itself 20 (Figure 1). Venous drainage (following an external pattern) takes place through the veins associated with these arteries and (following an internal pattern) penetrates the orbit through connections with ophthalmic veins 20 (Figure 2). Lymphatic drainage takes place mainly through the parotid lymph nodes; some of the drainage from the medial angle of the eye to the lymph vessels is associated with the angular and facial arteries, towards the submandibular lymph nodes. 20 COLOR OF THE SKIN IN THE PALPEBRAL REGION The palpebral skin''''''''s color results from the combination of several factors, some of genetic-racial origin (such as the amount of melanin pigment), others of individual or regional and even gender l origins, such as the thickness of the several components and the blood volume in their vessels.

{instruction} ========== In your answer, refer only to the context document. Do not employ any outside knowledge {question} ========== Summarize the information about periorbital hyperchromia in about 600 words. In bold at the end of the response, tell me what type of individuals are most affected by it. {passage 0} ========== INTRODUCTION Although periorbital hyperpigmentation (also called peri- palpebral hyperpigmentation, dark eyelids, dark eye circles, dark circles, or simply under-eye circles) is a mere color difference between the palpebral skin and the remaining facial skin, it makes people look tired or older, which negatively affects their quality of life. 1,-4 It has a higher prevalence in individuals with darker skin, hair and eyes, and affects age groups and genders equally. Nevertheless, there are a higher number of complaints from women, especially senior women. There are few studies about the etiology of this condition, however dark eye circles with a vascular component are known to present a dominant autoso- mal family inheritance pattern. 2,3 Periorbital hyperpigmentation seems to have multifactori- al causes that involve intrinsic factors (determined by the indi- vidual''''''''s genetics), and extrinsic factors (sun exposure, smoking, alcoholism and sleep deprivation, for instance). However, the presence of melanic pigment and hemosiderotic pigment in the affected sites is a distinctive feature in its etiopathogeny. 2-4 Melanic hyperpigmentation is more frequent in brunet adults, as a consequence of excessive and cumulative exposure to the sun, which increases the production of melanin, reduces the skin''''''''s thickness and increases the dilatation of blood vessels. 2,4,5 Intense vascularization is mainly found in people belong- ing to certain ethnic groups such as Arabs, Turks, Hindus, inhab- itants of the Iberian Peninsula and their respective descendants. In these ethnicities, its manifestation tends to take place earlier, often during childhood. In those individuals there is no change in the color of the skin; the eyelid appears darkened because the dilated vessels are visible due to the transparency of the skin. 2 In those cases, therefore, the problem is often aggravated when the lower eyelid''''''''s vessels are more dilated (e.g., from fatigue, insom- nia, oral breathing, crying), causing dermal blood extravasation. The liberation of ferric ions takes place locally, entailing the for- mation of free radicals that stimulate the melanocytes, which generates melanic pigmentation. 2, 4-6 Other causes noted as being responsible for the appearance of dark eye circles are post-inflammatory hyperpigmentation secondary to atopic and contact dermatitis, sleep deprivation, oral breathing, alcoholism, smoking, use of certain medications (contraceptives, chemotherapy, antipsychotic and some types of eye drops), the presence of palpebral sagging (due to aging) and of disorders that develop with hydric retention and palpebral edema (thyroid disorders, nephropathies, cardiopathies and pneumopathies) – all of which worsen the unattractive appear- ance of dark eye circles. 2-4,7 Various treatments have been proposed for periorbital hyperchromia, however there are few studies on their long-term efficacy. The main types of treatment are: topical application of depigmenting products, chemical peelings, dermabrasion, cryosurgery, fillings with hyaluronic acid, intense pulsed light, CO2, argon, ruby and excimer lasers. 2-4, 6, 8-12 PALPEBRAL ANATOMY The eyelids are tegumentary pleats that participate in facial expression and aesthetics, however their main function is to pro- tect the eyeballs through sensorial filtration actions carried out by the palpebral cilia, and the Meibomian and lachrymal glands'''''''' secretions. In this manner, the cornea remains hydrated and the closing movements of the eyes function as a barrier to external traumas and prevent the cornea from drying out. 13-17 The upper eyelid reaches upwards to the eyebrow, which separates it from the forehead. The lower eyelid extends down- wards up to the lower border of the orbit, and is delimited by the genian region. 15 The palpebral fissure, which measures 9-10 mm in adults, is determined by the interaction of the muscles that open and close the eyelids. To open the eyelid, the palpebral elevator mus- cle is assisted by two other accessory muscles (Muller''''''''s and frontalis muscles). 18 The aging process decreases the palpebral fis- sure''''''''s vertical opening, due to the progressive lowering of the upper eyelid, 14 which is caused by a decrease in the upper eye- lid lifter muscle''''''''s aponeurosis action. 15 The skin becomes more flaccid, less elastic and has a greater propensity to wrinkle 16. The orbicular and tarsal muscles, the orbital septum and the conjunctival mucous membrane also go through transforma- tions in the elderly. In addition, gravity and facial expressions influence the mechanical deformation of those structures. 17 A cohort study with 320 patients (aged 10-89) evaluated participants'''''''' eyelids frontally and laterally and found that there is a correlation between a decrease in the palpebral fissure and an increase in the age of patients. 19 PALPEBRAL REGION''''''''S SKIN AND SUBCUTANEOUS TISSUE Palpebral skin is the thinnest in the human body (< 1 mm). Its epidermis is constituted of stratified epithelium, which is very thin (0.4 mm) compared to that of the palmoplantar region (the thickness of which is approximately 1.6 mm). 13 The nasal portion of the palpebral skin has thinner hair and more sebaceous glands (i.e., it is softer and oilier) than its tem- poral portion. The transition between the eyelids'''''''' thin skin and the remaining facial skin is clinically observable. 13 The palpebral dermis is composed of loose conjunctive tissue, and is extremely thin in that region. It is absent in the pre-tarsal skin, in the medial and lateral ligaments of the eyelid, where the skin adheres to the underlying fibrous tissue. The thinness of the skin, combined with the lack of fatty tissue, gives that region its characteristic translucency. As a result, the accu- mulation of melanin and/or vessel dilatation in that region can be easily seen, through transparency, as bilateral homogeneous hyperpigmentation. 2,4,5,13 PALPEBRAL REGION''''''''S VENOUS AND LYMPH VASCULARIZATION The eyelids'''''''' arterial irrigation comes through many vessels: the supratrochlear, supraorbital, lachrymal and dorsum of the nose arteries (all originating in the facial artery); the angular artery (originating in the facial artery); the transverse artery (originating in the facial artery); the transverse facial artery (originating in the superficial temporal artery) and the branch- es of the superficial temporal artery itself 20 (Figure 1). Venous drainage (following an external pattern) takes place through the veins associated with these arteries and (following an internal pattern) penetrates the orbit through connections with ophthalmic veins 20 (Figure 2). Lymphatic drainage takes place mainly through the parotid lymph nodes; some of the drainage from the medial angle of the eye to the lymph vessels is associated with the angular and facial arteries, towards the submandibular lymph nodes. 20 COLOR OF THE SKIN IN THE PALPEBRAL REGION The palpebral skin''''''''s color results from the combination of several factors, some of genetic-racial origin (such as the amount of melanin pigment), others of individual or regional and even gender l origins, such as the thickness of the several components and the blood volume in their vessels. http://www.surgicalcosmetic.org.br/details/158/en-US/periorbital-hyperchromia

Use only the supplied context document in your answer and do not use outside information.

Based on the article, what stock prices have fallen the most?

**Dow Jones Futures: Market Rally, Nvidia Resilient As Tesla Skids** Dow Jones futures rose slightly after hours, along with S&P 500 futures and Nasdaq futures. Software makers UiPath (PATH) and SentinelOne (S) reported Wednesday night, along with homebuilder Lennar (LEN). The stock market rally had a constructive Wednesday. The Nasdaq fell but finished off lows and held the bulk of Tuesday's gains, much like AI rally leader Nvidia (NVDA). Many other big techs had quiet sessions after Tuesday's strong moves. Laggard Tesla (TSLA), however, broke lower, extending its long run of underperformance amid negative headlines. Market breadth was solid. While AI stocks have clearly led the market rally, a number of stocks in the commodity, travel and medical product spaces are in buy areas now. Freeport-McMoRan (FCX), PBF Energy (PBF) and Royal Caribbean (RCL) cleared a buy point. Shockwave Medical (SWAV) and Dexcom (DXCM) remain in buy areas. However, bullish sentiment has reached excessive levels, suggesting a pullback is likely in the coming days. The market rally has refused to take extended breaks, staging "cat nap" pullbacks for a day or two before quickly revving higher again and looking extended again. Nvidia and Dexcom stock are on IBD Leaderboard. Nvidia, SentinelOne and Royal Caribbean stock are on the IBD 50. Nvidia stock is on the IBD Big Cap 20. Dexcom was Wednesday's IBD Stock Of The Day. Dow Jones Futures Today Dow Jones futures were 0.1% above fair value. S&P 500 futures climbed 0.1% and Nasdaq 100 futures rose 0.2%. Remember that overnight action in Dow futures and elsewhere doesn't necessarily translate into actual trading in the next regular stock market session. Join IBD experts as they analyze leading stocks and the market on IBD Live Earnings Lennar earnings topped while revenue fell short. LEN stock fell slightly overnight. Shares dipped 0.3% in Wednesday's regular session to 165.50 after hitting a record high intraday. Lennar stock slightly extended from a flat base with a 156.01 buy point, according to MarketSmith analysis. UiPath earnings topped with the automation software maker guiding lower on Q1 revenue but up for fiscal 2025. PATH stock rose slightly late after initially surging in volatile action. Shares dipped 0.85% to 24.43 on Wednesday, but held onto the recent move above the 50-day following a failed recent breakout. A move above Wednesday's high of 25.33 would offer an early entry. SentinelOne narrowly beat fiscal Q4 views, but guided slightly lower on fiscal 2025 revenue. Shares tumbled overnight. SentinelOne stock fell 1 cent to 27.94 on Wednesday, briefly testing a downward-sloping trendline. That offered an early entry in an emerging base, but the imminent earnings report made that risky. Stock Market Rally The stock market rally had a mixed session, with the S&P 500 and Nasdaq falling modestly, ceding only a portion of Tuesday's gains. The Dow Jones Industrial Average rose 0.1% in Wednesday's stock market trading. Meanwhile, the S&P 500 index dipped 0.2%. The Nasdaq composite declined 0.5%, but it was an inside day to Tuesday's 1.5% pop. Nvidia fell 1.1% but was off lows in an inside day to Tuesday's 7.2% jump. The small-cap Russell 2000 edged up 0.3%. Breadth was modestly positive, though decliners narrowly led on the Nasdaq. While Nvidia and many AI hardware plays are clearly extended, there are some software, commodity, medical product, financial, energy and travel names that are actionable or setting up. U.S. crude oil prices popped 2.8% to $79.72 a barrel. Gasoline futures gained 2.9% — 5.3% this week — to their highest close in nearly six months. Copper futures jumped 3.25% to $4.0525 a pound, the highest close since April 2023. It was the biggest percentage gain since late 2022. The 10-year Treasury yield rose 3.5 basis points to 4.19%. Bullish Sentiment Excessive The Investors Intelligence bulls-bears sentiment gauge is reaching euphoric levels. Some 60.9% of investment advisors are bullish, above the 60% level seen as excessive. That suggests a pullback, perhaps a more serious one, is coming. But it doesn't have to happen right away. That's the highest point since mid-2021. Just 14.5% are bearish, also the lowest since 2021. A modest pause or pullback over several days or even weeks would likely cool sentiment, let more bases form and give the market room for a longer run. But that hasn't been the market's pattern. ETFs Among growth ETFs, the iShares Expanded Tech-Software Sector ETF (IGV) fell 0.7%. The VanEck Vectors Semiconductor ETF (SMH) slumped 2%. Nvidia stock is the No. 1 holding in SMH. Reflecting more-speculative story stocks, ARK Innovation ETF (ARKK) edged up 0.2% and ARK Genomics ETF (ARKG) rose 0.3%. Tesla stock is a major holding across Ark Invest's ETFs. UiPath also is a big Cathie Wood stock. SPDR S&P Metals & Mining ETF (XME) edged higher, with FCX stock in the ETF. U.S. Global Jets ETF (JETS) ascended 0.7%. SPDR S&P Homebuilders ETF (XHB) stepped up 1.5%, with Lennar stock a key holding. The Energy Select SPDR ETF (XLE) rallied 1.6% and the Health Care Select Sector SPDR Fund (XLV) fell 0.4%. The Industrial Select Sector SPDR Fund (XLI) gained 0.3%. And the Financial Select SPDR ETF (XLF) climbed 0.7%. Time The Market With IBD's ETF Market Strategy Stocks In Buy Areas Freeport-McMoRan stock gapped up 7.6% to 43.41, Wednesday's top S&P 500 performer. The copper and gold miner broke above a double-bottom base buy point of 40.99, closing out of range. However, on a weekly chart, FCX stock just topped a 43.42 cup-with-handle buy point. Southern Copper (SCCO) and more-diversified Teck Resources (TECK) also cleared bases Wednesday. PBF Energy stock leapt 9% to 54.96, clearing a 54.52 cup-with-handle buy point. PBF stock is 16% above its 50-day line. Refining peer Phillips 66 (PSX) decisively cleared a short consolidation Wednesday, while several oil and gas machinery and services firms have been actionable. Shockwave Medical stock climbed 1.8% to 269.37, testing the top of a short consolidation following an earnings gap from the 200-day line. SWAV stock already was actionable from breaking a downtrend in this recent action, which could be viewed as a handle to a huge base. Dexcom stock fell 2.7% to 131.68, falling just below a 132.03 buy point from a flat base within a much larger consolidation. Royal Caribbean stock climbed 1.8% to 132.11, clearing a 130.97 buy point from a messy flat base. Meanwhile, rival cruise line operator Carnival (CCL) cleared an aggressive entry while hotel giant Marriott Worldwide (MAR) is trying to clear a tight pattern. Tesla Stock Tesla stock skidded 4.5% to 169.50, hitting the lowest levels since last May. Shares have tumbled nearly 32% in 2024, the worst performer on the S&P 500 index. The relative strength line is at a 14-month low, reflecting Tesla's severe underperformance vs. the S&P 500 index in recent months. The RS line is the blue line in the charts provided. Before Wednesday's open, Wells Fargo downgraded Tesla to underweight and cut its price target to 125 from 200. The analyst joined a recent rush to slash first-quarter delivery targets. He now sees 2024 earnings per share nearly a third below consensus. And he expects deliveries to fall short. Wells Fargo also said a yet-unveiled cheap EV may be not be a boon for Tesla, citing "likely tough" economics. Late Wednesday, UBS cut its Tesla price target to 165 from 225, also slashing its first-quarter delivery targets. TSLA stock fell a fraction overnight. Fisker (FSR) plunged more than 40% late Wednesday, on a report that the U.S. EV startup and would-be Tesla rival is preparing for a possible bankruptcy filing.

Question: Based on the article, what stock prices have fallen the most? System Instruction: Use only the supplied context document in your answer and do not use outside information. Context: **Dow Jones Futures: Market Rally, Nvidia Resilient As Tesla Skids** Dow Jones futures rose slightly after hours, along with S&P 500 futures and Nasdaq futures. Software makers UiPath (PATH) and SentinelOne (S) reported Wednesday night, along with homebuilder Lennar (LEN). The stock market rally had a constructive Wednesday. The Nasdaq fell but finished off lows and held the bulk of Tuesday's gains, much like AI rally leader Nvidia (NVDA). Many other big techs had quiet sessions after Tuesday's strong moves. Laggard Tesla (TSLA), however, broke lower, extending its long run of underperformance amid negative headlines. Market breadth was solid. While AI stocks have clearly led the market rally, a number of stocks in the commodity, travel and medical product spaces are in buy areas now. Freeport-McMoRan (FCX), PBF Energy (PBF) and Royal Caribbean (RCL) cleared a buy point. Shockwave Medical (SWAV) and Dexcom (DXCM) remain in buy areas. However, bullish sentiment has reached excessive levels, suggesting a pullback is likely in the coming days. The market rally has refused to take extended breaks, staging "cat nap" pullbacks for a day or two before quickly revving higher again and looking extended again. Nvidia and Dexcom stock are on IBD Leaderboard. Nvidia, SentinelOne and Royal Caribbean stock are on the IBD 50. Nvidia stock is on the IBD Big Cap 20. Dexcom was Wednesday's IBD Stock Of The Day. Dow Jones Futures Today Dow Jones futures were 0.1% above fair value. S&P 500 futures climbed 0.1% and Nasdaq 100 futures rose 0.2%. Remember that overnight action in Dow futures and elsewhere doesn't necessarily translate into actual trading in the next regular stock market session. Join IBD experts as they analyze leading stocks and the market on IBD Live Earnings Lennar earnings topped while revenue fell short. LEN stock fell slightly overnight. Shares dipped 0.3% in Wednesday's regular session to 165.50 after hitting a record high intraday. Lennar stock slightly extended from a flat base with a 156.01 buy point, according to MarketSmith analysis. UiPath earnings topped with the automation software maker guiding lower on Q1 revenue but up for fiscal 2025. PATH stock rose slightly late after initially surging in volatile action. Shares dipped 0.85% to 24.43 on Wednesday, but held onto the recent move above the 50-day following a failed recent breakout. A move above Wednesday's high of 25.33 would offer an early entry. SentinelOne narrowly beat fiscal Q4 views, but guided slightly lower on fiscal 2025 revenue. Shares tumbled overnight. SentinelOne stock fell 1 cent to 27.94 on Wednesday, briefly testing a downward-sloping trendline. That offered an early entry in an emerging base, but the imminent earnings report made that risky. Stock Market Rally The stock market rally had a mixed session, with the S&P 500 and Nasdaq falling modestly, ceding only a portion of Tuesday's gains. The Dow Jones Industrial Average rose 0.1% in Wednesday's stock market trading. Meanwhile, the S&P 500 index dipped 0.2%. The Nasdaq composite declined 0.5%, but it was an inside day to Tuesday's 1.5% pop. Nvidia fell 1.1% but was off lows in an inside day to Tuesday's 7.2% jump. The small-cap Russell 2000 edged up 0.3%. Breadth was modestly positive, though decliners narrowly led on the Nasdaq. While Nvidia and many AI hardware plays are clearly extended, there are some software, commodity, medical product, financial, energy and travel names that are actionable or setting up. U.S. crude oil prices popped 2.8% to $79.72 a barrel. Gasoline futures gained 2.9% — 5.3% this week — to their highest close in nearly six months. Copper futures jumped 3.25% to $4.0525 a pound, the highest close since April 2023. It was the biggest percentage gain since late 2022. The 10-year Treasury yield rose 3.5 basis points to 4.19%. Bullish Sentiment Excessive The Investors Intelligence bulls-bears sentiment gauge is reaching euphoric levels. Some 60.9% of investment advisors are bullish, above the 60% level seen as excessive. That suggests a pullback, perhaps a more serious one, is coming. But it doesn't have to happen right away. That's the highest point since mid-2021. Just 14.5% are bearish, also the lowest since 2021. A modest pause or pullback over several days or even weeks would likely cool sentiment, let more bases form and give the market room for a longer run. But that hasn't been the market's pattern. ETFs Among growth ETFs, the iShares Expanded Tech-Software Sector ETF (IGV) fell 0.7%. The VanEck Vectors Semiconductor ETF (SMH) slumped 2%. Nvidia stock is the No. 1 holding in SMH. Reflecting more-speculative story stocks, ARK Innovation ETF (ARKK) edged up 0.2% and ARK Genomics ETF (ARKG) rose 0.3%. Tesla stock is a major holding across Ark Invest's ETFs. UiPath also is a big Cathie Wood stock. SPDR S&P Metals & Mining ETF (XME) edged higher, with FCX stock in the ETF. U.S. Global Jets ETF (JETS) ascended 0.7%. SPDR S&P Homebuilders ETF (XHB) stepped up 1.5%, with Lennar stock a key holding. The Energy Select SPDR ETF (XLE) rallied 1.6% and the Health Care Select Sector SPDR Fund (XLV) fell 0.4%. The Industrial Select Sector SPDR Fund (XLI) gained 0.3%. And the Financial Select SPDR ETF (XLF) climbed 0.7%. Time The Market With IBD's ETF Market Strategy Stocks In Buy Areas Freeport-McMoRan stock gapped up 7.6% to 43.41, Wednesday's top S&P 500 performer. The copper and gold miner broke above a double-bottom base buy point of 40.99, closing out of range. However, on a weekly chart, FCX stock just topped a 43.42 cup-with-handle buy point. Southern Copper (SCCO) and more-diversified Teck Resources (TECK) also cleared bases Wednesday. PBF Energy stock leapt 9% to 54.96, clearing a 54.52 cup-with-handle buy point. PBF stock is 16% above its 50-day line. Refining peer Phillips 66 (PSX) decisively cleared a short consolidation Wednesday, while several oil and gas machinery and services firms have been actionable. Shockwave Medical stock climbed 1.8% to 269.37, testing the top of a short consolidation following an earnings gap from the 200-day line. SWAV stock already was actionable from breaking a downtrend in this recent action, which could be viewed as a handle to a huge base. Dexcom stock fell 2.7% to 131.68, falling just below a 132.03 buy point from a flat base within a much larger consolidation. Royal Caribbean stock climbed 1.8% to 132.11, clearing a 130.97 buy point from a messy flat base. Meanwhile, rival cruise line operator Carnival (CCL) cleared an aggressive entry while hotel giant Marriott Worldwide (MAR) is trying to clear a tight pattern. Tesla Stock Tesla stock skidded 4.5% to 169.50, hitting the lowest levels since last May. Shares have tumbled nearly 32% in 2024, the worst performer on the S&P 500 index. The relative strength line is at a 14-month low, reflecting Tesla's severe underperformance vs. the S&P 500 index in recent months. The RS line is the blue line in the charts provided. Before Wednesday's open, Wells Fargo downgraded Tesla to underweight and cut its price target to 125 from 200. The analyst joined a recent rush to slash first-quarter delivery targets. He now sees 2024 earnings per share nearly a third below consensus. And he expects deliveries to fall short. Wells Fargo also said a yet-unveiled cheap EV may be not be a boon for Tesla, citing "likely tough" economics. Late Wednesday, UBS cut its Tesla price target to 165 from 225, also slashing its first-quarter delivery targets. TSLA stock fell a fraction overnight. Fisker (FSR) plunged more than 40% late Wednesday, on a report that the U.S. EV startup and would-be Tesla rival is preparing for a possible bankruptcy filing.

You must rely only on information contained in the prompt/context block to formulate your answer. No outside sources of information can be relied on.

What role do loan commitments play in a bank's liquidity risk?

Credit Risk For most banks, loans are the largest and most obvious source of credit risk. However, there are other pockets of credit risk both on and off the balance sheet, such as the investment portfolio, overdrafts, and letters of credit. Many products, activities, and services, such as derivatives, foreign exchange, and cash management services, also expose a bank to credit risk. The risk of repayment, i.e., the possibility that an obligor will fail to perform as agreed, is either lessened or increased by a bank’s credit risk management practices. A bank’s first defense against excessive credit risk is the initial credit-granting process − sound underwriting standards, an efficient, balanced Loan Portfolio Management 5 Comptroller’s Handbook approval process, and a competent lending staff. Because a bank cannot easily overcome borrowers with questionable capacity or character, these factors exert a strong influence on credit quality. Borrowers whose financial performance is poor or marginal, or whose repayment ability is dependent upon unproven projections can quickly become impaired by personal or external economic stress. Management of credit risk, however, must continue after a loan has been made, for sound initial credit decisions can be undermined by improper loan structuring or inadequate monitoring. Traditionally, banks have focused on oversight of individual loans in managing their overall credit risk. While this focus is important, banks should also view credit risk management in terms of portfolio segments and the entire portfolio. The focus on managing individual credit risk did not avert the credit crises of the 1980s. However, had the portfolio approach to risk management augmented these traditional risk management practices, banks might have at least reduced their losses. Effective management of the loan portfolio’s credit risk requires that the board and management understand and control the bank’s risk profile and its credit culture. To accomplish this, they must have a thorough knowledge of the portfolio’s composition and its inherent risks. They must understand the portfolio’s product mix, industry and geographic concentrations, average risk ratings, and other aggregate characteristics. They must be sure that the policies, processes, and practices implemented to control the risks of individual loans and portfolio segments are sound and that lending personnel adhere to them. Banks engaged in international lending face country risks that domestic lenders do not. Country risk encompasses all of the uncertainties arising from a nation’s economic, social, and political conditions that may affect the payment of foreigners’ debt and equity investments. Country risk includes the possibility of political and social upheaval, nationalization and expropriation of assets, governmental repudiation of external indebtedness, exchange controls, and currency devaluation or depreciation. Unless a nation repudiates its external debt, these developments might not make a loan uncollectible. However, even a delay in collection could weaken the lending bank. Loan Portfolio Management 6 Comptroller’s Handbook Transfer risk, which is a narrower form of country risk, is the possibility that an obligor will not be able to pay because the currency of payment is unavailable. This unavailability may be a matter of government policy. For example, although an individual borrower may be very successful and have sufficient local currency cash flow to pay its foreign (e.g., U.S. dollar) debt, the borrower’s country may not have sufficient U.S. dollars available to permit repayment of the foreign indebtedness. The transfer risk associated with banks’ exposures in foreign countries is evaluated by the Interagency Country Exposure Review Committee (ICERC). For examination purposes, the transfer risk rating assigned to a country by the ICERC applies to all bank assets in that country. However, examiners may classify individual loans and other assets more severely for credit risk reasons. Strategies for managing country risk will be discussed in “Country Risk Management,” a separate booklet in the Comptroller’s Handbook. Interest Rate Risk The level of interest rate risk attributed to the bank’s lending activities depends on the composition of its loan portfolio and the degree to which the terms of its loans (e.g., maturity, rate structure, embedded options) expose the bank’s revenue stream to changes in rates. Pricing and portfolio maturity decisions should be made with an eye to funding costs and maturities. When significant individual credits or portfolio segments are especially sensitive to interest rate risk, they should be periodically stress-tested. If the asset/liability management committee (ALCO), which typically is responsible for managing the bank’s interest rate risk, is to manage all of the bank’s positions, it must have sufficient reports on loan portfolio and pipeline composition and trends. These reports might include a maturing loans report, pipeline report, and rate and repricing report. Banks frequently shift interest rate risk to their borrowers by structuring loans with variable interest rates. Borrowers with marginal repayment capacity may experience financial difficulty if the interest rates on these loans increase. As part of the risk management process, banks should identify borrowers whose loans have heightened sensitivity to interest rate changes Loan Portfolio Management 7 Comptroller’s Handbook and develop strategies to mitigate the risk. One method is to require vulnerable borrowers to purchase interest rate protection or otherwise hedge the risk. The Comptroller’s Handbook booklet “Interest Rate Risk” provides guidance on interest rate risk management. Liquidity Risk Because of the size of the loan portfolio, effective management of liquidity risk requires that there be close ties to, and good information flow from, the lending function. Obviously, loans are a primary use of funds. And while controlling loan growth has always been a large part of liquidity management, historically the loan portfolio has not been viewed as a significant source of funds for liquidity management. Practices are changing, however. Banks can use the loan portfolio as a source of funds by reducing the total dollar volume of loans through sales, securitization, and portfolio run-off. In fact, banks are taking a more active role in managing their loan portfolios. While these activities are often initiated to manage credit risk, they have also improved liquidity. Banks increasingly are originating loans “for sale” or securitization. Consumer loans (mortgages, instalment loans, and credit cards) are routinely originated for immediate securitization. Many larger banks have been expanding their underwriting for the syndicated loan market. Additionally, banks are also expanding the packaging and sale of distressed credits and otherwise undesirable loans. As part of liquidity planning, a bank’s overall liquidity strategy should include the identification of those loans or loan portfolio segments that may be easily converted to cash. A loan’s liquidity hinges on such characteristics as its quality, pricing, scheduled maturities, and conformity to market standards for underwriting. Loans are also a source of liquidity when used as collateral for borrowings. The ease with which a bank can participate or sell loans to other lenders or investors (and the terms on which the bank can do so) will vary with market conditions, the type of loan, and the quality of loan. Information provided for liquidity analysis should include an assessment of these variables under various scenarios. Loan Portfolio Management 8 Comptroller’s Handbook Liquidity is also affected by the amount of the bank’s commitments to lend and the actual amount that borrowers draw against those commitments. A bank should have systems to track commitments and borrower usage. Knowledge of the types of commitments, deals in the pipeline, normal usage levels, and historically high usage levels are important in assessing whether available liquidity will be adequate for normal, seasonal, or emergency needs. Management information systems should distinguish between commitments that the bank is legally obligated to fund and those (guidance or advisory lines) that it is not. Any analysis of a bank’s ability to reduce or cut existing commitments must consider more than its legal obligation to lend. It should also consider reputation risk and the potential for lender-liability actions. The withdrawal or reduction of commitments can have significant ramifications for a bank. From a strategic perspective, any tightening of commitments may adversely affect a bank’s ability to maintain or grow a customer base if it is perceived as an unreliable lender in tight credit markets. A bank’s reputation may also suffer if it is perceived as unwilling to support community credit needs. Given these ancillary risks, bank management must carefully assess the implications of curtailing lending lines.

You must rely only on information contained in the prompt/context block to formulate your answer. No outside sources of information can be relied on. Credit Risk For most banks, loans are the largest and most obvious source of credit risk. However, there are other pockets of credit risk both on and off the balance sheet, such as the investment portfolio, overdrafts, and letters of credit. Many products, activities, and services, such as derivatives, foreign exchange, and cash management services, also expose a bank to credit risk. The risk of repayment, i.e., the possibility that an obligor will fail to perform as agreed, is either lessened or increased by a bank’s credit risk management practices. A bank’s first defense against excessive credit risk is the initial credit-granting process − sound underwriting standards, an efficient, balanced Loan Portfolio Management 5 Comptroller’s Handbook approval process, and a competent lending staff. Because a bank cannot easily overcome borrowers with questionable capacity or character, these factors exert a strong influence on credit quality. Borrowers whose financial performance is poor or marginal, or whose repayment ability is dependent upon unproven projections can quickly become impaired by personal or external economic stress. Management of credit risk, however, must continue after a loan has been made, for sound initial credit decisions can be undermined by improper loan structuring or inadequate monitoring. Traditionally, banks have focused on oversight of individual loans in managing their overall credit risk. While this focus is important, banks should also view credit risk management in terms of portfolio segments and the entire portfolio. The focus on managing individual credit risk did not avert the credit crises of the 1980s. However, had the portfolio approach to risk management augmented these traditional risk management practices, banks might have at least reduced their losses. Effective management of the loan portfolio’s credit risk requires that the board and management understand and control the bank’s risk profile and its credit culture. To accomplish this, they must have a thorough knowledge of the portfolio’s composition and its inherent risks. They must understand the portfolio’s product mix, industry and geographic concentrations, average risk ratings, and other aggregate characteristics. They must be sure that the policies, processes, and practices implemented to control the risks of individual loans and portfolio segments are sound and that lending personnel adhere to them. Banks engaged in international lending face country risks that domestic lenders do not. Country risk encompasses all of the uncertainties arising from a nation’s economic, social, and political conditions that may affect the payment of foreigners’ debt and equity investments. Country risk includes the possibility of political and social upheaval, nationalization and expropriation of assets, governmental repudiation of external indebtedness, exchange controls, and currency devaluation or depreciation. Unless a nation repudiates its external debt, these developments might not make a loan uncollectible. However, even a delay in collection could weaken the lending bank. Loan Portfolio Management 6 Comptroller’s Handbook Transfer risk, which is a narrower form of country risk, is the possibility that an obligor will not be able to pay because the currency of payment is unavailable. This unavailability may be a matter of government policy. For example, although an individual borrower may be very successful and have sufficient local currency cash flow to pay its foreign (e.g., U.S. dollar) debt, the borrower’s country may not have sufficient U.S. dollars available to permit repayment of the foreign indebtedness. The transfer risk associated with banks’ exposures in foreign countries is evaluated by the Interagency Country Exposure Review Committee (ICERC). For examination purposes, the transfer risk rating assigned to a country by the ICERC applies to all bank assets in that country. However, examiners may classify individual loans and other assets more severely for credit risk reasons. Strategies for managing country risk will be discussed in “Country Risk Management,” a separate booklet in the Comptroller’s Handbook. Interest Rate Risk The level of interest rate risk attributed to the bank’s lending activities depends on the composition of its loan portfolio and the degree to which the terms of its loans (e.g., maturity, rate structure, embedded options) expose the bank’s revenue stream to changes in rates. Pricing and portfolio maturity decisions should be made with an eye to funding costs and maturities. When significant individual credits or portfolio segments are especially sensitive to interest rate risk, they should be periodically stress-tested. If the asset/liability management committee (ALCO), which typically is responsible for managing the bank’s interest rate risk, is to manage all of the bank’s positions, it must have sufficient reports on loan portfolio and pipeline composition and trends. These reports might include a maturing loans report, pipeline report, and rate and repricing report. Banks frequently shift interest rate risk to their borrowers by structuring loans with variable interest rates. Borrowers with marginal repayment capacity may experience financial difficulty if the interest rates on these loans increase. As part of the risk management process, banks should identify borrowers whose loans have heightened sensitivity to interest rate changes Loan Portfolio Management 7 Comptroller’s Handbook and develop strategies to mitigate the risk. One method is to require vulnerable borrowers to purchase interest rate protection or otherwise hedge the risk. The Comptroller’s Handbook booklet “Interest Rate Risk” provides guidance on interest rate risk management. Liquidity Risk Because of the size of the loan portfolio, effective management of liquidity risk requires that there be close ties to, and good information flow from, the lending function. Obviously, loans are a primary use of funds. And while controlling loan growth has always been a large part of liquidity management, historically the loan portfolio has not been viewed as a significant source of funds for liquidity management. Practices are changing, however. Banks can use the loan portfolio as a source of funds by reducing the total dollar volume of loans through sales, securitization, and portfolio run-off. In fact, banks are taking a more active role in managing their loan portfolios. While these activities are often initiated to manage credit risk, they have also improved liquidity. Banks increasingly are originating loans “for sale” or securitization. Consumer loans (mortgages, instalment loans, and credit cards) are routinely originated for immediate securitization. Many larger banks have been expanding their underwriting for the syndicated loan market. Additionally, banks are also expanding the packaging and sale of distressed credits and otherwise undesirable loans. As part of liquidity planning, a bank’s overall liquidity strategy should include the identification of those loans or loan portfolio segments that may be easily converted to cash. A loan’s liquidity hinges on such characteristics as its quality, pricing, scheduled maturities, and conformity to market standards for underwriting. Loans are also a source of liquidity when used as collateral for borrowings. The ease with which a bank can participate or sell loans to other lenders or investors (and the terms on which the bank can do so) will vary with market conditions, the type of loan, and the quality of loan. Information provided for liquidity analysis should include an assessment of these variables under various scenarios. Loan Portfolio Management 8 Comptroller’s Handbook Liquidity is also affected by the amount of the bank’s commitments to lend and the actual amount that borrowers draw against those commitments. A bank should have systems to track commitments and borrower usage. Knowledge of the types of commitments, deals in the pipeline, normal usage levels, and historically high usage levels are important in assessing whether available liquidity will be adequate for normal, seasonal, or emergency needs. Management information systems should distinguish between commitments that the bank is legally obligated to fund and those (guidance or advisory lines) that it is not. Any analysis of a bank’s ability to reduce or cut existing commitments must consider more than its legal obligation to lend. It should also consider reputation risk and the potential for lender-liability actions. The withdrawal or reduction of commitments can have significant ramifications for a bank. From a strategic perspective, any tightening of commitments may adversely affect a bank’s ability to maintain or grow a customer base if it is perceived as an unreliable lender in tight credit markets. A bank’s reputation may also suffer if it is perceived as unwilling to support community credit needs. Given these ancillary risks, bank management must carefully assess the implications of curtailing lending lines. What role do loan commitments play in a bank's liquidity risk?

I want to only be given information based on the context provided. The answer should be within 60-70 words in length.

Can you summarize how the AICOA could help big companies?

The primary concern with this type of conduct involves monopoly leveraging.542 As discussed, leveraging theories of harm can take two forms. Offensive leveraging occurs when a firm attempts to use monopoly power in a primary market to extract additional profits from a secondary market.543 By contrast, defensive leveraging involves the use of monopoly power to gain an advantage in a secondary market so as to preserve a primary market monopoly—for example, by eliminating competitive threats that might emerge from the secondary market.544 Defensive leveraging may be a viable theory of harm under existing monopolization law.545 Offensive-leveraging claims, however, cannot succeed under Section 2 absent evidence that a defendant had a dangerous probability of monopolizing a secondary market; mere harm to competition in the secondary market is not sufficient.546 For some of the self-preferencing allegations against Big Tech firms, these limitations may preclude antitrust claims.547 It may be unlikely, for example, that Amazon will achieve monopoly power over most of the products that it sells on its marketplace. As a result, it would be difficult to challenge the preferential display of those products under an offensive-leveraging theory.548 This type of alleged favoritism may also be a weak foundation for a defensive-leveraging or monopoly-maintenance case; it is not clear that Amazon’s elevation of allegedly inferior products would help it maintain a putative e-commerce monopoly. Similarly, the case law governing refusals to deal may serve as an impediment to antitrust claims challenging platform self-preferencing. A platform operator’s favorable treatment of its own verticals relative to rivals that use its platform is typically less harmful to rivals than an outright refusal of access.549 Because antitrust imposes access duties only in a narrow set of circumstances, courts would likely find many forms of self-preferencing to be permissible if such conduct is evaluated as a refusal to deal.550 In the 118th Congress, the American Innovation and Choice Online Act (AICOA) would respond to these doctrinal difficulties by prohibiting covered platform operators from preferencing their own products and services “in a manner that would materially harm competition.”551 Given the ubiquity of self-preferencing by vertically integrated firms, the meaning of the “materially harm competition” standard is key to assessing the prohibition’s scope. However, many argue the meaning of that language is not clear.552 The bill does not by its terms clarify whether the “materially harm competition” standard embodies a consumer-welfare test or one of the alternative standards for assessing competitive harm urged by proponents of antitrust reform.553 As a result, it is unclear whether the AICOA would permit defendants to justify challenged conduct on the ground that it benefits consumers. If the AICOA becomes law, this may be a dispositive issue in many litigated cases. A wide range of platform self-preferencing may harm a firm’s rivals while also offering consumer benefits. For example, when Google displays a Google Maps result in response to a search query, it may disadvantage rival map services, but benefit consumers.554 Apple’s preinstallation of its own apps on iPhones, Microsoft’s inclusion of certain apps with its Windows operating system, and Amazon’s free provision of its video-streaming service to Amazon Prime members may have similar effects.555 It is not clear how the “materially harm competition” standard would apply to such practices. In cases that do not involve per se offenses, Sherman Act defendants typically have the opportunity to defend challenged conduct on the ground that it benefits consumers.556 To the extent that the “materially harm competition” standard is intended to incorporate prevailing concepts of competitive harm from the antitrust case law, then, consumer-welfare arguments would likely be cognizable In interpreting other industry-specific competition statutes, however, some courts and commentators have taken the view that “harm to competition” encompasses types of harm beyond those proscribed by the antitrust laws.557 Additionally, some of the AICOA’s proponents have rejected suggestions to amend the bill to adopt a consumer-welfare test.558 An interpretation that eschewed consumer-welfare justifications would also be consistent with the normative vision articulated by many advocates of antitrust reform. As discussed, the role that consumer welfare is meant to play in non-welfarist conceptions of “competition” is not clear.559 Much of the reformist literature, though, appears to reject the idea that courts and enforcers should balance different antitrust goals against one another.560 This context, along with the bill’s omission of other traditional antitrust concepts like market power, may cut against the argument that consumer-welfare arguments would be cognizable under the “materially harm competition” standard.561 The DCPCA appears to be more explicit about this issue. That legislation would make it presumptively unlawful for covered platforms to preference their own products and services, “regardless of any alleged procompetitive benefits or efficiencies.”562 Defendants could rebut an allegation of unlawful self-preferencing only by establishing by clear and convincing evidence that their conduct “did not result in any harm to the relevant aggrieved party.”563

The primary concern with this type of conduct involves monopoly leveraging.542 As discussed, leveraging theories of harm can take two forms. Offensive leveraging occurs when a firm attempts to use monopoly power in a primary market to extract additional profits from a secondary market.543 By contrast, defensive leveraging involves the use of monopoly power to gain an advantage in a secondary market so as to preserve a primary market monopoly—for example, by eliminating competitive threats that might emerge from the secondary market.544 Defensive leveraging may be a viable theory of harm under existing monopolization law.545 Offensive-leveraging claims, however, cannot succeed under Section 2 absent evidence that a defendant had a dangerous probability of monopolizing a secondary market; mere harm to competition in the secondary market is not sufficient.546 For some of the self-preferencing allegations against Big Tech firms, these limitations may preclude antitrust claims.547 It may be unlikely, for example, that Amazon will achieve monopoly power over most of the products that it sells on its marketplace. As a result, it would be difficult to challenge the preferential display of those products under an offensive-leveraging theory.548 This type of alleged favoritism may also be a weak foundation for a defensive-leveraging or monopoly-maintenance case; it is not clear that Amazon’s elevation of allegedly inferior products would help it maintain a putative e-commerce monopoly. Similarly, the case law governing refusals to deal may serve as an impediment to antitrust claims challenging platform self-preferencing. A platform operator’s favorable treatment of its own verticals relative to rivals that use its platform is typically less harmful to rivals than an outright refusal of access.549 Because antitrust imposes access duties only in a narrow set of circumstances, courts would likely find many forms of self-preferencing to be permissible if such conduct is evaluated as a refusal to deal.550 In the 118th Congress, the American Innovation and Choice Online Act (AICOA) would respond to these doctrinal difficulties by prohibiting covered platform operators from preferencing their own products and services “in a manner that would materially harm competition.”551 Given the ubiquity of self-preferencing by vertically integrated firms, the meaning of the “materially harm competition” standard is key to assessing the prohibition’s scope. However, many argue the meaning of that language is not clear.552 The bill does not by its terms clarify whether the “materially harm competition” standard embodies a consumer-welfare test or one of the alternative standards for assessing competitive harm urged by proponents of antitrust reform.553 As a result, it is unclear whether the AICOA would permit defendants to justify challenged conduct on the ground that it benefits consumers. If the AICOA becomes law, this may be a dispositive issue in many litigated cases. A wide range of platform self-preferencing may harm a firm’s rivals while also offering consumer benefits. For example, when Google displays a Google Maps result in response to a search query, it may disadvantage rival map services, but benefit consumers.554 Apple’s preinstallation of its own apps on iPhones, Microsoft’s inclusion of certain apps with its Windows operating system, and Amazon’s free provision of its video-streaming service to Amazon Prime members may have similar effects.555 It is not clear how the “materially harm competition” standard would apply to such practices. In cases that do not involve per se offenses, Sherman Act defendants typically have the opportunity to defend challenged conduct on the ground that it benefits consumers.556 To the extent that the “materially harm competition” standard is intended to incorporate prevailing concepts of competitive harm from the antitrust case law, then, consumer-welfare arguments would likely be cognizable In interpreting other industry-specific competition statutes, however, some courts and commentators have taken the view that “harm to competition” encompasses types of harm beyond those proscribed by the antitrust laws.557 Additionally, some of the AICOA’s proponents have rejected suggestions to amend the bill to adopt a consumer-welfare test.558 An interpretation that eschewed consumer-welfare justifications would also be consistent with the normative vision articulated by many advocates of antitrust reform. As discussed, the role that consumer welfare is meant to play in non-welfarist conceptions of “competition” is not clear.559 Much of the reformist literature, though, appears to reject the idea that courts and enforcers should balance different antitrust goals against one another.560 This context, along with the bill’s omission of other traditional antitrust concepts like market power, may cut against the argument that consumer-welfare arguments would be cognizable under the “materially harm competition” standard.561 The DCPCA appears to be more explicit about this issue. That legislation would make it presumptively unlawful for covered platforms to preference their own products and services, “regardless of any alleged procompetitive benefits or efficiencies.”562 Defendants could rebut an allegation of unlawful self-preferencing only by establishing by clear and convincing evidence that their conduct “did not result in any harm to the relevant aggrieved party.”563 Can you summarize how the AICOA could help big companies? I want to only be given information based on the context provided. The answer should be within 60-70 words in length.

[question] [user request] ===================== [text] [context document] ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

Hey I have a nintendo switch and thought about getting the OLED version. Hwoever, I hear the new switch is coming out pretty soon. But I thought it was releasing in 2024. Why are they pushing it to 2025? Also what will it look like and will I still be able to play my current games? Give me more than 300 words.

Nintendo Switch 2: Everything We Know About the New Console Nintendo’s new console is most likely arriving in 2025. Sarah Thwaites Avatar By Sarah Thwaites Updated: May 21, 2024 3:26 pm Posted: Apr 26, 2024 2:30 pm It’s been over six years since the Nintendo Switch launched in 2017, and after a long and successful reign, you may be wondering what new piece of hardware will be next. We’ve seen updates to the current switch with the OLED and Lite models, though we’re still in the dark on what Nintendo’s next-gen offering could be. After becoming the 3rd best-selling console in history this year, it’s fair to say that Nintendo might want to keep things close to its chest. Yet, even with all the secrecy surrounding the possibility of a new Nintendo Switch, we’ve collected all the details we could find about the mystery follow-up ahead of its eventual official announcement and release. Nintendo Switch 2 Release Date - Latest News While Nintendo hasn’t yet announced any official follow-up to their incredibly successful Nintendo Switch console, there are enough rumors swirling about to make us believe that the next Nintendo console will arrive sometime in 2025 rather than 2024. In February 2024, the Japanese publication Nikkei suggested that the proposed Nintendo Switch 2 would launch in March 2025 at the earliest, contradicting previous reports. While the article covered information we’ve heard before, like the proposed iterative design scheme, Nikkei did add that the 2025 date was likely due to the company stockpiling consoles to avoid scalping at launch. As any long-term Nintendo fan knows, procuring one of the company’s new consoles can be tricky business. Those who tried will remember how difficult it was to secure a Nintendo Switch at launch in 2017, with the console suffering from inflated pricing on the aftermarket due to crafty resellers. Adding to the intrigue about a potential date change, it looks like Nintendo won’t be exhibiting at this year’s Gamescom, an annual trade fair held in Cologne, Germany. As reported by GamesIndustry.biz, a representative of Nintendo of Europe issued a statement to the German outlet Games Wirtschaft, confirming the news. The statement reads, "Gamescom is a central event in Nintendo's event calendar. This year, however, after careful consideration, we decided against taking part in Cologne. Instead, players can try out the games for Nintendo Switch as part of other Germany-wide events." This decision, while not unprecedented for major players - PlayStation also missed the event in 2022 and 2023 - does raise the question of what we can expect from Nintendo in the latter half of 2024. Could this be a sign of a major announcement coming or a strategic shift in their marketing approach? Only time will tell. Nintendo’s president, Shuntaro Furukawa, confirmed in an interview with Nikkei, and translated by VGC, that Nintendo will support the current-gen Switch until at least March 2025. This sentiment is also backed up by previous comments Furukawa made regarding the future of the Nintendo Switch in a financial briefing Q&A in 2022. In this interview, he committed to focusing on “building long-term relationships with our consumers (through Nintendo Accounts)," he went on to reiterate ", While continuing to release new Nintendo Switch software for consumers to enjoy, we aim to maintain relationships across hardware generations through services that utilize Nintendo Accounts and by providing opportunities for them to experience our IP through other non-gaming channels." Even with all the juicy gossip, it’s best not to hold your breath on what’s coming from the Japanese tech titan’s next console until there is an official announcement; fingers crossed we’ll get that confirmation soon. Nintendo Switch 2 Price There are plenty of Nintendo Switch models to consider while shopping right now, with pricing shifting dramatically depending on the version you’re looking to invest in. Looking forward to a potential Switch 2, inflation and internal specs, amongst other variables, will likely play a part in what we’ll pay for a new console at launch. It’s hard to know what the pricing of this mystery device will be, but we’ve listed the RRP of the current range of Nintendo Switch models as a reference: Nintendo Switch Lite: $199.99 Nintendo Switch: $299.99 Nintendo Switch OLED: $349.99 Nintendo Switch 2 Models With the range of Nintendo Switch consoles currently on the market, you may be left wondering if you’ll have the same number of choices to pick between when the next iteration rolls around. The latest Nintendo Switch OLED model features a remarkable screen, and it feels like the future of the console, it being the most recent edition to Nintendo’s lineup. However, according to a VGC report, the next-gen Nintendo Switch may potentially feature an LCD screen instead. The current array of Nintendo Switch models are numerous and were released over the console’s multi-year lifespan, so it’s reasonable to believe there may be several versions of a potential Nintendo Switch follow-up, too. Nintendo Switch Design - What Will the Nintendo Switch 2 Look Like? There isn’t a lot of information on how Nintendo’s next-gen console will look, though there are plenty of features in the current-gen Nintendo Switch we’d love to see return for a follow-up console. VGC reported that development kits for the potential new console are already with partner studios, with sources citing some returning features. According to VGC’s report, the new Nintendo Switch could keep the portability of its predecessor and feature a cartridge slot for physical games. In May 2023, a patent was filed with the United States Patent Office and published in September, which suggests a potential revamped Joy-Con controller that would hopefully help with the notorious Joy-Con drift issue associated with the Nintendo Switch. The patent details a magnetic field for controls rather than the plastic circuit boards seen in the current generation console. However, it’s worth mentioning that patents don’t necessarily translate directly to future products, so there’s no guarantee on whether the Nintendo Switch 2 will feature updated Joy-Cons, and we’ll have to wait for official word from Nintendo on that front. Will the Nintendo Switch 2 be Backwards Compatible? As rumors swirl about the possibility of a Nintendo Switch 2, the question of backwards compatibility is naturally on everyone's lips. In the absence of any official reveals, there isn’t much to go on at this time. However, in a recent interview with Inverse, the aptly named Nintendo of America president, Doug Bowser, alluded to the future of the brand’s approach to software. While Bowser opted to deny commenting on anything related to the rumored console, he did talk about the Nintendo Account system that players’ digital libraries are currently tied to on the Nintendo Switch. “In the past, every device we transitioned to had a whole new account system. Creating the Nintendo Account will allow us to communicate with our players if and when we make a transition to a new platform, to help ease that process or transition.” This dedication to the Nintendo Account model could suggest that all of our favorite Nintendo Switch games may work on the company’s next console whenever it lands. Regardless, given the precious little that we know right now, we’ll have to take this information with a pinch of salt and not get ahead of ourselves. As it stands now, it is unclear whether or not Nintendo Switch accessories will be compatible with the new model either. It's possible that all of your Nintendo Switch controllers will work with the new console, but we don't yet know.

[question] Hey I have a nintendo switch and thought about getting the OLED version. Hwoever, I hear the new switch is coming out pretty soon. But I thought it was releasing in 2024. Why are they pushing it to 2025? Also what will it look like and will I still be able to play my current games? Give me more than 300 words. ===================== [text] Nintendo Switch 2: Everything We Know About the New Console Nintendo’s new console is most likely arriving in 2025. Sarah Thwaites Avatar By Sarah Thwaites Updated: May 21, 2024 3:26 pm Posted: Apr 26, 2024 2:30 pm It’s been over six years since the Nintendo Switch launched in 2017, and after a long and successful reign, you may be wondering what new piece of hardware will be next. We’ve seen updates to the current switch with the OLED and Lite models, though we’re still in the dark on what Nintendo’s next-gen offering could be. After becoming the 3rd best-selling console in history this year, it’s fair to say that Nintendo might want to keep things close to its chest. Yet, even with all the secrecy surrounding the possibility of a new Nintendo Switch, we’ve collected all the details we could find about the mystery follow-up ahead of its eventual official announcement and release. Nintendo Switch 2 Release Date - Latest News While Nintendo hasn’t yet announced any official follow-up to their incredibly successful Nintendo Switch console, there are enough rumors swirling about to make us believe that the next Nintendo console will arrive sometime in 2025 rather than 2024. In February 2024, the Japanese publication Nikkei suggested that the proposed Nintendo Switch 2 would launch in March 2025 at the earliest, contradicting previous reports. While the article covered information we’ve heard before, like the proposed iterative design scheme, Nikkei did add that the 2025 date was likely due to the company stockpiling consoles to avoid scalping at launch. As any long-term Nintendo fan knows, procuring one of the company’s new consoles can be tricky business. Those who tried will remember how difficult it was to secure a Nintendo Switch at launch in 2017, with the console suffering from inflated pricing on the aftermarket due to crafty resellers. Adding to the intrigue about a potential date change, it looks like Nintendo won’t be exhibiting at this year’s Gamescom, an annual trade fair held in Cologne, Germany. As reported by GamesIndustry.biz, a representative of Nintendo of Europe issued a statement to the German outlet Games Wirtschaft, confirming the news. The statement reads, "Gamescom is a central event in Nintendo's event calendar. This year, however, after careful consideration, we decided against taking part in Cologne. Instead, players can try out the games for Nintendo Switch as part of other Germany-wide events." This decision, while not unprecedented for major players - PlayStation also missed the event in 2022 and 2023 - does raise the question of what we can expect from Nintendo in the latter half of 2024. Could this be a sign of a major announcement coming or a strategic shift in their marketing approach? Only time will tell. Nintendo’s president, Shuntaro Furukawa, confirmed in an interview with Nikkei, and translated by VGC, that Nintendo will support the current-gen Switch until at least March 2025. This sentiment is also backed up by previous comments Furukawa made regarding the future of the Nintendo Switch in a financial briefing Q&A in 2022. In this interview, he committed to focusing on “building long-term relationships with our consumers (through Nintendo Accounts)," he went on to reiterate ", While continuing to release new Nintendo Switch software for consumers to enjoy, we aim to maintain relationships across hardware generations through services that utilize Nintendo Accounts and by providing opportunities for them to experience our IP through other non-gaming channels." Even with all the juicy gossip, it’s best not to hold your breath on what’s coming from the Japanese tech titan’s next console until there is an official announcement; fingers crossed we’ll get that confirmation soon. Nintendo Switch 2 Price There are plenty of Nintendo Switch models to consider while shopping right now, with pricing shifting dramatically depending on the version you’re looking to invest in. Looking forward to a potential Switch 2, inflation and internal specs, amongst other variables, will likely play a part in what we’ll pay for a new console at launch. It’s hard to know what the pricing of this mystery device will be, but we’ve listed the RRP of the current range of Nintendo Switch models as a reference: Nintendo Switch Lite: $199.99 Nintendo Switch: $299.99 Nintendo Switch OLED: $349.99 Nintendo Switch 2 Models With the range of Nintendo Switch consoles currently on the market, you may be left wondering if you’ll have the same number of choices to pick between when the next iteration rolls around. The latest Nintendo Switch OLED model features a remarkable screen, and it feels like the future of the console, it being the most recent edition to Nintendo’s lineup. However, according to a VGC report, the next-gen Nintendo Switch may potentially feature an LCD screen instead. The current array of Nintendo Switch models are numerous and were released over the console’s multi-year lifespan, so it’s reasonable to believe there may be several versions of a potential Nintendo Switch follow-up, too. Nintendo Switch Design - What Will the Nintendo Switch 2 Look Like? There isn’t a lot of information on how Nintendo’s next-gen console will look, though there are plenty of features in the current-gen Nintendo Switch we’d love to see return for a follow-up console. VGC reported that development kits for the potential new console are already with partner studios, with sources citing some returning features. According to VGC’s report, the new Nintendo Switch could keep the portability of its predecessor and feature a cartridge slot for physical games. In May 2023, a patent was filed with the United States Patent Office and published in September, which suggests a potential revamped Joy-Con controller that would hopefully help with the notorious Joy-Con drift issue associated with the Nintendo Switch. The patent details a magnetic field for controls rather than the plastic circuit boards seen in the current generation console. However, it’s worth mentioning that patents don’t necessarily translate directly to future products, so there’s no guarantee on whether the Nintendo Switch 2 will feature updated Joy-Cons, and we’ll have to wait for official word from Nintendo on that front. Will the Nintendo Switch 2 be Backwards Compatible? As rumors swirl about the possibility of a Nintendo Switch 2, the question of backwards compatibility is naturally on everyone's lips. In the absence of any official reveals, there isn’t much to go on at this time. However, in a recent interview with Inverse, the aptly named Nintendo of America president, Doug Bowser, alluded to the future of the brand’s approach to software. While Bowser opted to deny commenting on anything related to the rumored console, he did talk about the Nintendo Account system that players’ digital libraries are currently tied to on the Nintendo Switch. “In the past, every device we transitioned to had a whole new account system. Creating the Nintendo Account will allow us to communicate with our players if and when we make a transition to a new platform, to help ease that process or transition.” This dedication to the Nintendo Account model could suggest that all of our favorite Nintendo Switch games may work on the company’s next console whenever it lands. Regardless, given the precious little that we know right now, we’ll have to take this information with a pinch of salt and not get ahead of ourselves. As it stands now, it is unclear whether or not Nintendo Switch accessories will be compatible with the new model either. It's possible that all of your Nintendo Switch controllers will work with the new console, but we don't yet know. https://www.ign.com/articles/nintendo-switch-2-everything-we-know ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

"================ <TEXT PASSAGE> ======= [context document] ================ <QUESTION> ======= [user request] ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

What are the key differences between macronutrients and micronutrients in terms of their functions and the amounts required by the body and how they contribute to overall health? Explain in deep details in not more than 300 words.

What are the nutrients? The foods we eat contain nutrients. Nutrients are substances required by the body to perform its basic functions. Nutrients must be obtained from our diet since the human body can not make them. Nutrients have one or more of three basic functions: they provide energy, contribute to body structure, and/or regulate chemical processes in the body. These basic functions allow us to detect and respond to environmental surroundings, move, excrete wastes, breathe, grow, and reproduce. There are six classes of nutrients required for the body to function and maintain overall health. These are carbohydrates, lipids, proteins, water, vitamins, and minerals. Foods also contain non-nutrient that may be harmful such as natural toxins common in plant foods and additives like some dyes and preservatives or beneficial like antioxidants. macronutrients Nutrients that are needed in large amounts are called macronutrients. There are three classes of macronutrients: carbohydrates, lipids, and proteins. These can be metabolically processed into cellular energy. The energy from macronutrients comes from their chemical bonds. This chemical energy is converted into cellular energy used to perform work, allowing our bodies to conduct their basic functions. A unit of measurement of food energy is the calorie. On nutrition food labels, the amount given for “calories” is actually equivalent to each calorie multiplied by one thousand. A kilocalorie (Calorie) is the amount of heat generated by a particular macronutrient that raises the temperature of 1 kilogram of water 1 degree Celsius. On the Nutrition Facts panel, the calories within a particular food are expressed as kilocalories, which is commonly denoted as “Calories” with a capital “C” (1 kcal = 1 Calorie = 1,000 calories). Water is also a macronutrient in the sense that you require a large amount of it, but unlike the other macronutrients, it does not provide calories. carbohydrates Carbohydrates are molecules composed of carbon, hydrogen, and oxygen. The major food sources of carbohydrates are grains, milk, fruits, and starchy vegetables, like potatoes. Non-starchy vegetables also contain carbohydrates but in lesser quantities. Carbohydrates are broadly classified into two forms based on their chemical structure: simple carbohydrates, simple sugars, and complex carbohydrates. Simple carbohydrates consist of one or two basic units. Examples of simple sugars include sucrose, the type of sugar you would have in a bowl on the breakfast table, and glucose, the type of sugar that circulates in your blood. Complex carbohydrates are long chains of simple sugars that can be unbranched or branched. During digestion, the body breaks down digestible complex carbohydrates into simple sugars, mostly glucose. Glucose is then transported to all our cells, stored, used to make energy, or used to build macromolecules. Fiber is also a complex carbohydrate, but digestive enzymes cannot break it down in the human intestine. As a result, it passes through the digestive tract undigested unless the bacteria that inhabit the colon or large intestine break it down. One gram of digestible carbohydrates yields four kilocalories of energy for the body’s cells to perform work. Besides providing energy and serving as building blocks for bigger macromolecules, carbohydrates are essential for the nervous system’s proper functioning, heart, and kidneys. As mentioned, glucose can be stored in the body for future use. In humans, the storage molecule of carbohydrates is called glycogen, and in plants, it is known as starch. Glycogen and starch are complex carbohydrates. protein Proteins are macromolecules composed of chains of subunits called amino acids. Amino acids are simple subunits composed of carbon, oxygen, hydrogen, and nitrogen. Food sources of proteins include meats, dairy products, seafood, and various plant-based foods, most notably soy. The word protein comes from a Greek word meaning “of primary importance,” which is an apt description of these macronutrients; they are also known colloquially as the “workhorses” of life. Proteins provide four kilocalories of energy per gram; however, providing energy is not protein’s most important function. Proteins provide structure to bones, muscles, and skin and play a role in conducting most of the chemical reactions that take place in the body. Scientists estimate that greater than one-hundred thousand different proteins exist within the human body. The genetic codes in DNA are basically protein recipes that determine the order in which 20 different amino acids are bound together to make thousands of specific proteins. lipids Lipids are also a family of molecules composed of carbon, hydrogen, and oxygen, but they are insoluble in water, unlike carbohydrates. Lipids are found predominantly in butter, oils, meats, dairy products, nuts, seeds, and processed foods. The three main types of lipids are triglycerides (triacylglycerols), phospholipids, and sterols. The main job of lipids is to provide or store energy. Lipids provide more energy per gram than carbohydrates (nine kilocalories per gram of lipids versus four kilocalories per gram of carbohydrates). In addition to energy storage, lipids serve as a major component of cell membranes, surround and protect organs (in fat-storing tissues), provide insulation to aid in temperature regulation, and regulate many other body functions. water There is one other nutrient that we must have in large quantities: water. Water does not contain carbon but is composed of two hydrogens and one oxygen per molecule of water. More than 60 percent of your total body weight is water. Without it, nothing could be transported in or out of the body, chemical reactions would not occur, organs would not be cushioned, and body temperature would fluctuate widely. On average, an adult consumes just over two liters of water per day from food and drink combined. Since water is so critical for life’s basic processes, the amount of water input and output is significant, a topic we will explore in detail micronutrients Micronutrients are nutrients required by the body in lesser amounts but are still essential for carrying out bodily functions. Micronutrients include all the essential minerals and vitamins. There are sixteen essential minerals and thirteen vitamins. In contrast to carbohydrates, lipids, and proteins, micronutrients are not sources of energy (calories), but they assist in the process as cofactors or components of enzymes (i.e., coenzymes). Enzymes are proteins that catalyze chemical reactions in the body and are involved in all aspects of body functions, from producing energy to digesting nutrients to building macromolecules. Micronutrients play many essential roles in the body.

"================ <TEXT PASSAGE> ======= What are the nutrients? The foods we eat contain nutrients. Nutrients are substances required by the body to perform its basic functions. Nutrients must be obtained from our diet since the human body can not make them. Nutrients have one or more of three basic functions: they provide energy, contribute to body structure, and/or regulate chemical processes in the body. These basic functions allow us to detect and respond to environmental surroundings, move, excrete wastes, breathe, grow, and reproduce. There are six classes of nutrients required for the body to function and maintain overall health. These are carbohydrates, lipids, proteins, water, vitamins, and minerals. Foods also contain non-nutrient that may be harmful such as natural toxins common in plant foods and additives like some dyes and preservatives or beneficial like antioxidants. macronutrients Nutrients that are needed in large amounts are called macronutrients. There are three classes of macronutrients: carbohydrates, lipids, and proteins. These can be metabolically processed into cellular energy. The energy from macronutrients comes from their chemical bonds. This chemical energy is converted into cellular energy used to perform work, allowing our bodies to conduct their basic functions. A unit of measurement of food energy is the calorie. On nutrition food labels, the amount given for “calories” is actually equivalent to each calorie multiplied by one thousand. A kilocalorie (Calorie) is the amount of heat generated by a particular macronutrient that raises the temperature of 1 kilogram of water 1 degree Celsius. On the Nutrition Facts panel, the calories within a particular food are expressed as kilocalories, which is commonly denoted as “Calories” with a capital “C” (1 kcal = 1 Calorie = 1,000 calories). Water is also a macronutrient in the sense that you require a large amount of it, but unlike the other macronutrients, it does not provide calories. carbohydrates Carbohydrates are molecules composed of carbon, hydrogen, and oxygen. The major food sources of carbohydrates are grains, milk, fruits, and starchy vegetables, like potatoes. Non-starchy vegetables also contain carbohydrates but in lesser quantities. Carbohydrates are broadly classified into two forms based on their chemical structure: simple carbohydrates, simple sugars, and complex carbohydrates. Simple carbohydrates consist of one or two basic units. Examples of simple sugars include sucrose, the type of sugar you would have in a bowl on the breakfast table, and glucose, the type of sugar that circulates in your blood. Complex carbohydrates are long chains of simple sugars that can be unbranched or branched. During digestion, the body breaks down digestible complex carbohydrates into simple sugars, mostly glucose. Glucose is then transported to all our cells, stored, used to make energy, or used to build macromolecules. Fiber is also a complex carbohydrate, but digestive enzymes cannot break it down in the human intestine. As a result, it passes through the digestive tract undigested unless the bacteria that inhabit the colon or large intestine break it down. One gram of digestible carbohydrates yields four kilocalories of energy for the body’s cells to perform work. Besides providing energy and serving as building blocks for bigger macromolecules, carbohydrates are essential for the nervous system’s proper functioning, heart, and kidneys. As mentioned, glucose can be stored in the body for future use. In humans, the storage molecule of carbohydrates is called glycogen, and in plants, it is known as starch. Glycogen and starch are complex carbohydrates. protein Proteins are macromolecules composed of chains of subunits called amino acids. Amino acids are simple subunits composed of carbon, oxygen, hydrogen, and nitrogen. Food sources of proteins include meats, dairy products, seafood, and various plant-based foods, most notably soy. The word protein comes from a Greek word meaning “of primary importance,” which is an apt description of these macronutrients; they are also known colloquially as the “workhorses” of life. Proteins provide four kilocalories of energy per gram; however, providing energy is not protein’s most important function. Proteins provide structure to bones, muscles, and skin and play a role in conducting most of the chemical reactions that take place in the body. Scientists estimate that greater than one-hundred thousand different proteins exist within the human body. The genetic codes in DNA are basically protein recipes that determine the order in which 20 different amino acids are bound together to make thousands of specific proteins. lipids Lipids are also a family of molecules composed of carbon, hydrogen, and oxygen, but they are insoluble in water, unlike carbohydrates. Lipids are found predominantly in butter, oils, meats, dairy products, nuts, seeds, and processed foods. The three main types of lipids are triglycerides (triacylglycerols), phospholipids, and sterols. The main job of lipids is to provide or store energy. Lipids provide more energy per gram than carbohydrates (nine kilocalories per gram of lipids versus four kilocalories per gram of carbohydrates). In addition to energy storage, lipids serve as a major component of cell membranes, surround and protect organs (in fat-storing tissues), provide insulation to aid in temperature regulation, and regulate many other body functions. water There is one other nutrient that we must have in large quantities: water. Water does not contain carbon but is composed of two hydrogens and one oxygen per molecule of water. More than 60 percent of your total body weight is water. Without it, nothing could be transported in or out of the body, chemical reactions would not occur, organs would not be cushioned, and body temperature would fluctuate widely. On average, an adult consumes just over two liters of water per day from food and drink combined. Since water is so critical for life’s basic processes, the amount of water input and output is significant, a topic we will explore in detail micronutrients Micronutrients are nutrients required by the body in lesser amounts but are still essential for carrying out bodily functions. Micronutrients include all the essential minerals and vitamins. There are sixteen essential minerals and thirteen vitamins. In contrast to carbohydrates, lipids, and proteins, micronutrients are not sources of energy (calories), but they assist in the process as cofactors or components of enzymes (i.e., coenzymes). Enzymes are proteins that catalyze chemical reactions in the body and are involved in all aspects of body functions, from producing energy to digesting nutrients to building macromolecules. Micronutrients play many essential roles in the body. https://open.maricopa.edu/nutritionessentials/chapter/essential-nutrients/#:~:text=Nutrients%20have%20one%20or%20more,breathe%2C%20grow%2C%20and%20reproduce. ================ <QUESTION> ======= What are the key differences between macronutrients and micronutrients in terms of their functions and the amounts required by the body and how they contribute to overall health? Explain in deep details in not more than 300 words. ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> [user request] <TEXT> [context document]

Can you tell me about some of the health benefits of eating leafy greens listed in the articles and what are some popular leafy greens to incorporate into my diet/ways to use them. is is better to eat them cooked or raw. make the reply less than 250 words

While we all know that organic, non-GMO fruits and vegetables of any kind are good for us, some are far better than others. Fortunately, many crowd favorites such as spinach, kale, and collard greens are packed with vitamins, minerals, fiber, and even protein. Not to mention, dark leafy greens are very versatile and can be incorporated into your diet in fun, delicious ways. If you still need convincing, I’m about to tell you about all the amazing benefits of leafy greens. Unless you’ve been taking notes, you might have missed all the leafy greens I’ve mentioned so far. Don’t worry! I’ve put together this convenient list of the healthiest leafy green vegetables for you to reference: Kale Spinach Collard greens Broccoli Broccoli sprouts Cabbage Beet greens Watercress Arugula Mustard greens Swiss chard Bok choy Romaine lettuce Raw Vegetables vs. Cooked Vegetables: Which is Better? I get asked all the time if it’s better to eat raw or cooked vegetables. The answer may surprise you! While eating raw vegetables provides your body with optimal levels of folate and water-soluble vitamins, the nutrients in cooked vegetables are actually easier to digest and absorb. However, I’m going to let you in on the most delicious and easiest way to enough leafy greens in your diet – Organic Greens! The Best Way to Get More Leafy Greens While it’s ideal to get these incredible benefits from real, whole foods, not all of these foods are always available, in season, or grown in optimal soil. It can be difficult to get the benefits of leafy greens from diet alone. That’s why Organic Greens is a great option to have when you’re just too busy to prepare a big salad or smoothie, or when you’re looking to stay healthy while on the go. One scoop of Organic Greens is a nutritional powerhouse, containing 14 USDA-certified organic plant foods, including green superstars spinach, kale, alfalfa, moringa, and broccoli sprouts. It’s perfect for anyone who: Is looking to save a lot of time versus juicing their produce every morning Needs a tasty, inexpensive alternative to pricey juice bar offerings Travels often and wants a doctor-designed source of organic nutrition while eating out Wants to mitigate stress and balanced hormone health Organic Greens is an easy and convenient way to ensure you’re getting all the amazing benefits of leafy greens! I drink a glass every day! Adding more leafy greens into your diet is a great way to support optimal health, reduce bloating, facilitate a healthy stress response, support bone health, healthy aging, and gut health, and help reduce oxidative damage from free radicals. Leafy greens are the nutritional powerhouse! Benefits of Leafy Greens FAQs What are the benefits of dark leafy greens? Adding more green leafy vegetables into your diet can support optimal brain health, fight belly bloat, relieve stress, support bone health, healthy aging, boost digestive enzymes, and tame the toxins, among many other health benefits. What are the best leafy green vegetables? The best leafy vegetables include spinach, kale, collard greens, chard, turnip greens, arugula, and watercress. How often should I eat leafy greens? According to the USDA, the optimal amount of leafy greens is between 3-5 servings per day. That’s a lot! By far, the easiest way to get your optimal daily intake of leafy green vegetables is Organic Greens.

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> Can you tell me about some of the health benefits of eating leafy greens listed in the articles and what are some popular leafy greens to incorporate into my diet/ways to use them. is is better to eat them cooked or raw. make the reply less than 250 words <TEXT> While we all know that organic, non-GMO fruits and vegetables of any kind are good for us, some are far better than others. Fortunately, many crowd favorites such as spinach, kale, and collard greens are packed with vitamins, minerals, fiber, and even protein. Not to mention, dark leafy greens are very versatile and can be incorporated into your diet in fun, delicious ways. If you still need convincing, I’m about to tell you about all the amazing benefits of leafy greens. Unless you’ve been taking notes, you might have missed all the leafy greens I’ve mentioned so far. Don’t worry! I’ve put together this convenient list of the healthiest leafy green vegetables for you to reference: Kale Spinach Collard greens Broccoli Broccoli sprouts Cabbage Beet greens Watercress Arugula Mustard greens Swiss chard Bok choy Romaine lettuce Raw Vegetables vs. Cooked Vegetables: Which is Better? I get asked all the time if it’s better to eat raw or cooked vegetables. The answer may surprise you! While eating raw vegetables provides your body with optimal levels of folate and water-soluble vitamins, the nutrients in cooked vegetables are actually easier to digest and absorb. However, I’m going to let you in on the most delicious and easiest way to enough leafy greens in your diet – Organic Greens! The Best Way to Get More Leafy Greens While it’s ideal to get these incredible benefits from real, whole foods, not all of these foods are always available, in season, or grown in optimal soil. It can be difficult to get the benefits of leafy greens from diet alone. That’s why Organic Greens is a great option to have when you’re just too busy to prepare a big salad or smoothie, or when you’re looking to stay healthy while on the go. One scoop of Organic Greens is a nutritional powerhouse, containing 14 USDA-certified organic plant foods, including green superstars spinach, kale, alfalfa, moringa, and broccoli sprouts. It’s perfect for anyone who: Is looking to save a lot of time versus juicing their produce every morning Needs a tasty, inexpensive alternative to pricey juice bar offerings Travels often and wants a doctor-designed source of organic nutrition while eating out Wants to mitigate stress and balanced hormone health Organic Greens is an easy and convenient way to ensure you’re getting all the amazing benefits of leafy greens! I drink a glass every day! Adding more leafy greens into your diet is a great way to support optimal health, reduce bloating, facilitate a healthy stress response, support bone health, healthy aging, and gut health, and help reduce oxidative damage from free radicals. Leafy greens are the nutritional powerhouse! Benefits of Leafy Greens FAQs What are the benefits of dark leafy greens? Adding more green leafy vegetables into your diet can support optimal brain health, fight belly bloat, relieve stress, support bone health, healthy aging, boost digestive enzymes, and tame the toxins, among many other health benefits. What are the best leafy green vegetables? The best leafy vegetables include spinach, kale, collard greens, chard, turnip greens, arugula, and watercress. How often should I eat leafy greens? According to the USDA, the optimal amount of leafy greens is between 3-5 servings per day. That’s a lot! By far, the easiest way to get your optimal daily intake of leafy green vegetables is Organic Greens. https://www.amymyersmd.com/article/benefits-leafy-greens

System Instructions: Do not use any outside sources. Do not use any prior knowledge. Respond using only the provided text.

Question: What is the difference between the sideline and locker room evaluations?

Context: 2. Game Day Procedures a. Pregame Medical Team Meeting. Sixty (60) minutes prior to kickoff, all medicalstaff will meet in the referees’ locker room. Expected personnel include: Head Team Physician and Head Team Primary Care Sports Medicine Physician, and Head Team ATC from each team and UNCs, both Booth ATC Spotters, lead EMS paramedic for the field,referee, VTML, and the airway management physician. The pregame medical meeting is to be led by the home team Head Team Physician. Items to be covered include: introductions of medicalstaff; location of the ambulance, transport cart,spine board, defibrillator, and advanced airway equipment; review of EAP medical facilities; and location of x-ray equipment. Medicalstaffshall confirm who is responsible for verifying a concussion evaluation of an athlete, i.e., “closing the loop.” Booth ATC spotters shall review the Medical Time-Out procedures with officials. b. “No-Go” Signs and Symptoms. If a player exhibits or reports any of the following signs or symptoms of concussion, he must be removed immediately from the field of play and transported to the locker room. If a neutral sideline observer or a member of the player’s Club’s medical team observes a player exhibit or receives a report that a player has experienced any of the following signs or symptoms, the player shall be considered to have suffered a concussion and may not return to participation (practice or play) on the same day under any circumstances: i. Loss of Consciousness (including Impact Seizure and/or “fencing posture”); ii. Ataxia (abnormality of balance/stability, motor coordination, or dysfunctional speech); Amended As of October 8, 2022 iii. Confusion; or iv. Amnesia c. NFL Sideline Concussion Assessment (Sideline Survey) If a player exhibits or reports a sign or symptom of concussion (defined above), spinal cord neuropraxia or a concern is raised by the Club’s athletic trainer,Club physicians, Booth ATC Spotter, coach, teammate, game official or sideline or Booth UNCs(collectively referredto as “gameday medical personnel”)the player must be immediately removed to the sideline orstabilized on the field, as needed, the player’s helmet must be taken away from him, and the player must undergo the entire NFL Sideline Concussion Assessment1 which, at a minimum, must consist of the following: i. A review of the “No-Go” criteria listed above (Loss of Consciousness (including impact seizure and/or “fencing posture”), Ataxia, Confusion, andAmnesia), which, if present, requires the player to be brought to the lockerroom immediately and he shall not return to play; ii. Inquiry regarding the history of the event, including before, during and after the suspected mechanism of injury; iii. Review of concussion signs and symptoms (See, Section I (C and D)); iv. All Maddocks’ questions; v. Complete Video Review of the injury (detailed below), including discussion with theBooth UNC; and vi. Focused Neurological Exam, inclusive of the following: (A)Cervical Spine Examination (including range of motion and pain); (B) Evaluation of speech; (C) Testing of gait, coordination, and balance; and (D)Eye Movements and Pupillary Exam. The foregoing shall be: (i) conducted inside the medical evaluation tent on the Sideline (or in the Locker Room if the Club medical staff elects to conduct it in the Locker Room); (ii) performed using the tablet or other technology assigned by the NFL, and (iii) completion of each component of the Sideline Survey shall be confirmed using the same. If any elements of the sideline assessment are positive, inconclusive, or suspicious for the presence of a concussion, the player must be escorted to the locker room immediately for the complete NFL Locker Room Comprehensive Concussion Assessment. Also, if the player demonstrates worsening or progressing symptoms at any point, he is to be brought to the 1 The Club physician/sideline UNC unit will be co-located for all concussion evaluates and management both on and off the field. The sideline UNC may present his/her own questions or conduct additional testing and shall assist in the diagnosis and treatment of concussion. Amended As of October 8, 2022 locker room for further evaluation including the complete NFL Locker Room Comprehensive Concussion Assessment unless clinically contraindicated. Only medical personnel deemed essential to the care of the athlete may be present for the tent and/or locker room evaluation. This includes the team physician best qualified to evaluate concussion, the Club athletic trainer, and the sideline UNC. The sideline UNC may present his/her own questions or conduct additional testing and shall not be prevented in from so doing. If, upon completing the Sideline Survey, the Club physician, after consultation with the sideline UNC, concludes that the player did notsustain a concussion, then the playermay return to play. Bestpracticesfor concussion assessment include periodic checks of the player by the Club physician, sideline UNC or other medical personnel to determine whether he has developed any of the signs orsymptoms of concussion that would necessitate a locker room evaluation. UNC Involvement in Sideline Concussion Assessment: 1. The Club physician will consult in private with the members of his/her team’s medical staff designated to identify, diagnose and treat potentially concussed players, the sideline UNC and, as necessary, the Club’s ATC, prior to making his/her decision regarding whether the player will return to the game. 2. If the Club physician determines that the player shall not return to play (based on the criteria listed in Section 2.a. above) and therefore there is no need to complete the SidelineConcussionAssessment, the Club physician and the sideline UNC shall accompany the player to the locker room to evaluate the player using the NFL Locker Room Comprehensive Concussion Evaluation (see below). For more serious injury, the EAP will be activated, if indicated. 3. The Club physician remains responsible for all final decisions regarding Return-to-Play. However, the Club physician will consult with his/her sideline UNC team member prior to reaching his/her decision. If the sideline UNC disagrees with the Club physician’s decision to return the player to play or remove the athlete, the sideline UNC will be given an opportunity to explain the basis of his/her opinion. This will be discussed in a collegial fashion in private as to why the player should or should not be returned to the game. The Club physician will communicate his or her final decision to the player. Amended As of October 8, 2022 10 4. As soon as practical, following the evaluation, the individual designated at the Pregame Medical Team Meeting shall notify the booth medical personnel that an evaluation was conducted (“close the loop”). d. NFL Locker Room Comprehensive Concussion Assessment (Locker Room Exam) The NFL Locker Room Comprehensive Concussion Assessment is the standardized acute evaluation tool that has been developed by the NFL’s Head, Neck and Spine Committee to be used by Clubs’ medical staffs and designated UNCs to evaluate potential concussions during practices and on game day (see Attachment A). This evaluation is based on the Standardized Concussion Assessment Tool (SCAT 5) published by the International Concussion in Sport Group (McCrory, et al., 2017), modified for use in the NFL (Attachment A). The NFL Locker Room Comprehensive Concussion Assessment can be used to aid in the diagnosis of concussion even if there is a delayed onset of symptoms. The ongoing use of the Locker Room Comprehensive Concussion Assessment in conjunction with the preseason baseline and post-injury testing provides detailed data regarding each athlete’s injury and recovery course. Being able to compare the results from the NFL Locker Room Comprehensive Concussion Assessment to the baseline information obtained in the preseason improves the value of this instrument. Clubs shall maintain and upload to the EMR all NFL Locker Room Comprehensive Concussion Assessment exams and a copy of the same shall be given to both the player and the team medical staff. In all circumstances, the Club physician responsible for concussion evaluation shall assess the player in conjunction with the sideline UNC. The Club physician shall be responsible for determining whether the player is diagnosed as having a concussion. The athlete may have a concussion despite being able to complete the NFL Locker Room Comprehensive Concussion Assessment “within normal limits” compared to baseline, due to the potential limitations of the Assessment. Such limitations underscore the importance of knowing the athlete and the subtle deficits in their personality and behaviors that can occur with concussive injury. The signs and symptoms of concussion listed above (Section I, C and D), although frequently observed or reported, are not an exhaustive list. The NFL Locker Room Comprehensive Concussion Assessment is intended to capture these elements in a standardized format. The neurocognitive assessment in the NFL Locker Room Comprehensive Concussion Assessment is brief and does not replace a more comprehensive neurological evaluation or more formal neurocognitive testing. The Amended As of October 8, 2022 11 modified Balance Error Scoring System (mBESS) is an important component of the NFL Locker Room Comprehensive Concussion Assessment and has been validated as a useful adjunct in assessing concussive injury.

System Instructions: Do not use any outside sources. Do not use any prior knowledge. Respond using only the provided text. Question: What is the difference between the sideline and locker room evaluations? Context: 2. Game Day Procedures a. Pregame Medical Team Meeting. Sixty (60) minutes prior to kickoff, all medicalstaff will meet in the referees’ locker room. Expected personnel include: Head Team Physician and Head Team Primary Care Sports Medicine Physician, and Head Team ATC from each team and UNCs, both Booth ATC Spotters, lead EMS paramedic for the field,referee, VTML, and the airway management physician. The pregame medical meeting is to be led by the home team Head Team Physician. Items to be covered include: introductions of medicalstaff; location of the ambulance, transport cart,spine board, defibrillator, and advanced airway equipment; review of EAP medical facilities; and location of x-ray equipment. Medicalstaffshall confirm who is responsible for verifying a concussion evaluation of an athlete, i.e., “closing the loop.” Booth ATC spotters shall review the Medical Time-Out procedures with officials. b. “No-Go” Signs and Symptoms. If a player exhibits or reports any of the following signs or symptoms of concussion, he must be removed immediately from the field of play and transported to the locker room. If a neutral sideline observer or a member of the player’s Club’s medical team observes a player exhibit or receives a report that a player has experienced any of the following signs or symptoms, the player shall be considered to have suffered a concussion and may not return to participation (practice or play) on the same day under any circumstances: i. Loss of Consciousness (including Impact Seizure and/or “fencing posture”); ii. Ataxia (abnormality of balance/stability, motor coordination, or dysfunctional speech); Amended As of October 8, 2022 iii. Confusion; or iv. Amnesia c. NFL Sideline Concussion Assessment (Sideline Survey) If a player exhibits or reports a sign or symptom of concussion (defined above), spinal cord neuropraxia or a concern is raised by the Club’s athletic trainer,Club physicians, Booth ATC Spotter, coach, teammate, game official or sideline or Booth UNCs(collectively referredto as “gameday medical personnel”)the player must be immediately removed to the sideline orstabilized on the field, as needed, the player’s helmet must be taken away from him, and the player must undergo the entire NFL Sideline Concussion Assessment1 which, at a minimum, must consist of the following: i. A review of the “No-Go” criteria listed above (Loss of Consciousness (including impact seizure and/or “fencing posture”), Ataxia, Confusion, andAmnesia), which, if present, requires the player to be brought to the lockerroom immediately and he shall not return to play; ii. Inquiry regarding the history of the event, including before, during and after the suspected mechanism of injury; iii. Review of concussion signs and symptoms (See, Section I (C and D)); iv. All Maddocks’ questions; v. Complete Video Review of the injury (detailed below), including discussion with theBooth UNC; and vi. Focused Neurological Exam, inclusive of the following: (A)Cervical Spine Examination (including range of motion and pain); (B) Evaluation of speech; (C) Testing of gait, coordination, and balance; and (D)Eye Movements and Pupillary Exam. The foregoing shall be: (i) conducted inside the medical evaluation tent on the Sideline (or in the Locker Room if the Club medical staff elects to conduct it in the Locker Room); (ii) performed using the tablet or other technology assigned by the NFL, and (iii) completion of each component of the Sideline Survey shall be confirmed using the same. If any elements of the sideline assessment are positive, inconclusive, or suspicious for the presence of a concussion, the player must be escorted to the locker room immediately for the complete NFL Locker Room Comprehensive Concussion Assessment. Also, if the player demonstrates worsening or progressing symptoms at any point, he is to be brought to the 1 The Club physician/sideline UNC unit will be co-located for all concussion evaluates and management both on and off the field. The sideline UNC may present his/her own questions or conduct additional testing and shall assist in the diagnosis and treatment of concussion. Amended As of October 8, 2022 locker room for further evaluation including the complete NFL Locker Room Comprehensive Concussion Assessment unless clinically contraindicated. Only medical personnel deemed essential to the care of the athlete may be present for the tent and/or locker room evaluation. This includes the team physician best qualified to evaluate concussion, the Club athletic trainer, and the sideline UNC. The sideline UNC may present his/her own questions or conduct additional testing and shall not be prevented in from so doing. If, upon completing the Sideline Survey, the Club physician, after consultation with the sideline UNC, concludes that the player did notsustain a concussion, then the playermay return to play. Bestpracticesfor concussion assessment include periodic checks of the player by the Club physician, sideline UNC or other medical personnel to determine whether he has developed any of the signs orsymptoms of concussion that would necessitate a locker room evaluation. UNC Involvement in Sideline Concussion Assessment: 1. The Club physician will consult in private with the members of his/her team’s medical staff designated to identify, diagnose and treat potentially concussed players, the sideline UNC and, as necessary, the Club’s ATC, prior to making his/her decision regarding whether the player will return to the game. 2. If the Club physician determines that the player shall not return to play (based on the criteria listed in Section 2.a. above) and therefore there is no need to complete the SidelineConcussionAssessment, the Club physician and the sideline UNC shall accompany the player to the locker room to evaluate the player using the NFL Locker Room Comprehensive Concussion Evaluation (see below). For more serious injury, the EAP will be activated, if indicated. 3. The Club physician remains responsible for all final decisions regarding Return-to-Play. However, the Club physician will consult with his/her sideline UNC team member prior to reaching his/her decision. If the sideline UNC disagrees with the Club physician’s decision to return the player to play or remove the athlete, the sideline UNC will be given an opportunity to explain the basis of his/her opinion. This will be discussed in a collegial fashion in private as to why the player should or should not be returned to the game. The Club physician will communicate his or her final decision to the player. Amended As of October 8, 2022 10 4. As soon as practical, following the evaluation, the individual designated at the Pregame Medical Team Meeting shall notify the booth medical personnel that an evaluation was conducted (“close the loop”). d. NFL Locker Room Comprehensive Concussion Assessment (Locker Room Exam) The NFL Locker Room Comprehensive Concussion Assessment is the standardized acute evaluation tool that has been developed by the NFL’s Head, Neck and Spine Committee to be used by Clubs’ medical staffs and designated UNCs to evaluate potential concussions during practices and on game day (see Attachment A). This evaluation is based on the Standardized Concussion Assessment Tool (SCAT 5) published by the International Concussion in Sport Group (McCrory, et al., 2017), modified for use in the NFL (Attachment A). The NFL Locker Room Comprehensive Concussion Assessment can be used to aid in the diagnosis of concussion even if there is a delayed onset of symptoms. The ongoing use of the Locker Room Comprehensive Concussion Assessment in conjunction with the preseason baseline and post-injury testing provides detailed data regarding each athlete’s injury and recovery course. Being able to compare the results from the NFL Locker Room Comprehensive Concussion Assessment to the baseline information obtained in the preseason improves the value of this instrument. Clubs shall maintain and upload to the EMR all NFL Locker Room Comprehensive Concussion Assessment exams and a copy of the same shall be given to both the player and the team medical staff. In all circumstances, the Club physician responsible for concussion evaluation shall assess the player in conjunction with the sideline UNC. The Club physician shall be responsible for determining whether the player is diagnosed as having a concussion. The athlete may have a concussion despite being able to complete the NFL Locker Room Comprehensive Concussion Assessment “within normal limits” compared to baseline, due to the potential limitations of the Assessment. Such limitations underscore the importance of knowing the athlete and the subtle deficits in their personality and behaviors that can occur with concussive injury. The signs and symptoms of concussion listed above (Section I, C and D), although frequently observed or reported, are not an exhaustive list. The NFL Locker Room Comprehensive Concussion Assessment is intended to capture these elements in a standardized format. The neurocognitive assessment in the NFL Locker Room Comprehensive Concussion Assessment is brief and does not replace a more comprehensive neurological evaluation or more formal neurocognitive testing. The Amended As of October 8, 2022 11 modified Balance Error Scoring System (mBESS) is an important component of the NFL Locker Room Comprehensive Concussion Assessment and has been validated as a useful adjunct in assessing concussive injury.

Draw your answer from the above text only. Write in complete sentences and limit your answer to 150 words and 2 paragraphs. Do not use bullet points or bolding.

Detail the strategies the government is employing to encourage compliance in the tax system.

1.10 Increasing the effectiveness of the Office of Tax Simplification (OTS) – The government is publishing its first five-year review of the OTS, launched in March 2021, to examine the effectiveness of the OTS. It makes eight recommendations. 1.11 Response to Office of Tax Simplification Review of Capital Gains Tax (CGT) – The government is publishing its response to the OTS’s two-part review of CGT. The government has carefully considered the OTS’s recommendations and will keep the CGT system under review to ensure it is simple and efficient. The government has accepted five of the technical recommendations in the OTS’s second report and will work towards their implementation. 1.12 Response to Office of Tax Simplification Review of Inheritance Tax (IHT) – The government is publishing its response to the OTS’s review of the design of IHT. It has decided not to proceed with any changes at this point in time. The government responded to the OTS’s review of the administration of IHT in March 2021. 6 Chapter 2 Tackling non-compliance 2.1 Since 2010 the government has introduced over 150 new measures and invested over £2 billion in HMRC to tackle non-compliance in the tax system – this has secured and protected over £250 billion which would otherwise have gone unpaid. Significant reforms include: the introduction of the General Anti-Abuse Rule; Accelerated Payments; the implementation of the OECD Base Erosion and Profit Shifting Action Plan; and a range of measures to clamp down on promoters of tax avoidance. The measures announced in this document build on that strong base and further the government’s aim for everyone to pay the tax that is legally due, no matter who they are. 2.2 Modernising tax debt collection for non-paying businesses – The government is publishing a call for evidence on how HMRC can modernise its collection of tax debts to reflect the changing nature of the economy, where an increased use of e-commerce has given rise to new business practices – including the conduct of business in the UK without having a presence or physical assets here. The call for evidence also seeks views on HMRC’s approach to the small minority of business taxpayers who do not engage with HMRC and hold off paying their tax for as long as they can, forcing HMRC to resort to costly and time-consuming enforcement action. The proposals will not affect taxpayers who are in temporary financial difficulty and need support from HMRC to get back onto a sustainable financial footing – including those affected by the Covid-19 pandemic. 2.3 OECD’s Model Mandatory Disclosure Rules to tackle non-compliance – At Spring Budget 2021, the government announced that it would implement the OECD’s Model Mandatory Disclosure Rules. The government is now issuing a technical consultation and draft regulations. Mandatory Disclosure Rules require advisers (and sometimes taxpayers) to report information to the tax authorities on certain prescribed arrangements and structures, including those that could circumvent existing tax transparency reporting rules known as the Common Reporting Standard. This information will be exchanged with relevant tax authorities to help deter non-compliance, assist in identifying and challenging evasion, and support the development of tax policy. 2.4 Improving Transfer Pricing Documentation – The government is publishing a summary of responses to the consultation that closed in June 2021. It will legislate in 2022 to require businesses that are in scope of country-by-country reporting to maintain a master file and local file in line with OECD Base Erosion and Profit Shifting Action 13, and a supporting 7 summary audit trail. These changes will take effect from April 2023. The government will continue to review the case for companies to submit an International Dealings Schedule. 2.5 Extending tax conditionality to licences in Scotland and Northern Ireland – The government is publishing a summary of responses to the consultation on extending tax conditionality to certain licences in Scotland and Northern Ireland from April 2023. This makes the renewal of certain licences conditional on applicants completing checks that confirm they are appropriately registered for tax. The policy will be developed through continued engagement with the Devolved Administrations and is consistent with reforms which come into force in England and Wales in April 2022. Licensing bodies will have to obtain confirmation that an applicant has completed the check before deciding on their renewal application, making it more difficult for traders to operate in the hidden economy. The government remains committed to exploring further the wider application of tax conditionality. 2.6 Strengthening and modernising Individual Savings Accounts (ISA) compliance and penalties – In December 2020, the Economic Secretary to the Treasury announced that: “The Treasury is urgently looking at the sufficiency of checks on IF [Innovative Finance] ISA managers and the penalties regime.” Following that announcement, the government is now publishing a call for evidence on proposals to enhance ISA compliance, which will help determine how the current approach can be strengthened and modernised to encourage ISA managers and investors to get things right first time. The proposals apply to all types of ISA – Cash, Stocks and Shares, Junior, Lifetime and Innovative Finance. 2.7 Consulting on making Stamp Duty Land Tax (SDLT) reliefs fairer – The government is publishing a consultation on the SDLT reliefs for purchases of mixed property and multiple dwellings. These reliefs are being exploited by some purchasers to unfairly reduce their tax liability. This consultation sets out potential changes to make the system fairer and reduce the scope for misuse and incorrect claims. 2.8 New stakeholder forum on tackling offshore tax non-compliance – The government has established an HMRC stakeholder forum with representative bodies and agents to explore ideas to tackle offshore tax non-compliance. This follows from the publication of two discussion documents in spring 2021, as part of implementing HMRC’s ‘No Safe Havens’ strategy. The documents sought views on how to help taxpayers reduce offshore noncompliance in relation to non-UK income, gains and assets, and how to reduce and prevent international tax debt. 2.9 Exploring the potential of VAT split payment – The government is committed to exploring further VAT split payment, an alternative method of VAT collection where the tax element of a digital payment could be remitted directly to HMRC. While the work is at an exploratory stage, the government will continue to assess the potential of split payment both for tackling overseas VAT non-compliance and wider tax modernisation. The government 8 is grateful for the ongoing input of stakeholders in the payments industry and will continue to take this work forward collaboratively, including through the Industry Working Group established in 2018. 2.10 Use of marketed tax avoidance schemes in the UK – HMRC is publishing its annual report on the use of marketed tax avoidance schemes in the UK. It sets out the numbers and characteristics of taxpayers using avoidance schemes in the tax year 2019-2020. The report includes data on occupations, locations, ages and the average declared incomes of those involved in avoidance. 9 Chapter 3 Further tax policy announcements 3.1 It is important that the tax system continues to be fit for the modern world, and that government continues to take action to level the playing field and increase transparency. The policies set out in this section open new consultations on promising areas for potential reform and set out next steps on reform work already underway. Taxes fit for the modern world 3.2 Ensuring Landfill Tax continues to support environmental objectives – In spring 2021, the government announced it would review aspects of Landfill Tax in England and Northern Ireland. It is now launching a call for evidence, focused on how Landfill Tax can continue to support the government's ambitious environmental objectives, including achieving zero avoidable waste by 2050.

Detail the strategies the government is employing to encourage compliance in the tax system. 1.10 Increasing the effectiveness of the Office of Tax Simplification (OTS) – The government is publishing its first five-year review of the OTS, launched in March 2021, to examine the effectiveness of the OTS. It makes eight recommendations. 1.11 Response to Office of Tax Simplification Review of Capital Gains Tax (CGT) – The government is publishing its response to the OTS’s two-part review of CGT. The government has carefully considered the OTS’s recommendations and will keep the CGT system under review to ensure it is simple and efficient. The government has accepted five of the technical recommendations in the OTS’s second report and will work towards their implementation. 1.12 Response to Office of Tax Simplification Review of Inheritance Tax (IHT) – The government is publishing its response to the OTS’s review of the design of IHT. It has decided not to proceed with any changes at this point in time. The government responded to the OTS’s review of the administration of IHT in March 2021. 6 Chapter 2 Tackling non-compliance 2.1 Since 2010 the government has introduced over 150 new measures and invested over £2 billion in HMRC to tackle non-compliance in the tax system – this has secured and protected over £250 billion which would otherwise have gone unpaid. Significant reforms include: the introduction of the General Anti-Abuse Rule; Accelerated Payments; the implementation of the OECD Base Erosion and Profit Shifting Action Plan; and a range of measures to clamp down on promoters of tax avoidance. The measures announced in this document build on that strong base and further the government’s aim for everyone to pay the tax that is legally due, no matter who they are. 2.2 Modernising tax debt collection for non-paying businesses – The government is publishing a call for evidence on how HMRC can modernise its collection of tax debts to reflect the changing nature of the economy, where an increased use of e-commerce has given rise to new business practices – including the conduct of business in the UK without having a presence or physical assets here. The call for evidence also seeks views on HMRC’s approach to the small minority of business taxpayers who do not engage with HMRC and hold off paying their tax for as long as they can, forcing HMRC to resort to costly and time-consuming enforcement action. The proposals will not affect taxpayers who are in temporary financial difficulty and need support from HMRC to get back onto a sustainable financial footing – including those affected by the Covid-19 pandemic. 2.3 OECD’s Model Mandatory Disclosure Rules to tackle non-compliance – At Spring Budget 2021, the government announced that it would implement the OECD’s Model Mandatory Disclosure Rules. The government is now issuing a technical consultation and draft regulations. Mandatory Disclosure Rules require advisers (and sometimes taxpayers) to report information to the tax authorities on certain prescribed arrangements and structures, including those that could circumvent existing tax transparency reporting rules known as the Common Reporting Standard. This information will be exchanged with relevant tax authorities to help deter non-compliance, assist in identifying and challenging evasion, and support the development of tax policy. 2.4 Improving Transfer Pricing Documentation – The government is publishing a summary of responses to the consultation that closed in June 2021. It will legislate in 2022 to require businesses that are in scope of country-by-country reporting to maintain a master file and local file in line with OECD Base Erosion and Profit Shifting Action 13, and a supporting 7 summary audit trail. These changes will take effect from April 2023. The government will continue to review the case for companies to submit an International Dealings Schedule. 2.5 Extending tax conditionality to licences in Scotland and Northern Ireland – The government is publishing a summary of responses to the consultation on extending tax conditionality to certain licences in Scotland and Northern Ireland from April 2023. This makes the renewal of certain licences conditional on applicants completing checks that confirm they are appropriately registered for tax. The policy will be developed through continued engagement with the Devolved Administrations and is consistent with reforms which come into force in England and Wales in April 2022. Licensing bodies will have to obtain confirmation that an applicant has completed the check before deciding on their renewal application, making it more difficult for traders to operate in the hidden economy. The government remains committed to exploring further the wider application of tax conditionality. 2.6 Strengthening and modernising Individual Savings Accounts (ISA) compliance and penalties – In December 2020, the Economic Secretary to the Treasury announced that: “The Treasury is urgently looking at the sufficiency of checks on IF [Innovative Finance] ISA managers and the penalties regime.” Following that announcement, the government is now publishing a call for evidence on proposals to enhance ISA compliance, which will help determine how the current approach can be strengthened and modernised to encourage ISA managers and investors to get things right first time. The proposals apply to all types of ISA – Cash, Stocks and Shares, Junior, Lifetime and Innovative Finance. 2.7 Consulting on making Stamp Duty Land Tax (SDLT) reliefs fairer – The government is publishing a consultation on the SDLT reliefs for purchases of mixed property and multiple dwellings. These reliefs are being exploited by some purchasers to unfairly reduce their tax liability. This consultation sets out potential changes to make the system fairer and reduce the scope for misuse and incorrect claims. 2.8 New stakeholder forum on tackling offshore tax non-compliance – The government has established an HMRC stakeholder forum with representative bodies and agents to explore ideas to tackle offshore tax non-compliance. This follows from the publication of two discussion documents in spring 2021, as part of implementing HMRC’s ‘No Safe Havens’ strategy. The documents sought views on how to help taxpayers reduce offshore noncompliance in relation to non-UK income, gains and assets, and how to reduce and prevent international tax debt. 2.9 Exploring the potential of VAT split payment – The government is committed to exploring further VAT split payment, an alternative method of VAT collection where the tax element of a digital payment could be remitted directly to HMRC. While the work is at an exploratory stage, the government will continue to assess the potential of split payment both for tackling overseas VAT non-compliance and wider tax modernisation. The government 8 is grateful for the ongoing input of stakeholders in the payments industry and will continue to take this work forward collaboratively, including through the Industry Working Group established in 2018. 2.10 Use of marketed tax avoidance schemes in the UK – HMRC is publishing its annual report on the use of marketed tax avoidance schemes in the UK. It sets out the numbers and characteristics of taxpayers using avoidance schemes in the tax year 2019-2020. The report includes data on occupations, locations, ages and the average declared incomes of those involved in avoidance. 9 Chapter 3 Further tax policy announcements 3.1 It is important that the tax system continues to be fit for the modern world, and that government continues to take action to level the playing field and increase transparency. The policies set out in this section open new consultations on promising areas for potential reform and set out next steps on reform work already underway. Taxes fit for the modern world 3.2 Ensuring Landfill Tax continues to support environmental objectives – In spring 2021, the government announced it would review aspects of Landfill Tax in England and Northern Ireland. It is now launching a call for evidence, focused on how Landfill Tax can continue to support the government's ambitious environmental objectives, including achieving zero avoidable waste by 2050. Draw your answer from the above text only. Write in complete sentences and limit your answer to 150 words and 2 paragraphs. Do not use bullet points or bolding.

All information in the response should be sourced from the information provided in the prompt.

What are the mental effects of experiencing an anaphylaxis episode as they relate to growth and continued living?

After Anaphylaxis: Learning From the Experience Having experienced your own allergic reaction or witnessing someone else having an allergic reaction, especially a severe one (anaphylaxis), can be extremely upsetting and scary. Nevertheless, it can be an opportunity to learn and feel more confident. Embrace the experience and learn from it. In order for it to not let it get you down, here are things to think about: Are you sure of the trigger that caused the allergic reaction? Confirm with your doctor! Review if it is an obvious exposure to a known allergen trigger or if it is a mystery. You would not want to be avoiding a food that is not the real trigger nor want to miss an unexpected food allergen that is a true trigger. If it is not clear what triggered the reaction, it is especially important to review with your doctor. Keep ingredient labels, consider storing any leftover food, and ask for all possible ingredients or known allergens used around the food that caused the problem. Do not assume it was a cross contact. Consider where it happened, what your child was doing at the time, and any circumstances that are different than usual. Did you respond to the symptoms with appropriate treatment? Always more to learn! This is a great learning opportunity to review with your doctor how you recognized and treated the allergic reaction. What did you do right? What could you have done better? After-care of anaphylaxis includes addressing the emotional toll! o You may be sad, nervous, and distrustful for a while. This is completely normal. This feeling should pass with time. Normal routines should return in a few weeks. It is normal for people to feel guilty, worried, anxious or unsure about “what is safe”. o Accidents happen; it is a learning experience and an opportunity to do better. See the next page on “Handling the Emotional Impact of Anaphylaxis” for more details. Stay Positive Focus on all of the success in daily life, not just on food allergy or this reaction. The reaction was a setback, but you managed and learned! Reward positive behaviors (carrying/using medications, “no thank you” to unsafe foods, asking good questions, etc.). What to do if things are not the same after having anaphylaxis Experiencing anaphylaxis can sometimes result in longer-term increased anxiety, or lead to post-traumatic stress. It may cause a feeling of “not knowing what is safe anymore”. This can result in avoidance of food or situations that everyone knows is safe but cause too much anxiety. If life is not back to normal in a few weeks, it may become necessary to address negative behaviors and feelings. You may need help. That is normal and it is OK! In the companion sheet, we provide some more information about what to expect after anaphylaxis and how to address the emotional impact pro-actively. Help is available. Talk to your doctor about referral to a mental health professional. Very effective approaches are available and can make life-changing improvements. Some examples of what you can do: Learn coaching techniques to help your child face safe but anxiety-provoking situations. Learn whether the experience is “expected and normal” after an anaphylactic reaction or should be addressed with more assistance to get back on track. Learn relaxation techniques. Learn about the benefits of counseling, cognitive behavioral treatment or medications. These approaches are only recommended if they are essential to help get through an episode of increased stress. Handling the Emotional Impact of Anaphylaxis – Tips & Suggestions Anaphylactic reactions can be stressful. This handout reviews general points that both parents and patients may wish to consider in the immediate and long-term management of the emotional impact. These are general suggestions and may not be applicable to all individuals. Please talk to your physician about individualized care from a mental health expert if needed. THE EMOTIONAL IMPACT OF A REACTION EVOLVES OVER TIME – WHAT ONE DOES AND FEELS DURING OR IMMEDIATELY AFTER THE EVENT IS NOT THE SAME AS WHAT HAPPENS LATER ON. WHAT TO DO DURING ANAPHYLAXIS OR SUSPECTED ANAPHYLAXIS? Follow your Doctor’s orders regarding the administration of epinephrine, anti-histamines and further emergency care, if needed. Parent: try to project calm while doing so, if possible. However, if you are not calm and cannot project it, do not get too upset about it. The task now is to handle the event itself. WHAT TO DO IMMEDIATELY AFTER THE EVENT IS UNDER CONTROL? OK to admit that you are or were afraid, if that is the case. Parent: try to point out that the event was handled well, if that were the case. Parent: ask the child how he or she feels - but do not persist. It is ok if the child does not want to talk. If the child discloses distress, say that this is normal and that indeed, the event was distressing. Validate the emotion and emphasize safety. Physical contact (e.g. a hug) may be appropriate. WHAT TO DO LATER ON (WEEKS / MONTHS)? If indicated, there may be a need to re-evaluate “safety” (what is and is not safe to eat) given the event. This is best done with the help of an allergist. Ask your child how they feel. Try to send the message that your child can talk with you about feeling distressed, that it is normal to feel some stress even after the event has passed, and that it is a good idea to speak with you about it. Initially, there may be increased anxiety in general, or in situations that were previously thought of as safe. This is normal. This anxiety is expected to get better over the course of a few months (not necessarily immediately). If it does not subside, or if it gets worse after a month, intervention / assistance may be needed. Adjustment after the event may include addressing the feeling that the world is less safe. The event may lead to a re-evaluation of safety; the task is to arrive at a new understanding of safety. Sometimes, this process gets derailed and the child’s feelings that she or he are not safe turn into persistent distress, an anxiety disorder, a post-traumatic stress disorder (PTSD), and other reactions. Those are best managed with the help of a mental health professional. Relaxation techniques, cognitive-behavioral therapy, supportive therapy, and psychiatric medications are all options that would work for specific types of symptoms in specific instances. The preference should be for short-term, targeted interventions, unless a chronic mental health condition is diagnosed in addition to a specific response to an event. THE SILVER LINING Overcoming a period of distress may increase resilience and help the patient face other future challenges!

system instructions: All information should be sourced solely from the information provided in the prompt. question: What are the mental effects of experiencing an anaphylaxis episode as they relate to growth and continued living? context block: After Anaphylaxis: Learning From the Experience Having experienced your own allergic reaction or witnessing someone else having an allergic reaction, especially a severe one (anaphylaxis), can be extremely upsetting and scary. Nevertheless, it can be an opportunity to learn and feel more confident. Embrace the experience and learn from it. In order for it to not let it get you down, here are things to think about: Are you sure of the trigger that caused the allergic reaction? Confirm with your doctor! Review if it is an obvious exposure to a known allergen trigger or if it is a mystery. You would not want to be avoiding a food that is not the real trigger nor want to miss an unexpected food allergen that is a true trigger. If it is not clear what triggered the reaction, it is especially important to review with your doctor. Keep ingredient labels, consider storing any leftover food, and ask for all possible ingredients or known allergens used around the food that caused the problem. Do not assume it was a cross contact. Consider where it happened, what your child was doing at the time, and any circumstances that are different than usual. Did you respond to the symptoms with appropriate treatment? Always more to learn! This is a great learning opportunity to review with your doctor how you recognized and treated the allergic reaction. What did you do right? What could you have done better? After-care of anaphylaxis includes addressing the emotional toll! o You may be sad, nervous, and distrustful for a while. This is completely normal. This feeling should pass with time. Normal routines should return in a few weeks. It is normal for people to feel guilty, worried, anxious or unsure about “what is safe”. o Accidents happen; it is a learning experience and an opportunity to do better. See the next page on “Handling the Emotional Impact of Anaphylaxis” for more details. Stay Positive Focus on all of the success in daily life, not just on food allergy or this reaction. The reaction was a setback, but you managed and learned! Reward positive behaviors (carrying/using medications, “no thank you” to unsafe foods, asking good questions, etc.). What to do if things are not the same after having anaphylaxis Experiencing anaphylaxis can sometimes result in longer-term increased anxiety, or lead to post-traumatic stress. It may cause a feeling of “not knowing what is safe anymore”. This can result in avoidance of food or situations that everyone knows is safe but cause too much anxiety. If life is not back to normal in a few weeks, it may become necessary to address negative behaviors and feelings. You may need help. That is normal and it is OK! In the companion sheet, we provide some more information about what to expect after anaphylaxis and how to address the emotional impact pro-actively. Help is available. Talk to your doctor about referral to a mental health professional. Very effective approaches are available and can make life-changing improvements. Some examples of what you can do: Learn coaching techniques to help your child face safe but anxiety-provoking situations. Learn whether the experience is “expected and normal” after an anaphylactic reaction or should be addressed with more assistance to get back on track. Learn relaxation techniques. Learn about the benefits of counseling, cognitive behavioral treatment or medications. These approaches are only recommended if they are essential to help get through an episode of increased stress. Handling the Emotional Impact of Anaphylaxis – Tips & Suggestions Anaphylactic reactions can be stressful. This handout reviews general points that both parents and patients may wish to consider in the immediate and long-term management of the emotional impact. These are general suggestions and may not be applicable to all individuals. Please talk to your physician about individualized care from a mental health expert if needed. THE EMOTIONAL IMPACT OF A REACTION EVOLVES OVER TIME – WHAT ONE DOES AND FEELS DURING OR IMMEDIATELY AFTER THE EVENT IS NOT THE SAME AS WHAT HAPPENS LATER ON. WHAT TO DO DURING ANAPHYLAXIS OR SUSPECTED ANAPHYLAXIS? Follow your Doctor’s orders regarding the administration of epinephrine, anti-histamines and further emergency care, if needed. Parent: try to project calm while doing so, if possible. However, if you are not calm and cannot project it, do not get too upset about it. The task now is to handle the event itself. WHAT TO DO IMMEDIATELY AFTER THE EVENT IS UNDER CONTROL? OK to admit that you are or were afraid, if that is the case. Parent: try to point out that the event was handled well, if that were the case. Parent: ask the child how he or she feels - but do not persist. It is ok if the child does not want to talk. If the child discloses distress, say that this is normal and that indeed, the event was distressing. Validate the emotion and emphasize safety. Physical contact (e.g. a hug) may be appropriate. WHAT TO DO LATER ON (WEEKS / MONTHS)? If indicated, there may be a need to re-evaluate “safety” (what is and is not safe to eat) given the event. This is best done with the help of an allergist. Ask your child how they feel. Try to send the message that your child can talk with you about feeling distressed, that it is normal to feel some stress even after the event has passed, and that it is a good idea to speak with you about it. Initially, there may be increased anxiety in general, or in situations that were previously thought of as safe. This is normal. This anxiety is expected to get better over the course of a few months (not necessarily immediately). If it does not subside, or if it gets worse after a month, intervention / assistance may be needed. Adjustment after the event may include addressing the feeling that the world is less safe. The event may lead to a re-evaluation of safety; the task is to arrive at a new understanding of safety. Sometimes, this process gets derailed and the child’s feelings that she or he are not safe turn into persistent distress, an anxiety disorder, a post-traumatic stress disorder (PTSD), and other reactions. Those are best managed with the help of a mental health professional. Relaxation techniques, cognitive-behavioral therapy, supportive therapy, and psychiatric medications are all options that would work for specific types of symptoms in specific instances. The preference should be for short-term, targeted interventions, unless a chronic mental health condition is diagnosed in addition to a specific response to an event. THE SILVER LINING Overcoming a period of distress may increase resilience and help the patient face other future challenges!

Respond using only the information found within the text provided in the prompt. Avoid any mention of the government, its agencies, or specific regulations. If there are multiple paragraphs, each paragraph should be no longer than four sentences and must contain a clear introductory statement in the first sentence. If appropriate, format the response as a bulleted list. If information found in the text seems likely related to any legal or regulatory compliance, please include a disclaimer at the end of the response, in italics and enclosed in brackets, that explains the response is based only on the information provided.

What are ten strategies that are accepted for controlling disease in organic crops?

Crop pest, weed, and disease management practice (§205.206) Producers must implement management practices to prevent crop pests, weeds, and diseases that include but are not limited to the following: Accepted pest controls:  Crop rotation and soil and crop nutrient management practices as outlined above.  Sanitation measures to remove disease vectors, weeds seeds and pest organisms.  Cultural practices to enhance crop health such as plant species and variety selection with regard to suitability for site-specific conditions and resistance to pests, weeds, and disease.  Mechanical and physical methods for controlling pest problems, such as: o Biological controls (natural predators and parasites, habitat to promote biodiversity) o Nonsynthetic controls such as lures, traps, fencing and repellants Accepted weed controls:  Mulching with fully biodegradable materials  Mowing  Livestock grazing  Hand weeding or mechanical cultivation  Flame, heat, or electrical means  Plastic or synthetic mulches if removed from the field at the end of the growing/harvest season Accepted disease controls:  Management practices which suppress the spread of disease organisms. Examples include plant spacing, choosing resistant varieties, and crop rotations. In greenhouses, this can also include the proper control of environmental factors such as ventilation, humidity and temperature.  Application of nonsynthetic biological, botanical, or mineral inputs When the above pest, weed and disease preventative management practices are not sufficient, the following practices are accepted:  Application of a biological or botanical substance  Application of a substance included on the National List of synthetic substances allowed for use in organic crop production Prohibited controls:  Synthetic mulches or remnants left to photo-degrade in the field  Synthetic herbicides, pesticides or fungicides with the exception of those included on the National List of synthetic substances allowed for use in organic crop production  Newspaper with color inks  Biodegradable plastic mulch films not compliant with the NOP guidance  Nonsynthetic substances included on the National List of nonsynthetic substances prohibited for use in organic crop production Post-Harvest Handling (§205.270 – 205.272) Sanitation Proper sanitation is required at all levels of handling, transport and storage. The use of disinfectants (chlorine materials, hydrogen peroxide) applied to storage containers and handling equipment must be consistent with the National List. Irrigation and Wash Water Ground and surface waters are a potential source for a wide range of contaminants. Verify your certifier’s recommendations for water testing of irrigation and wash water. Water used in direct post-harvest crop or food contact is permitted to contain chlorine materials at levels approved by the Food and Drug Administration or the Environmental Protection Agency for such purpose. However, rinsing with potable water that does not exceed the maximum residual disinfectant limit for the chlorine material under the Safe Drinking Water Act (4ppm) must immediately follow this permitted use. Certified operators should monitor the chlorine level of the final rinse water, the point at which the water last contacts the organic product. The level of chlorine in the final rinse water must meet limits as set forth by the Safe Drinking Water Act (4ppm). Commingling and contact with prohibited substances It is required that producers implement measures to prevent the commingling of organic and nonorganic products. It is also required that organic producers protect organic products from contact with prohibited substances. Split Operations Operations that choose to produce organic and non-organic livestock products or to hire services from custom operators that may service non-organic and organic clients, must implement measures necessary to prevent the commingling of organic and non-organic crop products. Accepted practices  Mechanical or biological methods including but not limited to cooking, baking, heating, drying, preserving, dehydrating, freezing, and chilling crop products.  Non-synthetic materials, such as rock powders, diatomaceous earth, and herbal preparations to repel storage pests, must be consistent with the National List of nonsynthetic substances prohibited for use in organic crop production.  The use of synthetic materials, such as floating agents, must be consistent with the National List of synthetic substances allowed for use in organic crop production.

What are ten strategies that are accepted for controlling disease in organic crops? quoted text: Crop pest, weed, and disease management practice (§205.206) Producers must implement management practices to prevent crop pests, weeds, and diseases that include but are not limited to the following: Accepted pest controls:  Crop rotation and soil and crop nutrient management practices as outlined above.  Sanitation measures to remove disease vectors, weeds seeds and pest organisms.  Cultural practices to enhance crop health such as plant species and variety selection with regard to suitability for site-specific conditions and resistance to pests, weeds, and disease.  Mechanical and physical methods for controlling pest problems, such as: o Biological controls (natural predators and parasites, habitat to promote biodiversity) o Nonsynthetic controls such as lures, traps, fencing and repellants Accepted weed controls:  Mulching with fully biodegradable materials  Mowing  Livestock grazing  Hand weeding or mechanical cultivation  Flame, heat, or electrical means  Plastic or synthetic mulches if removed from the field at the end of the growing/harvest season Accepted disease controls:  Management practices which suppress the spread of disease organisms. Examples include plant spacing, choosing resistant varieties, and crop rotations. In greenhouses, this can also include the proper control of environmental factors such as ventilation, humidity and temperature.  Application of nonsynthetic biological, botanical, or mineral inputs When the above pest, weed and disease preventative management practices are not sufficient, the following practices are accepted:  Application of a biological or botanical substance  Application of a substance included on the National List of synthetic substances allowed for use in organic crop production Prohibited controls:  Synthetic mulches or remnants left to photo-degrade in the field  Synthetic herbicides, pesticides or fungicides with the exception of those included on the National List of synthetic substances allowed for use in organic crop production  Newspaper with color inks  Biodegradable plastic mulch films not compliant with the NOP guidance  Nonsynthetic substances included on the National List of nonsynthetic substances prohibited for use in organic crop production Post-Harvest Handling (§205.270 – 205.272) Sanitation Proper sanitation is required at all levels of handling, transport and storage. The use of disinfectants (chlorine materials, hydrogen peroxide) applied to storage containers and handling equipment must be consistent with the National List. Irrigation and Wash Water Ground and surface waters are a potential source for a wide range of contaminants. Verify your certifier’s recommendations for water testing of irrigation and wash water. Water used in direct post-harvest crop or food contact is permitted to contain chlorine materials at levels approved by the Food and Drug Administration or the Environmental Protection Agency for such purpose. However, rinsing with potable water that does not exceed the maximum residual disinfectant limit for the chlorine material under the Safe Drinking Water Act (4ppm) must immediately follow this permitted use. Certified operators should monitor the chlorine level of the final rinse water, the point at which the water last contacts the organic product. The level of chlorine in the final rinse water must meet limits as set forth by the Safe Drinking Water Act (4ppm). Commingling and contact with prohibited substances It is required that producers implement measures to prevent the commingling of organic and nonorganic products. It is also required that organic producers protect organic products from contact with prohibited substances. Split Operations Operations that choose to produce organic and non-organic livestock products or to hire services from custom operators that may service non-organic and organic clients, must implement measures necessary to prevent the commingling of organic and non-organic crop products. Accepted practices  Mechanical or biological methods including but not limited to cooking, baking, heating, drying, preserving, dehydrating, freezing, and chilling crop products.  Non-synthetic materials, such as rock powders, diatomaceous earth, and herbal preparations to repel storage pests, must be consistent with the National List of nonsynthetic substances prohibited for use in organic crop production.  The use of synthetic materials, such as floating agents, must be consistent with the National List of synthetic substances allowed for use in organic crop production. system instruction: Respond using only the information found within the text provided in the prompt. Avoid any mention of the government, its agencies, or specific regulations. If there are multiple paragraphs, each paragraph should be no longer than four sentences and must contain a clear introductory statement in the first sentence. If appropriate, format the response as a bulleted list. If information found in the text seems likely related to any legal or regulatory compliance, please include a disclaimer at the end of the response, in italics and enclosed in brackets, that explains the response is based only on the information provided.

[question] [user request] ===================== [text] [context document] ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

What is the differences and advantages of using wastewater as a surveillance tool as opposed to clinical testing? Despite using wastewater as a surveillance method, what piece of information if missing makes it a challenge to detect VOIs and VOCs? What are the advantages and disadvantages of using Illumina seq and Nanopore seq? What has past studies lacked that this study brings to light? What has led to the increase of NGS methods to detect variants? Why would using both seq methods produce a more robust variant call?

1. Introduction The SARS-CoV-2 genome is constantly evolving, with mutations happening at a rate of about once every 2 weeks [1]. While not all mutations change the characteristics of the virus, some mutations have proven to be of greater concern. Variants of interest (VOI) are labelled as such when an observed lineage is shown to have mutations potentially causing increased transmissibility or virulence, among other attributes [2]. Health organisations may reclassify these variants as variants of concern (VOC) if there is a demonstrable impact on epidemiological data. These viruses are labelled by WHO and assigned a lineage based on PANGO nomenclature [3]. Wastewater surveillance has emerged as a crucial tool in tracking mutations in the SARS-CoV-2 genome. Samples of untreated wastewater can be collected to provide useful information about the spread of COVID-19 in the community, without relying on clinical testing [4,5]. As clinical sampling mainly relies on symptomatic testing, wastewater sampling can provide unbiased and consistent data which can be used to inform appropriate public health responses. It is used to detect variants earlier and provide more context on the transmissibility and COVID-19 levels in communities, particularly where access to clinical testing is not readily available. As wastewater samples consist of a mixture of fragmented RNA from many sources, it can be difficult to accurately identify mutations and variants, particularly those without a known lineage [6]. Next-generation sequencing has proven to be an important tool in pandemic surveillance, particularly in the early detection and spread of variants [7-9]. With a high rate of occurrence of mutations and increased transmissibility, the need to provide high throughput data generation in a relatively short time frame has led to the development of a number of tools and protocols using next-generation sequencing, such as SARS-CoV-2 specific primers and tools to determine lineage in samples. These sequencing methods have been useful in analysing clinical and environmental samples, assisting in tracking viral load, transmission, contact tracing, and virus evolution [8]. Illumina and Nanopore sequencing are two next-generation sequencing technologies that have become major tools in genomic research. Illumina sequencing is a second-generation sequencing technology that uses sequencing by synthesis (SBS), where a reversible fluorescent terminator is used to detect the nucleotide sequence [10,11]. Nanopore sequencing is a thirdgeneration sequencing technology that uses the current changes in a charged protein nanopore from the molecule passing through to determine the specific sequence [10,12]. Multiple studies have been done on the comparison of Nanopore and Illumina sequencing, highlighting their various advantages in different applications [13-15]. Illumina sequencing is widely regarded as being highly accurate, consistently sequencing around 99.5-99.9% accuracy, and the higher depth of reads enables it to be a useful tool in circumstances with poor sequencing coverage, such as wastewater surveillance [16]. Nanopore sequencing has the ability to produce ultra-long reads, only limited by the sample preparation and quality, and is useful in genomic assembly and spanning entire regions of repetitive bases and structural variation [17]. Furthermore, real-time analysis of sequences and portability of sequencing devices has benefits in the field. Studies have been completed comparing Illumina and Nanopore sequencing on clinical and wastewater SARSCoV-2 samples, which focuses on benchmarking parameters such as genome coverage and depth and variant calling on samples. However, they did not explore the combination of the two sequencing technologies as a method to improve detection of variants [18-20]. In this work, we look to highlight the advantages of both Illumina and Nanopore sequencing in tracking SARSCoV-2 variants from wastewater samples. Mutational analysis on samples sequenced with both methods allows for a comparison of major variants identified among each dataset.

[question] What is the differences and advantages of using wastewater as a surveillance tool as opposed to clinical testing? Despite using wastewater as a surveillance method, what piece of information if missing makes it a challenge to detect VOIs and VOCs? What are the advantages and disadvantages of using Illumina seq and Nanopore seq? What has past studies lacked that this study brings to light? What has led to the increase of NGS methods to detect variants? Why would using both seq methods produce a more robust variant call? ===================== [text] 1. Introduction The SARS-CoV-2 genome is constantly evolving, with mutations happening at a rate of about once every 2 weeks [1]. While not all mutations change the characteristics of the virus, some mutations have proven to be of greater concern. Variants of interest (VOI) are labelled as such when an observed lineage is shown to have mutations potentially causing increased transmissibility or virulence, among other attributes [2]. Health organisations may reclassify these variants as variants of concern (VOC) if there is a demonstrable impact on epidemiological data. These viruses are labelled by WHO and assigned a lineage based on PANGO nomenclature [3]. Wastewater surveillance has emerged as a crucial tool in tracking mutations in the SARS-CoV-2 genome. Samples of untreated wastewater can be collected to provide useful information about the spread of COVID-19 in the community, without relying on clinical testing [4,5]. As clinical sampling mainly relies on symptomatic testing, wastewater sampling can provide unbiased and consistent data which can be used to inform appropriate public health responses. It is used to detect variants earlier and provide more context on the transmissibility and COVID-19 levels in communities, particularly where access to clinical testing is not readily available. As wastewater samples consist of a mixture of fragmented RNA from many sources, it can be difficult to accurately identify mutations and variants, particularly those without a known lineage [6]. Next-generation sequencing has proven to be an important tool in pandemic surveillance, particularly in the early detection and spread of variants [7-9]. With a high rate of occurrence of mutations and increased transmissibility, the need to provide high throughput data generation in a relatively short time frame has led to the development of a number of tools and protocols using next-generation sequencing, such as SARS-CoV-2 specific primers and tools to determine lineage in samples. These sequencing methods have been useful in analysing clinical and environmental samples, assisting in tracking viral load, transmission, contact tracing, and virus evolution [8]. Illumina and Nanopore sequencing are two next-generation sequencing technologies that have become major tools in genomic research. Illumina sequencing is a second-generation sequencing technology that uses sequencing by synthesis (SBS), where a reversible fluorescent terminator is used to detect the nucleotide sequence [10,11]. Nanopore sequencing is a thirdgeneration sequencing technology that uses the current changes in a charged protein nanopore from the molecule passing through to determine the specific sequence [10,12]. Multiple studies have been done on the comparison of Nanopore and Illumina sequencing, highlighting their various advantages in different applications [13-15]. Illumina sequencing is widely regarded as being highly accurate, consistently sequencing around 99.5-99.9% accuracy, and the higher depth of reads enables it to be a useful tool in circumstances with poor sequencing coverage, such as wastewater surveillance [16]. Nanopore sequencing has the ability to produce ultra-long reads, only limited by the sample preparation and quality, and is useful in genomic assembly and spanning entire regions of repetitive bases and structural variation [17]. Furthermore, real-time analysis of sequences and portability of sequencing devices has benefits in the field. Studies have been completed comparing Illumina and Nanopore sequencing on clinical and wastewater SARSCoV-2 samples, which focuses on benchmarking parameters such as genome coverage and depth and variant calling on samples. However, they did not explore the combination of the two sequencing technologies as a method to improve detection of variants [18-20]. In this work, we look to highlight the advantages of both Illumina and Nanopore sequencing in tracking SARSCoV-2 variants from wastewater samples. Mutational analysis on samples sequenced with both methods allows for a comparison of major variants identified among each dataset. https://www.medrxiv.org/content/10.1101/2024.08.07.24311639v1.full.pdf ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

Do not use any outside information, but only the information in the context to inform your answer. Write your response as a news article with a neutral tone.

In 2003, how had financial reporting in the Federal Government progressed?

MANAGEMENT’S DISCUSSION AND ANALYSIS Introduction The quality and timeliness of financial reporting in the Federal Government has come a long way since the first Governmentwide report subject to audit issued in March 1998 for fiscal year 1997. At that time, only 8 of the 24 Chief Financial Officers Act (CFO Act) agencies received clean opinions on their 1997 financial statements. This year, 20 of the 24 agencies received clean opinions and 21 of the 32 entities, most significant to these statements, had audited financial statements issued by the end of the calendar year. This improvement in both quality and timeliness was concurrent with the application of new accounting principles and new accounting systems, and involved performing reconciliations that had never been attempted before. This has been a monumental effort requiring years of planning and preparation and the efforts of thousands. However, we still have much to accomplish before we meet our objective of timely, useful financial reporting. The accompanying 2003 Financial Report of the United States Government is required by 31 U.S.C. § 331(e)(1) to be submitted to Congress by March 31, and consists of Management’s Discussion and Analysis (MD&A), Statements of Net Cost, Statements of Operations and Changes in Net Position, Reconciliations of Net Operating Cost and Unified Budget Deficit, Statements of Changes in Cash Balance from Unified Budget and Other Activities, Balance Sheets, Stewardship Information (Unaudited), Notes to the Financial Statements, and Supplemental Information (Unaudited). Each section is preceded by a description of its contents. Executive Summary Purpose This Financial Report of the United States Government is prepared to give the President, Congress, and the American people information about the financial position of the Federal Government. This report provides, on an accrual basis of accounting, a broad, comprehensive view of the Federal Government’s finances that is not available elsewhere. It states the Government’s financial position and condition, its revenues and costs, assets and liabilities, and other obligations and commitments. It also discusses important financial issues and significant conditions that may affect future operations. Operating Results Revenues were down by $81.7 billion primarily due to lower tax collections and costs were up by $225.8 billion due to, among other things, fighting the global war on terrorism. This resulted in a net operating cost of $665.0 billion. This compares with the net operating cost of $364.9 billion for fiscal year 2002. This MD&A discusses results in a historical context and includes a chart (page 17) that shows the relationship of prior U.S. budget deficits as a percentage of the U.S. gross domestic product (GDP), which is the total value of goods and services produced in the United States. Economic Results After recovering in fiscal year 2002 from the economic downturn, the economy continued to accelerate in fiscal year 2003 and achieved strong growth. The rate of increase in real GDP picked up in each of the last three quarters of the fiscal year and productivity continued to record substantial gains. The labor market stabilized in fiscal year 2003 following job losses in the previous year and in the final quarter of the fiscal year, employment began to increase. Improvement in the economy was aided by new fiscal policies in 2003, but the lingering effect of the recession and loss in equity wealth, the war with Iraq, homeland security spending, and lower taxes enacted to stimulate growth contributed to a widening in the Federal budget deficit to $374.8 billion for the fiscal year. Overall Perspective The 2003 balance sheet shows assets of $1,394 billion and liabilities of $8,499 billion, for a balance or negative net position of $7,105 billion. The Government’s responsibilities to make future payments for social insurance and certain other programs are not shown as liabilities according to Federal accounting standards; however, they are measured in other contexts. These programmatic commitments remain Federal responsibilities and as currently structured will have a significant claim on budgetary resources in the future. Significant Reporting Items for Fiscal Year 2003 Department of Defense Property Addition In fiscal year 2003, the Department of Defense’s (DOD) reported general property, plant, and equipment, net increased by $323.7 billion or 264.2 percent over fiscal year 2002. The majority of this increase was due to the initial recording of the value of DOD’s military equipment. Beginning with the fiscal year 2003 financial statements, DOD was required to record on the balance sheet the value of its military equipment under the new Statement of Federal Financial Accounting Standard No. 23, Eliminating the Category National Defense Property, Plant, and Equipment (SFFAS No. 23) issued by the Federal Accounting Standards Advisory Board (FASAB) in May 2003. SFFAS No. 23 establishes generally accepted accounting principles for valuing and reporting military equipment in Federal financial statements. Previously, military equipment was reported as national defense property, plant, and equipment in the Stewardship Information section of this report. Creation of the Department of Homeland Security On March 1, 2003, more than 20 entities and offices and some 180,000 employees were transferred into the Department of Homeland Security (DHS). The creation of the DHS in 2003 was the most significant transformation of the Federal Government since 1947 when the various branches of the U.S. Armed Forces were merged into a new Department of Defense. In the aftermath of the September 11, 2001, terrorist attacks, the President and the Congress recognized the need to coordinate the efforts of many Federal agencies, offices, and programs which had responsibility for various aspects of protecting and securing our homeland. President Bush proposed the creation of DHS, and Congress passed legislation establishing this new department. See the U.S. Government Structure & Performance section of this report for further details and a chart showing the entities transferred into DHS. Iraq Operations In March 2003, an international coalition led by the United States liberated Iraq and is overseeing a transformation. The vision for a sovereign, stable, prosperous, and democratic Iraq centered on four goals: establishing a secure environment, restoring essential services, promoting economic growth, and developing good governance through a legitimate constitutional government. To conduct military operations and address these goals in 2003, several sources of funding were used: appropriated and nonappropriated funds (seized and vested assets and the Development Fund for Iraq). U.S. agencies obligated $3.9 billion in appropriated funds for Iraq relief, renewal, and construction. Congress also appropriated funds to DOD for Operation Iraqi Freedom in the Emergency Wartime Supplemental Appropriations Act, 2003 (Public Law 108-11) the Consolidated Appropriations Resolution, 2003 (Public Law 108-7). DOD obligated $42.4 billion for incremental costs in support of Iraqi Freedom. For further discussion of the cost of Iraq operations and funding sources and uses, see Iraq Operations in the Financial Results section at the end of the Revenue and Cost Summary. As recently as 1996, not only were just six agencies able to issue financial statements with clean opinions, but most agencies took as least 5 months to issue them. Before implementing the Improved Financial Performance Initiative of the President’s Management Agenda, 18 of 24 of the Government’s major agencies received clean opinions on their audited financial reports, however, it still took 5 months to prepare most of them. Today, most major agencies are getting clean audit opinions and issuing them in a condensed period of time. A clean audit opinion provides assurance that agencies are responsibly accounting for the people’s money. If it takes them 5 months to issue audited financial statements, however, it is a good indication they do not have timely and accurate financial information available on a regular basis. That is why the Administration is working with all agencies to close their books more quickly. Eight agencies have accelerated the issuance of audited financial reports to 45 days after year end, which is the 2004 Governmentwide requirement. One particular agency of note is the U.S. Agency for International Development (USAID), which not only accelerated the reporting of its financial statements, but also received a clean opinion for the first time in its history. Additionally, agencies are now reporting quarterly financial information in addition to the end of the year data. Through the first quarter of fiscal year 2004, four agencies–Education, Environmental Protection Agency (EPA), National Science Foundation (NSF), and SSA – have demonstrated their ability to use timely and accurate financial information to make decisions about program management. For example, Education uses up-to-the-minute financial data to track whether schools are receiving the appropriate amount of Federal funds. In addition, EPA’s Leaking Underground Storage Tank program negotiates performance commitments with grantees and provides resources based on those commitments. If a grantee is not meeting its commitments, EPA may withhold some resources from the nonperformers and redirect those resources to grantees that are meeting their commitments.

In 2003, how had financial reporting in the Federal Government progressed? Instructions: Do not use any outside information, but only the information in the context to inform your answer. Write your response as a news article with a neutral tone. Context: MANAGEMENT’S DISCUSSION AND ANALYSIS Introduction The quality and timeliness of financial reporting in the Federal Government has come a long way since the first Governmentwide report subject to audit issued in March 1998 for fiscal year 1997. At that time, only 8 of the 24 Chief Financial Officers Act (CFO Act) agencies received clean opinions on their 1997 financial statements. This year, 20 of the 24 agencies received clean opinions and 21 of the 32 entities, most significant to these statements, had audited financial statements issued by the end of the calendar year. This improvement in both quality and timeliness was concurrent with the application of new accounting principles and new accounting systems, and involved performing reconciliations that had never been attempted before. This has been a monumental effort requiring years of planning and preparation and the efforts of thousands. However, we still have much to accomplish before we meet our objective of timely, useful financial reporting. The accompanying 2003 Financial Report of the United States Government is required by 31 U.S.C. § 331(e)(1) to be submitted to Congress by March 31, and consists of Management’s Discussion and Analysis (MD&A), Statements of Net Cost, Statements of Operations and Changes in Net Position, Reconciliations of Net Operating Cost and Unified Budget Deficit, Statements of Changes in Cash Balance from Unified Budget and Other Activities, Balance Sheets, Stewardship Information (Unaudited), Notes to the Financial Statements, and Supplemental Information (Unaudited). Each section is preceded by a description of its contents. Executive Summary Purpose This Financial Report of the United States Government is prepared to give the President, Congress, and the American people information about the financial position of the Federal Government. This report provides, on an accrual basis of accounting, a broad, comprehensive view of the Federal Government’s finances that is not available elsewhere. It states the Government’s financial position and condition, its revenues and costs, assets and liabilities, and other obligations and commitments. It also discusses important financial issues and significant conditions that may affect future operations. Operating Results Revenues were down by $81.7 billion primarily due to lower tax collections and costs were up by $225.8 billion due to, among other things, fighting the global war on terrorism. This resulted in a net operating cost of $665.0 billion. This compares with the net operating cost of $364.9 billion for fiscal year 2002. This MD&A discusses results in a historical context and includes a chart (page 17) that shows the relationship of prior U.S. budget deficits as a percentage of the U.S. gross domestic product (GDP), which is the total value of goods and services produced in the United States. Economic Results After recovering in fiscal year 2002 from the economic downturn, the economy continued to accelerate in fiscal year 2003 and achieved strong growth. The rate of increase in real GDP picked up in each of the last three quarters of the fiscal year and productivity continued to record substantial gains. The labor market stabilized in fiscal year 2003 following job losses in the previous year and in the final quarter of the fiscal year, employment began to increase. Improvement in the economy was aided by new fiscal policies in 2003, but the lingering effect of the recession and loss in equity wealth, the war with Iraq, homeland security spending, and lower taxes enacted to stimulate growth contributed to a widening in the Federal budget deficit to $374.8 billion for the fiscal year. Overall Perspective The 2003 balance sheet shows assets of $1,394 billion and liabilities of $8,499 billion, for a balance or negative net position of $7,105 billion. The Government’s responsibilities to make future payments for social insurance and certain other programs are not shown as liabilities according to Federal accounting standards; however, they are measured in other contexts. These programmatic commitments remain Federal responsibilities and as currently structured will have a significant claim on budgetary resources in the future. Significant Reporting Items for Fiscal Year 2003 Department of Defense Property Addition In fiscal year 2003, the Department of Defense’s (DOD) reported general property, plant, and equipment, net increased by $323.7 billion or 264.2 percent over fiscal year 2002. The majority of this increase was due to the initial recording of the value of DOD’s military equipment. Beginning with the fiscal year 2003 financial statements, DOD was required to record on the balance sheet the value of its military equipment under the new Statement of Federal Financial Accounting Standard No. 23, Eliminating the Category National Defense Property, Plant, and Equipment (SFFAS No. 23) issued by the Federal Accounting Standards Advisory Board (FASAB) in May 2003. SFFAS No. 23 establishes generally accepted accounting principles for valuing and reporting military equipment in Federal financial statements. Previously, military equipment was reported as national defense property, plant, and equipment in the Stewardship Information section of this report. Creation of the Department of Homeland Security On March 1, 2003, more than 20 entities and offices and some 180,000 employees were transferred into the Department of Homeland Security (DHS). The creation of the DHS in 2003 was the most significant transformation of the Federal Government since 1947 when the various branches of the U.S. Armed Forces were merged into a new Department of Defense. In the aftermath of the September 11, 2001, terrorist attacks, the President and the Congress recognized the need to coordinate the efforts of many Federal agencies, offices, and programs which had responsibility for various aspects of protecting and securing our homeland. President Bush proposed the creation of DHS, and Congress passed legislation establishing this new department. See the U.S. Government Structure & Performance section of this report for further details and a chart showing the entities transferred into DHS. Iraq Operations In March 2003, an international coalition led by the United States liberated Iraq and is overseeing a transformation. The vision for a sovereign, stable, prosperous, and democratic Iraq centered on four goals: establishing a secure environment, restoring essential services, promoting economic growth, and developing good governance through a legitimate constitutional government. To conduct military operations and address these goals in 2003, several sources of funding were used: appropriated and nonappropriated funds (seized and vested assets and the Development Fund for Iraq). U.S. agencies obligated $3.9 billion in appropriated funds for Iraq relief, renewal, and construction. Congress also appropriated funds to DOD for Operation Iraqi Freedom in the Emergency Wartime Supplemental Appropriations Act, 2003 (Public Law 108-11) the Consolidated Appropriations Resolution, 2003 (Public Law 108-7). DOD obligated $42.4 billion for incremental costs in support of Iraqi Freedom. For further discussion of the cost of Iraq operations and funding sources and uses, see Iraq Operations in the Financial Results section at the end of the Revenue and Cost Summary. As recently as 1996, not only were just six agencies able to issue financial statements with clean opinions, but most agencies took as least 5 months to issue them. Before implementing the Improved Financial Performance Initiative of the President’s Management Agenda, 18 of 24 of the Government’s major agencies received clean opinions on their audited financial reports, however, it still took 5 months to prepare most of them. Today, most major agencies are getting clean audit opinions and issuing them in a condensed period of time. A clean audit opinion provides assurance that agencies are responsibly accounting for the people’s money. If it takes them 5 months to issue audited financial statements, however, it is a good indication they do not have timely and accurate financial information available on a regular basis. That is why the Administration is working with all agencies to close their books more quickly. Eight agencies have accelerated the issuance of audited financial reports to 45 days after year end, which is the 2004 Governmentwide requirement. One particular agency of note is the U.S. Agency for International Development (USAID), which not only accelerated the reporting of its financial statements, but also received a clean opinion for the first time in its history. Additionally, agencies are now reporting quarterly financial information in addition to the end of the year data. Through the first quarter of fiscal year 2004, four agencies–Education, Environmental Protection Agency (EPA), National Science Foundation (NSF), and SSA – have demonstrated their ability to use timely and accurate financial information to make decisions about program management. For example, Education uses up-to-the-minute financial data to track whether schools are receiving the appropriate amount of Federal funds. In addition, EPA’s Leaking Underground Storage Tank program negotiates performance commitments with grantees and provides resources based on those commitments. If a grantee is not meeting its commitments, EPA may withhold some resources from the nonperformers and redirect those resources to grantees that are meeting their commitments.

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> [user request] <TEXT> [context document]

Elon Musk is sending people to space! This is crazy lol. There was a recent exploration where a few non astronauts went up. They're just rich people flexing their money. How experirced is the owner with trips to space? What are some specs from the trip and how did this trip benefit the company?

Tech billionaire returns to Earth after first private spacewalk By MARCIA DUNN Updated 10:38 AM EDT, September 15, 2024 Share CAPE CANAVERAL, Fla. (AP) — A billionaire spacewalker returned to Earth with his crew on Sunday, ending a five-day trip that lifted them higher than anyone has traveled since NASA’s moonwalkers. SpaceX’s capsule splashed down in the Gulf of Mexico near Florida’s Dry Tortugas in the predawn darkness, carrying tech entrepreneur Jared Isaacman, two SpaceX engineers and a former Air Force Thunderbird pilot. They pulled off the first private spacewalk while orbiting nearly 460 miles (740 kilometers) above Earth, higher than the International Space Station and Hubble Space Telescope. Their spacecraft hit a peak altitude of 875 miles (1,408 kilometers) following Tuesday’s liftoff. Isaacman became only the 264th person to perform a spacewalk since the former Soviet Union scored the first in 1965, and SpaceX’s Sarah Gillis the 265th. Until now, all spacewalks were done by professional astronauts. RELATED COVERAGE Image Iran says it successfully launched a satellite in its program criticized by West over missile fears Image Stuck-in-space astronauts reflect on being left behind and adjusting to life in orbit Image Striking Boeing factory workers say they are ready to hold out for a better contract “We are mission complete,” Isaacman radioed as the capsule bobbed in the water, awaiting the recovery team. Within an hour, all four were out of their spacecraft, pumping their fists with joy as they emerged onto the ship’s deck. It was the first time SpaceX aimed for a splashdown near the Dry Tortugas, a cluster of islands 70 miles (113 kilometers) west of Key West. To celebrate the new location, SpaceX employees brought a big, green turtle balloon to Mission Control at company headquarters in Hawthorne, California. The company usually targets closer to the Florida coast, but two weeks of poor weather forecasts prompted SpaceX to look elsewhere. During Thursday’s commercial spacewalk, the Dragon capsule’s hatch was open barely a half-hour. Isaacman emerged only up to his waist to briefly test SpaceX’s brand new spacesuit followed by Gillis, who was knee high as she flexed her arms and legs for several minutes. Gillis, a classically trained violinist, also held a performance in orbit earlier in the week. Image This image made from SpaceX video shows the four-member crew including tech entrepreneur Jared Isaacman, third left, seated in its capsule as they wait to get off the capsule after it landed in the Gulf of Mexico near Florida’s Dry Tortugas early Sunday, Sept. 15, 2024. (SpaceX via AP) The spacewalk lasted less than two hours, considerably shorter than those at the International Space Station. Most of that time was needed to depressurize the entire capsule and then restore the cabin air. Even SpaceX’s Anna Menon and Scott “Kidd” Poteet, who remained strapped in, wore spacesuits. SpaceX considers the brief exercise a starting point to test spacesuit technology for future, longer missions to Mars. This was Isaacman’s second chartered flight with SpaceX, with two more still ahead under his personally financed space exploration program named Polaris after the North Star. He paid an undisclosed sum for his first spaceflight in 2021, taking along contest winners and a pediatric cancer survivor while raising more than $250 million for St. Jude Children’s Research Hospital. For the just completed so-called Polaris Dawn mission, the founder and CEO of the Shift4 credit card-processing company shared the cost with SpaceX. Isaacman won’t divulge how much he spent. ___ The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. The AP is solely responsible for all content.

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> Elon Musk is sending people to space! This is crazy lol. There was a recent exploration where a few non astronauts went up. They're just rich people flexing their money. How experirced is the owner with trips to space? What are some specs from the trip and how did this trip benefit the company? <TEXT> Tech billionaire returns to Earth after first private spacewalk By MARCIA DUNN Updated 10:38 AM EDT, September 15, 2024 Share CAPE CANAVERAL, Fla. (AP) — A billionaire spacewalker returned to Earth with his crew on Sunday, ending a five-day trip that lifted them higher than anyone has traveled since NASA’s moonwalkers. SpaceX’s capsule splashed down in the Gulf of Mexico near Florida’s Dry Tortugas in the predawn darkness, carrying tech entrepreneur Jared Isaacman, two SpaceX engineers and a former Air Force Thunderbird pilot. They pulled off the first private spacewalk while orbiting nearly 460 miles (740 kilometers) above Earth, higher than the International Space Station and Hubble Space Telescope. Their spacecraft hit a peak altitude of 875 miles (1,408 kilometers) following Tuesday’s liftoff. Isaacman became only the 264th person to perform a spacewalk since the former Soviet Union scored the first in 1965, and SpaceX’s Sarah Gillis the 265th. Until now, all spacewalks were done by professional astronauts. RELATED COVERAGE Image Iran says it successfully launched a satellite in its program criticized by West over missile fears Image Stuck-in-space astronauts reflect on being left behind and adjusting to life in orbit Image Striking Boeing factory workers say they are ready to hold out for a better contract “We are mission complete,” Isaacman radioed as the capsule bobbed in the water, awaiting the recovery team. Within an hour, all four were out of their spacecraft, pumping their fists with joy as they emerged onto the ship’s deck. It was the first time SpaceX aimed for a splashdown near the Dry Tortugas, a cluster of islands 70 miles (113 kilometers) west of Key West. To celebrate the new location, SpaceX employees brought a big, green turtle balloon to Mission Control at company headquarters in Hawthorne, California. The company usually targets closer to the Florida coast, but two weeks of poor weather forecasts prompted SpaceX to look elsewhere. During Thursday’s commercial spacewalk, the Dragon capsule’s hatch was open barely a half-hour. Isaacman emerged only up to his waist to briefly test SpaceX’s brand new spacesuit followed by Gillis, who was knee high as she flexed her arms and legs for several minutes. Gillis, a classically trained violinist, also held a performance in orbit earlier in the week. Image This image made from SpaceX video shows the four-member crew including tech entrepreneur Jared Isaacman, third left, seated in its capsule as they wait to get off the capsule after it landed in the Gulf of Mexico near Florida’s Dry Tortugas early Sunday, Sept. 15, 2024. (SpaceX via AP) The spacewalk lasted less than two hours, considerably shorter than those at the International Space Station. Most of that time was needed to depressurize the entire capsule and then restore the cabin air. Even SpaceX’s Anna Menon and Scott “Kidd” Poteet, who remained strapped in, wore spacesuits. SpaceX considers the brief exercise a starting point to test spacesuit technology for future, longer missions to Mars. This was Isaacman’s second chartered flight with SpaceX, with two more still ahead under his personally financed space exploration program named Polaris after the North Star. He paid an undisclosed sum for his first spaceflight in 2021, taking along contest winners and a pediatric cancer survivor while raising more than $250 million for St. Jude Children’s Research Hospital. For the just completed so-called Polaris Dawn mission, the founder and CEO of the Shift4 credit card-processing company shared the cost with SpaceX. Isaacman won’t divulge how much he spent. ___ The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. The AP is solely responsible for all content. https://apnews.com/article/spacex-private-spacewalk-polaris-dawn-e5635c75b15b2f298e426b4992bcde86

You must respond using only information contained in the provided context block.

Why are auto service advisors exempt from overtime pay? Respond in at least 200 words

The Supreme Court concluded recently that car dealership employees who discuss service options with customers are exempt from the Fair Labor Standards Act’s (FLSA) overtime pay requirement. In Encino Motorcars, LLC v. Navarro, the Court determined that these so-called “service advisors” fell within the statute’s exemption for “any salesman, partsman, or mechanic primarily engaged in selling or servicing automobiles[.]” While the Court’s decision would seem to affect only a small group of employees, it is notable for what it said with regard to interpreting the FLSA. Justice Thomas, writing for the majority, rejected the long-followed principle that the FLSA’s exemptions should be construed narrowly to promote the statute’s remedial purpose. The majority maintained that the exemptions are entitled to nothing more than a “fair reading” because the FLSA “gives no ‘textual indication’ that its exemptions should be construed narrowly . . .” Application of this new fair reading standard could result in a greater number of employees being deemed exempt from the FLSA’s overtime pay requirement. A dramatic increase in exempt workers could prompt Congress to consider an amendment to the FLSA that perhaps identifies the exemptions with more specificity or prescribes a new standard for evaluating the exempt status of employees. The FLSA requires the payment of overtime compensation at a rate of not less than one and one-half times an employee’s hourly rate for hours worked in excess of a 40-hour workweek. Section 13 of the FLSA identifies numerous employees who are exempt from this requirement. In addition to the automobile salesmen, partsmen, and mechanics discussed in Encino Motorcars, individuals employed as seamen, specified agricultural workers, and certain computer employees are also exempt. Workers employed in a bona fide executive, administrative, or professional capacity arguably comprise the largest category of exempt workers. Since 1945, the Supreme Court has characterized the FLSA as “humanitarian and remedial legislation” designed to ensure “a fair day’s pay for a fair day’s work.” In A.H. Phillips, Inc. v. Walling, the Court declined to find employees working in the warehouse and central office of an interstate grocery store chain exempt from the statute’s overtime pay requirement. While the store chain attempted to characterize the employees as within the FLSA’s now-repealed section 13(a)(2) exemption for “any employee engaged in any retail or service establishment the greater part of whose selling or servicing is in Congressional Research Service https://crsreports.congress.gov LSB10122 Congressional Research Service 2 intrastate commerce,” the Court maintained that these workers performed duties in a wholesale environment that was distinct from the retail establishment contemplated by the exemption. The Court explained in A.H. Phillips that any exemption from humanitarian and remedial legislation must be narrowly construed and give due regard to the law’s plain meaning and congressional intent: “To extend an exemption to other than those plainly and unmistakably within its terms and spirit is to abuse the interpretative process and to frustrate the announced will of the people.” After reviewing the terms used in section 13(a)(2) and the exemption’s legislative history, the Court distinguished the warehouse and central office workers from other employees who should be exempt under that section. The Court reasoned that the terms used in section 13(a)(2) indicate that only those employees engaged in a retail or service establishment that operates primarily in local commerce are to be exempt. Moreover, the Court noted that Congress’s interest in exempting only those workers regularly engaged in local retailing activities was supported by section 13(a)(2)’s legislative history. This history showed a congressional understanding that local retail concerns “do not sufficiently influence the stream of interstate commerce to warrant imposing the wage and hour requirements on them.” The exemption guaranteed that the employees of small retail establishments would be exempt from the FLSA’s requirements. Unlike these kinds of employees, the warehouse and central office workers in A.H. Phillips were like the employees of an independent wholesaler that dealt constantly with incoming and outgoing interstate shipments. In subsequent decisions, the Court has continued to interpret the FLSA’s exemptions narrowly. In Mitchell v. Kentucky Finance Co., for example, the Court concluded that the employees of a company making personal loans were not exempt from the FLSA’s overtime pay and recordkeeping requirements. The company argued that it was a retail or service establishment within the meaning of section 13(a)(2), and that its employees should be exempt from the relevant requirements. Citing the exemption’s legislative history, however, the Court determined that personal loan companies and other financial institutions were not meant to be covered by section 13(a)(2). The Court emphasized that the FLSA’s exemptions are to be narrowly construed, and noted that businesses that were meant to have an exemption were specifically provided one by the statute.

System instruction: You must respond using only information contained in the provided context block. Question: Why are auto service advisors exempt from overtime pay? Respond in at least 200 words Context Block: The Supreme Court concluded recently that car dealership employees who discuss service options with customers are exempt from the Fair Labor Standards Act’s (FLSA) overtime pay requirement. In Encino Motorcars, LLC v. Navarro, the Court determined that these so-called “service advisors” fell within the statute’s exemption for “any salesman, partsman, or mechanic primarily engaged in selling or servicing automobiles[.]” While the Court’s decision would seem to affect only a small group of employees, it is notable for what it said with regard to interpreting the FLSA. Justice Thomas, writing for the majority, rejected the long-followed principle that the FLSA’s exemptions should be construed narrowly to promote the statute’s remedial purpose. The majority maintained that the exemptions are entitled to nothing more than a “fair reading” because the FLSA “gives no ‘textual indication’ that its exemptions should be construed narrowly . . .” Application of this new fair reading standard could result in a greater number of employees being deemed exempt from the FLSA’s overtime pay requirement. A dramatic increase in exempt workers could prompt Congress to consider an amendment to the FLSA that perhaps identifies the exemptions with more specificity or prescribes a new standard for evaluating the exempt status of employees. The FLSA requires the payment of overtime compensation at a rate of not less than one and one-half times an employee’s hourly rate for hours worked in excess of a 40-hour workweek. Section 13 of the FLSA identifies numerous employees who are exempt from this requirement. In addition to the automobile salesmen, partsmen, and mechanics discussed in Encino Motorcars, individuals employed as seamen, specified agricultural workers, and certain computer employees are also exempt. Workers employed in a bona fide executive, administrative, or professional capacity arguably comprise the largest category of exempt workers. Since 1945, the Supreme Court has characterized the FLSA as “humanitarian and remedial legislation” designed to ensure “a fair day’s pay for a fair day’s work.” In A.H. Phillips, Inc. v. Walling, the Court declined to find employees working in the warehouse and central office of an interstate grocery store chain exempt from the statute’s overtime pay requirement. While the store chain attempted to characterize the employees as within the FLSA’s now-repealed section 13(a)(2) exemption for “any employee engaged in any retail or service establishment the greater part of whose selling or servicing is in Congressional Research Service https://crsreports.congress.gov LSB10122 Congressional Research Service 2 intrastate commerce,” the Court maintained that these workers performed duties in a wholesale environment that was distinct from the retail establishment contemplated by the exemption. The Court explained in A.H. Phillips that any exemption from humanitarian and remedial legislation must be narrowly construed and give due regard to the law’s plain meaning and congressional intent: “To extend an exemption to other than those plainly and unmistakably within its terms and spirit is to abuse the interpretative process and to frustrate the announced will of the people.” After reviewing the terms used in section 13(a)(2) and the exemption’s legislative history, the Court distinguished the warehouse and central office workers from other employees who should be exempt under that section. The Court reasoned that the terms used in section 13(a)(2) indicate that only those employees engaged in a retail or service establishment that operates primarily in local commerce are to be exempt. Moreover, the Court noted that Congress’s interest in exempting only those workers regularly engaged in local retailing activities was supported by section 13(a)(2)’s legislative history. This history showed a congressional understanding that local retail concerns “do not sufficiently influence the stream of interstate commerce to warrant imposing the wage and hour requirements on them.” The exemption guaranteed that the employees of small retail establishments would be exempt from the FLSA’s requirements. Unlike these kinds of employees, the warehouse and central office workers in A.H. Phillips were like the employees of an independent wholesaler that dealt constantly with incoming and outgoing interstate shipments. In subsequent decisions, the Court has continued to interpret the FLSA’s exemptions narrowly. In Mitchell v. Kentucky Finance Co., for example, the Court concluded that the employees of a company making personal loans were not exempt from the FLSA’s overtime pay and recordkeeping requirements. The company argued that it was a retail or service establishment within the meaning of section 13(a)(2), and that its employees should be exempt from the relevant requirements. Citing the exemption’s legislative history, however, the Court determined that personal loan companies and other financial institutions were not meant to be covered by section 13(a)(2). The Court emphasized that the FLSA’s exemptions are to be narrowly construed, and noted that businesses that were meant to have an exemption were specifically provided one by the statute.

Only use the information provided in the prompt to answer the question. Use no external sources or prior knowledge. Use 150 words or less. Question: What are the differences between OSI RM and TCP/IP layers?

Question: What are the differences between OSI RM and TCP/IP layers?

2.2.2 ISO MODEL The International Standards Organization (ISO), based in Geneva Switzerland, is composed of groups for various countries that set standards working towards the establishment of world-wide standards for communication and data exchange. One notable accomplishment has been the development of a reference model that contains specifications for a network architecture for connecting dissimilar computers, with a main goal being that of producing an open and non-proprietary method of data communication. This reference model, called the Open Systems Interconnect Reference Model (OSI RM), was developed in 1981 (?) and revised in 1984. The OSI RM uses 7 layers, each independent of each other, to allow computers to exchange data. To transfer a message from user A to user B, the data has to pass through the 7 layers on user's A machine, before being transmitted through the selected medium. At the receiving computer of user B, the data must then pass through the 7 layers again, this time in reverse sequence, before being received by user B. For data to be transferred, it must pass through all 7 layers on both computers. Each layer follows a relatively strict specification and this allows the differing layers to be produced and implemented by different concerns. Each layer can then interface with its neighboring layers even though they may have been developed by different groups. One way of viewing the activities of the layers is that as the original message passes down the layers towards the medium on the computer of user A, additional information, for both formatting or addressing information, is added to the beginning or end of the message. The additional information is added to ensure correct communication. At the other end (i.e. at user B) this information is gradually stripped off at the data passes through the 7 layers - this time in reverse order. The layers are arranged in order as follows: Layer 7, Application Layer. This layer defines network applications such as error recovery, flow control and network access. Note that user applications are not part of the layers. Layer 6, Presentation Layer. This layer determines the format used to exchange data in such aspects as data translation, encryption and protocol conversion. The data from user A is translated to a common syntax that can be understood by user B. In this way it specifies how applications can connect to the network and to user B. Layer 5, Session Layer. This layer controls the communication session between computers. It is responsible for establishing and removing communication sessions between computers. Additional address translations and security are also performed. This layer therefore instigates a data transfer session between user A and user B so that an extended data transfer can take place. Layer 4, Transport Layer. This layer is responsible for ensuring that data is delivered free of error and provides some flow control. This layer ensures that data is transferred as part of the session instigated by the Session Layer. Layer 3, Network Layer. This layer handles the delivery of data by determining the route for the information to follow. The data is divided into packets with addressing information attached. It also translates address from names into numbers. Intermediate addresses are also attached. Layer 2, Data Link Layer. This layer defines the network control mechanism and prepares the packets for transmission. Layer 1, Physical Layer. This layer is concerned with the transmission of binary data between stations and defines the connections. The connection definition includes such aspects as mechanical, electrical,, topology and bandwidth aspects. At the receiving end the process is reversed so that the binary data that is received is translated back into the original message for User B. Note that each layer communicates only with it's immediate neighbors. For example the Transport Layer only communicates with the Session Layer and with the Network Layer. Each network architecture can be defined by a set of protocols for each of the layers. This allows for a degree of simplification and modularity in design. In spite of an enormous amount of worked and effort having been expended on the ISO RM, very little of it is in use compared to TCP/IP (described in the following section). Perhaps one reason is that the OSI RM is Internet Technologies Overview Page 2-3 extremely complex and it takes a long time to implement all the functions. However a more likely reason is that TCP/IP is in widespread use and has preempted much of the work on implementing the OSI RM. 2.2.3 TCP/IP The Internet grew out of the Cold War in the 1960s as a response to the issue of making sure that computer networks could survive a nuclear weapons attack. The problem was that a nuclear war could destroy much of the military communications and computer networks and that military control would then be lost. An approach was therefore needed whereby the networks could operate even when substantive portions had been destroyed. A number of possible network structures were proposed, with most using analogue approaches with relatively sophisticated mechanisms for making sure that network connections were maintained. Such approaches were difficult to implement effectively since all possible scenarios of damage to the network had to be preprogrammed into the network control algorithms. This structure was unwieldy and it was difficult to make changes to the network. Also proposed, but not implemented at that time, was the structure that was to form the basis of the Internet. This approach was based on a simple and elegant digital model of a very decentralized network and is described in more detail below. Such a network is digital in nature and was therefore dependent on readily available computing power. Such power was becoming available in the 1970s and it was then that the University of California at Berkeley received a contract from the United States Department of Defense to develop a computer network that would: 1. Operate on a wide variety of computer hardware with differing communications media 2. Reconfigure itself if portions of the network failed The earlier proposed network of data packets being directed by routers was implemented under this contract in a network structure formulated as a series of protocols which are described under the general heading of Transmission Control Protocol and Internet Protocol (TCP/IP). TCP/IP is described in more detail later. 2.2.5 TCP/IP STRUCTURE TCP/IP consists of a whole series of protocols, applications and services that together support the powerful capabilities of Internet technologies. Whereas the OSI RM has seven layers the TCP/IP can be thought of as consisting of five layers: The application layer containing such protocols and applications as Simple Mail Transfer Protocol (SMPT), File Transfer Protocol (FTP), Hypertext Transfer Protocol (HTTP) and Telnet. The transport layer contains such protocols as Transmission Control Protocol (TCP) and User Datagram Protocol (UDP). The Internet layer contains such protocols as Internet Protocol (IP), Internet Control Message Protocol (ICMP), Address Resolution Protocol (ARP), and Reverse Address Resolution Protocol (RARP) The data link layer and The physical layer handle the hardware connections. A wide variety of hardware network connections are possible ranging from token ring to Ethernet and from twisted pair cables to fiber optic cables. As with the OSI RM, each message that is being transmitted must be passed down through the layers to the hardware, while the reverse happens on the receiving machine. Another way of looking at the TCP/IP set is to categorize it into upper layers (the application layer) midlayers (the transport and Internet layer) and into lower layers (the data link and physical layers). The upper layers handle the applications, while the lower layers handle the hardware connections. The mid-layers form the core of TCP/IP. Note that not all protocols, applications and services are used on all sessions, rather each can be used under particular scenarios. For example TCP/IP is often combined with Ethernet for a specific hardware implementation. Ethernet is a protocol for the data link and physical layers that uses carrier-sense multipleaccess with collision detection (CSMA-CD). It is simple to install and is available for a wide range of computer hardware. An arrangement such as TCP/IP with Ethernet (with twisted pair cables) therefore covers the mid and lower layers. Alternatively TCP/IP may connect to a token ring network where transmission is only allowed if the node has a token passed to it from another node on the network. In this case the data link and physical layers of the TCP/IP protocol suite are concerned with the interface to the token ring network. It should be noted that this modular approach allows for a wide variety of configurations to be possible. Ironically, the modular approach also allows for the use of Internet technologies that address the upper layers (such as WWW browsers) to use non-TCP/IP networks (Novell networks as an example).

2.2.2 ISO MODEL The International Standards Organization (ISO), based in Geneva Switzerland, is composed of groups for various countries that set standards working towards the establishment of world-wide standards for communication and data exchange. One notable accomplishment has been the development of a reference model that contains specifications for a network architecture for connecting dissimilar computers, with a main goal being that of producing an open and non-proprietary method of data communication. This reference model, called the Open Systems Interconnect Reference Model (OSI RM), was developed in 1981 (?) and revised in 1984. The OSI RM uses 7 layers, each independent of each other, to allow computers to exchange data. To transfer a message from user A to user B, the data has to pass through the 7 layers on user's A machine, before being transmitted through the selected medium. At the receiving computer of user B, the data must then pass through the 7 layers again, this time in reverse sequence, before being received by user B. For data to be transferred, it must pass through all 7 layers on both computers. Each layer follows a relatively strict specification and this allows the differing layers to be produced and implemented by different concerns. Each layer can then interface with its neighboring layers even though they may have been developed by different groups. One way of viewing the activities of the layers is that as the original message passes down the layers towards the medium on the computer of user A, additional information, for both formatting or addressing information, is added to the beginning or end of the message. The additional information is added to ensure correct communication. At the other end (i.e. at user B) this information is gradually stripped off at the data passes through the 7 layers - this time in reverse order. The layers are arranged in order as follows: Layer 7, Application Layer. This layer defines network applications such as error recovery, flow control and network access. Note that user applications are not part of the layers. Layer 6, Presentation Layer. This layer determines the format used to exchange data in such aspects as data translation, encryption and protocol conversion. The data from user A is translated to a common syntax that can be understood by user B. In this way it specifies how applications can connect to the network and to user B. Layer 5, Session Layer. This layer controls the communication session between computers. It is responsible for establishing and removing communication sessions between computers. Additional address translations and security are also performed. This layer therefore instigates a data transfer session between user A and user B so that an extended data transfer can take place. Layer 4, Transport Layer. This layer is responsible for ensuring that data is delivered free of error and provides some flow control. This layer ensures that data is transferred as part of the session instigated by the Session Layer. Layer 3, Network Layer. This layer handles the delivery of data by determining the route for the information to follow. The data is divided into packets with addressing information attached. It also translates address from names into numbers. Intermediate addresses are also attached. Layer 2, Data Link Layer. This layer defines the network control mechanism and prepares the packets for transmission. Layer 1, Physical Layer. This layer is concerned with the transmission of binary data between stations and defines the connections. The connection definition includes such aspects as mechanical, electrical,, topology and bandwidth aspects. At the receiving end the process is reversed so that the binary data that is received is translated back into the original message for User B. Note that each layer communicates only with it's immediate neighbors. For example the Transport Layer only communicates with the Session Layer and with the Network Layer. Each network architecture can be defined by a set of protocols for each of the layers. This allows for a degree of simplification and modularity in design. In spite of an enormous amount of worked and effort having been expended on the ISO RM, very little of it is in use compared to TCP/IP (described in the following section). Perhaps one reason is that the OSI RM is Internet Technologies Overview Page 2-3 extremely complex and it takes a long time to implement all the functions. However a more likely reason is that TCP/IP is in widespread use and has preempted much of the work on implementing the OSI RM. 2.2.3 TCP/IP The Internet grew out of the Cold War in the 1960s as a response to the issue of making sure that computer networks could survive a nuclear weapons attack. The problem was that a nuclear war could destroy much of the military communications and computer networks and that military control would then be lost. An approach was therefore needed whereby the networks could operate even when substantive portions had been destroyed. A number of possible network structures were proposed, with most using analogue approaches with relatively sophisticated mechanisms for making sure that network connections were maintained. Such approaches were difficult to implement effectively since all possible scenarios of damage to the network had to be preprogrammed into the network control algorithms. This structure was unwieldy and it was difficult to make changes to the network. Also proposed, but not implemented at that time, was the structure that was to form the basis of the Internet. This approach was based on a simple and elegant digital model of a very decentralized network and is described in more detail below. Such a network is digital in nature and was therefore dependent on readily available computing power. Such power was becoming available in the 1970s and it was then that the University of California at Berkeley received a contract from the United States Department of Defense to develop a computer network that would: 1. Operate on a wide variety of computer hardware with differing communications media 2. Reconfigure itself if portions of the network failed The earlier proposed network of data packets being directed by routers was implemented under this contract in a network structure formulated as a series of protocols which are described under the general heading of Transmission Control Protocol and Internet Protocol (TCP/IP). TCP/IP is described in more detail later. 2.2.5 TCP/IP STRUCTURE TCP/IP consists of a whole series of protocols, applications and services that together support the powerful capabilities of Internet technologies. Whereas the OSI RM has seven layers the TCP/IP can be thought of as consisting of five layers: The application layer containing such protocols and applications as Simple Mail Transfer Protocol (SMPT), File Transfer Protocol (FTP), Hypertext Transfer Protocol (HTTP) and Telnet. The transport layer contains such protocols as Transmission Control Protocol (TCP) and User Datagram Protocol (UDP). The Internet layer contains such protocols as Internet Protocol (IP), Internet Control Message Protocol (ICMP), Address Resolution Protocol (ARP), and Reverse Address Resolution Protocol (RARP) The data link layer and The physical layer handle the hardware connections. A wide variety of hardware network connections are possible ranging from token ring to Ethernet and from twisted pair cables to fiber optic cables. As with the OSI RM, each message that is being transmitted must be passed down through the layers to the hardware, while the reverse happens on the receiving machine. Another way of looking at the TCP/IP set is to categorize it into upper layers (the application layer) midlayers (the transport and Internet layer) and into lower layers (the data link and physical layers). The upper layers handle the applications, while the lower layers handle the hardware connections. The mid-layers form the core of TCP/IP. Note that not all protocols, applications and services are used on all sessions, rather each can be used under particular scenarios. For example TCP/IP is often combined with Ethernet for a specific hardware implementation. Ethernet is a protocol for the data link and physical layers that uses carrier-sense multipleaccess with collision detection (CSMA-CD). It is simple to install and is available for a wide range of computer hardware. An arrangement such as TCP/IP with Ethernet (with twisted pair cables) therefore covers the mid and lower layers. Alternatively TCP/IP may connect to a token ring network where transmission is only allowed if the node has a token passed to it from another node on the network. In this case the data link and physical layers of the TCP/IP protocol suite are concerned with the interface to the token ring network. It should be noted that this modular approach allows for a wide variety of configurations to be possible. Ironically, the modular approach also allows for the use of Internet technologies that address the upper layers (such as WWW browsers) to use non-TCP/IP networks (Novell networks as an example). Only use the information provided in the prompt to answer the question. Use no external sources or prior knowledge. Use 150 words or less. Question: What are the differences between OSI RM and TCP/IP layers?

Draw your answer solely from the text provided, without the use of any prior knowledge or external sources. Limit your answer to 250 words. Use bullet points.

What were Montana's reasons for the attempted TikTok ban?

Montana’s TikTok legislation prompted substantial public commentary. According to the law’s preamble, SB 419 supports the “health and safety of Montanans” by preventing TikTok’s operation in the state and also expresses concerns about TikTok’s parent company being subject to control by the People’s Republic of China (PRC), gathering of user information, and “dangerous content.” (The broader policy issues related to the legislation are beyond the scope of this Sidebar.) TikTok and several of its users filed suit in federal district court following passage of the law. TikTok’s complaint asserted violations of several constitutional rights and provisions (the prohibition against bills of attainder, the Commerce Clause, the First Amendment, and the Supremacy Clause). Other challengers, comprising TikTok creators and users, made similar arguments. The court found the plaintiffs’ arguments compelling, concluding they likely would succeed on the merits. The court determined that the plaintiffs established irreparable harm to their business interests and granted the preliminary injunction, which prevented SB 419 from taking effect until the court’s final resolution of the case. Issues Presented to the Ninth Circuit on Appeal Attorneys for Montana unsuccessfully argued to the district court that the law represents a valid exercise of Montana’s police power, that it does not violate any of the claimed constitutional provisions, that federal law does not preempt the ban, and that the ban would have only an indirect, and thus permissible, effect on interstate commerce. Montana then appealed the district court’s order granting the preliminary injunction to the Ninth Circuit. In its opening brief, Montana asserts that SB 419 has a “common sense consumer protection purpose” and that the district court erred in concluding that TikTok and its users would win their constitutional arguments. Montana also argues that the district court erred in its application of the remaining preliminary injunction factors. A selection of Montana’s various arguments, ordered as they appear in the brief, follows: • Police Powers. Montana asserts that protecting consumers is an exercise of police power, under which states have significant discretion. • Data Access. Montana asserts that, based on news reports, the U.S. user data that TikTok collects likely is available to the PRC at will, underscoring that the Montana legislature enacted SB 419 to protect Montana consumers’ data privacy, not to impact the editorial control of the platform. • Burden Shifting. Montana asserts that the district court, in concluding that TikTok and its users would prevail on their constitutional claims, erroneously shifted the evidentiary burden for proving those claims to Montana.

Draw your answer solely from the text provided, without the use of any prior knowledge or external sources. Limit your answer to 250 words. Use bullet points. "Montana’s TikTok legislation prompted substantial public commentary. According to the law’s preamble, SB 419 supports the “health and safety of Montanans” by preventing TikTok’s operation in the state and also expresses concerns about TikTok’s parent company being subject to control by the People’s Republic of China (PRC), gathering of user information, and “dangerous content.” (The broader policy issues related to the legislation are beyond the scope of this Sidebar.) TikTok and several of its users filed suit in federal district court following passage of the law. TikTok’s complaint asserted violations of several constitutional rights and provisions (the prohibition against bills of attainder, the Commerce Clause, the First Amendment, and the Supremacy Clause). Other challengers, comprising TikTok creators and users, made similar arguments. The court found the plaintiffs’ arguments compelling, concluding they likely would succeed on the merits. The court determined that the plaintiffs established irreparable harm to their business interests and granted the preliminary injunction, which prevented SB 419 from taking effect until the court’s final resolution of the case. Issues Presented to the Ninth Circuit on Appeal Attorneys for Montana unsuccessfully argued to the district court that the law represents a valid exercise of Montana’s police power, that it does not violate any of the claimed constitutional provisions, that federal law does not preempt the ban, and that the ban would have only an indirect, and thus permissible, effect on interstate commerce. Montana then appealed the district court’s order granting the preliminary injunction to the Ninth Circuit. In its opening brief, Montana asserts that SB 419 has a “common sense consumer protection purpose” and that the district court erred in concluding that TikTok and its users would win their constitutional arguments. Montana also argues that the district court erred in its application of the remaining preliminary injunction factors. A selection of Montana’s various arguments, ordered as they appear in the brief, follows: • Police Powers. Montana asserts that protecting consumers is an exercise of police power, under which states have significant discretion. • Data Access. Montana asserts that, based on news reports, the U.S. user data that TikTok collects likely is available to the PRC at will, underscoring that the Montana legislature enacted SB 419 to protect Montana consumers’ data privacy, not to impact the editorial control of the platform. • Burden Shifting. Montana asserts that the district court, in concluding that TikTok and its users would prevail on their constitutional claims, erroneously shifted the evidentiary burden for proving those claims to Montana." What were Montana's reasons for the attempted TikTok ban?

Use the text provided by the user to answer all questions. Do not use any other information, including your stored data, to answer any questions. Answer in a numbered list and provide support for each item.

Which branches of physics are involved in the study of the brain, and how do they contribute to the understanding of neuroscience?

The brain is a complex organ characterized by heterogeneous patterns of structural connections supporting unparalleled feats of cognition and a wide range of behaviors. New noninvasive imaging techniques now allow these patterns to be carefully and comprehensively mapped in individual humans and animals. Yet, it remains a fundamental challenge to understand how the brain’s structural wiring supports cognitive processes, with major implications for the personalized treatment of mental health disorders. Here, we review recent efforts to meet this challenge that draw on intuitions, models, and theories from physics, spanning the domains of statistical mechanics, information theory, and dynamical systems and control. We begin by considering the organizing principles of brain network architecture instantiated in structural wiring under constraints of symmetry, spatial embedding, and energy minimization. We next consider models of brain network function that stipulate how neural activity propagates along these structural connections, producing the long-range interactions and collective dynamics that support a rich repertoire of system functions. Finally, we consider perturbative experiments and models for brain network control, which leverage the physics of signal transmission along structural wires to infer intrinsic control processes that support goal-directed behavior and to inform stimulation-based therapies for neurological disease and psychiatric disorders. Throughout, we highlight several open questions in the physics of brain network structure, function, and control that will require creative efforts from physicists willing to brave the complexities of living matter. 2 It is our good fortune as physicists to seek to understand the nature of the observable world around us. In this inquiry, we need not reach to contemporary science to appreciate the fact that our perception of the world around us is inextricably linked to the world within us: the mind. Indeed, even Aristotle c. 350 B.C. noted that it is by mapping the structure of the world that the human comes to understand their own mind 1. “Mind thinks itself because it shares the nature of the object of thought; for it becomes an object of thought in coming into contact with and thinking its objects, so that mind and object of thought are the same” 2. Over the ensuing 2000-plus years, it has not completely escaped notice that the mappers of the world have unique contributions to offer the mapping of the mind (from Thales of Miletus, c. 624–546 B.C., to Leonardo Da Vinci, 1452–1519). More recently, it is notable that nearly all famous physicists of the early 20th century– Albert Einstein, Niels Bohr, Erwin Schroedinger, Werner Heisenberg, Max Born– considered the philosophical implications of their observations and theories 3. In the post-war era, philosophical musings turned to particularly conspicuous empirical contributions at the intersection of neuroscience and artificial intelligence, spanning polymath John von Neumann’s work enhancing our understanding of computational architectures 4 and physicist John Hopfield’s invention of the associative neural network, which revolutionized our understanding of collective computation 5. In the contemporary study of the mind and its fundamental organ– the brain– nearly all of the domains of physics, perhaps with the exception of relativity, are not only relevant but truly essential, motivating the early coinage of the term neurophysics some four decades ago 6. The fundamentals of electricity and magnetism prove critical for building theoretical models of neurons and the transmission of action potentials 7. These theories are being increasingly informed by mechanics to understand how force-generating and load-bearing proteins bend, curl, kink, buckle, constrict, and stretch to mediate neuronal signaling and plasticity 8. Principles from thermodynamics come into play when predicting how the brain samples the environment (action) or shifts the distribution of information that it encodes (perception) 9. Collectively, theories of brain function are either buttressed or dismantled by imaging, with common tools including magnetic resonance imaging 10 and magnetoencephalography 11, the latter being built on superconducting quantum interference devices and next-generation quantum sensors that can be embedded into a system that 3 can be worn like a helmet, revolutionizing our ability to measure brain function while allowing free and natural movement 12. Moreover, recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods to explore brain function by enabling simultaneous measurement and manipulation of the activity of thousands or even millions of neurons 13. Beyond its relevance for continued imaging advancements 14, optics has come to the fore of neuroscience over the last decade with the development of optogenetics, an approach that uses light to alter neural processing at the level of single spikes and synaptic events, offering reliable, millisecond-timescale control of excitatory and inhibitory synaptic transmission 15. Such astounding advances, enabled by the intersection of physics and neuroscience, have motivated the construction of a National Brain Observatory at the Argonne National Laboratory (Director: Peter Littlewood, previously of Cavendish Laboratories) funded by the National Science Foundation, as well as frequent media coverage including titles in the APS News such as “Physicists, the Brain is Calling You.”16 And as physicists answer the call, our understanding of the brain deepens and our ability to mark and measure its component parts expands. Yet alongside this growing systematization and archivation, we have begun to face an increasing realization that it is the interactions between hundreds or thousands of neurons that generate the mind’s functional states 13. Indeed, from interactions among neural components emerge computation 17, communication 18, and information propagation 19. We can confidently state of neuroscience what Henri Poincare, the French mathematician, theoretical physicist, and philosopher of science, states of science generally: “The aim of science is not things themselves, as the dogmatists in their simplicity imagine, but the relations among things; outside these relations there is no reality knowable.”20 The overarching goal of mapping these interactions in neural systems has motivated multibillion-dollar investments across the United States (the Brain Initiative generally, and the Human Connectome Project specifically 21), the European Union (the Blue Brain Project 22), China (the China Brain Project 23), and Japan (Japan’s Brain/MINDS project 24)

Use the text provided by the user to answer all questions. Do not use any other information, including your stored data, to answer any questions. Answer in a numbered list and provide support for each item. The brain is a complex organ characterized by heterogeneous patterns of structural connections supporting unparalleled feats of cognition and a wide range of behaviors. New noninvasive imaging techniques now allow these patterns to be carefully and comprehensively mapped in individual humans and animals. Yet, it remains a fundamental challenge to understand how the brain’s structural wiring supports cognitive processes, with major implications for the personalized treatment of mental health disorders. Here, we review recent efforts to meet this challenge that draw on intuitions, models, and theories from physics, spanning the domains of statistical mechanics, information theory, and dynamical systems and control. We begin by considering the organizing principles of brain network architecture instantiated in structural wiring under constraints of symmetry, spatial embedding, and energy minimization. We next consider models of brain network function that stipulate how neural activity propagates along these structural connections, producing the long-range interactions and collective dynamics that support a rich repertoire of system functions. Finally, we consider perturbative experiments and models for brain network control, which leverage the physics of signal transmission along structural wires to infer intrinsic control processes that support goal-directed behavior and to inform stimulation-based therapies for neurological disease and psychiatric disorders. Throughout, we highlight several open questions in the physics of brain network structure, function, and control that will require creative efforts from physicists willing to brave the complexities of living matter. 2 It is our good fortune as physicists to seek to understand the nature of the observable world around us. In this inquiry, we need not reach to contemporary science to appreciate the fact that our perception of the world around us is inextricably linked to the world within us: the mind. Indeed, even Aristotle c. 350 B.C. noted that it is by mapping the structure of the world that the human comes to understand their own mind 1. “Mind thinks itself because it shares the nature of the object of thought; for it becomes an object of thought in coming into contact with and thinking its objects, so that mind and object of thought are the same” 2. Over the ensuing 2000-plus years, it has not completely escaped notice that the mappers of the world have unique contributions to offer the mapping of the mind (from Thales of Miletus, c. 624–546 B.C., to Leonardo Da Vinci, 1452–1519). More recently, it is notable that nearly all famous physicists of the early 20th century– Albert Einstein, Niels Bohr, Erwin Schroedinger, Werner Heisenberg, Max Born– considered the philosophical implications of their observations and theories 3. In the post-war era, philosophical musings turned to particularly conspicuous empirical contributions at the intersection of neuroscience and artificial intelligence, spanning polymath John von Neumann’s work enhancing our understanding of computational architectures 4 and physicist John Hopfield’s invention of the associative neural network, which revolutionized our understanding of collective computation 5. In the contemporary study of the mind and its fundamental organ– the brain– nearly all of the domains of physics, perhaps with the exception of relativity, are not only relevant but truly essential, motivating the early coinage of the term neurophysics some four decades ago 6. The fundamentals of electricity and magnetism prove critical for building theoretical models of neurons and the transmission of action potentials 7. These theories are being increasingly informed by mechanics to understand how force-generating and load-bearing proteins bend, curl, kink, buckle, constrict, and stretch to mediate neuronal signaling and plasticity 8. Principles from thermodynamics come into play when predicting how the brain samples the environment (action) or shifts the distribution of information that it encodes (perception) 9. Collectively, theories of brain function are either buttressed or dismantled by imaging, with common tools including magnetic resonance imaging 10 and magnetoencephalography 11, the latter being built on superconducting quantum interference devices and next-generation quantum sensors that can be embedded into a system that 3 can be worn like a helmet, revolutionizing our ability to measure brain function while allowing free and natural movement 12. Moreover, recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods to explore brain function by enabling simultaneous measurement and manipulation of the activity of thousands or even millions of neurons 13. Beyond its relevance for continued imaging advancements 14, optics has come to the fore of neuroscience over the last decade with the development of optogenetics, an approach that uses light to alter neural processing at the level of single spikes and synaptic events, offering reliable, millisecond-timescale control of excitatory and inhibitory synaptic transmission 15. Such astounding advances, enabled by the intersection of physics and neuroscience, have motivated the construction of a National Brain Observatory at the Argonne National Laboratory (Director: Peter Littlewood, previously of Cavendish Laboratories) funded by the National Science Foundation, as well as frequent media coverage including titles in the APS News such as “Physicists, the Brain is Calling You.”16 And as physicists answer the call, our understanding of the brain deepens and our ability to mark and measure its component parts expands. Yet alongside this growing systematization and archivation, we have begun to face an increasing realization that it is the interactions between hundreds or thousands of neurons that generate the mind’s functional states 13. Indeed, from interactions among neural components emerge computation 17, communication 18, and information propagation 19. We can confidently state of neuroscience what Henri Poincare, the French mathematician, theoretical physicist, and philosopher of science, states of science generally: “The aim of science is not things themselves, as the dogmatists in their simplicity imagine, but the relations among things; outside these relations there is no reality knowable.”20 The overarching goal of mapping these interactions in neural systems has motivated multibillion-dollar investments across the United States (the Brain Initiative generally, and the Human Connectome Project specifically 21), the European Union (the Blue Brain Project 22), China (the China Brain Project 23), and Japan (Japan’s Brain/MINDS project 24) Which branches of physics are involved in the study of the brain, and how do they contribute to the understanding of neuroscience?

Only use the text below to answer.

What are the definitions of the acronyms defined in this text?

Mpox is a rare zoonotic disease caused by infection with monkeypox virus (MPXV) which belongs to the Orthopoxvirus genus in the family Poxviridae1. The specific animal reservoir of MPXV remains unknown. MPXV is found naturally in certain Central and West African countries. There are two main clades (variants) of mpox: Clade one (I) (formerly Congo Basin clade) and Clade two (II) (formerly West African clade). Clade II consists of two subclades (IIa and IIb). In addition to systemic symptoms, mpox is characterised by painful skin rash or mucosal lesions. Person to person transmission occurs through close contact with lesions, body fluids, respiratory droplets and contaminated materials such as bedding. Most cases of mpox infection are mild. Infections due to clade I are associated with more severe disease and a higher case fatality ratio. Until April 2022, export of mpox beyond endemic regions in Africa was rare, and limited to cases that had travelled to endemic areas, or to zoonotic transmission from imported animals.1 On 16 May 2022, the UK Health Security Agency reported four mpox cases among men with no links to an endemic area, and who self-identified as gay, bisexual and other men who have sex with men (gbMSM).2 On 18 May 2022, Portugal reported five confirmed and 20 suspect mpox cases among gbMSM.3 Global case numbers increased quickly. By 25 May 2022, 219 confirmed cases had been reported worldwide.4 On 23 July 2022, the World Health Organization (WHO), declared the global mpox outbreak a Public Health Emergency of International Concern (PHEIC).5 Since 1 January 2022 and as of 8 May 2023, 87,377 confirmed cases including 140 deaths, have been reported from 111 countries.6 Isolates from outbreak cases belonged to MPXV Clade II (previously known as the West African clade) - specifically subclade IIb. 7 On 10 May 2023, WHO determined mpox no longer constituted a PHEIC.8 We describe the epidemiology of mpox cases and the response to the mpox outbreak between May 2022 and May 2023. Mpox was made a notifiable disease in Ireland on 27 May 2022.9 Cases were reported to Ireland’s Computerised Infectious Disease Reporting (CIDR) system.10 In addition to the standard notification, Public Health Areas (PHAs) collected additional data about cases, including demographic factors, clinical details, potential exposures and vaccination history. Laboratory testing for MPXV was undertaken at the National Virus Reference Laboratory11and the Molecular Virology Laboratory at St James’s Hospital. PHAs also undertook contact tracing and risk assessment for close contacts. A national database was developed which allowed information on mpox close contacts to be recorded, including the setting in which exposure may have occurred (i.e. household, sexual, occupational), and vaccination status (e.g. previously vaccinated, or provided with postexposure prophylaxis). 12, 13 Data are presented on all confirmed mpox cases notified on CIDR up to midnight 27 May 2023 and extracted on 30 May 2023. Epidemiology of mpox cases Between 27 May 2022 and 27 May 2023, 229 confirmed cases of mpox were notified. The first case was notified on 31 May 2022 (week 22 2022) (Figure 1). The earliest known date of onset of symptoms among confirmed cases was 13 May 2022 (week 19 2022). Cases peaked in week 34 2022 (21-27 August 2022). In the first 23 weeks of 2023, only two confirmed cases were notified, one each in January and April. Gender was male in 226 cases and female in three cases. Median age was 35 years (range 16-68 years), with 46% of cases aged between 18-34 years and 79.8% aged between 18-44 years. The majority of cases were either born in Ireland (46.8%) or Latin America (32.3%). Summary characteristics of confirmed mpox cases are presented in Table 1. Contact tracing Interim public health guidance for the management of mpox outbreak cases and their contacts was released on 3 June 2022, adapted from earlier guidance for sporadic mpox cases.14 The purpose of contact tracing initially was to limit transmission, to identify vulnerable contacts at risk for more severe disease (pregnant women, young children and immunocompromised), and to raise awareness among contacts so that they would seek medical help early if they became symptomatic. Later, when vaccine was available, eligible contact were offered post exposure prophylaxis (PEP) vaccination. Initially, mpox was viewed as a High Consequence Infectious Disease (HCID) with high-risk contacts recommended to quarantine for 21 days.15 As understanding of the clinical severity and transmission risks increased, this approach was modified. Following ongoing dynamic risk assessments; quarantine of contacts was no longer required; there was a progressive easing of the definition of a high-risk contact; and cases (and their clinical samples and waste) linked to the global outbreak i.e. caused by MPXV subclade IIb, were no longer managed as HCID. Establishment of an Incident Management Team A national incident management team (IMT) first met on 16 May 2022, the same day as the UK first issued their alert. Given the close links between gbMSM communities across Europe, and in particular between Ireland and the UK, the likelihood of cases arising in Ireland was considered high. The IMT was responsible for monitoring of national and global situation, ongoing risk assessment, and advising on and coordinating the response measures. The IMT initially met daily when the event first emerged, and then weekly. Recognising the breadth of the response required, involving input across many different parts of the health service, and in particular the magnitude of implementing a national vaccination programme, the IMT transitioned into a National Crisis Management Team (NCMT) led by the Acute Operations division of the HSE in September 2022. The IMT and subsequent NCMT included representation from a wide range of disciplines and sectors across the health service including: public health; virology; clinical services including sexual health, infectious diseases, paediatrics, obstetrics, occupational health and general practice; infection prevention and control; the National Immunisation Office (NIO); the HSE Sexual Health and Crisis Pregnancy Programme (SHCPP); the National Ambulance Service; HSE Communications; acute hospital and community operations. From the onset, the IMT included representation from the gbMSM community with members from the Gay Health Network (GHN), an alliance of organisations with mandates to promote the sexual health of gbMSM in Ireland, and the MPOWER programme at HIV Ireland, a peer-driven communitylevel programme focusing on the sexual health and wellbeing among gbMSM16, 17. On transitioning to the NCMT format, MPOWER continued to be represented on the group. Guidance and service development IMT members initially, and subsequently the Pathways of Care Programme of the NCMT, worked with the Health Protection Research and Guideline Development Unit in developing and maintaining a suite of guidance on clinical and public health management of probable and confirmed cases and their close contacts, including assessment and testing, contact tracing, infection prevention and control, transportation, and waste management.18 Guidance was reviewed and updated at regular intervals as the outbreak evolved and understanding increased. Community engagement Supported by the Sexual Health Crisis Pregnancy Programme (SHCPP) and HSE Communications, GHN and MPOWER continued to develop and deliver a range of communications and engagement activities for the gbMSM community including posters at social venues and events, social media messaging, adverts and news pieces in gbMSM media, out-reach activities and community stakeholder events. This collaborative and peerled approach ensured the delivery of key messaging that is intended to be informative but not stigmatising. It has been recognised as an example of best practice for risk communication and community engagement on mpox by ECDC and the WHO.19, 20 Vaccination On 27 May 2022, Ireland’s National Immunisation Advisory Committee (NIAC) recommended that modified Vaccinia Ankara-Bavarian Nordic (MVA-BN), be offered to high and intermediate risk contacts of a case of mpox as PEP and healthcare workers at highest risk of exposure as pre-exposure prophylaxis (PREP).21 On 13 June 2022, the first doses of MVA-BN vaccine were delivered to community vaccination centres (CVCs), where PEP was primarily administered, occasionally supported by mobile vaccination teams, hospitals, and PHA teams.21 On 29 July 2022, NIAC recommended mpox vaccine as PrEP to those at high risk of exposure. Given the limited vaccine supply in the context of a global outbreak, the HSE through the advice and guidance of clinical and ethical experts and by working closely with gbMSM advocacy and support groups, offered PrEP in a phased manner. In the first phase (commencing August 2022), eligible people (gbMSM and transgender people who had a notification of early infectious syphilis between December 2021 and July 2022) were invited for vaccination in sexual health clinics. In November 2022, PrEP vaccination was extended to self-identified individuals at risk of mpox who could register online for vaccination and was administered in CVCs.23 Based on advice of the EMA, on 22 August NIAC endorsed lower dose intradermal administration rather than subcutaneous administration. This increased the number of people who could be offered vaccination23, 24. By the end of May 2023, 5,214 people had been fully vaccinated.

What are the definitions of the acronyms defined in this text? Only use the text below to answer. Mpox is a rare zoonotic disease caused by infection with monkeypox virus (MPXV) which belongs to the Orthopoxvirus genus in the family Poxviridae1. The specific animal reservoir of MPXV remains unknown. MPXV is found naturally in certain Central and West African countries. There are two main clades (variants) of mpox: Clade one (I) (formerly Congo Basin clade) and Clade two (II) (formerly West African clade). Clade II consists of two subclades (IIa and IIb). In addition to systemic symptoms, mpox is characterised by painful skin rash or mucosal lesions. Person to person transmission occurs through close contact with lesions, body fluids, respiratory droplets and contaminated materials such as bedding. Most cases of mpox infection are mild. Infections due to clade I are associated with more severe disease and a higher case fatality ratio. Until April 2022, export of mpox beyond endemic regions in Africa was rare, and limited to cases that had travelled to endemic areas, or to zoonotic transmission from imported animals.1 On 16 May 2022, the UK Health Security Agency reported four mpox cases among men with no links to an endemic area, and who self-identified as gay, bisexual and other men who have sex with men (gbMSM).2 On 18 May 2022, Portugal reported five confirmed and 20 suspect mpox cases among gbMSM.3 Global case numbers increased quickly. By 25 May 2022, 219 confirmed cases had been reported worldwide.4 On 23 July 2022, the World Health Organization (WHO), declared the global mpox outbreak a Public Health Emergency of International Concern (PHEIC).5 Since 1 January 2022 and as of 8 May 2023, 87,377 confirmed cases including 140 deaths, have been reported from 111 countries.6 Isolates from outbreak cases belonged to MPXV Clade II (previously known as the West African clade) - specifically subclade IIb. 7 On 10 May 2023, WHO determined mpox no longer constituted a PHEIC.8 We describe the epidemiology of mpox cases and the response to the mpox outbreak between May 2022 and May 2023. Mpox was made a notifiable disease in Ireland on 27 May 2022.9 Cases were reported to Ireland’s Computerised Infectious Disease Reporting (CIDR) system.10 In addition to the standard notification, Public Health Areas (PHAs) collected additional data about cases, including demographic factors, clinical details, potential exposures and vaccination history. Laboratory testing for MPXV was undertaken at the National Virus Reference Laboratory11and the Molecular Virology Laboratory at St James’s Hospital. PHAs also undertook contact tracing and risk assessment for close contacts. A national database was developed which allowed information on mpox close contacts to be recorded, including the setting in which exposure may have occurred (i.e. household, sexual, occupational), and vaccination status (e.g. previously vaccinated, or provided with postexposure prophylaxis). 12, 13 Data are presented on all confirmed mpox cases notified on CIDR up to midnight 27 May 2023 and extracted on 30 May 2023. Epidemiology of mpox cases Between 27 May 2022 and 27 May 2023, 229 confirmed cases of mpox were notified. The first case was notified on 31 May 2022 (week 22 2022) (Figure 1). The earliest known date of onset of symptoms among confirmed cases was 13 May 2022 (week 19 2022). Cases peaked in week 34 2022 (21-27 August 2022). In the first 23 weeks of 2023, only two confirmed cases were notified, one each in January and April. Gender was male in 226 cases and female in three cases. Median age was 35 years (range 16-68 years), with 46% of cases aged between 18-34 years and 79.8% aged between 18-44 years. The majority of cases were either born in Ireland (46.8%) or Latin America (32.3%). Summary characteristics of confirmed mpox cases are presented in Table 1. Contact tracing Interim public health guidance for the management of mpox outbreak cases and their contacts was released on 3 June 2022, adapted from earlier guidance for sporadic mpox cases.14 The purpose of contact tracing initially was to limit transmission, to identify vulnerable contacts at risk for more severe disease (pregnant women, young children and immunocompromised), and to raise awareness among contacts so that they would seek medical help early if they became symptomatic. Later, when vaccine was available, eligible contact were offered post exposure prophylaxis (PEP) vaccination. Initially, mpox was viewed as a High Consequence Infectious Disease (HCID) with high-risk contacts recommended to quarantine for 21 days.15 As understanding of the clinical severity and transmission risks increased, this approach was modified. Following ongoing dynamic risk assessments; quarantine of contacts was no longer required; there was a progressive easing of the definition of a high-risk contact; and cases (and their clinical samples and waste) linked to the global outbreak i.e. caused by MPXV subclade IIb, were no longer managed as HCID. Establishment of an Incident Management Team A national incident management team (IMT) first met on 16 May 2022, the same day as the UK first issued their alert. Given the close links between gbMSM communities across Europe, and in particular between Ireland and the UK, the likelihood of cases arising in Ireland was considered high. The IMT was responsible for monitoring of national and global situation, ongoing risk assessment, and advising on and coordinating the response measures. The IMT initially met daily when the event first emerged, and then weekly. Recognising the breadth of the response required, involving input across many different parts of the health service, and in particular the magnitude of implementing a national vaccination programme, the IMT transitioned into a National Crisis Management Team (NCMT) led by the Acute Operations division of the HSE in September 2022. The IMT and subsequent NCMT included representation from a wide range of disciplines and sectors across the health service including: public health; virology; clinical services including sexual health, infectious diseases, paediatrics, obstetrics, occupational health and general practice; infection prevention and control; the National Immunisation Office (NIO); the HSE Sexual Health and Crisis Pregnancy Programme (SHCPP); the National Ambulance Service; HSE Communications; acute hospital and community operations. From the onset, the IMT included representation from the gbMSM community with members from the Gay Health Network (GHN), an alliance of organisations with mandates to promote the sexual health of gbMSM in Ireland, and the MPOWER programme at HIV Ireland, a peer-driven communitylevel programme focusing on the sexual health and wellbeing among gbMSM16, 17. On transitioning to the NCMT format, MPOWER continued to be represented on the group. Guidance and service development IMT members initially, and subsequently the Pathways of Care Programme of the NCMT, worked with the Health Protection Research and Guideline Development Unit in developing and maintaining a suite of guidance on clinical and public health management of probable and confirmed cases and their close contacts, including assessment and testing, contact tracing, infection prevention and control, transportation, and waste management.18 Guidance was reviewed and updated at regular intervals as the outbreak evolved and understanding increased. Community engagement Supported by the Sexual Health Crisis Pregnancy Programme (SHCPP) and HSE Communications, GHN and MPOWER continued to develop and deliver a range of communications and engagement activities for the gbMSM community including posters at social venues and events, social media messaging, adverts and news pieces in gbMSM media, out-reach activities and community stakeholder events. This collaborative and peerled approach ensured the delivery of key messaging that is intended to be informative but not stigmatising. It has been recognised as an example of best practice for risk communication and community engagement on mpox by ECDC and the WHO.19, 20 Vaccination On 27 May 2022, Ireland’s National Immunisation Advisory Committee (NIAC) recommended that modified Vaccinia Ankara-Bavarian Nordic (MVA-BN), be offered to high and intermediate risk contacts of a case of mpox as PEP and healthcare workers at highest risk of exposure as pre-exposure prophylaxis (PREP).21 On 13 June 2022, the first doses of MVA-BN vaccine were delivered to community vaccination centres (CVCs), where PEP was primarily administered, occasionally supported by mobile vaccination teams, hospitals, and PHA teams.21 On 29 July 2022, NIAC recommended mpox vaccine as PrEP to those at high risk of exposure. Given the limited vaccine supply in the context of a global outbreak, the HSE through the advice and guidance of clinical and ethical experts and by working closely with gbMSM advocacy and support groups, offered PrEP in a phased manner. In the first phase (commencing August 2022), eligible people (gbMSM and transgender people who had a notification of early infectious syphilis between December 2021 and July 2022) were invited for vaccination in sexual health clinics. In November 2022, PrEP vaccination was extended to self-identified individuals at risk of mpox who could register online for vaccination and was administered in CVCs.23 Based on advice of the EMA, on 22 August NIAC endorsed lower dose intradermal administration rather than subcutaneous administration. This increased the number of people who could be offered vaccination23, 24. By the end of May 2023, 5,214 people had been fully vaccinated.

You are given a reference document. You must only use information found in the reference document to answer the question asked.

According to this document is the combination of paracetamol and ibuprofen effective?

NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs): Making safer treatment choices Non-steroidal anti-inflammatory drugs (NSAIDs) are successfully used to treat a wide range of painful conditions. However, NSAIDs should be prescribed with caution as courses of just a few days, even at doses within prescribing recommendations, can be associated with serious adverse effects in susceptible patients. In primary care, paracetamol is recommended in preference to NSAIDs, where appropriate. If a patient is likely to benefit from NSAID treatment naproxen or ibuprofen are recommended first-line, at the lowest effective dose, for the shortest possible time. Patients taking NSAIDs who are at increased risk of complications require regular monitoring. How NSAIDs work determines their risk and How NSAIDs work, the patient’s age and the condition being guides their use treated also need to be taken into account when these issues are discussed with patients. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequently prescribed medicines for analgesia in primary care, after paracetamol.1 However, NSAID use can be NSAIDs and cyclo-oxygenase (COX) selectivity associated with a range of serious adverse effects including: The cyclo-oxygenase-1 (COX-1) and COX-2 enzymes produce cardiovascular events, gastrointestinal complications, renal prostaglandins following the metabolism of omega-6 failure and hypersensitivity reactions. Even if the risk of an polyunsaturated fatty acid (arachidonic acid).3 Prostaglandins individual patient experiencing an NSAID-related adverse are chemical messengers that mediate inflammation, fever and event is relatively low, the frequent use of NSAIDs within the sensation of pain.3 The analgesic and anti-inflammatory the community means that the potential for NSAID-related effects of NSAIDs are produced through the prevention of adverse events to occur is a concern. NSAID use therefore prostaglandin production by inhibition of COX activity. The requires careful consideration of individual patient risk factors. clinical effects and the risk profiles of the different NSAIDs are To maximise patient safety it is recommended that clinicians largely determined by their differential ability to inhibit the consider the following points before prescribing an NSAID:2 COX-1 and/or COX-2 enzymes and their half-lives. Prescribe all NSAIDs with caution, in all patient groups, COX-1 is widely distributed in the body but is concentrated even over short periods of time in cells of the stomach, kidney, endothelium and in platelets.4 Prescribe the lowest effective NSAID dose, for the Prostaglandins catalysed by COX-1 activity control renal shortest possible time, and review the need for perfusion, promote platelet aggregation and provide continued use at each consultation gastroprotection by regulating mucous secretion.4 Inhibition Older patients, patients with increased cardiovascular of COX-1 can cause adverse gastrointestinal effects.4 risk, patients with type 2 diabetes, and patients with reduced renal function or a history of renal problems COX-2 is induced by inflammation and it is present in are at increased risk of NSAID-related complications and macrophages, leukocytes, fibroblasts and synovial cells. 4 should be advised about adverse effects and regularly Prostaglandins formed via COX-2 activity mediate pain, monitored when taking NSAIDs inflammation, fever and inhibit platelet aggregation.3 Naproxen (up to 1000 mg per day) or ibuprofen (up NSAIDs that inhibit both COX-1 and COX-2 enzymes are termed to 1200 mg per day) are the recommended first-line non-selective NSAIDs, while NSAIDs which predominately choices for adults based on our current knowledge of inhibit COX-2 enzymes are termed COX-2 inhibitors. NSAIDs and cardiovascular risk; ibuprofen is the most appropriate NSAID for children NSAIDs and COX inhibition Avoid prescribing long-acting formulations of NSAIDs, Ibuprofen, naproxen and diclofenac are non-selective NSAIDs. where possible, as these are associated with an increased However, diclofenac inhibits COX-2 relatively more than risk of gastrointestinal adverse effects COX-1.5 Many of the NSAIDs available in New Zealand have similar indications, e.g. musculoskeletal pain and inflammation, COX-1 is weakly inhibited and COX-2 is strongly inhibited then therefore these three medicines account for 97% of all the risk of thrombosis will be increased. NSAID prescribing.1 Other non-selective NSAIDs indicated for specific conditions include: tenoxicam (inflammatory Naproxen use (up to 1000 mg per day) does not appear to arthropathy, dysmenorrhoea, post-operative pain and acute be associated with increased vascular risk, based on current gout), tiaprofenic acid (inflammatory arthropathy), ketoprofen evidence.8 This may be because COX-1 inhibition by naproxen (inflammatory arthropathy), mefenamic acid (dysmenorrhoea is sufficiently prolonged and intense to effectively block and menorrhagia) and sulindac (inflammatory arthropathy).6 platelet activation and counterbalance the prothrombotic effect of COX-2 inhibition.8 Meloxicam is currently the only subsidised (Special Authority) COX-2 inhibitor in New Zealand. At low doses meloxicam mainly NSAID half-life also influences treatment choice inhibits COX-2. As the dose of meloxicam increases COX-1 is NSAIDs can be divided into short-acting NSAIDs with half-lives increasingly inhibited. For example, there is an increased rate less than six hours and long-acting NSAIDs. NSAIDs with a of serious gastrointestinal adverse events at a dose of 15 mg short half-life, e.g. ibuprofen, have a relatively quick onset of per day, compared to 7.5 mg per day.7 action and are better suited for the treatment of acute pain. NSAIDs with longer half-lives, e.g. naproxen, or in long-acting Celecoxib and etoricoxib COX-2 inhibitors are also available in formulations are more suited for the treatment of chronic New Zealand, but are not subsidised. conditions, as they require only once or twice daily dosing. However, persistent exposure to NSAIDs is an independent Check the New Zealand Formulary or Pharmaceutical determinant of gastrointestinal effects therefore NSAIDs with Schedule for the subsidy details of NSAIDs a long-half life, or NSAIDs in a slow-release formulation, are associated with an increased risk of gastrointestinal adverse events (see: “NSAIDs and gastrointestinal complications”, Page COX selectivity and cardiovascular risk 13).9 COX-2 inhibitors were initially developed on the rationale that selective inhibition of COX-2 might replicate the anti- inflammatory and analgesic effects of non-selective NSAIDs Choosing an analgesic regimen while reducing gastrointestinal adverse effects. However, The WHO analgesic ladder recommends paracetamol and/or it was later discovered that COX-2 activity inhibits platelet an NSAID first-line for pain management. The relative efficacy aggregation, therefore NSAIDs that block COX-2 promote of paracetamol and NSAIDs depends on the underlying thrombosis and events such as myocardial infarction become condition causing the pain. Specifically, NSAIDs are more more likely (see: “Cardiovascular risk in people taking NSAIDs”, effective than paracetamol in the treatment of inflammatory Page 12).3 It is now thought that the relative degree to which conditions, such as gout or rheumatoid arthritis, and in different NSAIDs inhibit both COX-1 and COX-2, and the effect the treatment of dental and menstrual pain.3, 10 For tension that this has on platelet aggregation, determines the likelihood headache or following orthopaedic surgery paracetamol is of each NSAID causing cardiovascular events.8 For example, if reported to provide equivalent analgesia to NSAIDs.10 Paracetamol and codeine may have variable efficacy The effectiveness of paracetamol and codeine may vary toxicity, even at low doses. This can result in respiratory depending on a person’s level of expression of the CYP2D6 depression. It is estimated that among Europeans up to enzyme. People deficient in this enzyme are unable to 10% of people will be either ultra-fast or slow metabolisers convert codeine to morphine and may not receive pain of codeine.14 The prevalence of fast and slow metabolisers relief from its use. Conversely, people who are ultra-fast of codeine among Māori and Pacific peoples is not metabolisers of codeine are at increased risk of opioid known. Paracetamol is safer than NSAIDs for most conditions Paracetamol is considered to be a safer treatment choice than NSAIDs in people at increased risk of NSAID-related Combination paracetamol and ibuprofen adverse effects, e.g. children or older patients, patients with There are an increasing number of products being cardiovascular or renal co-morbidities or diabetes, or patients marketed to the public that contain both paracetamol with a previous history of gastrointestinal symptoms or NSAID and ibuprofen. It is uncertain whether the concomitant hypersensitivity (see: “Hypersensitivity to NSAIDs”, Page use of paracetamol and ibuprofen significantly improves 16). Paracetamol is also recommended by United Kingdom analgesia compared to the use of NSAIDs alone. Studies guidelines for the long-term treatment of back pain and have produced mixed results and outcomes may be degenerative conditions, such as osteoarthritis, due to its influenced by the cause of the pain being studied. It is superior tolerability.3 also not clear whether the combined use of paracetamol and ibuprofen increases the risk of adverse effects. Compared to NSAIDs, paracetamol has:3 Minimal gastrointestinal toxicity A Cochrane review of the analgesic efficacy of paracetamol Little effect on blood pressure and ibuprofen in the treatment of post-operative pain, concluded that combinations of paracetamol plus No association with myocardial infarction ibuprofen provided better analgesia than either medicine No interaction with the antiplatelet effect of aspirin alone.12 It was also concluded that the combination treatment reduced the need for additional analgesia to Paracetamol can be given for mild to moderate pain in adults be administered and reduced the risk of adverse events at the recommended dose of 0.5 – 1 g, every four to six hours, occurring.12 A study of approximately 900 patients using to a maximum of 4 g per day.6 The major adverse effect paracetamol or ibuprofen, or a combination of the two, associated with paracetamol is liver damage due to overdose for the treatment of osteoarthritis of the knee found and it should not be prescribed to patients with liver disease.6 significantly more patients achieved pain control at ten days and at 13 weeks with the combination treatment Consider adding codeine to paracetamol in select patients compared to paracetamol alone, but there was not a If the risk of NSAID-related adverse events is high, it may be statistically significant difference compared to using appropriate to consider adding codeine to paracetamol, in ibuprofen alone.15 In contrast, a small study of 90 patients preference to NSAID treatment.11 For example, an older patient randomised to one of three treatment groups in an with osteoarthritis, diabetes and chronic kidney disease (CKD) emergency department setting found that combination may be particularly susceptible to the nephrotoxic effects of treatment with paracetamol and ibuprofen did not provide NSAIDs (see “NSAIDs and renal function”, Page 14). more effective pain relief following musculoskeletal injury compared to either medicine alone.16 An appropriate starting dose of codeine in combination with paracetamol for mild to moderate pain in adults is 15 A large British study funded by a pharmaceutical company mg, every four hours, as required.6 Codeine can be given in reported that compared to the use of the paracetamol and doses up to 60 mg, if required, but the total dose should not ibuprofen alone, the combined use of the two medicines exceed 240 mg per day.6 The main adverse effects of codeine did not increase the number of adverse effects.17 However, are gastrointestinal disturbance and potential respiratory in the treatment of osteoarthritis of the knee a trend depression.6 The effectiveness of codeine may vary between towards increased dyspepsia, diarrhoea and blood loss individuals due to genetic differences in metabolism, and it may was reported in patients using a combination product.15 not be an appropriate choice for all patients (see: “Paracetamol with codeine may have variable efficacy”, previous page). The lack of a demonstrated strong synergistic analgesic effect between paracetamol and ibuprofen, suggests that Combining paracetamol with NSAIDs may be appropriate the two medicines may have similar modes of actions The combination of paracetamol with NSAIDs may provide and their effects may not be additive.18 The lack of clear more effective analgesia for some patients, e.g. for post- evidence of improved analgesia has led some experts to surgical pain, than either medicine alone.12 This combination question the value of combination products containing treatment may allow the dose of NSAID required to achieve paracetamol and ibuprofen.18 analgesia to be reduced (compared to NSAID treatment alone) therefore reducing the amount NSAID-related risk the patient is exposed to.12 However, this approach does not appear to Diclofenac (75 – 150 mg, daily, in two or three divided doses) be effective for all conditions (see: “Combination paracetamol is indicated for acute pain and inflammation, in inflammatory and ibuprofen”, Page 11). If a combination of paracetamol arthropathy and other musculoskeletal disorders.6 However, and NSAIDs is used to treat pain, consider titrating the NSAID diclofenac at doses of ≥ 150 mg per day is associated with an dose downwards as pain becomes more manageable, while increased risk of cardiovascular events (see below). Diclofenac continuing treatment with paracetamol at the same dose. use is contraindicated in patients who have had a myocardial The NSAID can then be withdrawn, before paracetamol, and infarction in the previous 12 months.6 treatment with paracetamol continued, as required. When prescribing NSAIDs following muscle injury, short courses, i.e. three to seven days, are preferable to longer term Review and intensify lifestyle modifications to manage use.19 pain Long-term pain, as with any chronic condition, requires continual review and ongoing lifestyle modifications to prevent Cardiovascular risk in people taking NSAIDs a decline in the quality of the patient’s life. For example, a Prescribe long-term NASIDs with caution to people with an person with osteoarthritis is likely to benefit from intensifying elevated cardiovascular risk, particularly if they have had a exercise and weight loss programmes.13 previous cardiovascular event. All non-selective NSAIDs and COX-2 inhibitors are associated with increased cardiovascular risk - except naproxen up to 1000 mg per day or ibuprofen up Reducing the risk of NSAID use to 1200 mg per day.2, 20 This increased risk begins within the If it is decided that NSAID treatment is appropriate, having first week of treatment and translates to an additional three weighed the risks versus benefits of treatment, ensure the major vascular events per 1000 patients, per year.8, 21 patient’s history is known before an NSAID is prescribed. In particular:3 NSAID use has also been found to approximately double the Ensure the patient is aware which over-the-counter (OTC) risk of hospital admission due to heart failure and increase products contain NSAIDs and that they know that they systolic blood pressure by an average of 2 – 3 mmHg.3, 8 The should not take any other NSAID-containing products effect NSAIDs have on blood pressure may be more dramatic while they are being treated with an NSAID in people with pre-existing hypertension and in people Determine if the patient has any co-morbidities that may taking antihypertensives (see: “NSAIDs and renal function”, increase the risk of NSAID treatment, e.g. cardiovascular Page 14).3 Blood pressure should be monitored in patients disease, CKD, diabetes, hypertension or duodenal ulcer with hypertension and older patients within the first month of initiating long-term NSAID treatment, and then routinely Query if the patient is taking any medicines that may monitored as part of ongoing management.3 interact with NSAIDs, e.g. angiotensin converting enzyme (ACE) inhibitors, angiotensin-II receptor blockers (ARBs), NSAIDs increase cardiovascular risk across all patient diuretics, clopidogrel, warfarin, dabigatran or aspirin groups Discuss any history of NSAID-related adverse effects A large study found that there was a relative increase in with the patient. Their preference may affect the dosing cardiovascular risk, mainly attributed to coronary events, of regimen. Some patients may prefer to tolerate adverse approximately 33% in patients using high-dose diclofenac effects if a higher dose is likely to result in improved (> 150 mg), COX-2 inhibitors (celecoxib, rofecoxib, etoricoxib symptom control, while other patients may take the and lumiracoxib) and high-dose ibuprofen.8 Importantly, the opposite view. trial found that there was no statistical difference in this risk between patient groups with low or high predicted five-year Naproxen (up to 1000 mg per day) or ibuprofen (up to 1200 cardiovascular risk.8 The significance of this study to primary mg per day) are recommended first-line choices if NSAIDs care in New Zealand is that an increased cardiovascular risk are required, due to the lower risk of cardiovascular events has been an under-recognised concern in many patients occurring when these medicines are taken at these doses, taking non-selective NSAIDs. compared to other NSAIDs.2 N.B. The recommended maximum dose of ibuprofen is 2400 mg/day;6 this higher dose may be Short-term and long-term use of NSAIDs is associated with necessary, and appropriate, for some patients, but is associated increased cardiovascular risk. Advise patients who have had with increased cardiovascular risk. a previous cardiovascular event that even one or two doses of ibuprofen or diclofenac may increase their risk of a recurrent event. A study of over 83 000 patients with prior myocardial infarction found that NSAID use increased the risk of recurrent Aspirin and cardiovascular risk myocardial infarction or death by 1.45 times during the first It is unknown if aspirin use, which irreversibly inhibits seven days of treatment and this risk persisted throughout COX-1, influences the apparently neutral cardiovascular the course of treatment.21 The greatest risk was associated effects of naproxen. A large study has found evidence that with diclofenac which increased the risk of myocardial aspirin may confer a cardioprotective effect in patients infarction and/or death by 3.26 times at day one to seven of taking COX-2 inhibitors, but not in patients taking treatment.21 Naproxen was not associated with an increased ibuprofen.23 Further studies are required to characterise risk of myocardial infarction or death during the 14 week the cardiovascular effects of aspirin in people taking study duration.21 naproxen. A practical approach to the issue of a possible NSAIDs and gastrointestinal complications interaction between NSAIDs and aspirin prescribed for Gastrointestinal adverse events are increased two to four-fold cardioprotection is to minimise the combined use of by the use of all NSAIDs and this increase is dose dependent. these medicines in patients with elevated cardiovascular Gastrointestinal complications associated with NSAID use risk. The use of aspirin for the primary prevention of include: dyspepsia, gastrointestinal bleeding, peptic ulcers cardiovascular disease is controversial. Current evidence and perforations of the upper gastrointestinal tract.3, 9 This only justifies the use of low-dose aspirin for primary is because inhibition of the COX-1 enzyme reduces the prevention in patients with a five-year cardiovascular risk production of protective gastric mucous. In general NSAIDs of greater than 15%.24 Furthermore, patients with a high that have a long half-life or are taken in a long-acting cardiovascular risk should not be routinely prescribed formulation have a greater risk of gastrointestinal adverse long-term NSAIDs, if possible. Finally, patients with effects.9 Gastrointestinal symptoms are less common in increased cardiovascular risk are likely to be older and people taking COX-2 inhibitors, however, the risk is increased may have other co-morbidities that increase the risk of in patients who are concurrently taking aspirin.8 NSAID-related adverse effects. Therefore the number of patients whose cardiovascular risk is clinically affected by Risk factors for gastrointestinal adverse effects associated with any interaction between aspirin and NSAIDs in primary NSAID use include:3 care is likely to be small when NSAID use is carefully Age over 65 years managed. Previous adverse reaction to NSAIDs For further information see: “The use of antithrombotic The use of other medicines that may exacerbate any medicines in general practice: A consensus statement”, gastrointestinal adverse effects, e.g. anticoagulants, BPJ 39 (Oct, 2011). selective serotonin reuptake inhibitors (SSRIs) and corticosteroids Liver disease Chronic kidney disease (CKD) Smoking Excessive alcohol consumption Use of non-selective NSAIDs and COX-2 inhibitors in people with ulcerative colitis and Crohn’s disease may cause an exacerbation of symptoms.3 Paracetamol is generally better tolerated than NSAIDs in people at increased risk of gastrointestinal adverse effects. Diclofenac and COX-2 inhibitors appear to be the least likely NSAIDs to cause upper gastrointestinal perforation, obstruction or bleeds, while the risk is likely to be increased for patients taking ibuprofen and naproxen.8  Reducing the risk of gastrointestinal complications Advise patients to take NSAIDs with milk or food so the Reducing NSAID-related risk in Māori stomach is not empty and irritation is reduced.3 Consider NSAIDs are often used in the management of gout. Gout co-prescribing a proton pump inhibitor (PPI) prophylactically is more prevalent among Māori males (11.7%) compared in people aged over 45 years if NSAIDs are being used long- to European males (3.7%).22 Māori are also more severely term in the treatment of osteoarthritis, rheumatoid arthritis or affected by gout and are therefore more likely to be lower back pain.2 PPIs should be taken daily, rather than “as using NSAIDs to manage acute flares than non-Māori.22 needed” because PPIs require approximately three days to As Māori are approximately twice as likely as non-Māori achieve steady state inhibition of acid secretion and ulceration to die of cardiovascular disease, the use of NSAIDs in this or bleeding of the gastrointestinal tract can often occur in the population requires added caution. Prescribers should absence of dyspepsia.3, 25 be aware of the elevated cardiovascular risk amongst Māori when prescribing NSAIDs for gout and monitor for A Cochrane review found that both PPIs and histamine-2 adverse effects accordingly. In addition, management receptor antagonists, e.g. ranitidine, were effective at of gout among Māori patients should be intensified to preventing chronic NSAID-related gastric and duodenal reduce the likelihood of flares occurring and reduce the ulcers.26 Omeprazole for the prevention of NSAID-related need for NSAID treatment. Corticosteroids (oral or intra- ulcers can be initiated in adults at 20 mg, once daily, for four articular) or colchicine may be considered as treatment weeks and continued for another four weeks if gastrointestinal alternatives to naproxen for acute gout flare. symptoms have not completely resolved.6 Ranitidine can be initiated in adults, for protection against NSAID-related ulcers, For further information see: “An update on the at 150 mg, twice daily, or 300 mg at night, for up to eight management of gout”, BPJ 51 (Mar, 2013). weeks.6 Misoprostol is no longer routinely used in primary care for the prevention of NSAID-related ulcers as it is associated with diarrhoea and occasionally more severe adverse effects, even at low doses.6, 26 If a patient develops gastrointestinal symptoms during NSAID treatment another type of NSAID can be trialled, an alternative class of analgesic trialled, or a PPI prescribed. In patients with a high risk of developing gastrointestinal complications who require long-term NSAID treatment:3 Prescribe a PPI and advise the patient to discontinue the NSAID and contact a health professional if they notice any gastrointestinal symptoms, e.g. black stools Monitor haemoglobin levels for the first month of treatment. Long-term haemoglobin monitoring is recommended if bleeding is an ongoing clinical concern. If gastrointestinal adverse effects do develop, consider switching to another NSAID NSAIDs and renal function All medicines which block COX-2 are potentially nephrotoxic because they can reduce blood flow to the kidney by preventing prostaglandin-mediated vasodilation. This is particularly true in patients who are dehydrated. NSAIDs can also cause immune mediated acute kidney injury (AKI), e.g. acute interstitial nephritis. In New Zealand over 40% of all renal adverse reactions reported to the Centre for Adverse Reactions Monitoring (CARM) were associated with diclofenac.27 The Topical analgesics risk of AKI in patients taking NSAIDs and other potentially Topical NSAIDs are not subsidised in New Zealand, nephrotoxic medicines is greatest at the start of treatment, however, they are readily available over-the-counter therefore even short courses of NSAIDs should be avoided, if (OTC) and are frequently purchased for the treatment of possible, in patients at increased risk.28 soft tissue injuries, e.g. sports injuries. Topical NSAIDs, in combination with paracetamol, are recommended before All people with CKD should avoid NSAIDs where possible. oral NSAIDs or codeine in United Kingdom guidelines for CKD is a risk factor for AKI and one-quarter to one-third of the treatment of osteoarthritis.13 Topical NSAIDs are also all people aged over 64 years have CKD.29 Acute illness and/ preferred to oral NSAIDs by some clinicians for patients or hypovolaemia, even if mild, further increases the risk of aged over 75 years.3 AKI occurring in people with CKD who are taking NSAIDs. Patients with CKD who are taking NSAIDs should be advised Topical NSAIDs are considered to be as safe as placebo to discontinue use if they develop an acute illness, especially in the treatment of acute pain and therefore can be if they become dehydrated. Patients who have had a previous safely used by patients who are at risk of developing acute decline in renal function should have their notes flagged complications associated with oral NSAIDs. 35 Blood and be identified as at risk of NSAID-related AKI. concentrations of NSAIDs after applying topical products are typically less than 5% of those reached by using oral People with type 2 diabetes should avoid NSAIDs where NSAIDs.35 Approximately six or seven patients out of possible. Reduced renal function and albuminuria are both ten will experience successful pain control with topical risk factors for micro and macrovascular complications NSAIDs.35 However, a large proportion of this effect is that have increased prevalence in people with diabetes.30 because sprain-type injuries tend to improve without Preservation of renal function to prevent the development of treatment.35 CKD and to reduce cardiovascular risk is an essential part of the management of patients with type 2 diabetes. Topical capsaicin is also often used as an adjunctive treatment for osteoarthritis of the knee or hand.13 Topical NSAID nephrotoxicity can be exacerbated by ACE inhibitors capsaicin is currently subsidised for patients who have or ARBs as these medicines impair the regulation of blood osteoarthritis that is not responsive to paracetamol and flow leaving the kidney. Renal function can be compromised where oral NSAIDs are contraindicated. Topical capsaicin is even further if a patient is also taking a diuretic. The combined an irritant and should not be applied to the eyes, mucous potential effect of these three medicines has been referred membranes or broken skin.6 Hands should be washed to as the “triple whammy”. This can result in hyponatremia immediately after applying this medicine.6 or hyperkalemia, AKI and cardiac failure.3, 31 The risk of this occurring is greatest in the first 30 days of use.28 This combination of medicines should be prescribed with caution, particularly in people with CKD or diabetes. If patients develop an acute illness it may be appropriate to discontinue or reduce the dose of these medicines. In patients with reduced renal function who are taking NSAIDs, or in patients at increased risk of renal toxicity, serum creatinine and potassium should be measured after one to two weeks of treatment and then monitored regularly.3 For further information see: “Acute-on-chronic kidney disease: Prevention, diagnosis, management and referral in primary care”, BPJ 46 (Sep, 2012). Hypersensitivity to NSAIDs Use of NSAIDs in children NSAID/aspirin hypersensitivity is characterised by symptoms Ibuprofen is generally the preferred NSAID for use in children. ranging in speed of onset from anaphylaxis and bronchospasm Naproxen is not indicated for the short-term treatment of pain to delayed skin and systemic reactions occurring over weeks.32 and fever in children, but may be prescribed for rheumatoid The reaction is due to COX-1 inhibition and is not mediated by arthritis in children aged over five years.6 Diclofenac is the only IgE, therefore it is not a true allergy.32 NSAID hypersensitivity other NSAID available in New Zealand for the treatment of is reported to affect 0.5 – 1.9% of the general population.32 pain and inflammation in children aged under 12 years, but it However, reports of prevalence among adults with asthma is rarely prescribed for this purpose in primary care. are as high as 21% if aspirin provocation testing is used.32 In children the prevalence of NSAID hypersensitivity is lower and reported to be 0.3% – 5% as assessed by provocation.32 Fever and NSAID use in children Cutaneous hypersensitivity reactions are relatively infrequent Febrile illness accounts for a large proportion of childhood and affect 0.3% of the population.32 presentations to primary care. Between 20 – 40% of parents report an occurrence every year.36 Paracetamol (children aged NSAIDs can be routinely prescribed to patients with asthma over one month, 15 mg/kg per dose, every four hours, up to who have no previous history of NSAID-associated symptoms. four times daily, maximum 1 g per dose and 4 g per day) or However, the possibility of NSAID use increasing asthma ibuprofen (children aged under 12 years, 20 mg/kg in divided severity should be discussed with the patient first. Patients doses, to a maximum of 500 mg per day in children under 30 with asthma and nasal polyps or recurrent sinusitis are more kg) are both indicated for the treatment of pain and fever in likely to experience hypersensitivity to NSAIDs.33 People who children.6, 36 However, before prescribing ibuprofen for the have had a hypersensitivity reaction to a NSAID should avoid treatment of febrile illness consider emerging evidence that all non-selective NSAIDs as the reaction is likely to be a class suggests the use of NSAIDs in children may be associated with effect.32 an increased risk of AKI, especially in children who are obese (see below). NSAID use in women who are pregnant is not A paracetamol dosage calculator for children is available recommended from: Paracetamol is preferred to NSAIDs in women who are www.bpac.org.nz/resources/other/bmi_calc/bmiCalc.html pregnant because NSAID use in the first trimester doubles the risk of spontaneous abortion.3 Later in pregnancy NSAID use Management of fever in children should aim to improve is associated with premature closure of the ductus arteriosus comfort rather than reduce body temperature.37 Points to blood vessel, which can result in structural birth defects, consider when prescribing medicines specifically for fever in preterm delivery or low birth weight.34 NSAIDs may also delay children include:36 the onset of labour and increase blood loss during childbirth.3 Mild fevers (<38°C) do not need to be treated Paracetamol or ibuprofen should not be given for the Breast feeding while taking paracetamol or NSAIDs is considered sole purpose of reducing body temperature (see: “The safe due to the low concentrations of these medicines in benefits of inflammation and fever”) breast milk.34 However, aspirin use during lactation has been Medicines for fever should only be prescribed for as associated with significant adverse events in infants.34 Repeat long as the child is in discomfort. If discomfort is not doses of codeine should be avoided wherever possible in alleviated before the next dose is due, then switching, women who are breast feeding, as severe toxicity has been e.g. changing from paracetamol to ibuprofen, may be reported in infants whose mothers are ultra-fast metabolisers considered. Also consider medical review. (see: “Paracetamol and codeine may have variable efficacy”, Do not give paracetamol and ibuprofen at the same time Page 10).6 Paracetamol and ibuprofen do not prevent febrile convulsions and should not be prescribed specifically for this reason Ask if the child has taken any medicine for their current illness when assessing their condition. A failure to respond to prior treatment may indicate a more serious illness. Advise parents be a contributing factor to additional cases of multi-factorial of the need for children with fever to receive regular fluids.36 AKI.39 The majority of presentations occurred within the first Small quantities of water offered frequently are best, or breast seven days of treatment and doses were generally within milk if the child is being breast fed. Parents should not give recommended prescribing guidelines.39 Vomiting (74%) was NSAIDs to children who may be dehydrated, e.g. vomiting, the most frequent symptom followed by abdominal pain sunken eyes, tears or urine absent or if skin turgor is diminished. (67%) and decreased urine output (56%). 39 Children aged Tepid sponging is not recommended for the treatment of fever, under five years were most likely to require intensive treatment and children with fever should neither be over-wrapped nor and stay in hospital for longer.39 Obesity may be an important under dressed.36 Discussing the benefits of fever with parents risk factor for NSAID-induced AKI in children as almost half of may help to reduce parental distress. the patients admitted were at or above the 95th percentile for body mass index (BMI) or weight:length ratio.39 NSAIDs and acute kidney injury in children NSAIDs should be prescribed with caution in children with acute illness and/or volume depletion.38 ACKNOWLEDGEMENT: Thank you to Dr Chris Cameron, Children aged under five years and children who are obese General Physician and Clinical Pharmacologist, Chair, may be at greatest risk of NSAID-induced AKI. One study of Medicines Committee, Capital & Coast DHB, Wellington children admitted to hospital with AKI found that at least 2.7% Hospital for expert review of this article. of all instances were due to NSAID use, with NSAID use likely to The benefits of inflammation and fever The inflammatory response is triggered by damaged or infected cells releasing pro-inflammatory proteins. These signals cause local capillaries to increase in size and capillary membranes to become permeable, resulting in swelling as fluid accumulates locally. Attracted by the chemical signals, white blood cells pass through the capillary membranes and invade the area, attacking pathogens and consuming dead and infected cells. The increased body temperature acts to suppress bacterial growth, viral replication and therefore reduces the duration of infections. References 1. Ministry of Health. Pharmaceutical Collection. 2013. 21. Schjerning Olsen A-M, Fosbøl EL, Lindhardsen J, et al. Duration of 2. National Institute for Health and Care Excellence (NICE). Non-steroidal treatment with nonsteroidal anti-inflammatory drugs and impact anti-inflammatory drugs. Manchester: NICE; 2013. Available from: on risk of death and recurrent myocardial infarction in patients with www.nice.org.uk (Accessed Sep, 2013). prior myocardial infarction: a nationwide cohort study. Circulation. 3. Day RO, Graham GG. Non-steroidal anti-inflammatory drugs (NSAIDs). 2011;123(20):2226–35. BMJ. 2013;346:f3195. 22. Winnard D, Wright C, Taylor W, et al. National prevalence of gout 4. Longo D, Fauci A, Kasper D, et al. Chapter 293: Peptic ulcer disease and derived from administrative health data in Aotearoa New Zealand. related disorders. Harrison’s principles of internal medicine. 18th ed. Rheumatology. 2012;51:901–9. New York: McGraw Hill Medical; 2012. p. 2438-60. 23. Strand V. Are COX-2 inhibitors preferable to non-selective non-steroidal 5. Fosbøl EL, Gislason GH, Jacobsen S, et al. Risk of myocardial infarction anti-inflammatory drugs in patients with risk of cardiovascular events and death associated with the use of nonsteroidal anti-inflammatory taking low-dose aspirin? Lancet. 2007;370(9605):2138–51. drugs (NSAIDs) among healthy individuals: a nationwide cohort study. 24. New Zealand Guidelines Group. New Zealand primary care handbook Clin Pharmacol Ther. 2009;85(2):190–7. 2012. 3rd ed. Wellington: New Zealand Guidelines Group; 2012. 6. New Zealand Formulary (NZF). NZF v15. NZF; 2013. Available from: 25. Shin JM, Kim N. Pharmacokinetics and pharmacodynamics of the proton www.nzf.org.nz (Accessed Sep, 2013). pump inhibitors. J Neurogastroenterol Motil. 2013;19(1):25–35. 7. Singh G, Lanes S, Triadafilopoulos G. Risk of serious upper 26. Rostom A, Dube C, Wells G, et al. Prevention of NSAID- gastrointestinal and cardiovascular thromboembolic complications induced gastroduodenal ulcers. Cochrane Database Syst Rev. with meloxicam. Am J Med. 2004;117(2):100–6. 2002;4:CD002296. 8. Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular 27. Medsafe. Prescriber Update: NSAIDs and Acute Kidney Injury. 2013. and upper gastrointestinal effects of non-steroidal anti-inflammatory Available from: www.medsafe.govt.nz (Accessed Sep, 2013). drugs: meta-analyses of individual participant data from randomised 28. Lapi F, Azoulay L, Yin H, et al. Concurrent use of diuretics, angiotensin trials. Lancet. 2013;382(9894):769–79. converting enzyme inhibitors, and angiotensin receptor blockers with 9. Massó González EL, Patrignani P, Tacconelli S, García Rodríguez LA. non-steroidal anti-inflammatory drugs and risk of acute kidney injury: Variability among nonsteroidal antiinflammatory drugs in risk of upper nested case-control study. BMJ. 2013;346:e8525. gastrointestinal bleeding. Arthritis Rheum. 2010;62(6):1592–601. 29. Zhang Q-L, Rothenbacher D. Prevalence of chronic kidney disease 10. Sachs CJ. Oral analgesics for acute nonspecific pain. Am Fam Physician. in population-based studies: systematic review. BMC Public Health. 2005;71(5):913–8. 2008;8:117. 11. National Institute for Health Care and Excellence (NICE). Clinical 30. Doggen K, Nobels F, Scheen AJ, et al. Cardiovascular risk factors and Knowledge Summaries: NSAIDs - prescribing issues. NICE, 2013. complications associated with albuminuria and impaired renal function Available from: cks.nice.org.uk (Accessed Sep, 2013). in insulin-treated diabetes. J Diabetes Complicat. 2013;27(4):370–5. 12. Derry CJ, Derry S, Moore RA. Single dose oral ibuprofen plus 31. Fournier J-P, Lapeyre-Mestre M, Sommet A, et al. Laboratory monitoring paracetamol (acetaminophen) for acute postoperative pain. Cochrane of patients treated with antihypertensive drugs and newly exposed Database Syst Rev. 2013;6:CD010210. to non steroidal anti-inflammatory drugs: a cohort study. PLoS ONE. 13. National Institute for Health Care Excellence (NICE). Osteoarthritis: the 2012;7(3):e34187. care and management of osteoarthritis in adults. NICE: London; 2008. 32. Kowalski ML, Makowska JS, Blanca M, et al. Hypersensitivity to Available from: www.nice.org.uk (Accessed Sep, 2013). nonsteroidal anti-inflammatory drugs (NSAIDs) - classification, 14. de Leon J, Armstrong SC, Cozza KL. Clinical guidelines for psychiatrists diagnosis and management: review of the EAACI/ENDA and GA2LEN/ for the use of pharmacogenetic testing for CYP450 2D6 and CYP450 HANNA. Allergy. 2011;66(7):818–29. 2C19. Psychosomatics. 2006;47(1):75–85. 33. Risser A, Donovan D, Heintzman J, Page T. NSAID prescribing 15. Doherty M, Hawkey C, Goulder M, et al. A randomised controlled precautions. Am Fam Physician. 2009;80(12):1371–8. trial of ibuprofen, paracetamol or a combination tablet of ibuprofen/ 34. Kennedy D. Analgesics and pain relief in pregnancy and breastfeeding. paracetamol in community-derived people with knee pain. Ann Austr Prescr. 2011;34:8–10. Rheum Dis. 2011;70(9):1534–41. 35. Massey T, Derry S, Moore RA, McQuay HJ. Topical NSAIDs for acute pain 16. Bondarsky EE, Domingo AT, Matuza NM, et al. Ibuprofen vs in adults. Cochrane Database Syst Rev. 2010;(6):CD007402. acetaminophen vs their combination in the relief of musculoskeletal 36. National Institute for Health and Care Excellence (NICE). Feverish illness pain in the ED: a randomized, controlled trial. Am J Emerg Med. in children: Assessment and initial management in children younger 2013;9:1357–60. than five years. NICE: Manchester; 2013. Available from: www.nice.org. 17. de Vries F, Setakis E, van Staa T-P. Concomitant use of ibuprofen and uk (Accessed Sep, 2013). paracetamol and the risk of major clinical safety outcomes. Br J Clin 37. Sullivan JE, Farrar HC. Fever and antipyretic use in children. Pediatrics. Pharmacol. 2010;70(3):429–38. 2011;127(3):580–7. 18. Brune K, Hinz B. Paracetamol, ibuprofen, or a combination of both drugs 38. Brophy PD. Changing the paradigm in pediatric acute kidney injury. J against knee pain: an excellent new randomised clinical trial answers Pediatr. 2013;162(6):1094–6. old questions and suggests new therapeutic recommendations. Ann 39. Misurac JM, Knoderer CA, Leiser JD, et al. Nonsteroidal anti- Rheum Dis. 2011;70(9):1521–2. Inflammatory drugs are an important cause of acute kidney injury in 19. Feucht CL, Patel DR. Analgesics and anti-inflammatory medications in children. J Pediatr. 2013;162:1153–9. sports: use and abuse. Pediatr Clin North Am. 2010;57(3):751–74. 20. Trelle S, Reichenbach S, Wandel S, et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011;342:c7086.  COMING SOON The New Zealand Formulary for Children www.nzformulary.org 

You are given a reference document. You must only use information found in the reference document to answer the question asked. According to this document is the combination of paracetamol and ibuprofen effective? NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs): Making safer treatment choices Non-steroidal anti-inflammatory drugs (NSAIDs) are successfully used to treat a wide range of painful conditions. However, NSAIDs should be prescribed with caution as courses of just a few days, even at doses within prescribing recommendations, can be associated with serious adverse effects in susceptible patients. In primary care, paracetamol is recommended in preference to NSAIDs, where appropriate. If a patient is likely to benefit from NSAID treatment naproxen or ibuprofen are recommended first-line, at the lowest effective dose, for the shortest possible time. Patients taking NSAIDs who are at increased risk of complications require regular monitoring. How NSAIDs work determines their risk and How NSAIDs work, the patient’s age and the condition being guides their use treated also need to be taken into account when these issues are discussed with patients. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequently prescribed medicines for analgesia in primary care, after paracetamol.1 However, NSAID use can be NSAIDs and cyclo-oxygenase (COX) selectivity associated with a range of serious adverse effects including: The cyclo-oxygenase-1 (COX-1) and COX-2 enzymes produce cardiovascular events, gastrointestinal complications, renal prostaglandins following the metabolism of omega-6 failure and hypersensitivity reactions. Even if the risk of an polyunsaturated fatty acid (arachidonic acid).3 Prostaglandins individual patient experiencing an NSAID-related adverse are chemical messengers that mediate inflammation, fever and event is relatively low, the frequent use of NSAIDs within the sensation of pain.3 The analgesic and anti-inflammatory the community means that the potential for NSAID-related effects of NSAIDs are produced through the prevention of adverse events to occur is a concern. NSAID use therefore prostaglandin production by inhibition of COX activity. The requires careful consideration of individual patient risk factors. clinical effects and the risk profiles of the different NSAIDs are To maximise patient safety it is recommended that clinicians largely determined by their differential ability to inhibit the consider the following points before prescribing an NSAID:2 COX-1 and/or COX-2 enzymes and their half-lives. Prescribe all NSAIDs with caution, in all patient groups, COX-1 is widely distributed in the body but is concentrated even over short periods of time in cells of the stomach, kidney, endothelium and in platelets.4 Prescribe the lowest effective NSAID dose, for the Prostaglandins catalysed by COX-1 activity control renal shortest possible time, and review the need for perfusion, promote platelet aggregation and provide continued use at each consultation gastroprotection by regulating mucous secretion.4 Inhibition Older patients, patients with increased cardiovascular of COX-1 can cause adverse gastrointestinal effects.4 risk, patients with type 2 diabetes, and patients with reduced renal function or a history of renal problems COX-2 is induced by inflammation and it is present in are at increased risk of NSAID-related complications and macrophages, leukocytes, fibroblasts and synovial cells. 4 should be advised about adverse effects and regularly Prostaglandins formed via COX-2 activity mediate pain, monitored when taking NSAIDs inflammation, fever and inhibit platelet aggregation.3 Naproxen (up to 1000 mg per day) or ibuprofen (up NSAIDs that inhibit both COX-1 and COX-2 enzymes are termed to 1200 mg per day) are the recommended first-line non-selective NSAIDs, while NSAIDs which predominately choices for adults based on our current knowledge of inhibit COX-2 enzymes are termed COX-2 inhibitors. NSAIDs and cardiovascular risk; ibuprofen is the most appropriate NSAID for children NSAIDs and COX inhibition Avoid prescribing long-acting formulations of NSAIDs, Ibuprofen, naproxen and diclofenac are non-selective NSAIDs. where possible, as these are associated with an increased However, diclofenac inhibits COX-2 relatively more than risk of gastrointestinal adverse effects COX-1.5 Many of the NSAIDs available in New Zealand have similar indications, e.g. musculoskeletal pain and inflammation, COX-1 is weakly inhibited and COX-2 is strongly inhibited then therefore these three medicines account for 97% of all the risk of thrombosis will be increased. NSAID prescribing.1 Other non-selective NSAIDs indicated for specific conditions include: tenoxicam (inflammatory Naproxen use (up to 1000 mg per day) does not appear to arthropathy, dysmenorrhoea, post-operative pain and acute be associated with increased vascular risk, based on current gout), tiaprofenic acid (inflammatory arthropathy), ketoprofen evidence.8 This may be because COX-1 inhibition by naproxen (inflammatory arthropathy), mefenamic acid (dysmenorrhoea is sufficiently prolonged and intense to effectively block and menorrhagia) and sulindac (inflammatory arthropathy).6 platelet activation and counterbalance the prothrombotic effect of COX-2 inhibition.8 Meloxicam is currently the only subsidised (Special Authority) COX-2 inhibitor in New Zealand. At low doses meloxicam mainly NSAID half-life also influences treatment choice inhibits COX-2. As the dose of meloxicam increases COX-1 is NSAIDs can be divided into short-acting NSAIDs with half-lives increasingly inhibited. For example, there is an increased rate less than six hours and long-acting NSAIDs. NSAIDs with a of serious gastrointestinal adverse events at a dose of 15 mg short half-life, e.g. ibuprofen, have a relatively quick onset of per day, compared to 7.5 mg per day.7 action and are better suited for the treatment of acute pain. NSAIDs with longer half-lives, e.g. naproxen, or in long-acting Celecoxib and etoricoxib COX-2 inhibitors are also available in formulations are more suited for the treatment of chronic New Zealand, but are not subsidised. conditions, as they require only once or twice daily dosing. However, persistent exposure to NSAIDs is an independent Check the New Zealand Formulary or Pharmaceutical determinant of gastrointestinal effects therefore NSAIDs with Schedule for the subsidy details of NSAIDs a long-half life, or NSAIDs in a slow-release formulation, are associated with an increased risk of gastrointestinal adverse events (see: “NSAIDs and gastrointestinal complications”, Page COX selectivity and cardiovascular risk 13).9 COX-2 inhibitors were initially developed on the rationale that selective inhibition of COX-2 might replicate the anti- inflammatory and analgesic effects of non-selective NSAIDs Choosing an analgesic regimen while reducing gastrointestinal adverse effects. However, The WHO analgesic ladder recommends paracetamol and/or it was later discovered that COX-2 activity inhibits platelet an NSAID first-line for pain management. The relative efficacy aggregation, therefore NSAIDs that block COX-2 promote of paracetamol and NSAIDs depends on the underlying thrombosis and events such as myocardial infarction become condition causing the pain. Specifically, NSAIDs are more more likely (see: “Cardiovascular risk in people taking NSAIDs”, effective than paracetamol in the treatment of inflammatory Page 12).3 It is now thought that the relative degree to which conditions, such as gout or rheumatoid arthritis, and in different NSAIDs inhibit both COX-1 and COX-2, and the effect the treatment of dental and menstrual pain.3, 10 For tension that this has on platelet aggregation, determines the likelihood headache or following orthopaedic surgery paracetamol is of each NSAID causing cardiovascular events.8 For example, if reported to provide equivalent analgesia to NSAIDs.10 Paracetamol and codeine may have variable efficacy The effectiveness of paracetamol and codeine may vary toxicity, even at low doses. This can result in respiratory depending on a person’s level of expression of the CYP2D6 depression. It is estimated that among Europeans up to enzyme. People deficient in this enzyme are unable to 10% of people will be either ultra-fast or slow metabolisers convert codeine to morphine and may not receive pain of codeine.14 The prevalence of fast and slow metabolisers relief from its use. Conversely, people who are ultra-fast of codeine among Māori and Pacific peoples is not metabolisers of codeine are at increased risk of opioid known. Paracetamol is safer than NSAIDs for most conditions Paracetamol is considered to be a safer treatment choice than NSAIDs in people at increased risk of NSAID-related Combination paracetamol and ibuprofen adverse effects, e.g. children or older patients, patients with There are an increasing number of products being cardiovascular or renal co-morbidities or diabetes, or patients marketed to the public that contain both paracetamol with a previous history of gastrointestinal symptoms or NSAID and ibuprofen. It is uncertain whether the concomitant hypersensitivity (see: “Hypersensitivity to NSAIDs”, Page use of paracetamol and ibuprofen significantly improves 16). Paracetamol is also recommended by United Kingdom analgesia compared to the use of NSAIDs alone. Studies guidelines for the long-term treatment of back pain and have produced mixed results and outcomes may be degenerative conditions, such as osteoarthritis, due to its influenced by the cause of the pain being studied. It is superior tolerability.3 also not clear whether the combined use of paracetamol and ibuprofen increases the risk of adverse effects. Compared to NSAIDs, paracetamol has:3 Minimal gastrointestinal toxicity A Cochrane review of the analgesic efficacy of paracetamol Little effect on blood pressure and ibuprofen in the treatment of post-operative pain, concluded that combinations of paracetamol plus No association with myocardial infarction ibuprofen provided better analgesia than either medicine No interaction with the antiplatelet effect of aspirin alone.12 It was also concluded that the combination treatment reduced the need for additional analgesia to Paracetamol can be given for mild to moderate pain in adults be administered and reduced the risk of adverse events at the recommended dose of 0.5 – 1 g, every four to six hours, occurring.12 A study of approximately 900 patients using to a maximum of 4 g per day.6 The major adverse effect paracetamol or ibuprofen, or a combination of the two, associated with paracetamol is liver damage due to overdose for the treatment of osteoarthritis of the knee found and it should not be prescribed to patients with liver disease.6 significantly more patients achieved pain control at ten days and at 13 weeks with the combination treatment Consider adding codeine to paracetamol in select patients compared to paracetamol alone, but there was not a If the risk of NSAID-related adverse events is high, it may be statistically significant difference compared to using appropriate to consider adding codeine to paracetamol, in ibuprofen alone.15 In contrast, a small study of 90 patients preference to NSAID treatment.11 For example, an older patient randomised to one of three treatment groups in an with osteoarthritis, diabetes and chronic kidney disease (CKD) emergency department setting found that combination may be particularly susceptible to the nephrotoxic effects of treatment with paracetamol and ibuprofen did not provide NSAIDs (see “NSAIDs and renal function”, Page 14). more effective pain relief following musculoskeletal injury compared to either medicine alone.16 An appropriate starting dose of codeine in combination with paracetamol for mild to moderate pain in adults is 15 A large British study funded by a pharmaceutical company mg, every four hours, as required.6 Codeine can be given in reported that compared to the use of the paracetamol and doses up to 60 mg, if required, but the total dose should not ibuprofen alone, the combined use of the two medicines exceed 240 mg per day.6 The main adverse effects of codeine did not increase the number of adverse effects.17 However, are gastrointestinal disturbance and potential respiratory in the treatment of osteoarthritis of the knee a trend depression.6 The effectiveness of codeine may vary between towards increased dyspepsia, diarrhoea and blood loss individuals due to genetic differences in metabolism, and it may was reported in patients using a combination product.15 not be an appropriate choice for all patients (see: “Paracetamol with codeine may have variable efficacy”, previous page). The lack of a demonstrated strong synergistic analgesic effect between paracetamol and ibuprofen, suggests that Combining paracetamol with NSAIDs may be appropriate the two medicines may have similar modes of actions The combination of paracetamol with NSAIDs may provide and their effects may not be additive.18 The lack of clear more effective analgesia for some patients, e.g. for post- evidence of improved analgesia has led some experts to surgical pain, than either medicine alone.12 This combination question the value of combination products containing treatment may allow the dose of NSAID required to achieve paracetamol and ibuprofen.18 analgesia to be reduced (compared to NSAID treatment alone) therefore reducing the amount NSAID-related risk the patient is exposed to.12 However, this approach does not appear to Diclofenac (75 – 150 mg, daily, in two or three divided doses) be effective for all conditions (see: “Combination paracetamol is indicated for acute pain and inflammation, in inflammatory and ibuprofen”, Page 11). If a combination of paracetamol arthropathy and other musculoskeletal disorders.6 However, and NSAIDs is used to treat pain, consider titrating the NSAID diclofenac at doses of ≥ 150 mg per day is associated with an dose downwards as pain becomes more manageable, while increased risk of cardiovascular events (see below). Diclofenac continuing treatment with paracetamol at the same dose. use is contraindicated in patients who have had a myocardial The NSAID can then be withdrawn, before paracetamol, and infarction in the previous 12 months.6 treatment with paracetamol continued, as required. When prescribing NSAIDs following muscle injury, short courses, i.e. three to seven days, are preferable to longer term Review and intensify lifestyle modifications to manage use.19 pain Long-term pain, as with any chronic condition, requires continual review and ongoing lifestyle modifications to prevent Cardiovascular risk in people taking NSAIDs a decline in the quality of the patient’s life. For example, a Prescribe long-term NASIDs with caution to people with an person with osteoarthritis is likely to benefit from intensifying elevated cardiovascular risk, particularly if they have had a exercise and weight loss programmes.13 previous cardiovascular event. All non-selective NSAIDs and COX-2 inhibitors are associated with increased cardiovascular risk - except naproxen up to 1000 mg per day or ibuprofen up Reducing the risk of NSAID use to 1200 mg per day.2, 20 This increased risk begins within the If it is decided that NSAID treatment is appropriate, having first week of treatment and translates to an additional three weighed the risks versus benefits of treatment, ensure the major vascular events per 1000 patients, per year.8, 21 patient’s history is known before an NSAID is prescribed. In particular:3 NSAID use has also been found to approximately double the Ensure the patient is aware which over-the-counter (OTC) risk of hospital admission due to heart failure and increase products contain NSAIDs and that they know that they systolic blood pressure by an average of 2 – 3 mmHg.3, 8 The should not take any other NSAID-containing products effect NSAIDs have on blood pressure may be more dramatic while they are being treated with an NSAID in people with pre-existing hypertension and in people Determine if the patient has any co-morbidities that may taking antihypertensives (see: “NSAIDs and renal function”, increase the risk of NSAID treatment, e.g. cardiovascular Page 14).3 Blood pressure should be monitored in patients disease, CKD, diabetes, hypertension or duodenal ulcer with hypertension and older patients within the first month of initiating long-term NSAID treatment, and then routinely Query if the patient is taking any medicines that may monitored as part of ongoing management.3 interact with NSAIDs, e.g. angiotensin converting enzyme (ACE) inhibitors, angiotensin-II receptor blockers (ARBs), NSAIDs increase cardiovascular risk across all patient diuretics, clopidogrel, warfarin, dabigatran or aspirin groups Discuss any history of NSAID-related adverse effects A large study found that there was a relative increase in with the patient. Their preference may affect the dosing cardiovascular risk, mainly attributed to coronary events, of regimen. Some patients may prefer to tolerate adverse approximately 33% in patients using high-dose diclofenac effects if a higher dose is likely to result in improved (> 150 mg), COX-2 inhibitors (celecoxib, rofecoxib, etoricoxib symptom control, while other patients may take the and lumiracoxib) and high-dose ibuprofen.8 Importantly, the opposite view. trial found that there was no statistical difference in this risk between patient groups with low or high predicted five-year Naproxen (up to 1000 mg per day) or ibuprofen (up to 1200 cardiovascular risk.8 The significance of this study to primary mg per day) are recommended first-line choices if NSAIDs care in New Zealand is that an increased cardiovascular risk are required, due to the lower risk of cardiovascular events has been an under-recognised concern in many patients occurring when these medicines are taken at these doses, taking non-selective NSAIDs. compared to other NSAIDs.2 N.B. The recommended maximum dose of ibuprofen is 2400 mg/day;6 this higher dose may be Short-term and long-term use of NSAIDs is associated with necessary, and appropriate, for some patients, but is associated increased cardiovascular risk. Advise patients who have had with increased cardiovascular risk. a previous cardiovascular event that even one or two doses of ibuprofen or diclofenac may increase their risk of a recurrent event. A study of over 83 000 patients with prior myocardial infarction found that NSAID use increased the risk of recurrent Aspirin and cardiovascular risk myocardial infarction or death by 1.45 times during the first It is unknown if aspirin use, which irreversibly inhibits seven days of treatment and this risk persisted throughout COX-1, influences the apparently neutral cardiovascular the course of treatment.21 The greatest risk was associated effects of naproxen. A large study has found evidence that with diclofenac which increased the risk of myocardial aspirin may confer a cardioprotective effect in patients infarction and/or death by 3.26 times at day one to seven of taking COX-2 inhibitors, but not in patients taking treatment.21 Naproxen was not associated with an increased ibuprofen.23 Further studies are required to characterise risk of myocardial infarction or death during the 14 week the cardiovascular effects of aspirin in people taking study duration.21 naproxen. A practical approach to the issue of a possible NSAIDs and gastrointestinal complications interaction between NSAIDs and aspirin prescribed for Gastrointestinal adverse events are increased two to four-fold cardioprotection is to minimise the combined use of by the use of all NSAIDs and this increase is dose dependent. these medicines in patients with elevated cardiovascular Gastrointestinal complications associated with NSAID use risk. The use of aspirin for the primary prevention of include: dyspepsia, gastrointestinal bleeding, peptic ulcers cardiovascular disease is controversial. Current evidence and perforations of the upper gastrointestinal tract.3, 9 This only justifies the use of low-dose aspirin for primary is because inhibition of the COX-1 enzyme reduces the prevention in patients with a five-year cardiovascular risk production of protective gastric mucous. In general NSAIDs of greater than 15%.24 Furthermore, patients with a high that have a long half-life or are taken in a long-acting cardiovascular risk should not be routinely prescribed formulation have a greater risk of gastrointestinal adverse long-term NSAIDs, if possible. Finally, patients with effects.9 Gastrointestinal symptoms are less common in increased cardiovascular risk are likely to be older and people taking COX-2 inhibitors, however, the risk is increased may have other co-morbidities that increase the risk of in patients who are concurrently taking aspirin.8 NSAID-related adverse effects. Therefore the number of patients whose cardiovascular risk is clinically affected by Risk factors for gastrointestinal adverse effects associated with any interaction between aspirin and NSAIDs in primary NSAID use include:3 care is likely to be small when NSAID use is carefully Age over 65 years managed. Previous adverse reaction to NSAIDs For further information see: “The use of antithrombotic The use of other medicines that may exacerbate any medicines in general practice: A consensus statement”, gastrointestinal adverse effects, e.g. anticoagulants, BPJ 39 (Oct, 2011). selective serotonin reuptake inhibitors (SSRIs) and corticosteroids Liver disease Chronic kidney disease (CKD) Smoking Excessive alcohol consumption Use of non-selective NSAIDs and COX-2 inhibitors in people with ulcerative colitis and Crohn’s disease may cause an exacerbation of symptoms.3 Paracetamol is generally better tolerated than NSAIDs in people at increased risk of gastrointestinal adverse effects. Diclofenac and COX-2 inhibitors appear to be the least likely NSAIDs to cause upper gastrointestinal perforation, obstruction or bleeds, while the risk is likely to be increased for patients taking ibuprofen and naproxen.8  Reducing the risk of gastrointestinal complications Advise patients to take NSAIDs with milk or food so the Reducing NSAID-related risk in Māori stomach is not empty and irritation is reduced.3 Consider NSAIDs are often used in the management of gout. Gout co-prescribing a proton pump inhibitor (PPI) prophylactically is more prevalent among Māori males (11.7%) compared in people aged over 45 years if NSAIDs are being used long- to European males (3.7%).22 Māori are also more severely term in the treatment of osteoarthritis, rheumatoid arthritis or affected by gout and are therefore more likely to be lower back pain.2 PPIs should be taken daily, rather than “as using NSAIDs to manage acute flares than non-Māori.22 needed” because PPIs require approximately three days to As Māori are approximately twice as likely as non-Māori achieve steady state inhibition of acid secretion and ulceration to die of cardiovascular disease, the use of NSAIDs in this or bleeding of the gastrointestinal tract can often occur in the population requires added caution. Prescribers should absence of dyspepsia.3, 25 be aware of the elevated cardiovascular risk amongst Māori when prescribing NSAIDs for gout and monitor for A Cochrane review found that both PPIs and histamine-2 adverse effects accordingly. In addition, management receptor antagonists, e.g. ranitidine, were effective at of gout among Māori patients should be intensified to preventing chronic NSAID-related gastric and duodenal reduce the likelihood of flares occurring and reduce the ulcers.26 Omeprazole for the prevention of NSAID-related need for NSAID treatment. Corticosteroids (oral or intra- ulcers can be initiated in adults at 20 mg, once daily, for four articular) or colchicine may be considered as treatment weeks and continued for another four weeks if gastrointestinal alternatives to naproxen for acute gout flare. symptoms have not completely resolved.6 Ranitidine can be initiated in adults, for protection against NSAID-related ulcers, For further information see: “An update on the at 150 mg, twice daily, or 300 mg at night, for up to eight management of gout”, BPJ 51 (Mar, 2013). weeks.6 Misoprostol is no longer routinely used in primary care for the prevention of NSAID-related ulcers as it is associated with diarrhoea and occasionally more severe adverse effects, even at low doses.6, 26 If a patient develops gastrointestinal symptoms during NSAID treatment another type of NSAID can be trialled, an alternative class of analgesic trialled, or a PPI prescribed. In patients with a high risk of developing gastrointestinal complications who require long-term NSAID treatment:3 Prescribe a PPI and advise the patient to discontinue the NSAID and contact a health professional if they notice any gastrointestinal symptoms, e.g. black stools Monitor haemoglobin levels for the first month of treatment. Long-term haemoglobin monitoring is recommended if bleeding is an ongoing clinical concern. If gastrointestinal adverse effects do develop, consider switching to another NSAID NSAIDs and renal function All medicines which block COX-2 are potentially nephrotoxic because they can reduce blood flow to the kidney by preventing prostaglandin-mediated vasodilation. This is particularly true in patients who are dehydrated. NSAIDs can also cause immune mediated acute kidney injury (AKI), e.g. acute interstitial nephritis. In New Zealand over 40% of all renal adverse reactions reported to the Centre for Adverse Reactions Monitoring (CARM) were associated with diclofenac.27 The Topical analgesics risk of AKI in patients taking NSAIDs and other potentially Topical NSAIDs are not subsidised in New Zealand, nephrotoxic medicines is greatest at the start of treatment, however, they are readily available over-the-counter therefore even short courses of NSAIDs should be avoided, if (OTC) and are frequently purchased for the treatment of possible, in patients at increased risk.28 soft tissue injuries, e.g. sports injuries. Topical NSAIDs, in combination with paracetamol, are recommended before All people with CKD should avoid NSAIDs where possible. oral NSAIDs or codeine in United Kingdom guidelines for CKD is a risk factor for AKI and one-quarter to one-third of the treatment of osteoarthritis.13 Topical NSAIDs are also all people aged over 64 years have CKD.29 Acute illness and/ preferred to oral NSAIDs by some clinicians for patients or hypovolaemia, even if mild, further increases the risk of aged over 75 years.3 AKI occurring in people with CKD who are taking NSAIDs. Patients with CKD who are taking NSAIDs should be advised Topical NSAIDs are considered to be as safe as placebo to discontinue use if they develop an acute illness, especially in the treatment of acute pain and therefore can be if they become dehydrated. Patients who have had a previous safely used by patients who are at risk of developing acute decline in renal function should have their notes flagged complications associated with oral NSAIDs. 35 Blood and be identified as at risk of NSAID-related AKI. concentrations of NSAIDs after applying topical products are typically less than 5% of those reached by using oral People with type 2 diabetes should avoid NSAIDs where NSAIDs.35 Approximately six or seven patients out of possible. Reduced renal function and albuminuria are both ten will experience successful pain control with topical risk factors for micro and macrovascular complications NSAIDs.35 However, a large proportion of this effect is that have increased prevalence in people with diabetes.30 because sprain-type injuries tend to improve without Preservation of renal function to prevent the development of treatment.35 CKD and to reduce cardiovascular risk is an essential part of the management of patients with type 2 diabetes. Topical capsaicin is also often used as an adjunctive treatment for osteoarthritis of the knee or hand.13 Topical NSAID nephrotoxicity can be exacerbated by ACE inhibitors capsaicin is currently subsidised for patients who have or ARBs as these medicines impair the regulation of blood osteoarthritis that is not responsive to paracetamol and flow leaving the kidney. Renal function can be compromised where oral NSAIDs are contraindicated. Topical capsaicin is even further if a patient is also taking a diuretic. The combined an irritant and should not be applied to the eyes, mucous potential effect of these three medicines has been referred membranes or broken skin.6 Hands should be washed to as the “triple whammy”. This can result in hyponatremia immediately after applying this medicine.6 or hyperkalemia, AKI and cardiac failure.3, 31 The risk of this occurring is greatest in the first 30 days of use.28 This combination of medicines should be prescribed with caution, particularly in people with CKD or diabetes. If patients develop an acute illness it may be appropriate to discontinue or reduce the dose of these medicines. In patients with reduced renal function who are taking NSAIDs, or in patients at increased risk of renal toxicity, serum creatinine and potassium should be measured after one to two weeks of treatment and then monitored regularly.3 For further information see: “Acute-on-chronic kidney disease: Prevention, diagnosis, management and referral in primary care”, BPJ 46 (Sep, 2012). Hypersensitivity to NSAIDs Use of NSAIDs in children NSAID/aspirin hypersensitivity is characterised by symptoms Ibuprofen is generally the preferred NSAID for use in children. ranging in speed of onset from anaphylaxis and bronchospasm Naproxen is not indicated for the short-term treatment of pain to delayed skin and systemic reactions occurring over weeks.32 and fever in children, but may be prescribed for rheumatoid The reaction is due to COX-1 inhibition and is not mediated by arthritis in children aged over five years.6 Diclofenac is the only IgE, therefore it is not a true allergy.32 NSAID hypersensitivity other NSAID available in New Zealand for the treatment of is reported to affect 0.5 – 1.9% of the general population.32 pain and inflammation in children aged under 12 years, but it However, reports of prevalence among adults with asthma is rarely prescribed for this purpose in primary care. are as high as 21% if aspirin provocation testing is used.32 In children the prevalence of NSAID hypersensitivity is lower and reported to be 0.3% – 5% as assessed by provocation.32 Fever and NSAID use in children Cutaneous hypersensitivity reactions are relatively infrequent Febrile illness accounts for a large proportion of childhood and affect 0.3% of the population.32 presentations to primary care. Between 20 – 40% of parents report an occurrence every year.36 Paracetamol (children aged NSAIDs can be routinely prescribed to patients with asthma over one month, 15 mg/kg per dose, every four hours, up to who have no previous history of NSAID-associated symptoms. four times daily, maximum 1 g per dose and 4 g per day) or However, the possibility of NSAID use increasing asthma ibuprofen (children aged under 12 years, 20 mg/kg in divided severity should be discussed with the patient first. Patients doses, to a maximum of 500 mg per day in children under 30 with asthma and nasal polyps or recurrent sinusitis are more kg) are both indicated for the treatment of pain and fever in likely to experience hypersensitivity to NSAIDs.33 People who children.6, 36 However, before prescribing ibuprofen for the have had a hypersensitivity reaction to a NSAID should avoid treatment of febrile illness consider emerging evidence that all non-selective NSAIDs as the reaction is likely to be a class suggests the use of NSAIDs in children may be associated with effect.32 an increased risk of AKI, especially in children who are obese (see below). NSAID use in women who are pregnant is not A paracetamol dosage calculator for children is available recommended from: Paracetamol is preferred to NSAIDs in women who are www.bpac.org.nz/resources/other/bmi_calc/bmiCalc.html pregnant because NSAID use in the first trimester doubles the risk of spontaneous abortion.3 Later in pregnancy NSAID use Management of fever in children should aim to improve is associated with premature closure of the ductus arteriosus comfort rather than reduce body temperature.37 Points to blood vessel, which can result in structural birth defects, consider when prescribing medicines specifically for fever in preterm delivery or low birth weight.34 NSAIDs may also delay children include:36 the onset of labour and increase blood loss during childbirth.3 Mild fevers (<38°C) do not need to be treated Paracetamol or ibuprofen should not be given for the Breast feeding while taking paracetamol or NSAIDs is considered sole purpose of reducing body temperature (see: “The safe due to the low concentrations of these medicines in benefits of inflammation and fever”) breast milk.34 However, aspirin use during lactation has been Medicines for fever should only be prescribed for as associated with significant adverse events in infants.34 Repeat long as the child is in discomfort. If discomfort is not doses of codeine should be avoided wherever possible in alleviated before the next dose is due, then switching, women who are breast feeding, as severe toxicity has been e.g. changing from paracetamol to ibuprofen, may be reported in infants whose mothers are ultra-fast metabolisers considered. Also consider medical review. (see: “Paracetamol and codeine may have variable efficacy”, Do not give paracetamol and ibuprofen at the same time Page 10).6 Paracetamol and ibuprofen do not prevent febrile convulsions and should not be prescribed specifically for this reason Ask if the child has taken any medicine for their current illness when assessing their condition. A failure to respond to prior treatment may indicate a more serious illness. Advise parents be a contributing factor to additional cases of multi-factorial of the need for children with fever to receive regular fluids.36 AKI.39 The majority of presentations occurred within the first Small quantities of water offered frequently are best, or breast seven days of treatment and doses were generally within milk if the child is being breast fed. Parents should not give recommended prescribing guidelines.39 Vomiting (74%) was NSAIDs to children who may be dehydrated, e.g. vomiting, the most frequent symptom followed by abdominal pain sunken eyes, tears or urine absent or if skin turgor is diminished. (67%) and decreased urine output (56%). 39 Children aged Tepid sponging is not recommended for the treatment of fever, under five years were most likely to require intensive treatment and children with fever should neither be over-wrapped nor and stay in hospital for longer.39 Obesity may be an important under dressed.36 Discussing the benefits of fever with parents risk factor for NSAID-induced AKI in children as almost half of may help to reduce parental distress. the patients admitted were at or above the 95th percentile for body mass index (BMI) or weight:length ratio.39 NSAIDs and acute kidney injury in children NSAIDs should be prescribed with caution in children with acute illness and/or volume depletion.38 ACKNOWLEDGEMENT: Thank you to Dr Chris Cameron, Children aged under five years and children who are obese General Physician and Clinical Pharmacologist, Chair, may be at greatest risk of NSAID-induced AKI. One study of Medicines Committee, Capital & Coast DHB, Wellington children admitted to hospital with AKI found that at least 2.7% Hospital for expert review of this article. of all instances were due to NSAID use, with NSAID use likely to The benefits of inflammation and fever The inflammatory response is triggered by damaged or infected cells releasing pro-inflammatory proteins. These signals cause local capillaries to increase in size and capillary membranes to become permeable, resulting in swelling as fluid accumulates locally. Attracted by the chemical signals, white blood cells pass through the capillary membranes and invade the area, attacking pathogens and consuming dead and infected cells. The increased body temperature acts to suppress bacterial growth, viral replication and therefore reduces the duration of infections. References 1. Ministry of Health. Pharmaceutical Collection. 2013. 21. Schjerning Olsen A-M, Fosbøl EL, Lindhardsen J, et al. Duration of 2. National Institute for Health and Care Excellence (NICE). Non-steroidal treatment with nonsteroidal anti-inflammatory drugs and impact anti-inflammatory drugs. Manchester: NICE; 2013. Available from: on risk of death and recurrent myocardial infarction in patients with www.nice.org.uk (Accessed Sep, 2013). prior myocardial infarction: a nationwide cohort study. Circulation. 3. Day RO, Graham GG. Non-steroidal anti-inflammatory drugs (NSAIDs). 2011;123(20):2226–35. BMJ. 2013;346:f3195. 22. Winnard D, Wright C, Taylor W, et al. National prevalence of gout 4. Longo D, Fauci A, Kasper D, et al. Chapter 293: Peptic ulcer disease and derived from administrative health data in Aotearoa New Zealand. related disorders. Harrison’s principles of internal medicine. 18th ed. Rheumatology. 2012;51:901–9. New York: McGraw Hill Medical; 2012. p. 2438-60. 23. Strand V. Are COX-2 inhibitors preferable to non-selective non-steroidal 5. Fosbøl EL, Gislason GH, Jacobsen S, et al. Risk of myocardial infarction anti-inflammatory drugs in patients with risk of cardiovascular events and death associated with the use of nonsteroidal anti-inflammatory taking low-dose aspirin? Lancet. 2007;370(9605):2138–51. drugs (NSAIDs) among healthy individuals: a nationwide cohort study. 24. New Zealand Guidelines Group. New Zealand primary care handbook Clin Pharmacol Ther. 2009;85(2):190–7. 2012. 3rd ed. Wellington: New Zealand Guidelines Group; 2012. 6. New Zealand Formulary (NZF). NZF v15. NZF; 2013. Available from: 25. Shin JM, Kim N. Pharmacokinetics and pharmacodynamics of the proton www.nzf.org.nz (Accessed Sep, 2013). pump inhibitors. J Neurogastroenterol Motil. 2013;19(1):25–35. 7. Singh G, Lanes S, Triadafilopoulos G. Risk of serious upper 26. Rostom A, Dube C, Wells G, et al. Prevention of NSAID- gastrointestinal and cardiovascular thromboembolic complications induced gastroduodenal ulcers. Cochrane Database Syst Rev. with meloxicam. Am J Med. 2004;117(2):100–6. 2002;4:CD002296. 8. Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular 27. Medsafe. Prescriber Update: NSAIDs and Acute Kidney Injury. 2013. and upper gastrointestinal effects of non-steroidal anti-inflammatory Available from: www.medsafe.govt.nz (Accessed Sep, 2013). drugs: meta-analyses of individual participant data from randomised 28. Lapi F, Azoulay L, Yin H, et al. Concurrent use of diuretics, angiotensin trials. Lancet. 2013;382(9894):769–79. converting enzyme inhibitors, and angiotensin receptor blockers with 9. Massó González EL, Patrignani P, Tacconelli S, García Rodríguez LA. non-steroidal anti-inflammatory drugs and risk of acute kidney injury: Variability among nonsteroidal antiinflammatory drugs in risk of upper nested case-control study. BMJ. 2013;346:e8525. gastrointestinal bleeding. Arthritis Rheum. 2010;62(6):1592–601. 29. Zhang Q-L, Rothenbacher D. Prevalence of chronic kidney disease 10. Sachs CJ. Oral analgesics for acute nonspecific pain. Am Fam Physician. in population-based studies: systematic review. BMC Public Health. 2005;71(5):913–8. 2008;8:117. 11. National Institute for Health Care and Excellence (NICE). Clinical 30. Doggen K, Nobels F, Scheen AJ, et al. Cardiovascular risk factors and Knowledge Summaries: NSAIDs - prescribing issues. NICE, 2013. complications associated with albuminuria and impaired renal function Available from: cks.nice.org.uk (Accessed Sep, 2013). in insulin-treated diabetes. J Diabetes Complicat. 2013;27(4):370–5. 12. Derry CJ, Derry S, Moore RA. Single dose oral ibuprofen plus 31. Fournier J-P, Lapeyre-Mestre M, Sommet A, et al. Laboratory monitoring paracetamol (acetaminophen) for acute postoperative pain. Cochrane of patients treated with antihypertensive drugs and newly exposed Database Syst Rev. 2013;6:CD010210. to non steroidal anti-inflammatory drugs: a cohort study. PLoS ONE. 13. National Institute for Health Care Excellence (NICE). Osteoarthritis: the 2012;7(3):e34187. care and management of osteoarthritis in adults. NICE: London; 2008. 32. Kowalski ML, Makowska JS, Blanca M, et al. Hypersensitivity to Available from: www.nice.org.uk (Accessed Sep, 2013). nonsteroidal anti-inflammatory drugs (NSAIDs) - classification, 14. de Leon J, Armstrong SC, Cozza KL. Clinical guidelines for psychiatrists diagnosis and management: review of the EAACI/ENDA and GA2LEN/ for the use of pharmacogenetic testing for CYP450 2D6 and CYP450 HANNA. Allergy. 2011;66(7):818–29. 2C19. Psychosomatics. 2006;47(1):75–85. 33. Risser A, Donovan D, Heintzman J, Page T. NSAID prescribing 15. Doherty M, Hawkey C, Goulder M, et al. A randomised controlled precautions. Am Fam Physician. 2009;80(12):1371–8. trial of ibuprofen, paracetamol or a combination tablet of ibuprofen/ 34. Kennedy D. Analgesics and pain relief in pregnancy and breastfeeding. paracetamol in community-derived people with knee pain. Ann Austr Prescr. 2011;34:8–10. Rheum Dis. 2011;70(9):1534–41. 35. Massey T, Derry S, Moore RA, McQuay HJ. Topical NSAIDs for acute pain 16. Bondarsky EE, Domingo AT, Matuza NM, et al. Ibuprofen vs in adults. Cochrane Database Syst Rev. 2010;(6):CD007402. acetaminophen vs their combination in the relief of musculoskeletal 36. National Institute for Health and Care Excellence (NICE). Feverish illness pain in the ED: a randomized, controlled trial. Am J Emerg Med. in children: Assessment and initial management in children younger 2013;9:1357–60. than five years. NICE: Manchester; 2013. Available from: www.nice.org. 17. de Vries F, Setakis E, van Staa T-P. Concomitant use of ibuprofen and uk (Accessed Sep, 2013). paracetamol and the risk of major clinical safety outcomes. Br J Clin 37. Sullivan JE, Farrar HC. Fever and antipyretic use in children. Pediatrics. Pharmacol. 2010;70(3):429–38. 2011;127(3):580–7. 18. Brune K, Hinz B. Paracetamol, ibuprofen, or a combination of both drugs 38. Brophy PD. Changing the paradigm in pediatric acute kidney injury. J against knee pain: an excellent new randomised clinical trial answers Pediatr. 2013;162(6):1094–6. old questions and suggests new therapeutic recommendations. Ann 39. Misurac JM, Knoderer CA, Leiser JD, et al. Nonsteroidal anti- Rheum Dis. 2011;70(9):1521–2. Inflammatory drugs are an important cause of acute kidney injury in 19. Feucht CL, Patel DR. Analgesics and anti-inflammatory medications in children. J Pediatr. 2013;162:1153–9. sports: use and abuse. Pediatr Clin North Am. 2010;57(3):751–74. 20. Trelle S, Reichenbach S, Wandel S, et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011;342:c7086.  COMING SOON The New Zealand Formulary for Children www.nzformulary.org 

Don't include any information from other sources.

Make a table listing all of the acronyms and initialisms used in this text and what they mean.

Restless Legs Syndrome Restless legs syndrome (RLS) causes an unpleasant prickling or tingling in the legs, especially in the calves, that is relieved by moving or massaging them. People who have RLS feel a need to stretch or move their legs to get rid of the uncomfortable or painful feelings. As a result, it may be difficult to fall asleep and stay asleep. One or both legs may be affected. Some people also feel the sensations in their arms. These sensations also can occur when lying down or sitting for long periods of time, such as while at a desk, riding in a car, or watching a movie. Many people who have RLS also have brief limb movements during sleep, often with abrupt onset, occurring every 5–90 seconds. This condition, known as periodic limb movements in sleep (PLMS), can repeatedly awaken people who have RLS, reducing their total sleep time and interrupting their sleep. Some people have PLMS but have no abnormal sensations in their legs while awake. RLS affects 5–15 percent of Americans, and its prevalence increases with age. RLS occurs more often in women than men. One study found that RLS accounted for one-third of the insomnia seen in patients older than age 60. Children also can have RLS. In children, the condition may be associated with symptoms of attention-deficit hyperactivity disorder. However, it’s not fully known how the disorders are related. Sometimes “growing pains” can be mistaken for RLS. RLS is often inherited. Pregnancy, kidney failure, and anemia related to iron or vitamin deficiency can trigger or worsen RLS symptoms. Researchers suspect that these conditions cause an iron deficiency that results in a lack of dopamine, which is used by the brain to control physical sensation and limb movements. Doctors usually can diagnose RLS by patients’ symptoms and a telltale worsening of symptoms at night or while at rest. Some doctors may order a blood test to check ferretin levels (ferretin is a form of iron). Doctors also may ask people who have RLS to spend a night in a sleep laboratory, where they are monitored to rule out other sleep disorders and to document the excessive limb movements. RLS is treatable but not always curable. Dramatic improvements are seen quickly when patients are given dopamine-like drugs or iron supplements. Alternatively, people who have milder cases may be treated successfully with sedatives or behavioral strategies. These Common Sleep Disorders 48 Your Guide to Healthy Sleep n strategies include stretching, taking a hot bath, or massaging the legs before bedtime. Avoiding caffeinated beverages also can help reduce symptoms, and certain medications (e.g., some antidepressants, particularly selective serotonin reuptake inhibitors) may cause RLS. If iron or vitamin deficiency underlies RLS, symptoms may improve with prescribed iron, vitamin B12, or folate supplements. Some people may require anticonvulsant medications to control the creeping and crawling sensations in their limbs. Others who have severe symptoms that are associated with another medical disorder or that do not respond to normal treatments may need to be treated with pain relievers. Narcolepsy Narcolepsy’s main symptom is extreme and overwhelming daytime sleepiness, even after adequate nighttime sleep. In addition, nighttime sleep may be fragmented by frequent awakenings. People who have narcolepsy often fall asleep at inappropriate times and places. Although TV sitcoms occasionally feature these individuals to generate a few laughs, narcolepsy is no laughing matter. People who have narcolepsy experience daytime “sleep attacks” that last from seconds to more than one-half hour, can occur without warning, and may cause injury. These embarrassing sleep spells also can make it difficult to work and to maintain normal personal or social relationships. With narcolepsy, the usually sharp distinctions between being asleep and awake are blurred. Also, people who have narcolepsy tend to fall directly into dream-filled REM sleep, rather than enter REM sleep gradually after passing through the non-REM sleep stages first. In addition to overwhelming daytime sleepiness, narcolepsy has three other commonly associated symptoms, but these may not occur in all people: Sudden muscle weakness (cataplexy). This weakness is similar to the paralysis that normally occurs during REM sleep, but it lasts a few seconds to minutes while an individual is awake. Cataplexy tends to be triggered by sudden emotional reactions, such as anger, surprise, fear, or laughter. The weakness may show up as limpness at the neck, buckling of the knees, or sagging facial muscles affecting speech, or it may cause a complete body collapse. 49 Common Sleep Disorders At first, I was misdiagnosed with chronic fatigue syndrome, because I was in my forties and narcolepsy symptoms usually start during the teen years. Because I didn’t have any of the symptoms of chronic fatigue syndrome other than sleepiness, I went to a neurologist for help. He noticed the cataplexy (muscle weakness) right away, and then I was officially diagnosed with narcolepsy and then later on with borderline sleep apnea. “Even though there is no cure for narcolepsy, you can feel like you have control if you manage it well. “When you have narcolepsy, you live your life differently. But with a good plan and supportive friends and family, it all turns out OK. SZE-PING “ ” 50 Your Guide to Healthy Sleep n n Sleep paralysis. People who have narcolepsy may experience a temporary inability to talk or move when falling asleep or waking up, as if they were glued to their beds. Vivid dreams. These dreams can occur when people who have narcolepsy first fall asleep or wake up. The dreams are so lifelike that they can be confused with reality. Experts estimate that as many as 350,000 Americans have narcolepsy, but fewer than 50,000 are diagnosed. The disorder may be as widespread as Parkinson’s disease or multiple sclerosis, and more prevalent than cystic fibrosis, but it is less well known. Narcolepsy is often mistaken for depression, epilepsy, or the side effects of medicines. Narcolepsy can be difficult to diagnose in people who have only the symptom of excessive daytime sleepiness. It is usually diagnosed during an overnight sleep recording (PSG) that is followed by an MSLT. (See “How Are Sleep Disorders Diagnosed?” on page 44.) Both tests reveal symptoms of narcolepsy—the tendency to fall asleep rapidly and enter REM sleep early, even during brief naps. Narcolepsy can develop at any age, but the symptoms tend to appear first during adolescence or early adulthood. About 1 of every 10 people who have narcolepsy has a close family member who has the disorder, suggesting that one can inherit a tendency to develop narcolepsy. Studies suggest that a substance in the brain called hypocretin plays a key role in narcolepsy. Most people who have narcolepsy lack hypocretin, which promotes wakefulness. Scientists believe that an autoimmune reaction—perhaps triggered by disease, viral illness, or brain injury— specifically destroys the hypocretin-generating cells in the brains of people who have narcolepsy. 51 Eventually, researchers may develop a treatment for narcolepsy that restores hypocretin to normal levels. In the meantime, most people who have narcolepsy find some to all of their symptoms relieved by various drug treatments. For example, central nervous system stimulants can reduce daytime sleepiness. Antidepressants and other drugs that suppress REM sleep can prevent muscle weakness, sleep paralysis, and vivid dreaming. Doctors also usually recommend that people who have narcolepsy take short naps (10–15 minutes) two or three times a day, if possible, to help control excessive daytime sleepiness.

Make a table listing all of the acronyms and initialisms used in this text and what they mean. Don't include any information from other sources. Restless Legs Syndrome Restless legs syndrome (RLS) causes an unpleasant prickling or tingling in the legs, especially in the calves, that is relieved by moving or massaging them. People who have RLS feel a need to stretch or move their legs to get rid of the uncomfortable or painful feelings. As a result, it may be difficult to fall asleep and stay asleep. One or both legs may be affected. Some people also feel the sensations in their arms. These sensations also can occur when lying down or sitting for long periods of time, such as while at a desk, riding in a car, or watching a movie. Many people who have RLS also have brief limb movements during sleep, often with abrupt onset, occurring every 5–90 seconds. This condition, known as periodic limb movements in sleep (PLMS), can repeatedly awaken people who have RLS, reducing their total sleep time and interrupting their sleep. Some people have PLMS but have no abnormal sensations in their legs while awake. RLS affects 5–15 percent of Americans, and its prevalence increases with age. RLS occurs more often in women than men. One study found that RLS accounted for one-third of the insomnia seen in patients older than age 60. Children also can have RLS. In children, the condition may be associated with symptoms of attention-deficit hyperactivity disorder. However, it’s not fully known how the disorders are related. Sometimes “growing pains” can be mistaken for RLS. RLS is often inherited. Pregnancy, kidney failure, and anemia related to iron or vitamin deficiency can trigger or worsen RLS symptoms. Researchers suspect that these conditions cause an iron deficiency that results in a lack of dopamine, which is used by the brain to control physical sensation and limb movements. Doctors usually can diagnose RLS by patients’ symptoms and a telltale worsening of symptoms at night or while at rest. Some doctors may order a blood test to check ferretin levels (ferretin is a form of iron). Doctors also may ask people who have RLS to spend a night in a sleep laboratory, where they are monitored to rule out other sleep disorders and to document the excessive limb movements. RLS is treatable but not always curable. Dramatic improvements are seen quickly when patients are given dopamine-like drugs or iron supplements. Alternatively, people who have milder cases may be treated successfully with sedatives or behavioral strategies. These Common Sleep Disorders 48 Your Guide to Healthy Sleep n strategies include stretching, taking a hot bath, or massaging the legs before bedtime. Avoiding caffeinated beverages also can help reduce symptoms, and certain medications (e.g., some antidepressants, particularly selective serotonin reuptake inhibitors) may cause RLS. If iron or vitamin deficiency underlies RLS, symptoms may improve with prescribed iron, vitamin B12, or folate supplements. Some people may require anticonvulsant medications to control the creeping and crawling sensations in their limbs. Others who have severe symptoms that are associated with another medical disorder or that do not respond to normal treatments may need to be treated with pain relievers. Narcolepsy Narcolepsy’s main symptom is extreme and overwhelming daytime sleepiness, even after adequate nighttime sleep. In addition, nighttime sleep may be fragmented by frequent awakenings. People who have narcolepsy often fall asleep at inappropriate times and places. Although TV sitcoms occasionally feature these individuals to generate a few laughs, narcolepsy is no laughing matter. People who have narcolepsy experience daytime “sleep attacks” that last from seconds to more than one-half hour, can occur without warning, and may cause injury. These embarrassing sleep spells also can make it difficult to work and to maintain normal personal or social relationships. With narcolepsy, the usually sharp distinctions between being asleep and awake are blurred. Also, people who have narcolepsy tend to fall directly into dream-filled REM sleep, rather than enter REM sleep gradually after passing through the non-REM sleep stages first. In addition to overwhelming daytime sleepiness, narcolepsy has three other commonly associated symptoms, but these may not occur in all people: Sudden muscle weakness (cataplexy). This weakness is similar to the paralysis that normally occurs during REM sleep, but it lasts a few seconds to minutes while an individual is awake. Cataplexy tends to be triggered by sudden emotional reactions, such as anger, surprise, fear, or laughter. The weakness may show up as limpness at the neck, buckling of the knees, or sagging facial muscles affecting speech, or it may cause a complete body collapse. 49 Common Sleep Disorders At first, I was misdiagnosed with chronic fatigue syndrome, because I was in my forties and narcolepsy symptoms usually start during the teen years. Because I didn’t have any of the symptoms of chronic fatigue syndrome other than sleepiness, I went to a neurologist for help. He noticed the cataplexy (muscle weakness) right away, and then I was officially diagnosed with narcolepsy and then later on with borderline sleep apnea. “Even though there is no cure for narcolepsy, you can feel like you have control if you manage it well. “When you have narcolepsy, you live your life differently. But with a good plan and supportive friends and family, it all turns out OK. SZE-PING “ ” 50 Your Guide to Healthy Sleep n n Sleep paralysis. People who have narcolepsy may experience a temporary inability to talk or move when falling asleep or waking up, as if they were glued to their beds. Vivid dreams. These dreams can occur when people who have narcolepsy first fall asleep or wake up. The dreams are so lifelike that they can be confused with reality. Experts estimate that as many as 350,000 Americans have narcolepsy, but fewer than 50,000 are diagnosed. The disorder may be as widespread as Parkinson’s disease or multiple sclerosis, and more prevalent than cystic fibrosis, but it is less well known. Narcolepsy is often mistaken for depression, epilepsy, or the side effects of medicines. Narcolepsy can be difficult to diagnose in people who have only the symptom of excessive daytime sleepiness. It is usually diagnosed during an overnight sleep recording (PSG) that is followed by an MSLT. (See “How Are Sleep Disorders Diagnosed?” on page 44.) Both tests reveal symptoms of narcolepsy—the tendency to fall asleep rapidly and enter REM sleep early, even during brief naps. Narcolepsy can develop at any age, but the symptoms tend to appear first during adolescence or early adulthood. About 1 of every 10 people who have narcolepsy has a close family member who has the disorder, suggesting that one can inherit a tendency to develop narcolepsy. Studies suggest that a substance in the brain called hypocretin plays a key role in narcolepsy. Most people who have narcolepsy lack hypocretin, which promotes wakefulness. Scientists believe that an autoimmune reaction—perhaps triggered by disease, viral illness, or brain injury— specifically destroys the hypocretin-generating cells in the brains of people who have narcolepsy. 51 Eventually, researchers may develop a treatment for narcolepsy that restores hypocretin to normal levels. In the meantime, most people who have narcolepsy find some to all of their symptoms relieved by various drug treatments. For example, central nervous system stimulants can reduce daytime sleepiness. Antidepressants and other drugs that suppress REM sleep can prevent muscle weakness, sleep paralysis, and vivid dreaming. Doctors also usually recommend that people who have narcolepsy take short naps (10–15 minutes) two or three times a day, if possible, to help control excessive daytime sleepiness. Parasomnias (Abnormal Arousals) In some people, the walking, talking, and other body functions normally suppressed during sleep occur during certain sleep stages. Alternatively, the paralysis or vivid images usually experienced during dreaming may persist after awakening. These occurrences are collectively known as parasomnias and include confusional arousals (a mixed state of being both asleep and awake), sleep talking, sleep walking, night terrors, sleep paralysis, and REM sleep behavior disorder (acting out dreams). Most of these disorders— such as confusional arousals, sleep walking, and night terrors—are more common in children, who tend to outgrow them once they become adults. People who are sleep-deprived also may experience some of these disorders, including sleep walking and sleep paralysis. Sleep paralysis also commonly occurs in people who have narcolepsy. Certain medications or neurological disorders appear to lead to other parasomnias, such as REM sleep behavior disorder, and these parasomnias tend to occur more in elderly people. If you or a family member has persistent episodes of sleep paralysis, sleep walking, or acting out of dreams, talk with your doctor. Taking measures to assure the safety of children and other family members who have partial arousals from sleep is very important.

Do not use any information besides what is provided within the prompt. Do not use any prior knowledge or outside sources. Answer with section headings and bullet points.

Summarize each cosmetic regulation pre- and post-MoCRA.

Premarket Requirements Unlike its authority over drugs and some devices, FDA does not have the authority, either pre- or post-MoCRA, to require premarket approval of cosmetics or their ingredients, except for color additives.61 Prior to MoCRA, it was FDA’s position that manufacturers were responsible for substantiating the safety of their products and ingredients before the products were marketed.62 With the passage of MoCRA, manufacturers are now statutorily required to substantiate the safety of their products. MoCRA also expands upon required recordkeeping by manufacturers, packers, and distributors. A “responsible person”63 for a cosmetic product must ensure that it has been adequately tested to substantiate safety,64 and that records supporting this substantiation are maintained by the same responsible person.65 Certain products and facilities already regulated under Chapter V of FFDCA as a drug or device are exempt from MoCRA’s safety substantiation and recordkeeping requirements.66 However, if such a facility also manufactures or processes cosmetic products not subject to FFDCA Chapter V, the exemption does not apply to those particular cosmetic products.67 Enforcement Among various enforcement mechanisms, under MoCRA, FDA may access and copy all records related to a cosmetic product that it reasonably believes is likely adulterated and a serious danger Modernization of Cosmetics Regulation Act of 2022 (MoCRA) Congressional Research Service 9 to humans. FDA may access and copy all records necessary to determine whether a cosmetic or related product is adulterated and a serious threat to human health, barring certain cosmetic formula, personnel, research, and financial data records. Accessible records include those related to safety substantiation data for cosmetic products and their ingredients.68 Registration and Listing Prior to MoCRA, cosmetic manufacturers were not required to register their establishments or list their products with FDA. Instead, according to FDA regulations, owners or operators of establishments that manufactured or packaged cosmetics were requested to register with FDA.69 Likewise, previous to MoCRA, manufacturers, packers, and distributors of cosmetic products were requested to file a cosmetic product ingredient statement (CPIS) containing certain information on each cosmetic product they marketed.70 Entities could submit registration information and CPISs to FDA’s Voluntary Cosmetic Registration Program (VCRP).71 Under MoCRA, both facility72 registration and product listings are now required.73 Existing and new facilities that manufacture or process cosmetic products for distribution in the United States must be registered with FDA. These registrations must be renewed every two years and updated within 60 days of a content revision.74 Domestic facilities registering with FDA must provide the facility’s name, physical address, email address, and phone number, while foreign facilities must provide contact information for an agent within the United States and, if available, electronic contact information. Additionally, a facility must include its registration number, if one was previously assigned, and all brand names associated with cosmetic products sold that were manufactured or processed at that facility. The product categories and responsible person for each cosmetic product manufactured or processed at the facility must also be provided.75 Each responsible person must also ensure the submission of a cosmetic product listing with FDA that is renewed and updated annually.76 The product listing must contain the manufacturing or processing facility’s registration number, the responsible person’s name and contact number, the name of the cosmetic product as it appears on the label, the categories the cosmetic product falls under, and the product’s listing number. Additionally, the product listing must include a list of the cosmetic product’s ingredients, “including any fragrances, flavors, or colors, with each ingredient identified by name.”77 FDA will assign private product and facility identification numbers upon initial listing submission or registration.78 With the advent of MoCRA, FDA reported the VCRP had been discontinued and was no longer accepting submissions. In a draft guidance released in August 2023, FDA stated it is developing a new electronic submission portal for registration and listing information.79 FDA noted that this new portal is expected to be available by October 2023.80 In the interim, FDA requests that no registration or listing information be sent to the agency, adding that information previously listed in the VCRP will not be transferred.81 In September 2023, FDA released for comment draft versions of the prospective electronic submission portal, Cosmetics Direct, and paper forms.82 MoCRA exempts certain small businesses83 from both facility registration and product listing requirements.84 However, a small business is not exempt from these requirements if it is engaged in the manufacturing or processing of higher-risk cosmetic products that “regularly come into contact with [the] mucus membrane of the eye under conditions of use that are customary or usual,” “[c]osmetic products that are injected” (see the text box below), “intended for internal use,” or that are meant to “alter [one’s] appearance for more than 24 hours under conditions of use that are customary or usual and removal by the consumer is not part of such conditions of use that are customary or usual.”85 Additionally, certain products and facilities already regulated under Chapter V of FFDCA as a drug or device are exempt from facility registration and product listing requirements.86 However, if such a facility also manufactures or processes cosmetic products not subject to FFDCA Chapter V, the exemption does not apply.87 Enforcement Under MoCRA, if FDA determines that a cosmetic product has a reasonable probability of causing serious harm to human health, and if FDA has a reasonable belief that other products manufactured or processed at the same facility may be similarly affected, FDA may suspend the registration of the facility connected with such products.88 If a facility’s registration is suspended, any cosmetic product from that facility is barred from introduction or delivery for introduction into U.S. commerce.89 Before suspending a facility’s registration, the FDA must provide notice to a responsible person for the facility specifying the reason for suspension, as well as an opportunity, within five business days of the notice, to present a plan to correct the issue identified.90 FDA must provide the responsible person with the opportunity for an informal hearing to review actions required for registration reinstatement and why the facility registration should be reinstated.91 If, based upon the evidence presented at this informal hearing, FDA determines there are inadequate grounds to continue the suspension, the facility registration will be restored.92 However, if there is insufficient evidence presented, the suspension may continue, and FDA shall require the responsible person to submit a corrective action plan for review.93 If at any point FDA determines there is inadequate evidence to justify the continued suspension of a facility’s registration, the registration shall be promptly reinstated.94 Mandatory Recall Prior to MoCRA, FDA did not have the authority to order mandatory recalls of cosmetic products. The agency could, however, request a company to voluntarily recall cosmetic products of concern.114 Under MoCRA, a responsible person may still have the opportunity to voluntarily recall an adulterated or misbranded cosmetic; however, now FDA also has the authority to issue a mandatory recall.115 A mandatory recall may be initiated “[i]f the Secretary determines that there is a reasonable probability that a cosmetic is adulterated … or misbranded … and the use of or exposure to such cosmetic will cause serious adverse health consequences or death,” and the responsible person refuses to comply with a voluntary recall in a timely manner. Upon FDA issuing an order for a mandatory recall, the responsible person must immediately stop distributing the identified product.116 If such an order is issued, the responsible person is entitled to an opportunity for a timely informal hearing to review the adequacy of evidence for the order.117 Depending on the outcome of this review, the order may be vacated, continued until a specified date, or amended to further require the recall of the cosmetic product, along with other measures regarding notifications, timetables, and updates.118 FDA may require the responsible person to issue a notice of recall or ceased distribution to appropriate persons, including manufacturers, distributors, importers, and sellers.119 If a product is recalled, FDA must ensure that a press release announcing the action is published, as well as appropriate alerts and public notices, to provide consumers and retailers with information about the cosmetic product and the circumstances of the recall. If an image of the product is available and appropriate, FDA shall also ensure the publication of that image on its website.120 Certain products and facilities already regulated under Chapter V of FFDCA as a drug or device are exempt from MoCRA’s mandatory recall authority.121 However, if such a facility also manufactures or processes cosmetic products not subject to FFDCA Chapter V, the exemption does not apply to those particular cosmetic products.122

Summarize each cosmetic regulation pre- and post-MoCRA. Do not use any information besides what is provided within the prompt. Do not use any prior knowledge or outside sources. Answer with section headings and bullet points. Premarket Requirements Unlike its authority over drugs and some devices, FDA does not have the authority, either pre- or post-MoCRA, to require premarket approval of cosmetics or their ingredients, except for color additives.61 Prior to MoCRA, it was FDA’s position that manufacturers were responsible for substantiating the safety of their products and ingredients before the products were marketed.62 With the passage of MoCRA, manufacturers are now statutorily required to substantiate the safety of their products. MoCRA also expands upon required recordkeeping by manufacturers, packers, and distributors. A “responsible person”63 for a cosmetic product must ensure that it has been adequately tested to substantiate safety,64 and that records supporting this substantiation are maintained by the same responsible person.65 Certain products and facilities already regulated under Chapter V of FFDCA as a drug or device are exempt from MoCRA’s safety substantiation and recordkeeping requirements.66 However, if such a facility also manufactures or processes cosmetic products not subject to FFDCA Chapter V, the exemption does not apply to those particular cosmetic products.67 Enforcement Among various enforcement mechanisms, under MoCRA, FDA may access and copy all records related to a cosmetic product that it reasonably believes is likely adulterated and a serious danger Modernization of Cosmetics Regulation Act of 2022 (MoCRA) Congressional Research Service 9 to humans. FDA may access and copy all records necessary to determine whether a cosmetic or related product is adulterated and a serious threat to human health, barring certain cosmetic formula, personnel, research, and financial data records. Accessible records include those related to safety substantiation data for cosmetic products and their ingredients.68 Registration and Listing Prior to MoCRA, cosmetic manufacturers were not required to register their establishments or list their products with FDA. Instead, according to FDA regulations, owners or operators of establishments that manufactured or packaged cosmetics were requested to register with FDA.69 Likewise, previous to MoCRA, manufacturers, packers, and distributors of cosmetic products were requested to file a cosmetic product ingredient statement (CPIS) containing certain information on each cosmetic product they marketed.70 Entities could submit registration information and CPISs to FDA’s Voluntary Cosmetic Registration Program (VCRP).71 Under MoCRA, both facility72 registration and product listings are now required.73 Existing and new facilities that manufacture or process cosmetic products for distribution in the United States must be registered with FDA. These registrations must be renewed every two years and updated within 60 days of a content revision.74 Domestic facilities registering with FDA must provide the facility’s name, physical address, email address, and phone number, while foreign facilities must provide contact information for an agent within the United States and, if available, electronic contact information. Additionally, a facility must include its registration number, if one was previously assigned, and all brand names associated with cosmetic products sold that were manufactured or processed at that facility. The product categories and responsible person for each cosmetic product manufactured or processed at the facility must also be provided.75 Each responsible person must also ensure the submission of a cosmetic product listing with FDA that is renewed and updated annually.76 The product listing must contain the manufacturing or processing facility’s registration number, the responsible person’s name and contact number, the name of the cosmetic product as it appears on the label, the categories the cosmetic product falls under, and the product’s listing number. Additionally, the product listing must include a list of the cosmetic product’s ingredients, “including any fragrances, flavors, or colors, with each ingredient identified by name.”77 FDA will assign private product and facility identification numbers upon initial listing submission or registration.78 With the advent of MoCRA, FDA reported the VCRP had been discontinued and was no longer accepting submissions. In a draft guidance released in August 2023, FDA stated it is developing a new electronic submission portal for registration and listing information.79 FDA noted that this new portal is expected to be available by October 2023.80 In the interim, FDA requests that no registration or listing information be sent to the agency, adding that information previously listed in the VCRP will not be transferred.81 In September 2023, FDA released for comment draft versions of the prospective electronic submission portal, Cosmetics Direct, and paper forms.82 MoCRA exempts certain small businesses83 from both facility registration and product listing requirements.84 However, a small business is not exempt from these requirements if it is engaged in the manufacturing or processing of higher-risk cosmetic products that “regularly come into contact with [the] mucus membrane of the eye under conditions of use that are customary or usual,” “[c]osmetic products that are injected” (see the text box below), “intended for internal use,” or that are meant to “alter [one’s] appearance for more than 24 hours under conditions of use that are customary or usual and removal by the consumer is not part of such conditions of use that are customary or usual.”85 Additionally, certain products and facilities already regulated under Chapter V of FFDCA as a drug or device are exempt from facility registration and product listing requirements.86 However, if such a facility also manufactures or processes cosmetic products not subject to FFDCA Chapter V, the exemption does not apply.87 Enforcement Under MoCRA, if FDA determines that a cosmetic product has a reasonable probability of causing serious harm to human health, and if FDA has a reasonable belief that other products manufactured or processed at the same facility may be similarly affected, FDA may suspend the registration of the facility connected with such products.88 If a facility’s registration is suspended, any cosmetic product from that facility is barred from introduction or delivery for introduction into U.S. commerce.89 Before suspending a facility’s registration, the FDA must provide notice to a responsible person for the facility specifying the reason for suspension, as well as an opportunity, within five business days of the notice, to present a plan to correct the issue identified.90 FDA must provide the responsible person with the opportunity for an informal hearing to review actions required for registration reinstatement and why the facility registration should be reinstated.91 If, based upon the evidence presented at this informal hearing, FDA determines there are inadequate grounds to continue the suspension, the facility registration will be restored.92 However, if there is insufficient evidence presented, the suspension may continue, and FDA shall require the responsible person to submit a corrective action plan for review.93 If at any point FDA determines there is inadequate evidence to justify the continued suspension of a facility’s registration, the registration shall be promptly reinstated.94 Mandatory Recall Prior to MoCRA, FDA did not have the authority to order mandatory recalls of cosmetic products. The agency could, however, request a company to voluntarily recall cosmetic products of concern.114 Under MoCRA, a responsible person may still have the opportunity to voluntarily recall an adulterated or misbranded cosmetic; however, now FDA also has the authority to issue a mandatory recall.115 A mandatory recall may be initiated “[i]f the Secretary determines that there is a reasonable probability that a cosmetic is adulterated … or misbranded … and the use of or exposure to such cosmetic will cause serious adverse health consequences or death,” and the responsible person refuses to comply with a voluntary recall in a timely manner. Upon FDA issuing an order for a mandatory recall, the responsible person must immediately stop distributing the identified product.116 If such an order is issued, the responsible person is entitled to an opportunity for a timely informal hearing to review the adequacy of evidence for the order.117 Depending on the outcome of this review, the order may be vacated, continued until a specified date, or amended to further require the recall of the cosmetic product, along with other measures regarding notifications, timetables, and updates.118 FDA may require the responsible person to issue a notice of recall or ceased distribution to appropriate persons, including manufacturers, distributors, importers, and sellers.119 If a product is recalled, FDA must ensure that a press release announcing the action is published, as well as appropriate alerts and public notices, to provide consumers and retailers with information about the cosmetic product and the circumstances of the recall. If an image of the product is available and appropriate, FDA shall also ensure the publication of that image on its website.120 Certain products and facilities already regulated under Chapter V of FFDCA as a drug or device are exempt from MoCRA’s mandatory recall authority.121 However, if such a facility also manufactures or processes cosmetic products not subject to FFDCA Chapter V, the exemption does not apply to those particular cosmetic products.122

"================ <TEXT PASSAGE> ======= [context document] ================ <QUESTION> ======= [user request] ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

Based on this text, describe Ellana's background in medicine. Also, summarize her concerns about the changes that she is witnessing while working in Emergency Medicine.

Thank you, Senator Markey and Senator Warren for having me this morning. My name is Ellana Stinson. I am a board-certified emergency medicine physician and have practiced emergency medicine for 15 years. From 2013 to 2020, I worked on staff as an emergency medicine physician at Carney Hospital, Good Samaritan and the former Quincy Hospital, all part of the Steward Health System. In addition, over the past 11 years, I have worked intermittently throughout the country at various facilities run and operated by HCA, Envision, Tenant, Team Health and CHS. When I entered medicine, I deeply loved what I did. Caring for patients in their most vulnerable moments and working in beautifully orchestrated chaos while bearing witness to so many life changing moments filled me with pride at the end of each shift. Unfortunately, so much of what I loved about Emergency Medicine has changed drastically over the years. Initially, my time at Carney felt very fresh and fulfilling. Being able to serve a very diverse population in the Dorchester neighborhood of Boston was essentially how I always imagined my career trajectory, serving the most vulnerable populations. But when I could no longer care for my patients the way I would want a loved one treated, I had to make decisions to stay or go. Having spent time at several other Stewart facilities briefly, I began to realize how resources were being dwindled down and pulled from each facility. Most of the facilities no longer had certain speciality services and Quincy Hospital, eventually was taken down to bare bones before its ultimate closure. Not having blood products, respiratory therapy at times or certain specialty services no longer felt like I was able to provide safe or quality care. What is happening here in the Commonwealth is happening around the country. We have now seen the buyouts, mergers and acquisitions led by private equity firms of over 30% of hospitals in the US. Having spent time at other PE sites around the country the level of deprivation was seemingly worse in some areas. Increased wait times and critical shortage of staff leading to dangerous boarding levels and critically dangerous patient to nurse ratios in the emergency department, seeing upwards to 14 to 1 ratios at times. All of this only to be exacerbated by the pandemic which resulted in increased cost of care, infection rates, mortality and even death. Practicing medicine in many PE led places is no longer about patient safety and quality, but about making medical decisions and judgment due corporate decision making with profit motives at the expense of patients. Forcing staff to see patients in the waiting room in order to have it appear wait times were being reduced and improving door to doc times, calling codes for sepsis and strokes in order to find innovative ways to make profits. Increasingly daunting metrics required of physicians and other staff to meet were nearly unattainable and unsafe in many instances, but very much expected. In addition, many sites across the country began to remove emergency physicians from in-network, resulting in higher bills for patients known as surprise billing. These profit gaining practices not only harm patients but also increase financial burdens on patients who do not have a choice of where they will go when they are experiencing crushing chest pain or stroke-like symptoms. Especially when the next closest facility has been in some of my experiences, upwards to an hour away. Most of the facilities I worked in were in very vulnerable populations that were mostly people of color, low income, or had limited access to other facilities or primary care services. Forcing them to only seek their care at a PE backed site. It is also known that most of the buyouts are of hospitals and facilities already struggling or with higher Medicaid and Medicare populations which ultimately affects our most vulnerable populations. It is critical we consider not only the impact these facilities have on our health care system, but also on the worsening care access and quality being provided to those communities already harmed by historical injury. The financialization of medicine will continue to exacerbate health disparities despite work being done on the ground to close these gaps. In addition, these Private Equity backed facilities are where I typically run into other emergency physicians of color. As it pertains to myself and my colleagues, these practices often felt unsafe, which sparked many questions of medical legal risk as well as the emotional toll it takes on all of us who enter this profession to do no harm. In addition, being on staff at a PE backed facility also would not qualify physicians swimming in student debt for loan forgiveness. A profession once competitive when I first began my medical journey is now one of the least competitive fields to enter as students bear witness to the destruction of the profession. In 2023, 554 of the residency spots went unfilled. We also saw more PE backed hospitals opening residency programs that were not adequately equipped to provide the proper training for an emergency medicine trainee. We train to deal with hard stuff, but we are running out of options on how to continue providing safe and adequate care at these PE run facilities.

"================ <TEXT PASSAGE> ======= Thank you, Senator Markey and Senator Warren for having me this morning. My name is Ellana Stinson. I am a board-certified emergency medicine physician and have practiced emergency medicine for 15 years. From 2013 to 2020, I worked on staff as an emergency medicine physician at Carney Hospital, Good Samaritan and the former Quincy Hospital, all part of the Steward Health System. In addition, over the past 11 years, I have worked intermittently throughout the country at various facilities run and operated by HCA, Envision, Tenant, Team Health and CHS. When I entered medicine, I deeply loved what I did. Caring for patients in their most vulnerable moments and working in beautifully orchestrated chaos while bearing witness to so many life changing moments filled me with pride at the end of each shift. Unfortunately, so much of what I loved about Emergency Medicine has changed drastically over the years. Initially, my time at Carney felt very fresh and fulfilling. Being able to serve a very diverse population in the Dorchester neighborhood of Boston was essentially how I always imagined my career trajectory, serving the most vulnerable populations. But when I could no longer care for my patients the way I would want a loved one treated, I had to make decisions to stay or go. Having spent time at several other Stewart facilities briefly, I began to realize how resources were being dwindled down and pulled from each facility. Most of the facilities no longer had certain speciality services and Quincy Hospital, eventually was taken down to bare bones before its ultimate closure. Not having blood products, respiratory therapy at times or certain specialty services no longer felt like I was able to provide safe or quality care. What is happening here in the Commonwealth is happening around the country. We have now seen the buyouts, mergers and acquisitions led by private equity firms of over 30% of hospitals in the US. Having spent time at other PE sites around the country the level of deprivation was seemingly worse in some areas. Increased wait times and critical shortage of staff leading to dangerous boarding levels and critically dangerous patient to nurse ratios in the emergency department, seeing upwards to 14 to 1 ratios at times. All of this only to be exacerbated by the pandemic which resulted in increased cost of care, infection rates, mortality and even death. Practicing medicine in many PE led places is no longer about patient safety and quality, but about making medical decisions and judgment due corporate decision making with profit motives at the expense of patients. Forcing staff to see patients in the waiting room in order to have it appear wait times were being reduced and improving door to doc times, calling codes for sepsis and strokes in order to find innovative ways to make profits. Increasingly daunting metrics required of physicians and other staff to meet were nearly unattainable and unsafe in many instances, but very much expected. In addition, many sites across the country began to remove emergency physicians from in-network, resulting in higher bills for patients known as surprise billing. These profit gaining practices not only harm patients but also increase financial burdens on patients who do not have a choice of where they will go when they are experiencing crushing chest pain or stroke-like symptoms. Especially when the next closest facility has been in some of my experiences, upwards to an hour away. Most of the facilities I worked in were in very vulnerable populations that were mostly people of color, low income, or had limited access to other facilities or primary care services. Forcing them to only seek their care at a PE backed site. It is also known that most of the buyouts are of hospitals and facilities already struggling or with higher Medicaid and Medicare populations which ultimately affects our most vulnerable populations. It is critical we consider not only the impact these facilities have on our health care system, but also on the worsening care access and quality being provided to those communities already harmed by historical injury. The financialization of medicine will continue to exacerbate health disparities despite work being done on the ground to close these gaps. In addition, these Private Equity backed facilities are where I typically run into other emergency physicians of color. As it pertains to myself and my colleagues, these practices often felt unsafe, which sparked many questions of medical legal risk as well as the emotional toll it takes on all of us who enter this profession to do no harm. In addition, being on staff at a PE backed facility also would not qualify physicians swimming in student debt for loan forgiveness. A profession once competitive when I first began my medical journey is now one of the least competitive fields to enter as students bear witness to the destruction of the profession. In 2023, 554 of the residency spots went unfilled. We also saw more PE backed hospitals opening residency programs that were not adequately equipped to provide the proper training for an emergency medicine trainee. We train to deal with hard stuff, but we are running out of options on how to continue providing safe and adequate care at these PE run facilities. https://www.help.senate.gov/imo/media/doc/0758d69f-e26d-35a0-da6a-de806d3f5f1c/Stinson%20Testimony.pdf ================ <QUESTION> ======= Based on this text, describe Ellana's background in medicine. Also, summarize her concerns about the changes that she is witnessing while working in Emergency Medicine. ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

This task requires you to answer questions based solely on the information provided in the prompt. You are not allowed to use any external resources or prior knowledge. Draw your answer from the above text only. Lists should be presented in bullet point. Summaries should be a single paragraph of no more than 6 sentences.

According to the text provided, excluding Authentic, how many additional flavors has Celestial Seasonings created for their green teas?

The mature tea leaves with which regular green teas are made naturally contain high levels of tannins, which can sometimes cause bitterness. Celestial Seasonings created its smoother green teas by adding Bai Mu Dan white tea, whose delicate, silky flavor profile comes from selecting only the tender buds and low-tannin young leaves of the camellia sinensis plant. The white tea infusion creates a balanced and satisfying taste with the healthful antioxidants for which green and white tea are both known. New Celestial Seasonings Green Tea is available on store shelves in nine varieties, including Authentic, Honey Lemon Ginseng and Goji Berry Pomegranate.

[This task requires you to answer questions based solely on the information provided in the prompt. You are not allowed to use any external resources or prior knowledge. Draw your answer from the above text only. Lists should be presented in bullet point. Summaries should be a single paragraph of no more than 6 sentences.] [The mature tea leaves with which regular green teas are made naturally contain high levels of tannins, which can sometimes cause bitterness. Celestial Seasonings created its smoother green teas by adding Bai Mu Dan white tea, whose delicate, silky flavor profile comes from selecting only the tender buds and low-tannin young leaves of the camellia sinensis plant. The white tea infusion creates a balanced and satisfying taste with the healthful antioxidants for which green and white tea are both known. New Celestial Seasonings Green Tea is available on store shelves in nine varieties, including Authentic, Honey Lemon Ginseng and Goji Berry Pomegranate.] [According to the text provided, excluding Authentic, how many flavors has Celestial Seasonings created for their green teas?

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. [user request] [context document]

give me a 5-7 bullet point list of the errors made by the ai in the text. include why the ai using bias can be harmful and what affects bias

Some artificial intelligence tools for health care may get confused by the ways people of different genders and races talk, according to a new study led by CU Boulder computer scientist Theodora Chaspari. The study hinges on a, perhaps unspoken, reality of human society: Not everyone talks the same. Women, for example, tend to speak at a higher pitch than men, while similar differences can pop up between, say, white and Black speakers. Now, researchers have found that those natural variations could confound algorithms that screen humans for mental health concerns like anxiety or depression. The results add to a growing body of research showing that AI, just like people, can make assumptions based on race or gender. "If AI isn't trained well, or doesn't include enough representative data, it can propagate these human or societal biases," said Chaspari, associate professor in the Department of Computer Science. She and her colleagues published their findings July 24 in the journal Frontiers in Digital Health. Chaspari noted that AI could be a promising technology in the healthcare world. Finely tuned algorithms can sift through recordings of people speaking, searching for subtle changes in the way they talk that could indicate underlying mental health concerns. But those tools have to perform consistently for patients from many demographic groups, the computer scientist said. To find out if AI is up to the task, the researchers fed audio samples of real humans into a common set of machine learning algorithms. The results raised a few red flags: The AI tools, for example, seemed to underdiagnose women who were at risk of depression more than men -- an outcome that, in the real world, could keep people from getting the care they need. "With artificial intelligence, we can identify these fine-grained patterns that humans can't always perceive," said Chaspari, who conducted the work as a faculty member at Texas A&M University. "However, while there is this opportunity, there is also a lot of risk." Speech and emotions She added that the way humans talk can be a powerful window into their underlying emotions and wellbeing -- something that poets and playwrights have long known. Research suggests that people diagnosed with clinical depression often speak more softly and in more of a monotone than others. People with anxiety disorders, meanwhile, tend to talk with a higher pitch and with more "jitter," a measurement of the breathiness in speech. "We know that speech is very much influenced by one's anatomy," Chaspari said. "For depression, there have been some studies showing changes in the way vibrations in the vocal folds happen, or even in how the voice is modulated by the vocal tract." Over the years, scientists have developed AI tools to look for just those kinds of changes. Chaspari and her colleagues decided to put the algorithms under the microscope. To do that, the team drew on recordings of humans talking in a range of scenarios: In one, people had to give a 10 to 15 minute talk to a group of strangers. In another, men and women talked for a longer time in a setting similar to a doctor's visit. In both cases, the speakers separately filled out questionnaires about their mental health. The study included Michael Yang and Abd-Allah El-Attar, undergraduate students at Texas A&M. Fixing biases The results seemed to be all over the place. In the public speaking recordings, for example, the Latino participants reported that they felt a lot more nervous on average than the white or Black speakers. The AI, however, failed to detect that heightened anxiety. In the second experiment, the algorithms also flagged equal numbers of men and women as being at risk of depression. In reality, the female speakers had experienced symptoms of depression at much higher rates. Chaspari noted that the team's results are just a first step. The researchers will need to analyze recordings of a lot more people from a wide range of demographic groups before they can understand why the AI fumbled in certain cases -- and how to fix those biases. But, she said, the study is a sign that AI developers should proceed with caution before bringing AI tools into the medical world: "If we think that an algorithm actually underestimates depression for a specific group, this is something we need to inform clinicians about.

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. give me a 5-7 bullet point list of the errors made by the ai in the text. include why the ai using bias can be harmful and what affects bias Some artificial intelligence tools for health care may get confused by the ways people of different genders and races talk, according to a new study led by CU Boulder computer scientist Theodora Chaspari. The study hinges on a, perhaps unspoken, reality of human society: Not everyone talks the same. Women, for example, tend to speak at a higher pitch than men, while similar differences can pop up between, say, white and Black speakers. Now, researchers have found that those natural variations could confound algorithms that screen humans for mental health concerns like anxiety or depression. The results add to a growing body of research showing that AI, just like people, can make assumptions based on race or gender. "If AI isn't trained well, or doesn't include enough representative data, it can propagate these human or societal biases," said Chaspari, associate professor in the Department of Computer Science. She and her colleagues published their findings July 24 in the journal Frontiers in Digital Health. Chaspari noted that AI could be a promising technology in the healthcare world. Finely tuned algorithms can sift through recordings of people speaking, searching for subtle changes in the way they talk that could indicate underlying mental health concerns. But those tools have to perform consistently for patients from many demographic groups, the computer scientist said. To find out if AI is up to the task, the researchers fed audio samples of real humans into a common set of machine learning algorithms. The results raised a few red flags: The AI tools, for example, seemed to underdiagnose women who were at risk of depression more than men -- an outcome that, in the real world, could keep people from getting the care they need. "With artificial intelligence, we can identify these fine-grained patterns that humans can't always perceive," said Chaspari, who conducted the work as a faculty member at Texas A&M University. "However, while there is this opportunity, there is also a lot of risk." Speech and emotions She added that the way humans talk can be a powerful window into their underlying emotions and wellbeing -- something that poets and playwrights have long known. Research suggests that people diagnosed with clinical depression often speak more softly and in more of a monotone than others. People with anxiety disorders, meanwhile, tend to talk with a higher pitch and with more "jitter," a measurement of the breathiness in speech. "We know that speech is very much influenced by one's anatomy," Chaspari said. "For depression, there have been some studies showing changes in the way vibrations in the vocal folds happen, or even in how the voice is modulated by the vocal tract." Over the years, scientists have developed AI tools to look for just those kinds of changes. Chaspari and her colleagues decided to put the algorithms under the microscope. To do that, the team drew on recordings of humans talking in a range of scenarios: In one, people had to give a 10 to 15 minute talk to a group of strangers. In another, men and women talked for a longer time in a setting similar to a doctor's visit. In both cases, the speakers separately filled out questionnaires about their mental health. The study included Michael Yang and Abd-Allah El-Attar, undergraduate students at Texas A&M. Fixing biases The results seemed to be all over the place. In the public speaking recordings, for example, the Latino participants reported that they felt a lot more nervous on average than the white or Black speakers. The AI, however, failed to detect that heightened anxiety. In the second experiment, the algorithms also flagged equal numbers of men and women as being at risk of depression. In reality, the female speakers had experienced symptoms of depression at much higher rates. Chaspari noted that the team's results are just a first step. The researchers will need to analyze recordings of a lot more people from a wide range of demographic groups before they can understand why the AI fumbled in certain cases -- and how to fix those biases. But, she said, the study is a sign that AI developers should proceed with caution before bringing AI tools into the medical world: "If we think that an algorithm actually underestimates depression for a specific group, this is something we need to inform clinicians about. https://www.sciencedaily.com/releases/2024/08/240805134143.htm

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. [user request] [context document]

I'm looking to buy a new pair of headphones. I'm hoping to spend less than $100, while still getting good audio quality. Can you recommend a good option, and list out some of the defining features of the one you recommend?

We all want the best, but sometimes, the top-tier choice exceeds our budget. Thankfully, cheap Bluetooth headphones are easy to come by, and with the rise of wireless earbuds, premium headset prices have fallen dramatically. Although all of our picks are relatively affordable, none of them are inherently cheap. Whether you need active noise canceling (ANC), a compact design, or long battery life, we’ve got something to scratch your audio itch. Editors note: This article was updated on June 28th, 2024, to add new top picks. For under $100, the JLab JBuds Lux are crazy good value The JLab JBuds Lux ANC sitting atop a wooden desk. The JBuds Lux is a compelling buy under $80. The JLab JBuds Lux ANC punches well above its weight, offering exceptional value for under $100. These over-ear headphones feature active noise cancelation that does a decent job of hushing ambient noise, especially in the higher frequencies. While the ANC performance can’t match premium models, it’s impressive for the price. The sound quality is quite good, with an overall MDAQS score of 4.5/5, lauding the headphones’ faithful timbre and immersive soundstage. They have an elevated bass response and boosted treble that helps counter environmental noise during commutes. Other highlights include a 44-hour battery life, USB-C audio support, and a companion app with EQ and customization options. The JBuds Lux ANC may lack advanced features like head tracking, but they nail the fundamentals at a stellar price, making them one of the best budget ANC headphones you can buy. JLab JBuds Lux ANC SG recommended JLab JBuds Lux ANC USB-C audio • Sound quality • Comfort MSRP: $79.99 For under $100, these are crazy good value. As far as inexpensive ANC headphones go, the JLab JBuds Lux ANC are one of the best of 2024. They focus on the fundamentals, and not fighting the spec wars. The Anker Soundcore Space One has style Anker Soundcore Space One headphones next to cloth case and cables. Along with the headphones, you get a cloth carrying case, USB-C charging cable, and 3.5mm auxiliary cable. The Anker Soundcore Space One is a solid choice for consumers seeking noise canceling headphones under $100. The headphones have good isolation and active noise cancelation (ANC), wear detection, long battery life, and the inclusion of Bluetooth 5.3 with LDAC support. The companion app further allows customizable sound profiles and ANC adjustments. The absence of touch controls and an audio profile that leans towards over-emphasized bass and treble may deter some users. Additionally, the lack of audio-over-USB functionality limits its versatility compared to some competitors. Despite these drawbacks, the overall value proposition remains strong, especially considering the headphones’ effective noise cancelation, sound customization options through the app, and robust battery life of nearly 43 hours. Anker Soundcore Space One Anker Soundcore Space One Comfortable fit • Easy controls • Soundcore app MSRP: $99.99 Luxury features at a budget price. Listen and be heard with the Jabra Elite 45h The Jabra Elite 45h on-ear Bluetooth headphones next to a Samsung Galaxy S10e smartphone and wireless car keys on a white table. Bluetooth multipoint is available but not very reliable. The Jabra Elite 45h are on-ear headphones designed to be compact and portable enough to take anywhere—whether you’re commuting to work, running errands, or just putting your feet up at home. The swivel ear cups make it easy to shove into a backpack for easy transport. Top Deals See all deals Sennheiser Momentum 4 Wireless 37% off See price at Best Buy Sony WH-CH720N Headphones 48% off See price at Amazon Sony SRS-XE200 X-Series Speaker 47% off See price at Amazon Limited Time Deal! Edifier G2000 Gaming Speakers 34% off See price at Amazon Limited Time Deal! Edifier G1000 Gaming Speakers 41% off See price at Best Buy Deal of the Day! JBL Vibe Beam 40% off See price at Amazon Limited Time Deal! The headphones’ bass-heavy frequency response makes it hard to hear higher-pitched vocals. Fortunately, you can create a custom EQ in the Jabra Sound+ app (Android/iOS) and tinker all day long. If you don’t want to experiment, Jabra has a hearing test that informs an optimized sound profile. One of the best aspects of the Jabra Elite 45h is its microphone. It reproduces voices accurately, and even people with deep voices will be heard loud and clear. The microphone also does a good job of attenuating background noise and light wind, eliminating audible distractions during conference calls. Other features that make the Jabra Elite 45h a worthy investment include a 50+ hour battery life, USB-C fast charging, AAC codec support (which is great for iOS users), and an included two-year warranty that covers dust and water damage.

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. I'm looking to buy a new pair of headphones. I'm hoping to spend less than $100, while still getting good audio quality. Can you recommend a good option, and list out some of the defining features of the one you recommend? We all want the best, but sometimes, the top-tier choice exceeds our budget. Thankfully, cheap Bluetooth headphones are easy to come by, and with the rise of wireless earbuds, premium headset prices have fallen dramatically. Although all of our picks are relatively affordable, none of them are inherently cheap. Whether you need active noise canceling (ANC), a compact design, or long battery life, we’ve got something to scratch your audio itch. Editors note: This article was updated on June 28th, 2024, to add new top picks. For under $100, the JLab JBuds Lux are crazy good value The JLab JBuds Lux ANC sitting atop a wooden desk. The JBuds Lux is a compelling buy under $80. The JLab JBuds Lux ANC punches well above its weight, offering exceptional value for under $100. These over-ear headphones feature active noise cancelation that does a decent job of hushing ambient noise, especially in the higher frequencies. While the ANC performance can’t match premium models, it’s impressive for the price. The sound quality is quite good, with an overall MDAQS score of 4.5/5, lauding the headphones’ faithful timbre and immersive soundstage. They have an elevated bass response and boosted treble that helps counter environmental noise during commutes. Other highlights include a 44-hour battery life, USB-C audio support, and a companion app with EQ and customization options. The JBuds Lux ANC may lack advanced features like head tracking, but they nail the fundamentals at a stellar price, making them one of the best budget ANC headphones you can buy. JLab JBuds Lux ANC SG recommended JLab JBuds Lux ANC USB-C audio • Sound quality • Comfort MSRP: $79.99 For under $100, these are crazy good value. As far as inexpensive ANC headphones go, the JLab JBuds Lux ANC are one of the best of 2024. They focus on the fundamentals, and not fighting the spec wars. The Anker Soundcore Space One has style Anker Soundcore Space One headphones next to cloth case and cables. Along with the headphones, you get a cloth carrying case, USB-C charging cable, and 3.5mm auxiliary cable. The Anker Soundcore Space One is a solid choice for consumers seeking noise canceling headphones under $100. The headphones have good isolation and active noise cancelation (ANC), wear detection, long battery life, and the inclusion of Bluetooth 5.3 with LDAC support. The companion app further allows customizable sound profiles and ANC adjustments. The absence of touch controls and an audio profile that leans towards over-emphasized bass and treble may deter some users. Additionally, the lack of audio-over-USB functionality limits its versatility compared to some competitors. Despite these drawbacks, the overall value proposition remains strong, especially considering the headphones’ effective noise cancelation, sound customization options through the app, and robust battery life of nearly 43 hours. Anker Soundcore Space One Anker Soundcore Space One Comfortable fit • Easy controls • Soundcore app MSRP: $99.99 Luxury features at a budget price. Listen and be heard with the Jabra Elite 45h The Jabra Elite 45h on-ear Bluetooth headphones next to a Samsung Galaxy S10e smartphone and wireless car keys on a white table. Bluetooth multipoint is available but not very reliable. The Jabra Elite 45h are on-ear headphones designed to be compact and portable enough to take anywhere—whether you’re commuting to work, running errands, or just putting your feet up at home. The swivel ear cups make it easy to shove into a backpack for easy transport. Top Deals See all deals Sennheiser Momentum 4 Wireless 37% off See price at Best Buy Sony WH-CH720N Headphones 48% off See price at Amazon Sony SRS-XE200 X-Series Speaker 47% off See price at Amazon Limited Time Deal! Edifier G2000 Gaming Speakers 34% off See price at Amazon Limited Time Deal! Edifier G1000 Gaming Speakers 41% off See price at Best Buy Deal of the Day! JBL Vibe Beam 40% off See price at Amazon Limited Time Deal! The headphones’ bass-heavy frequency response makes it hard to hear higher-pitched vocals. Fortunately, you can create a custom EQ in the Jabra Sound+ app (Android/iOS) and tinker all day long. If you don’t want to experiment, Jabra has a hearing test that informs an optimized sound profile. One of the best aspects of the Jabra Elite 45h is its microphone. It reproduces voices accurately, and even people with deep voices will be heard loud and clear. The microphone also does a good job of attenuating background noise and light wind, eliminating audible distractions during conference calls. Other features that make the Jabra Elite 45h a worthy investment include a 50+ hour battery life, USB-C fast charging, AAC codec support (which is great for iOS users), and an included two-year warranty that covers dust and water damage. https://www.soundguys.com/best-cheap-bluetooth-headphones-100-28839/

"================ <TEXT PASSAGE> ======= [context document] ================ <QUESTION> ======= [user request] ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

My cousin in South Dakota wants to sell me his 1977 triple wide manufactured home that he has on a lot in a mobile home park there. I will move it to my improved land in New York and live there. Can I finance this home using a FHA mortgage loan?

II. ORIGINATION THROUGH POST-CLOSING/ENDORSEMENT B. Title II Insured Housing Programs Reverse Mortgages 2. Origination/Processing Handbook 4000.1 589 Last Revised: 05/20/2024 Mortgagee must determine whether the recorded Declaration and/or CC&Rs require prior approval by the association of any non-purchase money mortgage that will encumber the Property. In those situations where such a requirement exists, the Mortgagee must obtain the approval of the association in writing prior to origination of the HECM. Documentation concerning this approval must be maintained by the Mortgagee and made available to HUD upon request. (7) Property Assessed Clean Energy (a) Definition Property Assessed Clean Energy (PACE) refers to an alternative means of financing energy and other PACE-allowed improvements to residential properties using financing provided by private enterprises in conjunction with state and local governments. Generally, the repayment of the PACE obligation is collected in the same manner as a special assessment tax; it is collected by the local government rather than paid directly by the Borrower to the party providing the PACE financing. Generally, the PACE obligation is also secured in the same manner as a special assessment against the property. (b) Standard Properties which will remain encumbered with a PACE obligation are not eligible for an FHA-insured HECM. To be eligible for FHA insurance, the PACE obligation must be paid off in full prior to or at closing. The Borrower may use HECM proceeds to satisfy the PACE obligation. For HECM for Purchase transactions, see the Property Assessed Clean Energy section of the product sheet. (B) Property Types FHA’s programs differ from one another primarily in terms of what types of Properties and financing are eligible. Except as otherwise stated in this Handbook 4000.1, HECMs are limited to one- to four-unit Single Family Properties where the Borrower occupies one unit as their Principal Residence. FHA insures HECM financing on Real Property secured by: • detached or semi-detached dwellings • Manufactured Housing • townhouses or row houses • Condominium Units and Site Condominiums FHA will not insure HECMs secured by: • commercial enterprises • cooperative units • boarding houses • hotels, motels, and condotels II. ORIGINATION THROUGH POST-CLOSING/ENDORSEMENT B. Title II Insured Housing Programs Reverse Mortgages 2. Origination/Processing Handbook 4000.1 590 Last Revised: 05/20/2024 • tourist houses • private clubs • bed and breakfast establishments • other transient housing • Vacation Homes • fraternity and sorority houses (1) One-Unit A one-unit Property is a Single Family residential Property with a single Dwelling Unit, or with a single Dwelling Unit and a single ADU. (2) Two-Unit (a) Definition A two-unit Property is a Single Family residential Property with two individual dwellings. (b) Standard The Mortgagee must obtain a completed form HUD-92561. (3) Three- to Four-Unit A three- to four-unit Property is either: • a Single Family residential Property with three to four individual Dwelling Units; or • a Single Family residential Property with two individual Dwelling Units and one ADU or three individual Dwelling Units and one ADU. The Mortgagee must obtain a completed form HUD-92561. (4) Accessory Dwelling Unit (a) Definition An Accessory Dwelling Unit (ADU) refers to a single habitable living unit with means of separate ingress and egress that meets the minimum requirements for a living unit. An ADU is a private space that is subordinate in size and within, or detached from a primary one-unit Single Family dwelling, which together constitute a single interest in real estate. (b) Standard A Single Family residential one-unit Property with a single ADU remains a one-unit Property. For any Single Family residential Property with two or II. ORIGINATION THROUGH POST-CLOSING/ENDORSEMENT B. Title II Insured Housing Programs Reverse Mortgages 2. Origination/Processing Handbook 4000.1 591 Last Revised: 05/20/2024 more units, a separate additional Dwelling Unit must be considered as an additional unit. (5) Condominium Unit (a) Definitions A Condominium Unit refers to real estate consisting of a one-family Dwelling Unit in a Condominium Project. Condominium Project refers to a project in which one-family Dwelling Units are attached, semi-detached, detached, or Manufactured Home units, and in which owners hold an undivided interest in Common Elements. (b) Standard A Condominium Unit must be either located within an FHA-approved Condominium Project, meet FHA’s definition of a Site Condominium, or have completed the FHA Single-Unit Approval process before a Mortgage can be insured. (6) Site Condominiums (a) Definition A Site Condominium refers to: • a Condominium Project that consists entirely of Single Family detached dwellings that have no shared garages, or any other attached buildings; or • a Condominium Project that:  consists of Single Family detached or horizontally attached (townhouse-style) dwellings where the Unit consists of the dwelling and land;  does not contain any Manufactured Housing Units; and  is encumbered by a declaration of condominium covenants or a condominium form of ownership. (b) Standard Manufactured Housing condominium units may not be processed as Site Condominiums. The Unit owner must be responsible for all required insurance and maintenance costs associated with the Unit dwelling, excluding landscaping, of the Site Condominium. II. ORIGINATION THROUGH POST-CLOSING/ENDORSEMENT B. Title II Insured Housing Programs Reverse Mortgages 2. Origination/Processing Handbook 4000.1 592 Last Revised: 05/20/2024 Site Condominiums do not require Condominium Project Approval or Single- Unit Approval. Manufactured Housing (a) Definition Manufactured Housing is a Structure that is transportable in one or more sections. It may be part of a Condominium Project, provided the project meets applicable FHA requirements. (b) Standard To be eligible for FHA mortgage insurance as a Single Family Title II HECM, all Manufactured Housing must: • be designed as a one-family dwelling; • have a floor area of not less than 400 square feet; • have the HUD Certification Label affixed or have obtained a letter of label verification issued on behalf of HUD, evidencing the house was constructed on or after June 15, 1976, in compliance with the Federal Manufactured Home Construction and Safety Standards; • be classified as real estate (but need not be treated as real estate for purposes of state taxation); • be built and remain on a permanent chassis; • be designed to be used as a dwelling with a permanent foundation built in accordance with the Permanent Foundations Guide for Manufactured Housing (PFGMH); and • have been directly transported from the manufacturer or the dealership to the site. (c) Required Documentation (i) HUD Certification Label If the appraisal indicates the HUD Certification Label is missing from the Manufactured Housing unit, the Mortgagee must obtain label verification from the Institute for Building Technology and Safety (IBTS). (ii) PFGMH Certification The Mortgagee must obtain a certification by an engineer or architect, who is licensed/registered in the state where the Manufactured Home is located, attesting to compliance with the PFGMH. The Mortgagee may obtain a copy of the foundation certification from a previous FHA-insured Mortgage, showing that the foundation met the guidelines published in the PFGMH that were in effect at the time of II. ORIGINATION THROUGH POST-CLOSING/ENDORSEMENT B. Title II Insured Housing Programs Reverse Mortgages 2. Origination/Processing Handbook 4000.1 593 Last Revised: 05/20/2024 certification, provided there are no alterations and/or observable damage to the foundation since the date of the original certification. If the Appraiser notes additions or alterations to the Manufactured Housing unit, the Mortgagee must ensure the addition was addressed in the foundation certification. If the additions or alterations were not addressed in the foundation certification, the Mortgagee must obtain: • an inspection by the state administrative agency that inspects Manufactured Housing for compliance; or • certification of the structural integrity from a licensed structural engineer if the state does not employ inspectors

"================ <TEXT PASSAGE> ======= II. ORIGINATION THROUGH POST-CLOSING/ENDORSEMENT B. Title II Insured Housing Programs Reverse Mortgages 2. Origination/Processing Handbook 4000.1 589 Last Revised: 05/20/2024 Mortgagee must determine whether the recorded Declaration and/or CC&Rs require prior approval by the association of any non-purchase money mortgage that will encumber the Property. In those situations where such a requirement exists, the Mortgagee must obtain the approval of the association in writing prior to origination of the HECM. Documentation concerning this approval must be maintained by the Mortgagee and made available to HUD upon request. (7) Property Assessed Clean Energy (a) Definition Property Assessed Clean Energy (PACE) refers to an alternative means of financing energy and other PACE-allowed improvements to residential properties using financing provided by private enterprises in conjunction with state and local governments. Generally, the repayment of the PACE obligation is collected in the same manner as a special assessment tax; it is collected by the local government rather than paid directly by the Borrower to the party providing the PACE financing. Generally, the PACE obligation is also secured in the same manner as a special assessment against the property. (b) Standard Properties which will remain encumbered with a PACE obligation are not eligible for an FHA-insured HECM. To be eligible for FHA insurance, the PACE obligation must be paid off in full prior to or at closing. The Borrower may use HECM proceeds to satisfy the PACE obligation. For HECM for Purchase transactions, see the Property Assessed Clean Energy section of the product sheet. (B) Property Types FHA’s programs differ from one another primarily in terms of what types of Properties and financing are eligible. Except as otherwise stated in this Handbook 4000.1, HECMs are limited to one- to four-unit Single Family Properties where the Borrower occupies one unit as their Principal Residence. FHA insures HECM financing on Real Property secured by: • detached or semi-detached dwellings • Manufactured Housing • townhouses or row houses • Condominium Units and Site Condominiums FHA will not insure HECMs secured by: • commercial enterprises • cooperative units • boarding houses • hotels, motels, and condotels II. ORIGINATION THROUGH POST-CLOSING/ENDORSEMENT B. Title II Insured Housing Programs Reverse Mortgages 2. Origination/Processing Handbook 4000.1 590 Last Revised: 05/20/2024 • tourist houses • private clubs • bed and breakfast establishments • other transient housing • Vacation Homes • fraternity and sorority houses (1) One-Unit A one-unit Property is a Single Family residential Property with a single Dwelling Unit, or with a single Dwelling Unit and a single ADU. (2) Two-Unit (a) Definition A two-unit Property is a Single Family residential Property with two individual dwellings. (b) Standard The Mortgagee must obtain a completed form HUD-92561. (3) Three- to Four-Unit A three- to four-unit Property is either: • a Single Family residential Property with three to four individual Dwelling Units; or • a Single Family residential Property with two individual Dwelling Units and one ADU or three individual Dwelling Units and one ADU. The Mortgagee must obtain a completed form HUD-92561. (4) Accessory Dwelling Unit (a) Definition An Accessory Dwelling Unit (ADU) refers to a single habitable living unit with means of separate ingress and egress that meets the minimum requirements for a living unit. An ADU is a private space that is subordinate in size and within, or detached from a primary one-unit Single Family dwelling, which together constitute a single interest in real estate. (b) Standard A Single Family residential one-unit Property with a single ADU remains a one-unit Property. For any Single Family residential Property with two or II. ORIGINATION THROUGH POST-CLOSING/ENDORSEMENT B. Title II Insured Housing Programs Reverse Mortgages 2. Origination/Processing Handbook 4000.1 591 Last Revised: 05/20/2024 more units, a separate additional Dwelling Unit must be considered as an additional unit. (5) Condominium Unit (a) Definitions A Condominium Unit refers to real estate consisting of a one-family Dwelling Unit in a Condominium Project. Condominium Project refers to a project in which one-family Dwelling Units are attached, semi-detached, detached, or Manufactured Home units, and in which owners hold an undivided interest in Common Elements. (b) Standard A Condominium Unit must be either located within an FHA-approved Condominium Project, meet FHA’s definition of a Site Condominium, or have completed the FHA Single-Unit Approval process before a Mortgage can be insured. (6) Site Condominiums (a) Definition A Site Condominium refers to: • a Condominium Project that consists entirely of Single Family detached dwellings that have no shared garages, or any other attached buildings; or • a Condominium Project that:  consists of Single Family detached or horizontally attached (townhouse-style) dwellings where the Unit consists of the dwelling and land;  does not contain any Manufactured Housing Units; and  is encumbered by a declaration of condominium covenants or a condominium form of ownership. (b) Standard Manufactured Housing condominium units may not be processed as Site Condominiums. The Unit owner must be responsible for all required insurance and maintenance costs associated with the Unit dwelling, excluding landscaping, of the Site Condominium. II. ORIGINATION THROUGH POST-CLOSING/ENDORSEMENT B. Title II Insured Housing Programs Reverse Mortgages 2. Origination/Processing Handbook 4000.1 592 Last Revised: 05/20/2024 Site Condominiums do not require Condominium Project Approval or Single- Unit Approval. Manufactured Housing (a) Definition Manufactured Housing is a Structure that is transportable in one or more sections. It may be part of a Condominium Project, provided the project meets applicable FHA requirements. (b) Standard To be eligible for FHA mortgage insurance as a Single Family Title II HECM, all Manufactured Housing must: • be designed as a one-family dwelling; • have a floor area of not less than 400 square feet; • have the HUD Certification Label affixed or have obtained a letter of label verification issued on behalf of HUD, evidencing the house was constructed on or after June 15, 1976, in compliance with the Federal Manufactured Home Construction and Safety Standards; • be classified as real estate (but need not be treated as real estate for purposes of state taxation); • be built and remain on a permanent chassis; • be designed to be used as a dwelling with a permanent foundation built in accordance with the Permanent Foundations Guide for Manufactured Housing (PFGMH); and • have been directly transported from the manufacturer or the dealership to the site. (c) Required Documentation (i) HUD Certification Label If the appraisal indicates the HUD Certification Label is missing from the Manufactured Housing unit, the Mortgagee must obtain label verification from the Institute for Building Technology and Safety (IBTS). (ii) PFGMH Certification The Mortgagee must obtain a certification by an engineer or architect, who is licensed/registered in the state where the Manufactured Home is located, attesting to compliance with the PFGMH. The Mortgagee may obtain a copy of the foundation certification from a previous FHA-insured Mortgage, showing that the foundation met the guidelines published in the PFGMH that were in effect at the time of II. ORIGINATION THROUGH POST-CLOSING/ENDORSEMENT B. Title II Insured Housing Programs Reverse Mortgages 2. Origination/Processing Handbook 4000.1 593 Last Revised: 05/20/2024 certification, provided there are no alterations and/or observable damage to the foundation since the date of the original certification. If the Appraiser notes additions or alterations to the Manufactured Housing unit, the Mortgagee must ensure the addition was addressed in the foundation certification. If the additions or alterations were not addressed in the foundation certification, the Mortgagee must obtain: • an inspection by the state administrative agency that inspects Manufactured Housing for compliance; or • certification of the structural integrity from a licensed structural engineer if the state does not employ inspectors https://www.hud.gov/sites/dfiles/OCHCO/documents/40001-hsgh-update15-052024.pdf ================ <QUESTION> ======= My cousin in South Dakota wants to sell me his 1977 triple wide manufactured home that he has on a lot in a mobile home park there. I will move it to my improved land in New York and live there. Can I finance this home using a FHA mortgage loan? ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."