Showing papers by "Tufts University published in 2021"
Daniel J. Klionsky1, Amal Kamal Abdel-Aziz2, Sara Abdelfatah3, Mahmoud Abdellatif4 +2980 more•Institutions (777)
TL;DR: In this article, the authors present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes.
Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
1,129 citations
Université Paris-Saclay1, Autonomous University of Barcelona2, University of Cambridge3, National Institute for Occupational Safety and Health4, German Center for Neurodegenerative Diseases5, University of Bonn6, Harvard University7, University of Lausanne8, National Research Council9, University of Padua10, Heidelberg University11, Salk Institute for Biological Studies12, University of Minnesota13, Pasteur Institute14, Tel Aviv University15, Johns Hopkins University16, University of Portsmouth17, Katholieke Universiteit Leuven18, PSL Research University19, Trinity College, Dublin20, Baylor College of Medicine21, University College London22, University of Edinburgh23, Oregon Health & Science University24, National Institutes of Health25, Columbia University26, University of Rochester27, University of Copenhagen28, Ludwig Maximilian University of Munich29, University of Málaga30, Tufts University31, University of Freiburg32, Utrecht University33, Nihon University34, Max Delbrück Center for Molecular Medicine35, University of California, Los Angeles36, University of Yamanashi37, New York University38, University of British Columbia39, King Abdullah University of Science and Technology40, University of Wisconsin-Madison41, University of California, San Francisco42, McGill University43, University of Kentucky44, Kyushu University45, University of Bordeaux46, University of Minho47, Polytechnic Institute of Cávado and Ave48, University of Alabama at Birmingham49, University of Gothenburg50, University of Poitiers51, Cajal Institute52, King's College London53, University of Strasbourg54, Virginia Tech55, University of Düsseldorf56, Russian Academy of Sciences57, I.M. Sechenov First Moscow State Medical University58, University of Seville59, Georgia Institute of Technology60, University of Texas Health Science Center at Houston61, University of California, San Diego62, Universidade Federal do Rio Grande do Sul63, University of Ljubljana64, Ikerbasque65, University of Manchester66
TL;DR: In this article, the authors point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic vs-neuroprotective or A1-vs.A2.
Abstract: Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions.
797 citations
University of Oxford1, Australian National University2, Harvard University3, University of Bristol4, University of Manchester5, University of London6, London School of Economics and Political Science7, University of Cambridge8, Tufts University9, Imperial College London10, Medical Research Council11
TL;DR: The results indicate that, by using effective interventions, some countries could control the epidemic while avoiding stay-at-home orders, and this model accounts for uncertainty in key epidemiological parameters, such as the average delay from infection to death.
Abstract: Governments are attempting to control the COVID-19 pandemic with nonpharmaceutical interventions (NPIs). However, the effectiveness of different NPIs at reducing transmission is poorly understood. We gathered chronological data on the implementation of NPIs for several European, and other, countries between January and the end of May 2020. We estimate the effectiveness of NPIs, ranging from limiting gathering sizes, business closures, and closure of educational institutions to stay-at-home orders. To do so, we used a Bayesian hierarchical model that links NPI implementation dates to national case and death counts and supported the results with extensive empirical validation. Closing all educational institutions, limiting gatherings to 10 people or less, and closing face-to-face businesses each reduced transmission considerably. The additional effect of stay-at-home orders was comparatively small.
674 citations
Virginia Commonwealth University1, The Feinstein Institute for Medical Research2, University of California, Los Angeles3, Harvard University4, University of California, San Francisco5, Oregon Health & Science University6, University of Pittsburgh7, University of North Carolina at Chapel Hill8, Mayo Clinic9, George Mason University10, University of Alabama at Birmingham11, University of Virginia12, New York University13, Stanford University14, University of Massachusetts Medical School15, Boston University16, University of Missouri17, University of Hawaii18, Tufts University19
TL;DR: The US Preventive Services Task Force (USPSTF) concluded with moderate certainty that annual screening for lung cancer with LDCT has a moderate net benefit in persons at high risk of lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking as mentioned in this paper.
Abstract: Importance Lung cancer is the second most common cancer and the leading cause of cancer death in the US. In 2020, an estimated 228 820 persons were diagnosed with lung cancer, and 135 720 persons died of the disease. The most important risk factor for lung cancer is smoking. Increasing age is also a risk factor for lung cancer. Lung cancer has a generally poor prognosis, with an overall 5-year survival rate of 20.5%. However, early-stage lung cancer has a better prognosis and is more amenable to treatment. Objective To update its 2013 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review on the accuracy of screening for lung cancer with low-dose computed tomography (LDCT) and on the benefits and harms of screening for lung cancer and commissioned a collaborative modeling study to provide information about the optimum age at which to begin and end screening, the optimal screening interval, and the relative benefits and harms of different screening strategies compared with modified versions of multivariate risk prediction models. Population This recommendation statement applies to adults aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years. Evidence Assessment The USPSTF concludes with moderate certainty that annual screening for lung cancer with LDCT has a moderate net benefit in persons at high risk of lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking. Recommendation The USPSTF recommends annual screening for lung cancer with LDCT in adults aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation) This recommendation replaces the 2013 USPSTF statement that recommended annual screening for lung cancer with LDCT in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years.
600 citations
Innovations for Poverty Action1, Wageningen University and Research Centre2, Columbia University3, National Research University – Higher School of Economics4, Yale University5, University of Lagos6, Institute for Fiscal Studies7, Universidade Nova de Lisboa8, Lahore University of Management Sciences9, University of St Andrews10, Stockholm School of Economics11, Ghent University12, Alternatives13, Trinity College, Dublin14, University of Sierra Leone15, Kathmandu16, Cornell University17, University of Illinois at Chicago18, New York University Abu Dhabi19, Princeton University20, Stockholm University21, Tufts University22, University of Michigan23, Northwestern University24, London School of Economics and Political Science25
TL;DR: In this article, the authors analyzed COVID-19 vaccine acceptance across 15 survey samples covering 10 low and middle-income countries (LMICs) in Asia, Africa and South America, Russia (an upper-middle-income country) and the United States, including a total of 44,260 individuals.
Abstract: Widespread acceptance of COVID-19 vaccines is crucial for achieving sufficient immunization coverage to end the global pandemic, yet few studies have investigated COVID-19 vaccination attitudes in lower-income countries, where large-scale vaccination is just beginning. We analyze COVID-19 vaccine acceptance across 15 survey samples covering 10 low- and middle-income countries (LMICs) in Asia, Africa and South America, Russia (an upper-middle-income country) and the United States, including a total of 44,260 individuals. We find considerably higher willingness to take a COVID-19 vaccine in our LMIC samples (mean 80.3%; median 78%; range 30.1 percentage points) compared with the United States (mean 64.6%) and Russia (mean 30.4%). Vaccine acceptance in LMICs is primarily explained by an interest in personal protection against COVID-19, while concern about side effects is the most common reason for hesitancy. Health workers are the most trusted sources of guidance about COVID-19 vaccines. Evidence from this sample of LMICs suggests that prioritizing vaccine distribution to the Global South should yield high returns in advancing global immunization coverage. Vaccination campaigns should focus on translating the high levels of stated acceptance into actual uptake. Messages highlighting vaccine efficacy and safety, delivered by healthcare workers, could be effective for addressing any remaining hesitancy in the analyzed LMICs.
536 citations
Harvard University1, University of Michigan2, Icahn School of Medicine at Mount Sinai3, Yeshiva University4, Seton Hall University5, Rutgers University6, University of Pennsylvania7, Cornell University8, Rush University Medical Center9, Anschutz Medical Campus10, Northwestern University11, Medical College of Wisconsin12, Rowan University13, Tufts University14, Thomas Jefferson University15, University of Queensland16, Ochsner Health System17, Johns Hopkins University18, New York University19, Indiana University – Purdue University Indianapolis20, ProMedica21, University of Vermont22, University of Miami23, Vanderbilt University24
TL;DR: Among critically ill patients with COVID-19 in this cohort study, the risk of in-hospital mortality in this study was lower in patients treated with tocilizumab in the first 2 days of ICU admission compared with patients whose treatment did not include early use of tocilzumab, and the findings may be susceptible to unmeasured confounding.
Abstract: Importance Therapies that improve survival in critically ill patients with coronavirus disease 2019 (COVID-19) are needed. Tocilizumab, a monoclonal antibody against the interleukin 6 receptor, may counteract the inflammatory cytokine release syndrome in patients with severe COVID-19 illness. Objective To test whether tocilizumab decreases mortality in this population. Design, setting, and participants The data for this study were derived from a multicenter cohort study of 4485 adults with COVID-19 admitted to participating intensive care units (ICUs) at 68 hospitals across the US from March 4 to May 10, 2020. Critically ill adults with COVID-19 were categorized according to whether they received or did not receive tocilizumab in the first 2 days of admission to the ICU. Data were collected retrospectively until June 12, 2020. A Cox regression model with inverse probability weighting was used to adjust for confounding. Exposures Treatment with tocilizumab in the first 2 days of ICU admission. Main outcomes and measures Time to death, compared via hazard ratios (HRs), and 30-day mortality, compared via risk differences. Results Among the 3924 patients included in the analysis (2464 male [62.8%]; median age, 62 [interquartile range {IQR}, 52-71] years), 433 (11.0%) received tocilizumab in the first 2 days of ICU admission. Patients treated with tocilizumab were younger (median age, 58 [IQR, 48-65] vs 63 [IQR, 52-72] years) and had a higher prevalence of hypoxemia on ICU admission (205 of 433 [47.3%] vs 1322 of 3491 [37.9%] with mechanical ventilation and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of Conclusions and relevance Among critically ill patients with COVID-19 in this cohort study, the risk of in-hospital mortality in this study was lower in patients treated with tocilizumab in the first 2 days of ICU admission compared with patients whose treatment did not include early use of tocilizumab. However, the findings may be susceptible to unmeasured confounding, and further research from randomized clinical trials is needed.
359 citations
National Technical University of Athens1, University of Manchester2, University of Chile3, Iowa State University4, University of Waterloo5, University of Duisburg-Essen6, University of Hong Kong7, University of Michigan8, Hydro-Québec9, Imperial College London10, Tufts University11, Arizona State University12
TL;DR: This paper based on an IEEE PES report summarizes the major results of the work of the Task Force and presents extended definitions and classification of power system stability.
Abstract: Since the publication of the original paper on power system stability definitions in 2004, the dynamic behavior of power systems has gradually changed due to the increasing penetration of converter interfaced generation technologies, loads, and transmission devices. In recognition of this change, a Task Force was established in 2016 to re-examine and extend, where appropriate, the classic definitions and classifications of the basic stability terms to incorporate the effects of fast-response power electronic devices. This paper based on an IEEE PES report summarizes the major results of the work of the Task Force and presents extended definitions and classification of power system stability.
345 citations
Vanderbilt University1, Texas A&M University2, Scott & White Hospital3, University of Colorado Denver4, University of Iowa5, Wake Forest University6, Johns Hopkins University7, Hennepin County Medical Center8, Yeshiva University9, University of Washington10, Tufts University11, University of Utah12, University of Michigan13, Oregon Health & Science University14, Emory University15, Cleveland Clinic16, Stanford University17, University of California, Los Angeles18, University of Miami19, Washington University in St. Louis20, Ohio State University21
TL;DR: In this paper, a case-control analysis was conducted among 3,689 adults aged ≥18 years who were hospitalized at 21 U.S. hospitals across 18 states during March 11-August 15, 2021.
Abstract: Three COVID-19 vaccines are authorized or approved for use among adults in the United States (1,2). Two 2-dose mRNA vaccines, mRNA-1273 from Moderna and BNT162b2 from Pfizer-BioNTech, received Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) in December 2020 for persons aged ≥18 years and aged ≥16 years, respectively. A 1-dose viral vector vaccine (Ad26.COV2 from Janssen [Johnson & Johnson]) received EUA in February 2021 for persons aged ≥18 years (3). The Pfizer-BioNTech vaccine received FDA approval for persons aged ≥16 years on August 23, 2021 (4). Current guidelines from FDA and CDC recommend vaccination of eligible persons with one of these three products, without preference for any specific vaccine (4,5). To assess vaccine effectiveness (VE) of these three products in preventing COVID-19 hospitalization, CDC and collaborators conducted a case-control analysis among 3,689 adults aged ≥18 years who were hospitalized at 21 U.S. hospitals across 18 states during March 11-August 15, 2021. An additional analysis compared serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2, the virus that causes COVID-19, among 100 healthy volunteers enrolled at three hospitals 2-6 weeks after full vaccination with the Moderna, Pfizer-BioNTech, or Janssen COVID-19 vaccine. Patients with immunocompromising conditions were excluded. VE against COVID-19 hospitalizations was higher for the Moderna vaccine (93%; 95% confidence interval [CI] = 91%-95%) than for the Pfizer-BioNTech vaccine (88%; 95% CI = 85%-91%) (p = 0.011); VE for both mRNA vaccines was higher than that for the Janssen vaccine (71%; 95% CI = 56%-81%) (all p<0.001). Protection for the Pfizer-BioNTech vaccine declined 4 months after vaccination. Postvaccination anti-spike IgG and anti-RBD IgG levels were significantly lower in persons vaccinated with the Janssen vaccine than the Moderna or Pfizer-BioNTech vaccines. Although these real-world data suggest some variation in levels of protection by vaccine, all FDA-approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization.
302 citations
Oregon State University1, Oregon Health & Science University2, Johns Hopkins University3, University of Colorado Denver4, University of Iowa5, Sage Bionetworks6, Duke University7, Washington University in St. Louis8, University of North Carolina at Chapel Hill9, Stony Brook University10, University of Texas Medical Branch11, University of Washington12, Tufts Medical Center13, Scripps Research Institute14, Janssen Pharmaceutica15, University of Alabama at Birmingham16, Johns Hopkins University School of Medicine17, National Institutes of Health18, Columbia University19, Harvard University20, Durham University21, Tufts University22, University of Pittsburgh23, Palantir Technologies24
TL;DR: The N3C has demonstrated that a multisite collaborative learning health network can overcome barriers to rapidly build a scalable infrastructure incorporating multiorganizational clinical data for COVID-19 analytics.
298 citations
TL;DR: In this paper, the authors present updated estimates from the Global Burden of Disease (GBD) study on the prevalence of hearing loss in 2019, as well as the condition's associated disability.
253 citations
Carlos III Health Institute1, Universidad Pública de Navarra2, University of Navarra3, National University of Singapore4, Saint Louis University5, Charité6, Université du Québec à Montréal7, Agostino Gemelli University Polyclinic8, Universidade Federal do Rio Grande do Sul9, University of Milan10, University of Toulouse11, University of Melbourne12, Tufts University13, King's College London14, Wake Forest University15, University of Florida16, University of Miami17, Dalhousie University18, Baylor College of Medicine19, University of Otago20, Kyung Hee University21, The Chinese University of Hong Kong22, RMIT University23
TL;DR: In this paper, the authors provide evidence-based rationale for using exercise and physical activity (PA) for health promotion and disease prevention and treatment in older adults, and discuss the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability.
Abstract: The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent.
Centers for Disease Control and Prevention1, Vanderbilt University2, Tufts University3, Harvard University4, University of Colorado Denver5, Hennepin County Medical Center6, University of Utah7, Yeshiva University8, Oregon Health & Science University9, Ohio State University10, Wake Forest University11, Johns Hopkins University12, University of California, Los Angeles13, Stanford University14, Scott & White Hospital15, University of Michigan16, Saint Joseph Mercy Health System17, University of Pittsburgh18
TL;DR: In this paper, the effectiveness of partial or full vaccination with Pfizer-BioNTech or Moderna vaccines against COVID-19-associated hospitalization was assessed among adults aged ≥ 65 years.
Abstract: Adults aged ≥65 years are at increased risk for severe outcomes from COVID-19 and were identified as a priority group to receive the first COVID-19 vaccines approved for use under an Emergency Use Authorization (EUA) in the United States (1-3). In an evaluation at 24 hospitals in 14 states,* the effectiveness of partial or full vaccination† with Pfizer-BioNTech or Moderna vaccines against COVID-19-associated hospitalization was assessed among adults aged ≥65 years. Among 417 hospitalized adults aged ≥65 years (including 187 case-patients and 230 controls), the median age was 73 years, 48% were female, 73% were non-Hispanic White, 17% were non-Hispanic Black, 6% were Hispanic, and 4% lived in a long-term care facility. Adjusted vaccine effectiveness (VE) against COVID-19-associated hospitalization among adults aged ≥65 years was estimated to be 94% (95% confidence interval [CI] = 49%-99%) for full vaccination and 64% (95% CI = 28%-82%) for partial vaccination. These findings are consistent with efficacy determined from clinical trials in the subgroup of adults aged ≥65 years (4,5). This multisite U.S. evaluation under real-world conditions suggests that vaccination provided protection against COVID-19-associated hospitalization among adults aged ≥65 years. Vaccination is a critical tool for reducing severe COVID-19 in groups at high risk.
TL;DR: In this article, a low-temperature water-gas shift (WGS) catalyst is achieved by crowding platinum atoms and clusters on α-molybdenum carbide; the crowding protects the support from oxidation that would cause catalyst deactivation.
Abstract: The water–gas shift (WGS) reaction is an industrially important source of pure hydrogen (H2) at the expense of carbon monoxide and water1,2. This reaction is of interest for fuel-cell applications, but requires WGS catalysts that are durable and highly active at low temperatures3. Here we demonstrate that the structure (Pt1–Ptn)/α-MoC, where isolated platinum atoms (Pt1) and subnanometre platinum clusters (Ptn) are stabilized on α-molybdenum carbide (α-MoC), catalyses the WGS reaction even at 313 kelvin, with a hydrogen-production pathway involving direct carbon monoxide dissociation identified. We find that it is critical to crowd the α-MoC surface with Pt1 and Ptn species, which prevents oxidation of the support that would cause catalyst deactivation, as seen with gold/α-MoC (ref. 4), and gives our system high stability and a high metal-normalized turnover number of 4,300,000 moles of hydrogen per mole of platinum. We anticipate that the strategy demonstrated here will be pivotal for the design of highly active and stable catalysts for effective activation of important molecules such as water and carbon monoxide for energy production. A stable, low-temperature water–gas shift catalyst is achieved by crowding platinum atoms and clusters on α-molybdenum carbide; the crowding protects the support from oxidation that would cause catalyst deactivation.
Columbia University1, University of Glasgow2, National Institutes of Health3, Sahlgrenska University Hospital4, Monterrey Institute of Technology and Higher Education5, University of Palermo6, University of Cambridge7, Université de Montréal8, University of Western Ontario9, Wageningen University and Research Centre10, University of Toronto11, Tufts University12, French Institute of Health and Medical Research13, Copenhagen University Hospital14, University of Copenhagen15, Pasteur Institute16, University of Helsinki17, Hacettepe University18, University of Milan19
TL;DR: In this paper, a conceptual framework for the generation of remnants due to dysregulation of TRL production, lipolysis, and remodelling, as well as clearance of remnant lipoproteins from the circulation, and challenges in defining, quantifying, and assessing the atherogenic properties of remnant particles.
Abstract: Recent advances in human genetics, together with a large body of epidemiologic, preclinical, and clinical trial results, provide strong support for a causal association between triglycerides (TG), TG-rich lipoproteins (TRL), and TRL remnants, and increased risk of myocardial infarction, ischaemic stroke, and aortic valve stenosis. These data also indicate that TRL and their remnants may contribute significantly to residual cardiovascular risk in patients on optimized low-density lipoprotein (LDL)-lowering therapy. This statement critically appraises current understanding of the structure, function, and metabolism of TRL, and their pathophysiological role in atherosclerotic cardiovascular disease (ASCVD). Key points are (i) a working definition of normo- and hypertriglyceridaemic states and their relation to risk of ASCVD, (ii) a conceptual framework for the generation of remnants due to dysregulation of TRL production, lipolysis, and remodelling, as well as clearance of remnant lipoproteins from the circulation, (iii) the pleiotropic proatherogenic actions of TRL and remnants at the arterial wall, (iv) challenges in defining, quantitating, and assessing the atherogenic properties of remnant particles, and (v) exploration of the relative atherogenicity of TRL and remnants compared to LDL. Assessment of these issues provides a foundation for evaluating approaches to effectively reduce levels of TRL and remnants by targeting either production, lipolysis, or hepatic clearance, or a combination of these mechanisms. This consensus statement updates current understanding in an integrated manner, thereby providing a platform for new therapeutic paradigms targeting TRL and their remnants, with the aim of reducing the risk of ASCVD.
Vanderbilt University1, University of Colorado Denver2, University of Iowa3, Texas A&M University4, Scott & White Hospital5, Harvard University6, Wake Forest University7, Johns Hopkins University8, Hennepin County Medical Center9, Yeshiva University10, University of Washington11, Tufts University12, University of Utah13, University of Michigan14, Oregon Health & Science University15, Emory University16, Cleveland Clinic17, Stanford University18, University of California, Los Angeles19, University of Miami20, Washington University in St. Louis21, Ohio State University22
TL;DR: In this article, Pfizer-BioNTech or Moderna mRNA COVID-19 vaccines were evaluated in 21 hospitals in 18 states and the duration of mRNA vaccine effectiveness against COVID19-associated hospitalizations was assessed among adults aged ≥18 years.
Abstract: Real-world evaluations have demonstrated high effectiveness of vaccines against COVID-19-associated hospitalizations (1-4) measured shortly after vaccination; longer follow-up is needed to assess durability of protection. In an evaluation at 21 hospitals in 18 states, the duration of mRNA vaccine (Pfizer-BioNTech or Moderna) effectiveness (VE) against COVID-19-associated hospitalizations was assessed among adults aged ≥18 years. Among 3,089 hospitalized adults (including 1,194 COVID-19 case-patients and 1,895 non-COVID-19 control-patients), the median age was 59 years, 48.7% were female, and 21.1% had an immunocompromising condition. Overall, 141 (11.8%) case-patients and 988 (52.1%) controls were fully vaccinated (defined as receipt of the second dose of Pfizer-BioNTech or Moderna mRNA COVID-19 vaccines ≥14 days before illness onset), with a median interval of 65 days (range = 14-166 days) after receipt of second dose. VE against COVID-19-associated hospitalization during the full surveillance period was 86% (95% confidence interval [CI] = 82%-88%) overall and 90% (95% CI = 87%-92%) among adults without immunocompromising conditions. VE against COVID-19- associated hospitalization was 86% (95% CI = 82%-90%) 2-12 weeks and 84% (95% CI = 77%-90%) 13-24 weeks from receipt of the second vaccine dose, with no significant change between these periods (p = 0.854). Whole genome sequencing of 454 case-patient specimens found that 242 (53.3%) belonged to the B.1.1.7 (Alpha) lineage and 74 (16.3%) to the B.1.617.2 (Delta) lineage. Effectiveness of mRNA vaccines against COVID-19-associated hospitalization was sustained over a 24-week period, including among groups at higher risk for severe COVID-19; ongoing monitoring is needed as new SARS-CoV-2 variants emerge. To reduce their risk for hospitalization, all eligible persons should be offered COVID-19 vaccination.
Virginia Commonwealth University1, The Feinstein Institute for Medical Research2, University of California, Los Angeles3, Harvard University4, University of California, San Francisco5, Oregon Health & Science University6, University of North Carolina at Chapel Hill7, Mayo Clinic8, Virginia Tech9, George Mason University10, New York University11, University of Massachusetts Medical School12, Boston University13, Northwestern University14, University of Hawaii15, Tufts University16
TL;DR: The United States Preventable cause of disease, disability, and death in the US is attributed to cigarette smoking, including second-hand smoke exposure and complications in the offspring (such as sudden infant death syndrome and impaired lung function in childhood).
Abstract: Importance Tobacco use is the leading preventable cause of disease, disability, and death in the US In 2014, it was estimated that 480 000 deaths annually are attributed to cigarette smoking, including second hand smoke exposure Smoking during pregnancy can increase the risk of numerous adverse pregnancy outcomes (eg, miscarriage and congenital anomalies) and complications in the offspring (including sudden infant death syndrome and impaired lung function in childhood) In 2019, an estimated 506 million US adults (208% of the adult population) used tobacco; 140% of the US adult population currently smoked cigarettes and 45% of the adult population used electronic cigarettes (e-cigarettes) Among pregnant US women who gave birth in 2016, 72% reported smoking cigarettes while pregnant Objective To update its 2015 recommendation, the USPSTF commissioned a review to evaluate the benefits and harms of primary care interventions on tobacco use cessation in adults, including pregnant persons Population This recommendation statement applies to adults 18 years or older, including pregnant persons Evidence assessment The USPSTF concludes with high certainty that the net benefit of behavioral interventions and US Food and Drug Associated (FDA)-approved pharmacotherapy for tobacco smoking cessation, alone or combined, in nonpregnant adults who smoke is substantial The USPSTF concludes with high certainty that the net benefit of behavioral interventions for tobacco smoking cessation on perinatal outcomes and smoking cessation in pregnant persons is substantial The USPSTF concludes that the evidence on pharmacotherapy interventions for tobacco smoking cessation in pregnant persons is insufficient because few studies are available, and the balance of benefits and harms cannot be determined The USPSTF concludes that the evidence on the use of e-cigarettes for tobacco smoking cessation in adults, including pregnant persons, is insufficient, and the balance of benefits and harms cannot be determined The USPSTF has identified the lack of well-designed, randomized clinical trials on e-cigarettes that report smoking abstinence or adverse events as a critical gap in the evidence Recommendations The USPSTF recommends that clinicians ask all adults about tobacco use, advise them to stop using tobacco, and provide behavioral interventions and FDA-approved pharmacotherapy for cessation to nonpregnant adults who use tobacco (A recommendation) The USPSTF recommends that clinicians ask all pregnant persons about tobacco use, advise them to stop using tobacco, and provide behavioral interventions for cessation to pregnant persons who use tobacco (A recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of pharmacotherapy interventions for tobacco cessation in pregnant persons (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of e-cigarettes for tobacco cessation in adults, including pregnant persons The USPSTF recommends that clinicians direct patients who use tobacco to other tobacco cessation interventions with proven effectiveness and established safety (I statement)
TL;DR: The updated taxonomy of Negarnaviricota is presented, as now accepted by the ICTV, after the phylum was amended and emended in March 2020.
Abstract: In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
TL;DR: PHQ-9 has been widely validated and is recommended in a two-stage screening process, and longitudinal studies are necessary to provide evidence of long-term screening effectiveness.
Centers for Disease Control and Prevention1, University of Iowa2, Tufts University3, Harvard University4, University of Miami5, Louisiana State University6, Thomas Jefferson University7, Truman Medical Center8, University of Chicago9, University of Massachusetts Medical School10, University of Mississippi11, University of Alabama at Birmingham12, University of California, San Francisco13, University of Washington14, Colorado Department of Public Health and Environment15, Yale University16, Emory University17, University of New Mexico18, University of Rochester19, Oregon Health Authority20, Vanderbilt University21, Duke University22, Johns Hopkins University23, Rush University Medical Center24, University of Utah25, United States Department of Veterans Affairs26, University of Wisconsin-Madison27, Alaska Native Tribal Health Consortium28
TL;DR: In this article, a test-negative case-control study is underway to evaluate mRNA COVID-19 vaccine effectiveness (VE) against symptomatic illness among health care personnel at 33 U.S. sites across 25 states, and the results indicated that the VE of a single dose (measured 14 days after the first dose through 6 days after a second dose) was 82% (95% confidence interval [CI] = 74%-87), adjusted for age, race/ethnicity, and underlying medical conditions.
Abstract: Throughout the COVID-19 pandemic, health care personnel (HCP) have been at high risk for exposure to SARS-CoV-2, the virus that causes COVID-19, through patient interactions and community exposure (1). The Advisory Committee on Immunization Practices recommended prioritization of HCP for COVID-19 vaccination to maintain provision of critical services and reduce spread of infection in health care settings (2). Early distribution of two mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) to HCP allowed assessment of the effectiveness of these vaccines in a real-world setting. A test-negative case-control study is underway to evaluate mRNA COVID-19 vaccine effectiveness (VE) against symptomatic illness among HCP at 33 U.S. sites across 25 U.S. states. Interim analyses indicated that the VE of a single dose (measured 14 days after the first dose through 6 days after the second dose) was 82% (95% confidence interval [CI] = 74%-87%), adjusted for age, race/ethnicity, and underlying medical conditions. The adjusted VE of 2 doses (measured ≥7 days after the second dose) was 94% (95% CI = 87%-97%). VE of partial (1-dose) and complete (2-dose) vaccination in this population is comparable to that reported from clinical trials and recent observational studies, supporting the effectiveness of mRNA COVID-19 vaccines against symptomatic disease in adults, with strong 2-dose protection.
TL;DR: In this paper, the authors characterize the risk factors for and outcomes following COVID-19 infection in this population and identify clinical characteristics associated with COVID19 and risk factors associated with mortality among patients following.
Duke University1, Kyoto University2, University of Tsukuba3, Liverpool John Moores University4, University of Oslo5, University of California, Los Angeles6, Ibn Tofail University7, Kwame Nkrumah University of Science and Technology8, Maastricht University9, University of Wisconsin-Madison10, University of Strasbourg11, Philips12, University of Lausanne13, Vanderbilt University14, Baylor College of Medicine15, RMIT University16, Tufts University17, Norwegian School of Sport Sciences18, University of California, Irvine19, Humboldt University of Berlin20, University of the West Indies21, University of Glasgow22, University of California, Santa Barbara23, University of Aberdeen24, Chinese Academy of Sciences25, Pennington Biomedical Research Center26, Northwestern University27, University of Cape Town28, Imperial College London29, University of Agder30, Burton Snowboards31, Fred Hutchinson Cancer Research Center32, Moi University33, Helsinki University Central Hospital34, University of Brighton35, University of Edinburgh36, Washington University in St. Louis37, University of Southern California38, Tilburg University39, University of Copenhagen40, Stanford University41, Baylor University42, UCL Institute of Child Health43, Max Planck Society44, International Atomic Energy Agency45, Loyola University Chicago46, Maastricht University Medical Centre47
TL;DR: In this article, the authors analyzed a large, diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 years and found that fat-free mass-adjusted expenditure accelerates rapidly in neonates to ~50% above adult values at ~1 year; declines slowly to adult levels by ~20 years; remains stable in adulthood (20 to 60 years), even during pregnancy; then declines in older adults.
Abstract: Total daily energy expenditure ("total expenditure") reflects daily energy needs and is a critical variable in human health and physiology, but its trajectory over the life course is poorly studied. We analyzed a large, diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 years. Total expenditure increased with fat-free mass in a power-law manner, with four distinct life stages. Fat-free mass-adjusted expenditure accelerates rapidly in neonates to ~50% above adult values at ~1 year; declines slowly to adult levels by ~20 years; remains stable in adulthood (20 to 60 years), even during pregnancy; then declines in older adults. These changes shed light on human development and aging and should help shape nutrition and health strategies across the life span.
TL;DR: In this paper, the theory-led discovery of a rhodium-copper (RhCu) single-atom-alloy catalyst for propane dehydrogenation to propene was reported.
Abstract: The complexity of heterogeneous catalysts means that a priori design of new catalytic materials is difficult, but the well-defined nature of single-atom–alloy catalysts has made it feasible to perform unambiguous theoretical modeling and precise surface science experiments. Herein we report the theory-led discovery of a rhodium-copper (RhCu) single-atom–alloy catalyst for propane dehydrogenation to propene. Although Rh is not generally considered for alkane dehydrogenation, first-principles calculations revealed that Rh atoms disperse in Cu and exhibit low carbon-hydrogen bond activation barriers. Surface science experiments confirmed these predictions, and together these results informed the design of a highly active, selective, and coke-resistant RhCu nanoparticle catalyst that enables low-temperature nonoxidative propane dehydrogenation.
The Feinstein Institute for Medical Research1, Harvard University2, University of California, Los Angeles3, Albert Einstein College of Medicine4, Oregon Health & Science University5, University of Pittsburgh6, University of North Carolina at Chapel Hill7, Mayo Clinic8, Virginia Commonwealth University9, George Mason University10, University of Virginia11, New York University12, Stanford University13, University of Massachusetts Medical School14, Boston University15, University of Missouri16, University of Hawaii17, Tufts University18
TL;DR: In this article, the authors present a systematic review to evaluate screening for prediabetes and type 2 diabetes in asymptomatic, non-pregnant adults and preventive interventions for those with pre-diabetes.
Abstract: Importance An estimated 13% of all US adults (18 years or older) have diabetes, and 34.5% meet criteria for prediabetes. The prevalences of prediabetes and diabetes are higher in older adults. Estimates of the risk of progression from prediabetes to diabetes vary widely, perhaps because of differences in the definition of prediabetes or the heterogeneity of prediabetes. Diabetes is the leading cause of kidney failure and new cases of blindness among adults in the US. It is also associated with increased risks of cardiovascular disease, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis and was estimated to be the seventh leading cause of death in the US in 2017. Screening asymptomatic adults for prediabetes and type 2 diabetes may allow earlier detection, diagnosis, and treatment, with the ultimate goal of improving health outcomes. Objective To update its 2015 recommendation, the USPSTF commissioned a systematic review to evaluate screening for prediabetes and type 2 diabetes in asymptomatic, nonpregnant adults and preventive interventions for those with prediabetes. Population Nonpregnant adults aged 35 to 70 years seen in primary care settings who have overweight or obesity (defined as a body mass index ≥25 and ≥30, respectively) and no symptoms of diabetes. Evidence Assessment The USPSTF concludes with moderate certainty that screening for prediabetes and type 2 diabetes and offering or referring patients with prediabetes to effective preventive interventions has a moderate net benefit. Conclusions and Recommendation The USPSTF recommends screening for prediabetes and type 2 diabetes in adults aged 35 to 70 years who have overweight or obesity. Clinicians should offer or refer patients with prediabetes to effective preventive interventions. (B recommendation)
TL;DR: Environmental surveillance of SARS-CoV-2 RNA on high-touch surfaces may be a useful tool to provide early warning of COVID-19 case trends.
Abstract: Environmental surveillance of surface contamination is an unexplored tool for understanding transmission of SARS-CoV-2 in community settings. We conducted longitudinal swab sampling of high-touch non-porous surfaces in a Massachusetts town during a COVID-19 outbreak from April to June 2020. Twenty-nine of 348 (8.3%) surface samples were positive for SARS-CoV-2 RNA, including crosswalk buttons, trash can handles, and door handles of essential business entrances (grocery store, liquor store, bank, and gas station). The estimated risk of infection from touching a contaminated surface was low (less than 5 in 10,000) by quantitative microbial risk assessment, suggesting fomites play a minimal role in SARS-CoV-2 community transmission. The weekly percentage of positive samples (out of n = 33 unique surfaces per week) best predicted variation in city-level COVID-19 cases with a 7-day lead time. Environmental surveillance of SARS-CoV-2 RNA on high-touch surfaces may be a useful tool to provide early warning of COVID-19 case trends.
University of Oxford1, University of Strasbourg2, University of California, Berkeley3, Institute for Social Security and Services for State Workers4, Tufts University5, Tanta University6, University of Calabar7, University of Washington8, University College London9, University of Turin10, St George’s University Hospitals NHS Foundation Trust11, University of Brescia12, University of Milan13, Federal University of Maranhão14, Holy Family Hospital15, Aga Khan University16, Abubakar Tafawa Balewa University17, Gombe State university18, Universidade Federal de Minas Gerais19, University of Geneva20, Bayero University Kano21, University of Bordeaux22, Jikei University School of Medicine23, Keio University24, Translational Health Science and Technology Institute25, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico26, Memorial Hospital of South Bend27, Airlangga University28, University of Buenos Aires29, Universidad de Morón30, University of Illinois at Urbana–Champaign31, Harvard University32, University of Paris33, Vita-Salute San Raffaele University34, University of Nottingham35, University of Toronto36
TL;DR: In this article, the effect of COVID-19 during pregnancy on mothers and neonates was quantified with the risk factors known to be associated with preeclampsia analyzed in each group.
University of Nottingham1, Suffolk University2, University of Dundee3, Medway School of Pharmacy4, University of Innsbruck5, University of Bristol6, University of Edinburgh7, Stanford University8, Tel Aviv University9, Northeastern University10, Ludwig Maximilian University of Munich11, Aston University12, University of Washington13, University of Birmingham14, Tufts University15, University of California, San Francisco16, University of Ferrara17, Nanyang Technological University18, University of California, Irvine19, University of Ulm20, Ariel University21, University of Illinois at Chicago22, University of Copenhagen23, Yale University24, University of Lausanne25, University of Strathclyde26, University College London27, University of Queensland28, University of Virginia29, University of Pennsylvania30, University of Oxford31, University of British Columbia32, University of Texas Health Science Center at Houston33, University of California, Davis34, Catholic University of Leuven35, University of Michigan36, University of Connecticut37
TL;DR: The Concise Guide to PHARMACOLOGY 2021/22 as mentioned in this paper provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands.
Abstract: The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15539. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
TL;DR: In this article, the ATLAS particle-flow reconstruction method is used to reconstruct the topo-clusters of the proton-proton collision data with a center-of-mass energy of 13$ TeV collected by the LHC.
Abstract: Jet energy scale and resolution measurements with their associated uncertainties are reported for jets using 36-81 fb$^{-1}$ of proton-proton collision data with a centre-of-mass energy of $\sqrt{s}=13$ TeV collected by the ATLAS detector at the LHC. Jets are reconstructed using two different input types: topo-clusters formed from energy deposits in calorimeter cells, as well as an algorithmic combination of charged-particle tracks with those topo-clusters, referred to as the ATLAS particle-flow reconstruction method. The anti-$k_t$ jet algorithm with radius parameter $R=0.4$ is the primary jet definition used for both jet types. Jets are initially calibrated using a sequence of simulation-based corrections. Next, several $\textit{in situ}$ techniques are employed to correct for differences between data and simulation and to measure the resolution of jets. The systematic uncertainties in the jet energy scale for central jets ($|\eta| 2.5$ TeV). The relative jet energy resolution is measured and ranges from ($24 \pm 1.5$)% at 20 GeV to ($6 \pm 0.5$)% at 300 GeV.
TL;DR: In this article, the authors show that phytohormone-induced stress responses include cell wall and cuticle thickening, root and leaf morphology alteration, and anatomical changes of roots, stems and leaves, which in turn minimize the oxidative stress, water loss, and other adverse effects of drought.
Abstract: Drought stress negatively affects crop performance and weakens global food security. It triggers the activation of downstream pathways, mainly through phytohormones homeostasis and their signaling networks, which further initiate the biosynthesis of secondary metabolites (SMs). Roots sense drought stress, the signal travels to the above-ground tissues to induce systemic phytohormones signaling. The systemic signals further trigger the biosynthesis of SMs and stomatal closure to prevent water loss. SMs primarily scavenge reactive oxygen species (ROS) to protect plants from lipid peroxidation and also perform additional defense-related functions. Moreover, drought-induced volatile SMs can alert the plant tissues to perform drought stress mitigating functions in plants. Other phytohormone-induced stress responses include cell wall and cuticle thickening, root and leaf morphology alteration, and anatomical changes of roots, stems, and leaves, which in turn minimize the oxidative stress, water loss, and other adverse effects of drought. Exogenous applications of phytohormones and genetic engineering of phytohormones signaling and biosynthesis pathways mitigate the drought stress effects. Direct modulation of the SMs biosynthetic pathway genes or indirect via phytohormones' regulation provides drought tolerance. Thus, phytohormones and SMs play key roles in plant development under the drought stress environment in crop plants.
University of Toronto1, National Health and Medical Research Council2, Medicines and Healthcare Products Regulatory Agency3, Johns Hopkins University4, King's College London5, University of Paris6, University of Western Ontario7, University of Sydney8, Technical University of Berlin9, University of Nottingham10, National Institute for Health Research11, University of Ottawa12, Food and Drug Administration13, Tufts University14, University of Oxford15, Sichuan University16, FHI 36017, University of North Carolina at Chapel Hill18, Yale University19, American Medical Association20, Canadian Institutes of Health Research21, University of Texas at San Antonio22, South African Medical Research Council23, Lawrence Berkeley National Laboratory24, National Institutes of Health25, Makerere University26, University of Southern Denmark27
TL;DR: The CONSERVE (ConSORT and SpiritIT Extension for RCTs Revised in Extenuating Circumstances) guideline as mentioned in this paper aims to improve reporting of trial protocols and completed trials that undergo important modifications in response to extenuating circumstances.
Abstract: Importance Extenuating circumstances can trigger unplanned changes to randomized trials and introduce methodological, ethical, feasibility, and analytical challenges that can potentially compromise the validity of findings. Numerous randomized trials have required changes in response to the COVID-19 pandemic, but guidance for reporting such modifications is incomplete. Objective As a joint extension for the CONSORT and SPIRIT reporting guidelines, CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstances) aims to improve reporting of trial protocols and completed trials that undergo important modifications in response to extenuating circumstances. Evidence A panel of 37 international trial investigators, patient representatives, methodologists and statisticians, ethicists, funders, regulators, and journal editors convened to develop the guideline. The panel developed CONSERVE following an accelerated, iterative process between June 2020 and February 2021 involving (1) a rapid literature review of multiple databases (OVID Medline, OVID EMBASE, and EBSCO CINAHL) and gray literature sources from 2003 to March 2021; (2) consensus-based panelist meetings using a modified Delphi process and surveys; and (3) a global survey of trial stakeholders. Findings The rapid review yielded 41 673 citations, of which 38 titles were relevant, including emerging guidance from regulatory and funding agencies for managing the effects of the COVID-19 pandemic on trials. However, no generalizable guidance for all circumstances in which trials and trial protocols might face unanticipated modifications were identified. The CONSERVE panel used these findings to develop a consensus reporting guidelines following 4 rounds of meetings and surveys. Responses were received from 198 professionals from 34 countries, of whom 90% (n = 178) indicated that they understood the concept definitions and 85.4% (n = 169) indicated that they understood and could use the implementation tool. Feedback from survey respondents was used to finalize the guideline and confirm that the guideline’s core concepts were applicable and had utility for the trial community. CONSERVE incorporates an implementation tool and checklists tailored to trial reports and trial protocols for which extenuating circumstances have resulted in important modifications to the intended study procedures. The checklists include 4 sections capturing extenuating circumstances, important modifications, responsible parties, and interim data analyses. Conclusions and Relevance CONSERVE offers an extension to CONSORT and SPIRIT that could improve the transparency, quality, and completeness of reporting important modifications to trials in extenuating circumstances such as COVID-19.
Lea Berrang-Ford1, A. R. Siders2, Alexandra Lesnikowski3, Alexandra Paige Fischer4 +147 more•Institutions (87)
TL;DR: In this article, the authors present a systematic and comprehensive global stocktake of implemented human adaptation to climate change and identify eight priorities for global adaptation research: assess the effectiveness of adaptation responses, enhance the understanding of limits to adaptation, enable individuals and civil society to adapt, include missing places, scholars and scholarship, understand private sector responses, improve methods for synthesizing different forms of evidence, assess the adaptation at different temperature thresholds, and improve the inclusion of timescale and the dynamics of responses.
Abstract: Assessing global progress on human adaptation to climate change is an urgent priority. Although the literature on adaptation to climate change is rapidly expanding, little is known about the actual extent of implementation. We systematically screened >48,000 articles using machine learning methods and a global network of 126 researchers. Our synthesis of the resulting 1,682 articles presents a systematic and comprehensive global stocktake of implemented human adaptation to climate change. Documented adaptations were largely fragmented, local and incremental, with limited evidence of transformational adaptation and negligible evidence of risk reduction outcomes. We identify eight priorities for global adaptation research: assess the effectiveness of adaptation responses, enhance the understanding of limits to adaptation, enable individuals and civil society to adapt, include missing places, scholars and scholarship, understand private sector responses, improve methods for synthesizing different forms of evidence, assess the adaptation at different temperature thresholds, and improve the inclusion of timescale and the dynamics of responses. Determining progress in adaptation to climate change is challenging, yet critical as climate change impacts increase. A stocktake of the scientific literature on implemented adaptation now shows that adaptation is mostly fragmented and incremental, with evidence lacking for its impact on reducing risk.