Showing papers by "McMaster University published in 2019"
University of Pennsylvania1, University of Chicago2, University of Melbourne3, Emory University4, University of Cologne5, University of Kansas6, Medical University of Vienna7, Ohio State University8, University of California, San Francisco9, University of Texas MD Anderson Cancer Center10, Université de Montréal11, University of Minnesota12, McMaster University13, Royal Prince Alfred Hospital14, Karolinska Institutet15, University of Würzburg16, University of Michigan17, University of Oslo18, Novartis19, University of Lyon20
TL;DR: The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study.
Abstract: Background Patients with diffuse large B-cell lymphoma that is refractory to primary and second-line therapies or that has relapsed after stem-cell transplantation have a poor prognosis. The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study. Methods We conducted an international, phase 2, pivotal study of centrally manufactured tisagenlecleucel involving adult patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for or had disease progression after autologous hematopoietic stem-cell transplantation. The primary end point was the best overall response rate (i.e., the percentage of patients who had a complete or partial response), as judged by an independent review committee. Results A total of 93 patients received an infusion and were included in the evaluation of efficacy. The median time from infusion to data cutoff was 14 ...
2,086 citations
Harvard University1, University of Western Australia2, University of Texas Health Science Center at San Antonio3, McMaster University4, University of Washington5, Centers for Disease Control and Prevention6, University of Utah7, Primary Children's Hospital8, University of Pittsburgh9, University of Michigan10, Vanderbilt University11, University of Connecticut12, Baylor College of Medicine13, United States Department of Veterans Affairs14
TL;DR: Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions.
Abstract: Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia.Methods: A multidisciplinary panel conducted pra...
1,708 citations
TL;DR: A new Resistomes & Variants module provides analysis and statistical summary of in silico predicted resistance variants from 82 pathogens and over 100 000 genomes, able to summarize predicted resistance using the information included in CARD, identify trends in AMR mobility and determine previously undescribed and novel resistance variants.
Abstract: The Comprehensive Antibiotic Resistance Database (CARD; https://card.mcmaster.ca) is a curated resource providing reference DNA and protein sequences, detection models and bioinformatics tools on the molecular basis of bacterial antimicrobial resistance (AMR). CARD focuses on providing high-quality reference data and molecular sequences within a controlled vocabulary, the Antibiotic Resistance Ontology (ARO), designed by the CARD biocuration team to integrate with software development efforts for resistome analysis and prediction, such as CARD's Resistance Gene Identifier (RGI) software. Since 2017, CARD has expanded through extensive curation of reference sequences, revision of the ontological structure, curation of over 500 new AMR detection models, development of a new classification paradigm and expansion of analytical tools. Most notably, a new Resistomes & Variants module provides analysis and statistical summary of in silico predicted resistance variants from 82 pathogens and over 100 000 genomes. By adding these resistance variants to CARD, we are able to summarize predicted resistance using the information included in CARD, identify trends in AMR mobility and determine previously undescribed and novel resistance variants. Here, we describe updates and recent expansions to CARD and its biocuration process, including new resources for community biocuration of AMR molecular reference data.
1,526 citations
Rabin Medical Center1, University of Tartu2, University of Lausanne3, McMaster University4, University Hospital Southampton NHS Foundation Trust5, The Catholic University of America6, Geneva College7, Université libre de Bruxelles8, Jagiellonian University Medical College9, University of Hohenheim10
TL;DR: Particular conditions frequently observed in intensive care such as patients with dysphagia, frail patients, multiple trauma patients, abdominal surgery, sepsis, and obesity are discussed to guide the practitioner toward the best evidence based therapy.
1,474 citations
Tufts Medical Center1, University of Southampton2, University of Oxford3, University of Melbourne4, Erasmus University Rotterdam5, Duke University6, Lund University7, University of Otago8, McMaster University9, University of A Coruña10, National Autonomous University of Mexico11, Peking University12, Hospital for Special Surgery13, University of Tampere14, Health Science University15, University of Delaware16, Drexel University17, University of Warwick18, Coventry Health Care19
TL;DR: These guidelines offer comprehensive and patient-centered treatment profiles for individuals with Knee, Hip, and Polyarticular OA that are derived from expert consensus and based on objective review of high-quality meta-analytic data.
1,453 citations
TL;DR: A comparative analysis of electrocatalyst and carbon emissions assessment of CO2 products such as ethylene, ethanol, and carbon monoxide shows that electrocatalytic production has the potential to yield the greatest reduction in carbon emissions, provided that a steady supply of clean electricity is available.
Abstract: Electrocatalytic transformation of carbon dioxide (CO2) and water into chemical feedstocks offers the potential to reduce carbon emissions by shifting the chemical industry away from fossil fuel dependence. We provide a technoeconomic and carbon emission analysis of possible products, offering targets that would need to be met for economically compelling industrial implementation to be achieved. We also provide a comparison of the projected costs and CO2 emissions across electrocatalytic, biocatalytic, and fossil fuel-derived production of chemical feedstocks. We find that for electrosynthesis to become competitive with fossil fuel-derived feedstocks, electrical-to-chemical conversion efficiencies need to reach at least 60%, and renewable electricity prices need to fall below 4 cents per kilowatt-hour. We discuss the possibility of combining electro- and biocatalytic processes, using sequential upgrading of CO2 as a representative case. We describe the technical challenges and economic barriers to marketable electrosynthesized chemicals.
1,234 citations
Carleton University1, Michigan State University2, University of Saskatchewan3, University of California, Santa Barbara4, Federation University Australia5, University of Colorado Boulder6, McMaster University7, Mount Allison University8, University of Washington9, Cardiff University10, Queen's University11, Leibniz Association12, University of Hong Kong13
TL;DR: Efforts to reverse global trends in freshwater degradation now depend on bridging an immense gap between the aspirations of conservation biologists and the accelerating rate of species endangerment.
Abstract: In the 12 years since Dudgeon et al. (2006) reviewed major pressures on freshwater ecosystems, the biodiversity crisis in
the world’s lakes, reservoirs, rivers, streams and wetlands has deepened. While lakes, reservoirs and rivers cover only
2.3% of the Earth’s surface, these ecosystems host at least 9.5% of the Earth’s described animal species. Furthermore,
using the World Wide Fund for Nature’s Living Planet Index, freshwater population declines (83% between 1970 and
2014) continue to outpace contemporaneous declines in marine or terrestrial systems. The Anthropocene has brought
multiple new and varied threats that disproportionately impact freshwater systems. We document 12 emerging threats
to freshwater biodiversity that are either entirely new since 2006 or have since intensified: (i) changing climates; (ii)
e-commerce and invasions; (iii) infectious diseases; (iv) harmful algal blooms; (v) expanding hydropower; (vi) emerging
contaminants; (vii) engineered nanomaterials; (viii) microplastic pollution; (ix) light and noise; (x) freshwater salinisation;
(xi) declining calcium; and (xii) cumulative stressors. Effects are evidenced for amphibians, fishes, invertebrates, microbes,
plants, turtles and waterbirds, with potential for ecosystem-level changes through bottom-up and top-down processes.
In our highly uncertain future, the net effects of these threats raise serious concerns for freshwater ecosystems. However,
we also highlight opportunities for conservation gains as a result of novel management tools (e.g. environmental flows,
environmental DNA) and specific conservation-oriented actions (e.g. dam removal, habitat protection policies,managed
relocation of species) that have been met with varying levels of success.Moving forward, we advocate hybrid approaches
that manage fresh waters as crucial ecosystems for human life support as well as essential hotspots of biodiversity and
ecological function. Efforts to reverse global trends in freshwater degradation now depend on bridging an immense gap
between the aspirations of conservation biologists and the accelerating rate of species endangerment.
1,230 citations
Dresden University of Technology1, Brigham and Women's Hospital2, University of California, San Francisco3, University of Düsseldorf4, University of Pisa5, Northwestern University6, Medical University of Vienna7, National and Kapodistrian University of Athens8, Medical University of South Carolina9, University of Cambridge10, University of Barcelona11, The Feinstein Institute for Medical Research12, Toronto Western Hospital13, University of California, Los Angeles14, Humboldt University of Berlin15, Copenhagen University Hospital16, University of Michigan17, University of the Basque Country18, University Health Network19, University of Crete20, University of Zagreb21, University of Paris-Sud22, University of Hong Kong23, University of Calgary24, Hospital for Special Surgery25, University of Pécs26, University of Padua27, Medical University of Graz28, National Institutes of Health29, New York University30, Université Paris-Saclay31, University Hospital Complex Of Vigo32, University of Occupational and Environmental Health Japan33, University of Porto34, Leeds Teaching Hospitals NHS Trust35, Cedars-Sinai Medical Center36, Istanbul Bilim University37, McMaster University38
TL;DR: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism and the American College of Rheumatology (ACR).
Abstract: Objective To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Methods This international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects. Results The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. Conclusion These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research.
1,018 citations
TL;DR: This Review comprehensively assess the benefits and limitations of GWAS in human populations and discusses the relevance of performing more GWAS, with a focus on the cardiometabolic field.
Abstract: Genome-wide association studies (GWAS) involve testing genetic variants across the genomes of many individuals to identify genotype–phenotype associations. GWAS have revolutionized the field of complex disease genetics over the past decade, providing numerous compelling associations for human complex traits and diseases. Despite clear successes in identifying novel disease susceptibility genes and biological pathways and in translating these findings into clinical care, GWAS have not been without controversy. Prominent criticisms include concerns that GWAS will eventually implicate the entire genome in disease predisposition and that most association signals reflect variants and genes with no direct biological relevance to disease. In this Review, we comprehensively assess the benefits and limitations of GWAS in human populations and discuss the relevance of performing more GWAS. Despite the success of human genome-wide association studies (GWAS) in associating genetic variants and complex diseases or traits, criticisms of the usefulness of this study design remain. This Review assesses the pros and cons of GWAS, with a focus on the cardiometabolic field.
1,002 citations
TL;DR: This paper explores the role of Internet of Things (IoT) and its impact on supply chain management (SCM) through an extensive literature review and finds that most studies have focused on conceptualising the impact of IoT with limited analytical models and empirical studies.
Abstract: This paper explores the role of Internet of Things (IoT) and its impact on supply chain management (SCM) through an extensive literature review. Important aspects of IoT in SCM are covered including IoT definition, main IoT technology enablers and various SCM processes and applications. We offer several categorisation of the extant literature, such as based on methodology, industry sector and focus on a classification based on major supply chain processes. In addition, a bibliometric analysis of the literature is also presented. We find that most studies have focused on conceptualising the impact of IoT with limited analytical models and empirical studies. In addition, most studies have focused on the delivery supply chain process and the food and manufacturing supply chains. Areas of future SCM research that can support IoT implementation are also identified.
727 citations
Dresden University of Technology1, Brigham and Women's Hospital2, University of California, San Francisco3, University of Düsseldorf4, University of Pisa5, Northwestern University6, Medical University of Vienna7, National and Kapodistrian University of Athens8, University of Cyprus9, Medical University of South Carolina10, University of Cambridge11, University of Barcelona12, University Health Network13, The Feinstein Institute for Medical Research14, Toronto Western Hospital15, University of California, Los Angeles16, Humboldt University of Berlin17, Copenhagen University Hospital18, University of Michigan19, Harvard University20, University of the Basque Country21, University of Crete22, University of Kiel23, University Hospital Centre Zagreb24, University of Paris-Sud25, University of Hong Kong26, University of Calgary27, Hospital for Special Surgery28, University of Pécs29, University of Padua30, Medical University of Graz31, National Institutes of Health32, New York University33, Université Paris-Saclay34, University Hospital Complex Of Vigo35, University of Occupational and Environmental Health Japan36, University of Porto37, Leeds Teaching Hospitals NHS Trust38, University of Leeds39, Cedars-Sinai Medical Center40, Istanbul Bilim University41, McMaster University42, University of Paris43, University of Toronto44
TL;DR: These new classification criteria for systemic lupus erythematosus have excellent sensitivity and specificity, and were developed using rigorous methodology with multidisciplinary and international input.
Abstract: Objective To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Methods This international initiative had four phases. (1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort and a patient survey. (2) Criteria reduction by Delphi and nominal group technique exercises. (3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. (4) Refinement of weights and threshold scores in a new derivation cohort of 1001 subjects and validation compared with previous criteria in a new validation cohort of 1270 subjects. Results The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. Conclusion These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered and weighted criteria reflect current thinking about SLE and provide an improved foundation for SLE research.
TL;DR: There was a lack of evidence to support strong recommendations for various management approaches, and a large focus was placed on shared decision-making, especially with regard to second-line therapy.
20 Sep 2019
University of Wisconsin-Madison1, Philippines National Collegiate Athletic Association2, Western University of Health Sciences3, George Washington University4, International Olympic Committee5, University of São Paulo6, McGill University7, Stanford University8, University of Portsmouth9, University of Amsterdam10, University of Arizona11, Chung-Ang University12, University of Maryland, Baltimore13, McMaster University14, Kocaeli University15, Princeton University16, Rutgers University17, Vanderbilt University Medical Center18, University of Nebraska–Lincoln19, Stellenbosch University20
TL;DR: To advance a more standardised, evidence based approach to mental health symptoms and disorders in elite athletes, an International Olympic Committee Consensus Work Group critically evaluated the current state of science and provided recommendations.
Abstract: Mental health symptoms and disorders are common among elite athletes, may have sport related manifestations within this population and impair performance. Mental health cannot be separated from physical health, as evidenced by mental health symptoms and disorders increasing the risk of physical injury and delaying subsequent recovery. There are no evidence or consensus based guidelines for diagnosis and management of mental health symptoms and disorders in elite athletes. Diagnosis must differentiate character traits particular to elite athletes from psychosocial maladaptations.Management strategies should address all contributors to mental health symptoms and consider biopsychosocial factors relevant to athletes to maximise benefit and minimise harm. Management must involve both treatment of affected individual athletes and optimising environments in which all elite athletes train and compete. To advance a more standardised, evidence based approach to mental health symptoms and disorders in elite athletes, an International Olympic Committee Consensus Work Group critically evaluated the current state of science and provided recommendations.
National Center for Immunization and Respiratory Diseases1, University of California, San Diego2, Boston Children's Hospital3, University of Washington4, Northeast Ohio Medical University5, Brown University6, University of Virginia Health System7, Centers for Disease Control and Prevention8, University of Maryland, Baltimore9, Northwestern University10, Nova Scotia Health Authority11, University of Toronto12, Harvard University13, Duke University14, McMaster University15, Infectious Diseases Society of America16, University of Utah17
TL;DR: These clinical practice guidelines are an update of the guidelines published by the Infectious Diseases Society of America in 2009 and address new information regarding diagnostic testing, treatment and chemoprophylaxis with antiviral medications, and issues related to institutional outbreak management for seasonal influenza.
Abstract: These clinical practice guidelines are an update of the guidelines published by the Infectious Diseases Society of America (IDSA) in 2009, prior to the 2009 H1N1 influenza pandemic. This document addresses new information regarding diagnostic testing, treatment and chemoprophylaxis with antiviral medications, and issues related to institutional outbreak management for seasonal influenza. It is intended for use by primary care clinicians, obstetricians, emergency medicine providers, hospitalists, laboratorians, and infectious disease specialists, as well as other clinicians managing patients with suspected or laboratory-confirmed influenza. The guidelines consider the care of children and adults, including special populations such as pregnant and postpartum women and immunocompromised patients.
TL;DR: Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide and can be targeted towards vulnerable populations if they are informed by variations in mortality rates.
Abstract: Objectives To use the estimates from the Global Burden of Disease Study 2016 to describe patterns of suicide mortality globally, regionally, and for 195 countries and territories by age, sex, and Socio-demographic index, and to describe temporal trends between 1990 and 2016. Design Systematic analysis. Main outcome measures Crude and age standardised rates from suicide mortality and years of life lost were compared across regions and countries, and by age, sex, and Socio-demographic index (a composite measure of fertility, income, and education). Results The total number of deaths from suicide increased by 6.7% (95% uncertainty interval 0.4% to 15.6%) globally over the 27 year study period to 817 000 (762 000 to 884 000) deaths in 2016. However, the age standardised mortality rate for suicide decreased by 32.7% (27.2% to 36.6%) worldwide between 1990 and 2016, similar to the decline in the global age standardised mortality rate of 30.6%. Suicide was the leading cause of age standardised years of life lost in the Global Burden of Disease region of high income Asia Pacific and was among the top 10 leading causes in eastern Europe, central Europe, western Europe, central Asia, Australasia, southern Latin America, and high income North America. Rates for men were higher than for women across regions, countries, and age groups, except for the 15 to 19 age group. There was variation in the female to male ratio, with higher ratios at lower levels of Socio-demographic index. Women experienced greater decreases in mortality rates (49.0%, 95% uncertainty interval 42.6% to 54.6%) than men (23.8%, 15.6% to 32.7%). Conclusions Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide. Suicide mortality was variable across locations, between sexes, and between age groups. Suicide prevention strategies can be targeted towards vulnerable populations if they are informed by variations in mortality rates.
08 Aug 2019
TL;DR: An end-to-end trainable Convolutional Neural Network for single image dehazing, named GridDehazeNet, which implements a novel attention-based multi-scale estimation on a grid network, and an explanation as to why it is not necessarily beneficial to take advantage of the dimension reduction offered by the atmosphere scattering model.
Abstract: We propose an end-to-end trainable Convolutional Neural Network (CNN), named GridDehazeNet, for single image dehazing. The GridDehazeNet consists of three modules: pre-processing, backbone, and post-processing. The trainable pre-processing module can generate learned inputs with better diversity and more pertinent features as compared to those derived inputs produced by hand-selected pre-processing methods. The backbone module implements a novel attention-based multi-scale estimation on a grid network, which can effectively alleviate the bottleneck issue often encountered in the conventional multi-scale approach. The post-processing module helps to reduce the artifacts in the final output. Experimental results indicate that the GridDehazeNet outperforms the state-of-the-arts on both synthetic and real-world images. The proposed hazing method does not rely on the atmosphere scattering model, and we provide an explanation as to why it is not necessarily beneficial to take advantage of the dimension reduction offered by the atmosphere scattering model for image dehazing, even if only the dehazing results on synthetic images are concerned.
F. Kyle Satterstrom1, Jack A. Kosmicki1, Jiebiao Wang2, Michael S. Breen3 +150 more•Institutions (45)
TL;DR: Using an enhanced Bayesian framework to integrate de novo and case-control rare variation, 102 risk genes are identified at a false discovery rate of ≤ 0.1, consistent with multiple paths to an excitatory/inhibitory imbalance underlying ASD.
Abstract: We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n=35,584 total samples, 11,986 with ASD). Using an enhanced Bayesian framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate ≤ 0.1. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained for severe neurodevelopmental delay, while 53 show higher frequencies in individuals ascertained for ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most of the risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In human cortex single-cell gene expression data, expression of risk genes is enriched in both excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory/inhibitory imbalance underlying ASD.
Icahn School of Medicine at Mount Sinai1, Technische Universität München2, University of Florida3, University of Catania4, Aix-Marseille University5, Beth Israel Deaconess Medical Center6, McMaster University7, Food and Drug Administration8, Harvard University9, University of London10, Uppsala University11, Seoul National University Hospital12, Kyoto University13, Pharmaceuticals and Medical Devices Agency14, Columbia University Medical Center15, National University of Ireland, Galway16, Scripps Health17, Durham University18, Core Laboratories19, Erasmus University Medical Center20, University of Bern21, Paris Descartes University22, Duke University23
TL;DR: This research presents a novel probabilistic approach that allows us to assess the importance of knowing the carrier and removal status of canine coronavirus, as a source of infection for other animals.
Abstract: Identification and management of patients at high bleeding risk undergoing percutaneous coronary intervention are of major importance, but a lack of standardization in defining this population limi ...
TL;DR: A theoretical and practical framework for the development of effective antibiotic combinations is outlined and a productive strategy to address the widespread emergence of antibiotic-resistant strains is proposed.
Abstract: Antimicrobial resistance threatens a resurgence of life-threatening bacterial infections and the potential demise of many aspects of modern medicine. Despite intensive drug discovery efforts, no new classes of antibiotics have been developed into new medicines for decades, in large part owing to the stringent chemical, biological and pharmacological requisites for effective antibiotic drugs. Combinations of antibiotics and of antibiotics with non-antibiotic activity-enhancing compounds offer a productive strategy to address the widespread emergence of antibiotic-resistant strains. In this Review, we outline a theoretical and practical framework for the development of effective antibiotic combinations. Combinations of antibiotics and of antibiotics with non-antibiotic activity-enhancing compounds offer a productive strategy to address the widespread emergence of antibiotic-resistant strains. In this Review, Tyers and Wright outline a theoretical and practical framework for the development of effective drug combinations.
Columbia University1, University of Cincinnati2, University of Dundee3, Queen's University4, University of Texas MD Anderson Cancer Center5, Johns Hopkins University6, Kaiser Permanente7, University of Nottingham8, University of North Carolina at Chapel Hill9, McGill University10, Mayo Clinic11, University of Zurich12, University of Paris13, Pontifical Catholic University of Chile14, Erasmus University Rotterdam15, University of Iowa16, Monash University17, University of Melbourne18, University of Genoa19, Emory University20, National Jewish Health21, University of Sydney22, Stony Brook University23, St Thomas' Hospital24, Heidelberg University25, University of Michigan26, McMaster University27, University of New South Wales28, Cleveland Clinic29, University of Virginia30, Harvard University31, University of Adelaide32, University of Freiburg33, Southern Health NHS Foundation Trust34, University of Oxford35, University of Edinburgh36, University of Sassari37, University of Washington38, Cincinnati Children's Hospital Medical Center39, University of California, Los Angeles40
TL;DR: Control of Confounding and Reporting of Results in Causal Inference Studies Guidance for Authors from Editors of Respiratory, Sleep, and Critical Care Journals is published.
Abstract: Control of Confounding and Reporting of Results in Causal Inference Studies Guidance for Authors fromEditors of Respiratory, Sleep, andCritical Care Journals David J. Lederer*, Scott C. Bell*, Richard D. Branson*, James D. Chalmers*, Rachel Marshall*, David M. Maslove*, David E. Ost*, Naresh M. Punjabi*, Michael Schatz*, Alan R. Smyth*, Paul W. Stewart*, Samy Suissa*, Alex A. Adjei, Cezmi A. Akdis, Élie Azoulay, Jan Bakker, Zuhair K. Ballas, Philip G. Bardin, Esther Barreiro, Rinaldo Bellomo, Jonathan A. Bernstein, Vito Brusasco, Timothy G. Buchman, Sudhansu Chokroverty, Nancy A. Collop, James D. Crapo, Dominic A. Fitzgerald, Lauren Hale, Nicholas Hart, Felix J. Herth, Theodore J. Iwashyna, Gisli Jenkins, Martin Kolb, Guy B. Marks, Peter Mazzone, J. Randall Moorman, ThomasM.Murphy, Terry L. Noah, Paul Reynolds, Dieter Riemann, Richard E. Russell, Aziz Sheikh, Giovanni Sotgiu, Erik R. Swenson, Rhonda Szczesniak, Ronald Szymusiak, Jean-Louis Teboul, and Jean-Louis Vincent Department of Medicine and Department of Epidemiology, Columbia University Irving Medical Center, New York, New York; Editor-inChief, Annals of the American Thoracic Society; Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Queensland, Australia; Editor-in-Chief, Journal of Cystic Fibrosis; Department of Surgery, University of Cincinnati, Cincinnati, Ohio; Editor-in-Chief, Respiratory Care; University of Dundee, Dundee, Scotland; Deputy Chief Editor, European Respiratory Journal; London, England; Deputy Editor, The Lancet Respiratory Medicine; Department of Medicine, Queen’s University, Kingston, Ontario, Canada; Associate Editor for Data Science, Critical Care Medicine; Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas; Editor-in-Chief, Journal of Bronchology and Interventional Pulmonology; Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland; Deputy Editor-in-Chief, SLEEP; Department of Allergy, Kaiser Permanente Medical Center, San Diego, California; Editor-in-Chief, The Journal of Allergy & Clinical Immunology: In Practice; Division of Child Health, Obstetrics, and Gynecology, University of Nottingham, Nottingham, England; Joint Editor-in-Chief, Thorax; Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina; Associate Editor, Pediatric Pulmonology; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada; Advisor, COPD: Journal of Chronic Obstructive Pulmonary Disease; Department of Oncology, Mayo Clinic, Rochester, Minnesota; Editor-in-Chief, Journal of Thoracic Oncology; Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos, Switzerland; Editor-in-Chief, Allergy; St. Louis Hospital, University of Paris, Paris, France; Editor-in-Chief, Intensive Care Medicine; Department of Medicine, Columbia University Irving Medical Center, and Division of Pulmonary, Critical Care, and Sleep, NYU Langone Health, New York, New York; Department of Intensive Care Adults, Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Intensive Care, Pontificia Universidad Católica de Chile, Santiago, Chile; Editor-in-Chief, Journal of Critical Care; Department of Internal Medicine, University of Iowa and the Iowa City Veterans Affairs Medical Center, Iowa City, Iowa; Editor-in-Chief, The Journal of Allergy and Clinical Immunology; Monash Lung and Sleep, Monash Hospital and University, Melbourne, Victoria, Australia; Co-Editor-in-Chief, Respirology; Pulmonology Department, Muscle and Lung Cancer Research Group, Research Institute of Hospital del Mar and Centro de Investigación Biomédica en Red Enfermedades Respiratorias Instituto de Salud Carlos III, Barcelona, Spain; Editor-in-Chief, Archivos de Bronconeumologia; Department of Intensive Care Medicine, Austin Hospital and University of Melbourne, Melbourne, Victoria, Australia; Editor-in-Chief, Critical Care & Resuscitation; Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio; Editor-in-Chief, Journal of Asthma; Department of Internal Medicine, University of Genoa, Genoa, Italy; Editor-in-Chief, COPD: Journal of Chronic Obstructive Pulmonary Disease; Department of Surgery, Department of Anesthesiology, and Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, Georgia; Editor-in-Chief,Critical CareMedicine; JFKNewJersey Neuroscience Institute, HackensackMeridian Health–JFKMedical Center, Edison, New Jersey; Editor-in-Chief, Sleep Medicine; Department of Medicine and Department of Neurology, Emory University School of Medicine, Atlanta, Georgia; Editor-in-Chief, Journal of Clinical Sleep Medicine; Department of Medicine, National Jewish Hospital, Denver, Colorado; Editor-in-Chief, Journal of the COPD Foundation; The Children’s Hospital at Westmead, Sydney Medical School, University of
University of Paris1, McGill University2, Brigham and Women's Hospital3, Medical University of Vienna4, Case Western Reserve University5, Hospital General Universitario Gregorio Marañón6, Rambam Health Care Campus7, University College London8, Universidad Católica San Antonio de Murcia9, University of Geneva10, McMaster University11
TL;DR: The 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines, which are based on a systematic review of the literature published up to December, 2018, are presented along with a Grading of Recommendations Assessment Development and Evaluation scale methods.
Abstract: Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at a high risk of VTE recurrence and bleeding during anticoagulant therapy. The International Initiative on Thrombosis and Cancer is an independent academic working group aimed at establishing a global consensus for the treatment and prophylaxis of VTE in patients with cancer. The International Initiative on Thrombosis and Cancer last updated its evidence-based clinical practice guidelines in 2016 with a free, web-based mobile phone application, which was subsequently endorsed by the International Society on Thrombosis and Haemostasis. The 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines, which are based on a systematic review of the literature published up to December, 2018, are presented along with a Grading of Recommendations Assessment Development and Evaluation scale methods, with the support of the French National Cancer Institute. These guidelines were reviewed by an expanded international advisory committee and endorsed by the International Society on Thrombosis and Haemostasis. Results from head-to-head clinical trials that compared direct oral anticoagulant with low-molecular-weight heparin are also summarised, along with new evidence for the treatment and prophylaxis of VTE in patients with cancer.
University of Manitoba1, Boston University2, University of Michigan3, University of Maryland, Baltimore4, University of Wisconsin-Madison5, University of Minnesota6, University of Washington7, University of Amsterdam8, University of Miami9, Yale University10, Northwestern University11, Baylor College of Medicine12, Lund University13, McMaster University14
TL;DR: The current guideline updates the recommendations of the 2005 guideline, includes new recommendations for populations not previously addressed, and, where relevant, addresses the interpretation of nonlocalizing clinical symptoms in populations with a high prevalence of ASB.
Abstract: Asymptomatic bacteriuria (ASB) is a common finding in many populations, including healthy women and persons with underlying urologic abnormalities. The 2005 guideline from the Infectious Diseases Society of America recommended that ASB should be screened for and treated only in pregnant women or in an individual prior to undergoing invasive urologic procedures. Treatment was not recommended for healthy women; older women or men; or persons with diabetes, indwelling catheters, or spinal cord injury. The guideline did not address children and some adult populations, including patients with neutropenia, solid organ transplants, and nonurologic surgery. In the years since the publication of the guideline, further information relevant to ASB has become available. In addition, antimicrobial treatment of ASB has been recognized as an important contributor to inappropriate antimicrobial use, which promotes emergence of antimicrobial resistance. The current guideline updates the recommendations of the 2005 guideline, includes new recommendations for populations not previously addressed, and, where relevant, addresses the interpretation of nonlocalizing clinical symptoms in populations with a high prevalence of ASB.
20 Sep 2019
Baker IDI Heart and Diabetes Institute1, Saint Louis University2, University of Alberta3, Columbia University4, The Chinese University of Hong Kong5, Memorial Hospital of South Bend6, King's College London7, Heidelberg University8, National Institutes of Health9, National University of Singapore10, Sichuan University11, University of Amsterdam12, Kyung Hee University13, Uppsala University14, University of Oulu15, University of Helsinki16, University of Western Australia17, Harvard University18, Université du Québec à Montréal19, University of Zurich20, University of Maryland, Baltimore21, Queen's University22, University of Florida23, University of Miami24, McMaster University25, King Saud University26, University of Otago27, French Institute of Health and Medical Research28
TL;DR: The task force of the International Conference of Frailty and Sarcopenia Research developed these clinical practice guidelines to overview the current evidence-base and provide recommendations for the identification and management of frailty in older adults using the GRADE approach.
Abstract: Objective: The task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) developed these clinical practice guidelines to overview the current evidence-base and to provide recommendations for the identification and management of frailty in older adults. Methods: These recommendations were formed using the GRADE approach, which ranked the strength and certainty (quality) of the supporting evidence behind each recommendation. Where the evidence-base was limited or of low quality, Consensus Based Recommendations (CBRs) were formulated. The recommendations focus on the clinical and practical aspects of care for older people with frailty, and promote person-centred care. Recommendations for Screening and Assessment: The task force recommends that health practitioners case identify/screen all older adults for frailty using a validated instrument suitable for the specific setting or context (strong recommendation). Ideally, the screening instrument should exclude disability as part of the screening process. For individuals screened as positive for frailty, a more comprehensive clinical assessment should be performed to identify signs and underlying mechanisms of frailty (strong recommendation). Recommendations for Management: A comprehensive care plan for frailty should address polypharmacy (whether rational or nonrational), the management of sarcopenia, the treatable causes of weight loss, and the causes of exhaustion (depression, anaemia, hypotension, hypothyroidism, and B12 deficiency) (strong recommendation). All persons with frailty should receive social support as needed to address unmet needs and encourage adherence to a comprehensive care plan (strong recommendation). First-line therapy for the management of frailty should include a multi-component physical activity programme with a resistance-based training component (strong recommendation). Protein/caloric supplementation is recommended when weight loss or undernutrition are present (conditional recommendation). No recommendation was given for systematic additional therapies such as cognitive therapy, problem-solving therapy, vitamin D supplementation, and hormone-based treatment. Pharmacological treatment as presently available is not recommended therapy for the treatment of frailty.
TL;DR: In a systematic review, specific bacteria associated with microbiomes of patients with IBS vs controls were identified and studies are needed to determine whether these microbes are a product or cause of IBS.
TL;DR: This review follows the CoV outbreaks that are speculated to have originated in bats and reviews studies that have allowed researchers to identify unique adaptation in bats that may allow them to harbor CoVs without severe disease.
Abstract: Bats are speculated to be reservoirs of several emerging viruses including coronaviruses (CoVs) that cause serious disease in humans and agricultural animals. These include CoVs that cause severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), porcine epidemic diarrhea (PED) and severe acute diarrhea syndrome (SADS). Bats that are naturally infected or experimentally infected do not demonstrate clinical signs of disease. These observations have allowed researchers to speculate that bats are the likely reservoirs or ancestral hosts for several CoVs. In this review, we follow the CoV outbreaks that are speculated to have originated in bats. We review studies that have allowed researchers to identify unique adaptation in bats that may allow them to harbor CoVs without severe disease. We speculate about future studies that are critical to identify how bats can harbor multiple strains of CoVs and factors that enable these viruses to “jump” from bats to other mammals. We hope that this review will enable readers to identify gaps in knowledge that currently exist and initiate a dialogue amongst bat researchers to share resources to overcome present limitations.
TL;DR: An overview of the physiological functions of AMPK is provided and the potential of this enzyme as a therapeutic target across diverse disease areas is discussed and Pharmacological activation of AM PK and the associated drug development challenges are assessed.
Abstract: Since the discovery of AMP-activated protein kinase (AMPK) as a central regulator of energy homeostasis, many exciting insights into its structure, regulation and physiological roles have been revealed. While exercise, caloric restriction, metformin and many natural products increase AMPK activity and exert a multitude of health benefits, developing direct activators of AMPK to elicit beneficial effects has been challenging. However, in recent years, direct AMPK activators have been identified and tested in preclinical models, and a small number have entered clinical trials. Despite these advances, which disease(s) represent the best indications for therapeutic AMPK activation and the long-term safety of such approaches remain to be established.
TL;DR: These international clinical practice recommendations (CPR) for developmental coordination disorder (DCD) aim to address key questions on the definition, diagnosis, assessment, intervention, and psychosocial aspects of DCD relevant for clinical practice.
Abstract: Aim: These international clinical practice recommendations (CPR) for developmental coordination disorder (DCD), initiated by the European Academy of Childhood Disability (EACD), aim to address key questions on the definition, diagnosis, assessment, intervention, and psychosocial aspects of DCD relevant for clinical practice. Method: Key questions in five areas were considered through literature reviews and formal expert consensus. For recommendations based on evidence, literature searches on ‘mechanisms’, ‘assessment’, and ‘intervention’ were updated since the last recommendations in 2012. New searches were conducted for ‘psychosocial issues’ and ‘adolescents/adults’. Evidence was rated according to the Oxford Centre for Evidence-Based Medicine (level of evidence [LOE] 1–4) and transferred into recommendations. For recommendations based on formal consensus, two meetings of an international, multidisciplinary expert panel were conducted with a further five Delphi rounds to develop good clinical practice (GCP) recommendations. Results: Thirty-five recommendations were made. Eight were based on the evidence from literature reviews (three on ‘assessment’, five on ‘intervention’). Twenty-two were updated from the 2012 recommendations. New recommendations relate to diagnosis and assessment (two GCPs) and psychosocial issues (three GCPs). Additionally, one new recommendation (LOE) reflects active video games as adjuncts to more traditional activity-oriented and participation-oriented interventions, and two new recommendations (one GCP, one LOE) were made for adolescents and adults with DCD. Interpretation: The CPR–DCD is a comprehensive overview of DCD and current understanding based on research evidence and expert consensus. It reflects the state of the art for clinicians and scientists of varied disciplines. The international CPR–DCD may serve as a basis for national guidelines. What this paper adds: Updated international clinical practice guidelines on developmental coordination disorder (DCD). Refined and extended recommendations on clinical assessment and intervention for DCD. A critical synopsis of current research on mechanisms of DCD. A critical synopsis of psychosocial issues in DCD, with implications for clinical practice. The first international recommendations to consider adolescents and adults with DCD.
TL;DR: An overview of the state-of-the-art, recent developments as well as emerging trends in the field of nano- and microgels is provided.
Abstract: Nanogels and microgels are soft, deformable, and penetrable objects with an internal gel-like structure that is swollen by the dispersing solvent. Their softness and the potential to respond to external stimuli like temperature, pressure, pH, ionic strength, and different analytes make them interesting as soft model systems in fundamental research as well as for a broad range of applications, in particular in the field of biological applications. Recent tremendous developments in their synthesis open access to systems with complex architectures and compositions allowing for tailoring microgels with specific properties. At the same time state-of-the-art theoretical and simulation approaches offer deeper understanding of the behavior and structure of nano- and microgels under external influences and confinement at interfaces or at high volume fractions. Developments in the experimental analysis of nano- and microgels have become particularly important for structural investigations covering a broad range of length scales relevant to the internal structure, the overall size and shape, and interparticle interactions in concentrated samples. Here we provide an overview of the state-of-the-art, recent developments as well as emerging trends in the field of nano- and microgels. The following aspects build the focus of our discussion: tailoring (multi)functionality through synthesis; the role in biological and biomedical applications; the structure and properties as a model system, e.g., for densely packed arrangements in bulk and at interfaces; as well as the theory and computer simulation.