Showing papers by "University of Michigan published in 2021"
TL;DR: This study in a nationwide mass vaccination setting suggests that the BNT162b2 mRNA vaccine is effective for a wide range of Covid-19–related outcomes, a finding consistent with that of the randomized trial.
Abstract: Background As mass vaccination campaigns against coronavirus disease 2019 (Covid-19) commence worldwide, vaccine effectiveness needs to be assessed for a range of outcomes across diverse p...
1,660 citations
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
Harvard University1, State University of New York System2, French Institute of Health and Medical Research3, University of Toronto4, University of Texas Southwestern Medical Center5, Vanderbilt University6, Oregon Health & Science University7, University of Brescia8, Karolinska Institutet9, University of Paris10, Yale University11, Georgetown University12, Wrocław Medical University13, Duke University14, Lexicon Pharmaceuticals15, University of Michigan16
TL;DR: In patients with diabetes and recent worsening heart failure, sotagliflozin therapy, initiated before or shortly after discharge, resulted in a significantly lower total number of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure than placebo.
Abstract: Background Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure or death from cardiovascular causes among patients with stable heart failu...
913 citations
University of Washington1, St George’s University Hospitals NHS Foundation Trust2, McMaster University3, Agostino Gemelli University Polyclinic4, Emory University5, Federal University of São Paulo6, Ottawa Hospital7, St Thomas' Hospital8, University of Michigan9, Cooper University Hospital10, University of Kansas11, University of Amsterdam12, United Arab Emirates University13, University of Pittsburgh14, King Saud bin Abdulaziz University for Health Sciences15, University of São Paulo16, University of Minnesota17, Population Health Research Institute18, University of Toronto19, Humanitas University20, University of Kentucky21, Ghent University Hospital22, University of Tokyo23, Peking Union Medical College Hospital24, Hebron University25, Monash University26, Copenhagen University Hospital27, Liverpool School of Tropical Medicine28, Vanderbilt University29, Brigham and Women's Hospital30, Harvard University31, University of Ulsan32, University of Manitoba33, Makerere University34, Faculdade de Medicina de São José do Rio Preto35, Mount Sinai Hospital, Toronto36, Medanta37, University of the Witwatersrand38, New York University39, Washington University in St. Louis40, University of Alberta41, Hennepin County Medical Center42, University of Pennsylvania43, Hebrew University of Jerusalem44, Hadassah Medical Center45, Hochschule Hannover46, Brown University47
TL;DR: The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications as discussed by the authors, which are either strong or weak, or in the form of best practice statements.
Abstract: Background
Sepsis poses a global threat to millions of lives. The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications.
Methods
We formed a panel of 60 experts from 22 countries and 11 members of the public. The panel prioritized questions that are relevant to the recognition and management of sepsis and septic shock in adults. New questions and sections were addressed, relative to the previous guidelines. These questions were grouped under 6 subgroups (screening and early treatment, infection, hemodynamics, ventilation, additional therapies, and long-term outcomes and goals of care). With input from the panel and methodologists, professional medical librarians performed the search strategy tailored to either specific questions or a group of relevant questions. A dedicated systematic review team performed screening and data abstraction when indicated. For each question, the methodologists, with input from panel members, summarized the evidence assessed and graded the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The panel generated recommendations using the evidence-to-decision framework. Recommendations were either strong or weak, or in the form of best practice statements. When evidence was insufficient to support a recommendation, the panel was surveyed to generate “in our practice” statements.
Results
The SSC panel issued 93 statements: 15 best practice statements, 15 strong recommendations, and 54 weak recommendations and no recommendation was provided for 9 questions. The recommendations address several important clinical areas related to screening tools, acute resuscitation strategies, management of fluids and vasoactive agents, antimicrobials and diagnostic tests and the use of additional therapies, ventilation management, goals of care, and post sepsis care.
Conclusion
The SSC panel issued evidence-based recommendations to help support key stakeholders caring for adults with sepsis or septic shock and their families.
893 citations
Daniel Taliun1, Daniel N. Harris2, Michael D. Kessler2, Jedidiah Carlson1 +202 more•Institutions (61)
TL;DR: The Trans-Omics for Precision Medicine (TOPMed) project as discussed by the authors aims to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases.
Abstract: The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes)1 In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals) These rare variants provide insights into mutational processes and recent human evolutionary history The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 001% The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history
801 citations
University of Washington1, St George’s University Hospitals NHS Foundation Trust2, McMaster University3, Agostino Gemelli University Polyclinic4, Emory University5, Federal University of São Paulo6, Ottawa Hospital7, St Thomas' Hospital8, University of Michigan9, Cooper University Hospital10, University of Kansas11, University of Amsterdam12, United Arab Emirates University13, University of Pittsburgh14, King Saud bin Abdulaziz University for Health Sciences15, University of São Paulo16, University of Minnesota17, Population Health Research Institute18, University of Toronto19, Humanitas University20, University of Kentucky21, Ghent University Hospital22, University of Tokyo23, Peking Union Medical College Hospital24, Hebron University25, Monash University26, Copenhagen University Hospital27, Liverpool School of Tropical Medicine28, Vanderbilt University29, Brigham and Women's Hospital30, University of Ulsan31, University of Manitoba32, Makerere University33, Faculdade de Medicina de São José do Rio Preto34, National Institutes of Health35, Mount Sinai Hospital, Toronto36, Medanta37, University of the Witwatersrand38, New York University39, Washington University in St. Louis40, University of Alberta41, Hennepin County Medical Center42, Royal Brisbane and Women's Hospital43, University of Pennsylvania44, Hebrew University of Jerusalem45, Hochschule Hannover46, Brown University47
TL;DR: The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications as mentioned in this paper, which are either strong or weak, or in the form of best practice statements.
Abstract: Background
Sepsis poses a global threat to millions of lives. The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications.
Methods
We formed a panel of 60 experts from 22 countries and 11 members of the public. The panel prioritized questions that are relevant to the recognition and management of sepsis and septic shock in adults. New questions and sections were addressed, relative to the previous guidelines. These questions were grouped under 6 subgroups (screening and early treatment, infection, hemodynamics, ventilation, additional therapies, and long-term outcomes and goals of care). With input from the panel and methodologists, professional medical librarians performed the search strategy tailored to either specific questions or a group of relevant questions. A dedicated systematic review team performed screening and data abstraction when indicated. For each question, the methodologists, with input from panel members, summarized the evidence assessed and graded the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The panel generated recommendations using the evidence-to-decision framework. Recommendations were either strong or weak, or in the form of best practice statements. When evidence was insufficient to support a recommendation, the panel was surveyed to generate “in our practice” statements.
Results
The SSC panel issued 93 statements: 15 best practice statements, 15 strong recommendations, and 54 weak recommendations and no recommendation was provided for 9 questions. The recommendations address several important clinical areas related to screening tools, acute resuscitation strategies, management of fluids and vasoactive agents, antimicrobials and diagnostic tests and the use of additional therapies, ventilation management, goals of care, and post sepsis care.
Conclusion
The SSC panel issued evidence-based recommendations to help support key stakeholders caring for adults with sepsis or septic shock and their families.
664 citations
TL;DR: This paper presents a comprehensive review of the general architecture and principals of 1D CNNs along with their major engineering applications, especially focused on the recent progress in this field.
659 citations
Cornell University1, National University of Singapore2, University of New South Wales3, University of Lausanne4, University of Michigan5, Erasmus University Rotterdam6, Tel Aviv University7, University of Melbourne8, Singapore Management University9, University of Maryland, College Park10, University of Pennsylvania11, Eindhoven University of Technology12, Stanford University13, Concordia University14, London Business School15, Baylor University16, University College London17, California State University, Sacramento18, INSEAD19, Saint Louis University20, Nanyang Technological University21, University of Minnesota22, Harvard University23, University of Arkansas24, VU University Amsterdam25
TL;DR: A broad-scope overview provides an integrative approach for considering the implications of COVID-19 for work, workers, and organizations while also identifying issues for future research and insights to inform solutions.
Abstract: The impacts of COVID-19 on workers and workplaces across the globe have been dramatic. This broad review of prior research rooted in work and organizational psychology, and related fields, is intended to make sense of the implications for employees, teams, and work organizations. This review and preview of relevant literatures focuses on (a) emergent changes in work practices (e.g., working from home, virtual teamwork) and (b) emergent changes for workers (e.g., social distancing, stress, and unemployment). In addition, potential moderating factors (demographic characteristics, individual differences, and organizational norms) are examined given the likelihood that COVID-19 will generate disparate effects. This broad-scope overview provides an integrative approach for considering the implications of COVID-19 for work, workers, and organizations while also identifying issues for future research and insights to inform solutions. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
654 citations
Northwestern University1, University of California, San Francisco2, University of Michigan3, City of Hope National Medical Center4, Vanderbilt University5, Seattle Cancer Care Alliance6, Fox Chase Cancer Center7, University of Wisconsin-Madison8, University of Texas Southwestern Medical Center9, University of Utah10, University of Nebraska Medical Center11, University of Alabama at Birmingham12, University of California, Los Angeles13, University of South Florida14, Mayo Clinic15, Washington University in St. Louis16, Yale Cancer Center17, Stanford University18, Case Western Reserve University19, University of Colorado Boulder20, Brigham and Women's Hospital21, Ohio State University22, Roswell Park Cancer Institute23, University of Texas MD Anderson Cancer Center24, Harvard University25, University of California, San Diego26, Memorial Sloan Kettering Cancer Center27, University of Pennsylvania28, University of Tennessee29, Johns Hopkins University30, Duke University31, National Comprehensive Cancer Network32
TL;DR: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section as discussed by the authors.
Abstract: This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section. These updates include recommendations for first-line use of checkpoint inhibitors for mCRC, that is deficient mismatch repair/microsatellite instability-high, recommendations related to the use of biosimilars, and expanded recommendations for biomarker testing. The systemic therapy recommendations now include targeted therapy options for patients with mCRC that is HER2-amplified, or BRAF V600E mutation-positive. Treatment and management of nonmetastatic or resectable/ablatable metastatic disease are discussed in the complete version of the NCCN Guidelines for Colon Cancer available at NCCN.org. Additional topics covered in the complete version include risk assessment, staging, pathology, posttreatment surveillance, and survivorship.
589 citations
Harvard University1, State University of New York System2, University of Michigan3, University of Toronto4, University of Texas at Dallas5, Vanderbilt University6, Oregon Health & Science University7, Yale University8, University of Missouri–Kansas City9, Imperial College London10, Duke University11, University of Paris12
TL;DR: In patients with diabetes and chronic kidney disease, with or without albuminuria, sotagliflozin resulted in a lower risk of the composite of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart Failure than placebo but was associated with adverse events.
Abstract: Background The efficacy and safety of sodium–glucose cotransporter 2 inhibitors such as sotagliflozin in preventing cardiovascular events in patients with diabetes with chronic kidney dise...
541 citations
Innovations for Poverty Action1, Wageningen University and Research Centre2, National Research University – Higher School of Economics3, Columbia University4, 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.
European Bioinformatics Institute1, Newcastle upon Tyne Hospitals NHS Foundation Trust2, Newcastle University3, Oregon Health & Science University4, University of Genoa5, Istituto Giannina Gaslini6, University of Western Australia7, King Edward Memorial Hospital8, American College of Medical Genetics9, Anschutz Medical Campus10, Johns Hopkins University11, Ludwig Maximilian University of Munich12, Children's Hospital of Philadelphia13, Austrian Academy of Sciences14, University of Connecticut15, French Institute of Health and Medical Research16, Lawrence Berkeley National Laboratory17, University of Michigan18, University of Freiburg19, University of Luxembourg20, Oregon State University21, Chestnut Hill College22, Medical University of Graz23, Queen Mary University of London24, Hebrew University of Jerusalem25, University of Pennsylvania26
TL;DR: Recent major extensions of the Human Phenotype Ontology for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas are presented and new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease are presented.
Abstract: The Human Phenotype Ontology (HPO, https://hpo.jax.org) was launched in 2008 to provide a comprehensive logical standard to describe and computationally analyze phenotypic abnormalities found in human disease. The HPO is now a worldwide standard for phenotype exchange. The HPO has grown steadily since its inception due to considerable contributions from clinical experts and researchers from a diverse range of disciplines. Here, we present recent major extensions of the HPO for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas. For example, the seizure subontology now reflects the International League Against Epilepsy (ILAE) guidelines and these enhancements have already shown clinical validity. We present new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease. These efforts will benefit software such as Exomiser by improving the accuracy and scope of cross-species phenotype matching. The computational modeling strategy used by the HPO to define disease entities and phenotypic features and distinguish between them is explained in detail.We also report on recent efforts to translate the HPO into indigenous languages. Finally, we summarize recent advances in the use of HPO in electronic health record systems.
Johns Hopkins University1, Mayo Clinic2, Seattle Cancer Care Alliance3, University of Colorado Boulder4, University of Utah5, Fox Chase Cancer Center6, Northwestern University7, Case Western Reserve University8, University of Texas MD Anderson Cancer Center9, Brigham and Women's Hospital10, Duke University11, University of South Florida12, University of Texas Southwestern Medical Center13, Yale Cancer Center14, University of California, San Francisco15, Roswell Park Cancer Institute16, Harvard University17, University of Wisconsin-Madison18, University of Michigan19, Stanford University20, Vanderbilt University21, City of Hope National Medical Center22, Washington University in St. Louis23, University of Tennessee Health Science Center24, Ohio State University25, University of California, San Diego26, Memorial Sloan Kettering Cancer Center27, University of Pennsylvania28, University of California, Los Angeles29, National Comprehensive Cancer Network30
TL;DR: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC as mentioned in this paper.
Abstract: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.
TL;DR: The recent rapid progress in understanding the molecular mechanisms of ferroptosis is reviewed and the epigenetic, transcriptional, and posttranslational regulation of this process is focused on.
Abstract: Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death caused by lipid peroxidation, which is controlled by integrated oxidation and antioxidant systems. The iron-containing e...
TL;DR: In this article, the population of 47 compact binary mergers detected with a false-alarm rate of 0.614 were dynamically assembled, and the authors found that the BBH rate likely increases with redshift, but not faster than the star formation rate.
Abstract: We report on the population of 47 compact binary mergers detected with a false-alarm rate of 0.01 are dynamically assembled. Third, we estimate merger rates, finding RBBH = 23.9-+8.614.3 Gpc-3 yr-1 for BBHs and RBNS = 320-+240490 Gpc-3 yr-1 for binary neutron stars. We find that the BBH rate likely increases with redshift (85% credibility) but not faster than the star formation rate (86% credibility). Additionally, we examine recent exceptional events in the context of our population models, finding that the asymmetric masses of GW190412 and the high component masses of GW190521 are consistent with our models, but the low secondary mass of GW190814 makes it an outlier.
Fox Chase Cancer Center1, Vanderbilt University2, University of Tennessee Health Science Center3, University of Utah4, Washington University in St. Louis5, University of Pennsylvania6, University of Alabama at Birmingham7, Johns Hopkins University8, Roswell Park Cancer Institute9, University of California, Los Angeles10, Northwestern University11, University of Colorado Boulder12, Stanford University13, University of South Florida14, University of Texas MD Anderson Cancer Center15, University of California, San Francisco16, Duke University17, University of Michigan18, Seattle Cancer Care Alliance19, Memorial Sloan Kettering Cancer Center20, Case Western Reserve University21, University of Nebraska Medical Center22, Ohio State University23, Harvard University24, University of California, San Diego25, City of Hope National Medical Center26, Mayo Clinic27, University of Wisconsin-Madison28, Brigham and Women's Hospital29, National Comprehensive Cancer Network30
TL;DR: The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic or likely pathogenic variants associated with increased risk of breast, ovarian, and pancreatic cancer and recommended approaches to genetic testing/counseling and management strategies as mentioned in this paper.
Abstract: The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic or likely pathogenic variants associated with increased risk of breast, ovarian, and pancreatic cancer and recommended approaches to genetic testing/counseling and management strategies in individuals with these pathogenic or likely pathogenic variants. This manuscript focuses on cancer risk and risk management for BRCA-related breast/ovarian cancer syndrome and Li-Fraumeni syndrome. Carriers of a BRCA1/2 pathogenic or likely pathogenic variant have an excessive risk for both breast and ovarian cancer that warrants consideration of more intensive screening and preventive strategies. There is also evidence that risks of prostate cancer and pancreatic cancer are elevated in these carriers. Li-Fraumeni syndrome is a highly penetrant cancer syndrome associated with a high lifetime risk for cancer, including soft tissue sarcomas, osteosarcomas, premenopausal breast cancer, colon cancer, gastric cancer, adrenocortical carcinoma, and brain tumors.
TL;DR: This paper aims to fulfill the gap by presenting the highlights of the traditional methods and provide a comprehensive review of the most recent applications of ML and DL algorithms utilized for vibration-based structural damage detection in civil structures.
Manchester Metropolitan University1, National Oceanic and Atmospheric Administration2, University of Oxford3, German Aerospace Center4, Peking University5, Cooperative Institute for Research in Environmental Sciences6, University of Leeds7, National Center for Atmospheric Research8, Committee on Climate Change9, University of Michigan10, University of California, Irvine11, University of Reading12
TL;DR: CO2-warming-equivalent emissions based on global warming potentials (GWP* method) indicate that aviation emissions are currently warming the climate at approximately three times the rate of that associated with aviation CO2 emissions alone.
University of London1, National Institute for Health Research2, University of Auckland3, University of Cambridge4, Anglia Ruskin University5, Queen's University Belfast6, Sun Yat-sen University7, The Fred Hollows Foundation8, Mbarara University of Science and Technology9, Ministry of Health and Family Welfare10, University of Geneva11, St Thomas' Hospital12, Leeds Teaching Hospitals NHS Trust13, Southwest University of Visual Arts14, Orbis International15, International Agency for the Prevention of Blindness16, University of Cape Town17, University Hospitals Birmingham NHS Foundation Trust18, University of Michigan19, Emory University20, Johns Hopkins University21, Massachusetts Eye and Ear Infirmary22, University of São Paulo23, University of Nairobi24, Seva Foundation25, Tilganga Institute of Ophthalmology26, Heidelberg University27, University of New South Wales28, The George Institute for Global Health29, L V Prasad Eye Institute30, College of Health Sciences, Bahrain31, Muhimbili University of Health and Allied Sciences32, International Institute of Minnesota33, University of the West Indies34, University of Melbourne35, Kenya Medical Training College36, Federal University of São Paulo37, Capital Medical University38, Singapore National Eye Center39, National University of Singapore40, Pan American Health Organization41, Brien Holden Vision Institute42, University of Calabar43
TL;DR: In this paper, the authors defined eye health as maximised vision, ocular health, and functional ability, thereby contributing to overall health and wellbeing, social inclusion, and quality of life.
Google1, University of Michigan2, University of Massachusetts Amherst3, University of California, Santa Barbara4, University of California, Riverside5, Volkswagen6, University of California, Berkeley7, Ames Research Center8, Leiden University9, University of Erlangen-Nuremberg10, Harvard University11
TL;DR: The application of the Google Sycamore superconducting qubit quantum processor to combinatorial optimization problems with the quantum approximate optimization algorithm (QAOA) is demonstrated and an approximation ratio is obtained that is independent of problem size and for the first time, that performance increases with circuit depth.
Abstract: Faster algorithms for combinatorial optimization could prove transformative for diverse areas such as logistics, finance and machine learning. Accordingly, the possibility of quantum enhanced optimization has driven much interest in quantum technologies. Here we demonstrate the application of the Google Sycamore superconducting qubit quantum processor to combinatorial optimization problems with the quantum approximate optimization algorithm (QAOA). Like past QAOA experiments, we study performance for problems defined on the planar connectivity graph native to our hardware; however, we also apply the QAOA to the Sherrington–Kirkpatrick model and MaxCut, non-native problems that require extensive compilation to implement. For hardware-native problems, which are classically efficient to solve on average, we obtain an approximation ratio that is independent of problem size and observe that performance increases with circuit depth. For problems requiring compilation, performance decreases with problem size. Circuits involving several thousand gates still present an advantage over random guessing but not over some efficient classical algorithms. Our results suggest that it will be challenging to scale near-term implementations of the QAOA for problems on non-native graphs. As these graphs are closer to real-world instances, we suggest more emphasis should be placed on such problems when using the QAOA to benchmark quantum processors. It is hoped that quantum computers may be faster than classical ones at solving optimization problems. Here the authors implement a quantum optimization algorithm over 23 qubits but find more limited performance when an optimization problem structure does not match the underlying hardware.
University of California, San Francisco1, University of South Florida2, University of Michigan3, University of Tennessee Health Science Center4, Northwestern University5, Vanderbilt University6, Seattle Cancer Care Alliance7, City of Hope National Medical Center8, Duke University9, University of Colorado Boulder10, Ohio State University11, University of California, Los Angeles12, Fox Chase Cancer Center13, Harvard University14, Roswell Park Cancer Institute15, Case Western Reserve University16, Washington University in St. Louis17, University of Nebraska Medical Center18, Yale Cancer Center19, University of Wisconsin-Madison20, University of California, San Diego21, Pancreatic Cancer Action Network22, Johns Hopkins University23, University of Texas Southwestern Medical Center24, University of Alabama at Birmingham25, Memorial Sloan Kettering Cancer Center26, University of Utah27, Stanford University28, University of Pennsylvania29, University of Texas MD Anderson Cancer Center30, Brigham and Women's Hospital31, National Comprehensive Cancer Network32
Abstract: Pancreatic cancer is the fourth leading cause of cancer-related death among men and women in the United States. A major challenge in treatment remains patients' advanced disease at diagnosis. The NCCN Guidelines for Pancreatic Adenocarcinoma provides recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pancreatic cancer. Although survival rates remain relatively unchanged, newer modalities of treatment, including targeted therapies, provide hope for improving patient outcomes. Sections of the manuscript have been updated to be concordant with the most recent update to the guidelines. This manuscript focuses on the available systemic therapy approaches, specifically the treatment options for locally advanced and metastatic disease.
University of California, San Francisco1, University of Michigan2, University of California, Davis3, University of Puerto Rico4, Cornell University5, University of Southern California6, Ponce Health Sciences University7, Cedars-Sinai Medical Center8, Georgetown University9, Fundación Instituto Leloir10, City of Hope National Medical Center11, Boston University12, National Institutes of Health13, St. Jude Children's Research Hospital14, LSU Health Sciences Center New Orleans15
TL;DR: To eliminate cancer health disparities, it will be necessary to facilitate access to, and utilisation of, health services to all individuals, and to address structural inequities, including racism, that disproportionally affect racial/ethnic minorities in the USA.
Abstract: There are well-established disparities in cancer incidence and outcomes by race/ethnicity that result from the interplay between structural, socioeconomic, socio-environmental, behavioural and biological factors. However, large research studies designed to investigate factors contributing to cancer aetiology and progression have mainly focused on populations of European origin. The limitations in clinicopathological and genetic data, as well as the reduced availability of biospecimens from diverse populations, contribute to the knowledge gap and have the potential to widen cancer health disparities. In this review, we summarise reported disparities and associated factors in the United States of America (USA) for the most common cancers (breast, prostate, lung and colon), and for a subset of other cancers that highlight the complexity of disparities (gastric, liver, pancreas and leukaemia). We focus on populations commonly identified and referred to as racial/ethnic minorities in the USA-African Americans/Blacks, American Indians and Alaska Natives, Asians, Native Hawaiians/other Pacific Islanders and Hispanics/Latinos. We conclude that even though substantial progress has been made in understanding the factors underlying cancer health disparities, marked inequities persist. Additional efforts are needed to include participants from diverse populations in the research of cancer aetiology, biology and treatment. Furthermore, to eliminate cancer health disparities, it will be necessary to facilitate access to, and utilisation of, health services to all individuals, and to address structural inequities, including racism, that disproportionally affect racial/ethnic minorities in the USA.
Niamh Mullins1, Andreas J. Forstner2, Andreas J. Forstner3, Andreas J. Forstner4 +396 more•Institutions (119)
TL;DR: The authors performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci, including genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics.
Abstract: Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
TL;DR: In this article, the authors reported the observation of gravitational waves from two compact binary coalescences in LIGO's and Virgo's third observing run with properties consistent with neutron star-black hole (NSBH) binaries.
Abstract: We report the observation of gravitational waves from two compact binary coalescences in LIGO’s and Virgo’s third observing run with properties consistent with neutron star–black hole (NSBH) binaries. The two events are named GW200105_162426 and GW200115_042309, abbreviated as GW200105 and GW200115; the first was observed by LIGO Livingston and Virgo and the second by all three LIGO–Virgo detectors. The source of GW200105 has component masses 8.9−1.5+1.2 and 1.9−0.2+0.3M⊙ , whereas the source of GW200115 has component masses 5.7−2.1+1.8 and 1.5−0.3+0.7M⊙ (all measurements quoted at the 90% credible level). The probability that the secondary’s mass is below the maximal mass of a neutron star is 89%–96% and 87%–98%, respectively, for GW200105 and GW200115, with the ranges arising from different astrophysical assumptions. The source luminosity distances are 280−110+110 and 300−100+150Mpc , respectively. The magnitude of the primary spin of GW200105 is less than 0.23 at the 90% credible level, and its orientation is unconstrained. For GW200115, the primary spin has a negative spin projection onto the orbital angular momentum at 88% probability. We are unable to constrain the spin or tidal deformation of the secondary component for either event. We infer an NSBH merger rate density of 45−33+75Gpc−3yr−1 when assuming that GW200105 and GW200115 are representative of the NSBH population or 130−69+112Gpc−3yr−1 under the assumption of a broader distribution of component masses.
University of Michigan1, Cornell University2, University of Pennsylvania3, University of Massachusetts Medical School4, Baylor College of Medicine5, University of Naples Federico II6, Spanish National Research Council7, Complutense University of Madrid8, New York University9, University of Rome Tor Vergata10, Boston Children's Hospital11, NewYork–Presbyterian Hospital12, University of Pittsburgh13, French Institute of Health and Medical Research14, University of Paris15, National University of Cuyo16, Albert Einstein College of Medicine17, University of New Mexico18, Goethe University Frankfurt19, Weizmann Institute of Science20, University of Turku21, Sapienza University of Rome22, Virginia Commonwealth University23, St. Jude Children's Research Hospital24, Discovery Institute25, University of Copenhagen26, University of Tromsø27, Eötvös Loránd University28, Merck & Co.29, University of Freiburg30, Babraham Institute31, University of South Australia32, University of Adelaide33, University of Oviedo34, University of Chicago35, University of Graz36, National Institutes of Health37, Queens College38, City University of New York39, University of Tokyo40, University of Zurich41, University of British Columbia42, Austrian Academy of Sciences43, University of California, San Francisco44, Russian Academy of Sciences45, University Medical Center Groningen46, University of Cambridge47, University of Glasgow48, Rutgers University49, University of Padua50, Kazan Federal University51, University of Bern52, University of Oxford53, Oslo University Hospital54, University of Oslo55, Foundation for Research & Technology – Hellas56, University of Crete57, Francis Crick Institute58, Osaka University59, Harvard University60, Chinese Academy of Sciences61, Icahn School of Medicine at Mount Sinai62, Shanghai Jiao Tong University63, Karolinska Institutet64
TL;DR: In this paper, preclinical data linking autophagy dysfunction to the pathogenesis of major human disorders including cancer as well as cardiovascular, neurodegenerative, metabolic, pulmonary, renal, infectious, musculoskeletal, and ocular disorders.
Abstract: Autophagy is a core molecular pathway for the preservation of cellular and organismal homeostasis. Pharmacological and genetic interventions impairing autophagy responses promote or aggravate disease in a plethora of experimental models. Consistently, mutations in autophagy-related processes cause severe human pathologies. Here, we review and discuss preclinical data linking autophagy dysfunction to the pathogenesis of major human disorders including cancer as well as cardiovascular, neurodegenerative, metabolic, pulmonary, renal, infectious, musculoskeletal, and ocular disorders.
TL;DR: In this paper, the authors investigated the risk factors for fibrotic-like changes in the lung at 6-month follow-up chest CT of survivors of severe COVID-19 pneumonia.
Abstract: Background Little is known about the long-term lung radiographic changes in patients who have recovered from coronavirus disease 2019 (COVID-19), especially those with severe disease. Purpose To prospectively assess pulmonary sequelae and explore the risk factors for fibrotic-like changes in the lung at 6-month follow-up chest CT of survivors of severe COVID-19 pneumonia. Materials and Methods A total of 114 patients (80 [70%] men; mean age, 54 years ± 12) were studied prospectively. Initial and follow-up CT scans were obtained a mean of 17 days ± 11 and 175 days ± 20, respectively, after symptom onset. Lung changes (opacification, consolidation, reticulation, and fibrotic-like changes) and CT extent scores (score per lobe, 0-5; maximum score, 25) were recorded. Participants were divided into two groups on the basis of their 6-month follow-up CT scan: those with CT evidence of fibrotic-like changes (traction bronchiectasis, parenchymal bands, and/or honeycombing) (group 1) and those without CT evidence of fibrotic-like changes (group 2). Between-group differences were assessed with the Fisher exact test, two-sample t test, or Mann-Whitney U test. Multiple logistic regression analyses were performed to identify the independent predictive factors of fibrotic-like changes. Results At follow-up CT, evidence of fibrotic-like changes was observed in 40 of the 114 participants (35%) (group 1), whereas the remaining 74 participants (65%) showed either complete radiologic resolution (43 of 114, 38%) or residual ground-glass opacification or interstitial thickening (31 of 114, 27%) (group 2). Multivariable analysis identified age of greater than 50 years (odds ratio [OR]: 8.5; 95% CI: 1.9, 38; P = .01), heart rate greater than 100 beats per minute at admission (OR: 5.6; 95% CI: 1.1, 29; P = .04), duration of hospital stay greater than or equal to 17 days (OR: 5.5; 95% CI: 1.5, 21; P = .01), acute respiratory distress syndrome (OR: 13; 95% CI: 3.3, 55; P < .001), noninvasive mechanical ventilation (OR: 6.3; 95% CI: 1.3, 30; P = .02), and total CT score of 18 or more (OR: 4.2; 95% CI: 1.2, 14; P = .02) at initial CT as independent predictors for fibrotic-like changes in the lung at 6 months. Conclusion Six-month follow-up CT showed fibrotic-like changes in the lung in more than one-third of patients who survived severe coronavirus disease 2019 pneumonia. These changes were associated with an older age, acute respiratory distress syndrome, longer hospital stays, tachycardia, noninvasive mechanical ventilation, and higher initial chest CT score. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Wells et al in this issue.
Evgeny Epifanovsky, Andrew T.B. Gilbert1, Andrew T.B. Gilbert2, Xintian Feng3 +235 more•Institutions (54)
TL;DR: The Q-Chem quantum chemistry program package as discussed by the authors provides a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, and methods for computing vibronic spectra, the nuclear-electronic orbital method, and several different energy decomposition analysis techniques.
Abstract: This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange-correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear-electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an "open teamware" model and an increasingly modular design.
Harvard University1, University of Michigan2, Icahn School of Medicine at Mount Sinai3, Yeshiva University4, Rutgers University5, Seton Hall 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.
University of Colorado Boulder1, University of North Carolina at Chapel Hill2, University of Notre Dame3, University of South Florida4, Columbia University5, University of California, Irvine6, Rutgers University7, Stony Brook University8, University of Pittsburgh9, Yale University10, University of Oregon11, University of California, Berkeley12, Boston University13, Vanderbilt University14, University of Miami15, University of Minnesota16, Fordham University17, Harvard University18, Cornell University19, University of Michigan20, University of Central Florida21, University of California, Los Angeles22, University of Virginia23, Brown University24
TL;DR: COVID-19 is conceptualized as a unique, compounding, multidimensional stressor that will create a vast need for intervention and necessitate new paradigms for mental health service delivery and training.
Abstract: COVID-19 presents significant social, economic, and medical challenges. Because COVID-19 has already begun to precipitate huge increases in mental health problems, clinical psychological science must assert a leadership role in guiding a national response to this secondary crisis. In this article, COVID-19 is conceptualized as a unique, compounding, multidimensional stressor that will create a vast need for intervention and necessitate new paradigms for mental health service delivery and training. Urgent challenge areas across developmental periods are discussed, followed by a review of psychological symptoms that likely will increase in prevalence and require innovative solutions in both science and practice. Implications for new research directions, clinical approaches, and policy issues are discussed to highlight the opportunities for clinical psychological science to emerge as an updated, contemporary field capable of addressing the burden of mental illness and distress in the wake of COVID-19 and beyond. (PsycInfo Database Record (c) 2021 APA, all rights reserved).