Showing papers by "University of Toronto published in 2021"
Monash University1, University of Amsterdam2, University of Paris3, Bond University4, University of Texas Health Science Center at San Antonio5, University of Ottawa6, American University of Beirut7, Oregon Health & Science University8, University of York9, Ottawa Hospital Research Institute10, University of Southern Denmark11, Johns Hopkins University12, Brigham and Women's Hospital13, Indiana University14, University of Bristol15, University College London16, University of Toronto17
TL;DR: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement as discussed by the authors was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found.
Abstract: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.
16,613 citations
Harvard University1, University of California, San Francisco2, University of Amsterdam3, Northwestern University4, International Agency for Research on Cancer5, Aix-Marseille University6, University of Toronto7, The Chinese University of Hong Kong8, German Cancer Research Center9, University of Düsseldorf10, University of Turin11, Heidelberg University12, St. Jude Children's Research Hospital13
TL;DR: The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the classification of brain and spinal cord tumors as mentioned in this paper.
Abstract: The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the classification of brain and spinal cord tumors. Building on the 2016 updated fourth edition and the work of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy, the 2021 fifth edition introduces major changes that advance the role of molecular diagnostics in CNS tumor classification. At the same time, it remains wedded to other established approaches to tumor diagnosis such as histology and immunohistochemistry. In doing so, the fifth edition establishes some different approaches to both CNS tumor nomenclature and grading and it emphasizes the importance of integrated diagnoses and layered reports. New tumor types and subtypes are introduced, some based on novel diagnostic technologies such as DNA methylome profiling. The present review summarizes the major general changes in the 2021 fifth edition classification and the specific changes in each taxonomic category. It is hoped that this summary provides an overview to facilitate more in-depth exploration of the entire fifth edition of the WHO Classification of Tumors of the Central Nervous System.
2,908 citations
TL;DR: In this article, the authors used sea ice motion retrievals from Sentinel-1 imagery to report on the recent behavior of these ice arches and the associated ice fluxes, and they showed that the duration of arch formation has decreased over the past 20 years, while the ice area and volume fluxes along Nares Strait have both increased.
Abstract: The ice arches that usually develop at the northern and southern ends of Nares Strait play an important role in modulating the export of Arctic Ocean multi-year sea ice. The Arctic Ocean is evolving towards an ice pack that is younger, thinner, and more mobile and the fate of its multi-year ice is becoming of increasing interest. Here, we use sea ice motion retrievals from Sentinel-1 imagery to report on the recent behavior of these ice arches and the associated ice fluxes. We show that the duration of arch formation has decreased over the past 20 years, while the ice area and volume fluxes along Nares Strait have both increased. These results suggest that a transition is underway towards a state where the formation of these arches will become atypical with a concomitant increase in the export of multi-year ice accelerating the transition towards a younger and thinner Arctic ice pack.
2,774 citations
Monash University1, University of Ottawa2, University of Amsterdam3, University of Paris4, Bond University5, University of Texas Health Science Center at San Antonio6, American University of Beirut7, Oregon Health & Science University8, University of York9, Ottawa Hospital Research Institute10, University of Southern Denmark11, Johns Hopkins University12, Brigham and Women's Hospital13, Indiana University14, University of Bristol15, University College London16, University of Toronto17
TL;DR: The preferred reporting items for systematic reviews and meta-analyses (PRISMA 2020) as mentioned in this paper was developed to facilitate transparent and complete reporting of systematic reviews, and has been updated to reflect recent advances in systematic review methodology and terminology.
Abstract: The methods and results of systematic reviews should be reported in sufficient detail to allow users to assess the trustworthiness and applicability of the review findings. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was developed to facilitate transparent and complete reporting of systematic reviews and has been updated (to PRISMA 2020) to reflect recent advances in systematic review methodology and terminology. Here, we present the explanation and elaboration paper for PRISMA 2020, where we explain why reporting of each item is recommended, present bullet points that detail the reporting recommendations, and present examples from published reviews. We hope that changes to the content and structure of PRISMA 2020 will facilitate uptake of the guideline and lead to more transparent, complete, and accurate reporting of systematic reviews.
2,217 citations
Monash University1, University of Amsterdam2, University of Paris3, Bond University4, University of Texas Health Science Center at San Antonio5, University of Ottawa6, American University of Beirut7, Oregon Health & Science University8, University of York9, Ottawa Hospital Research Institute10, University of Southern Denmark11, Johns Hopkins University12, Brigham and Women's Hospital13, Indiana University14, University of Bristol15, University College London16, University of Toronto17
TL;DR: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement as discussed by the authors was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found.
Abstract: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.
2,192 citations
Monash University1, University of Amsterdam2, University of Paris3, Bond University4, University of Texas Health Science Center at San Antonio5, University of Ottawa6, American University of Beirut7, Oregon Health & Science University8, University of York9, Ottawa Hospital Research Institute10, University of Southern Denmark11, Johns Hopkins University12, Brigham and Women's Hospital13, Indiana University14, University of Bristol15, University College London16, University of Toronto17
TL;DR: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement as discussed by the authors was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found.
1,725 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, Harvard University30, Brigham and Women's Hospital31, 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
Monash University1, University of Amsterdam2, University of Paris3, Bond University4, University of Texas Health Science Center at San Antonio5, University of Ottawa6, American University of Beirut7, Oregon Health & Science University8, University of York9, Ottawa Hospital Research Institute10, University of Southern Denmark11, Johns Hopkins University12, Brigham and Women's Hospital13, Indiana University14, University of Bristol15, University College London16, University of Toronto17
TL;DR: The PRISMA 2020, an updated reporting guideline for systematic reviews and meta-analyses, was proposed by Page and colleagues as discussed by the authors, who describe the guidelines as "an updated reporting guidelines for systematic review and meta analysis".
Abstract: Matthew Page and co-authors describe PRISMA 2020, an updated reporting guideline for systematic reviews and meta-analyses.
824 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.
Monash University1, University of Amsterdam2, University of Paris3, Bond University4, University of Texas Health Science Center at San Antonio5, University of Ottawa6, American University of Beirut7, Oregon Health & Science University8, University of York9, Ottawa Hospital Research Institute10, University of Southern Denmark11, University of Colorado Denver12, Brigham and Women's Hospital13, Indiana University14, University of Bristol15, University College London16, University of Toronto17
TL;DR: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement as discussed by the authors was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found.
TL;DR: The PRISMA-S (Preferred Reporting Items for Systematic reviews and Meta-Analyses literature search extension) checklist as discussed by the authors was developed using a 3-stage Delphi survey process, followed by a consensus conference and public review process.
Abstract: Literature searches underlie the foundations of systematic reviews and related review types. Yet, the literature searching component of systematic reviews and related review types is often poorly reported. Guidance for literature search reporting has been diverse, and, in many cases, does not offer enough detail to authors who need more specific information about reporting search methods and information sources in a clear, reproducible way. This document presents the PRISMA-S (Preferred Reporting Items for Systematic reviews and Meta-Analyses literature search extension) checklist, and explanation and elaboration. The checklist was developed using a 3-stage Delphi survey process, followed by a consensus conference and public review process. The final checklist includes 16 reporting items, each of which is detailed with exemplar reporting and rationale. The intent of PRISMA-S is to complement the PRISMA Statement and its extensions by providing a checklist that could be used by interdisciplinary authors, editors, and peer reviewers to verify that each component of a search is completely reported and therefore reproducible.
University of Edinburgh1, Autonomous University of Madrid2, Pierre-and-Marie-Curie University3, University of Portsmouth4, University of Cape Town5, University of Wisconsin-Madison6, New Mexico State University7, Moscow State University8, New York University9, University of Utah10, University of Toronto11, Université Paris-Saclay12, University of Waterloo13, Sejong University14, Stanford University15, Max Planck Society16, University College London17, Texas Christian University18, National Autonomous University of Mexico19, University of Barcelona20, Universidad de Guanajuato21, Consejo Nacional de Ciencia y Tecnología22, Liverpool John Moores University23, Lawrence Berkeley National Laboratory24, Ohio State University25, École Polytechnique Fédérale de Lausanne26, University of Wyoming27, Haverford College28, University of Oxford29, University of Pittsburgh30, Perimeter Institute for Theoretical Physics31, California Institute of Technology32, Ohio University33, Swinburne University of Technology34, Fermilab35, University of Washington36, Korea Astronomy and Space Science Institute37, Brookhaven National Laboratory38, University of St Andrews39, Durham University40
TL;DR: In this article, the authors present the cosmological implications from final measurements of clustering using galaxies, quasars, and Lyα forests from the completed SDSS lineage of experiments in large-scale structure.
Abstract: We present the cosmological implications from final measurements of clustering using galaxies, quasars, and Lyα forests from the completed Sloan Digital Sky Survey (SDSS) lineage of experiments in large-scale structure. These experiments, composed of data from SDSS, SDSS-II, BOSS, and eBOSS, offer independent measurements of baryon acoustic oscillation (BAO) measurements of angular-diameter distances and Hubble distances relative to the sound horizon, rd, from eight different samples and six measurements of the growth rate parameter, fσ8, from redshift-space distortions (RSD). This composite sample is the most constraining of its kind and allows us to perform a comprehensive assessment of the cosmological model after two decades of dedicated spectroscopic observation. We show that the BAO data alone are able to rule out dark-energy-free models at more than eight standard deviations in an extension to the flat, ΛCDM model that allows for curvature. When combined with Planck Cosmic Microwave Background (CMB) measurements of temperature and polarization, under the same model, the BAO data provide nearly an order of magnitude improvement on curvature constraints relative to primary CMB constraints alone. Independent of distance measurements, the SDSS RSD data complement weak lensing measurements from the Dark Energy Survey (DES) in demonstrating a preference for a flat ΛCDM cosmological model when combined with Planck measurements. The combined BAO and RSD measurements indicate σ8=0.85±0.03, implying a growth rate that is consistent with predictions from Planck temperature and polarization data and with General Relativity. When combining the results of SDSS BAO and RSD, Planck, Pantheon Type Ia supernovae (SNe Ia), and DES weak lensing and clustering measurements, all multiple-parameter extensions remain consistent with a ΛCDM model. Regardless of cosmological model, the precision on each of the three parameters, ωΛ, H0, and σ8, remains at roughly 1%, showing changes of less than 0.6% in the central values between models. In a model that allows for free curvature and a time-evolving equation of state for dark energy, the combined samples produce a constraint ωk=-0.0022±0.0022. The dark energy constraints lead to w0=-0.909±0.081 and wa=-0.49-0.30+0.35, corresponding to an equation of state of wp=-1.018±0.032 at a pivot redshift zp=0.29 and a Dark Energy Task Force Figure of Merit of 94. The inverse distance ladder measurement under this model yields H0=68.18±0.79 km s-1 Mpc-1, remaining in tension with several direct determination methods; the BAO data allow Hubble constant estimates that are robust against the assumption of the cosmological model. In addition, the BAO data allow estimates of H0 that are independent of the CMB data, with similar central values and precision under a ΛCDM model. Our most constraining combination of data gives the upper limit on the sum of neutrino masses at mν<0.115 eV (95% confidence). Finally, we consider the improvements in cosmology constraints over the last decade by comparing our results to a sample representative of the period 2000-2010. We compute the relative gain across the five dimensions spanned by w, ωk, mν, H0, and σ8 and find that the SDSS BAO and RSD data reduce the total posterior volume by a factor of 40 relative to the previous generation. Adding again the Planck, DES, and Pantheon SN Ia samples leads to an overall contraction in the five-dimensional posterior volume of 3 orders of magnitude.
TL;DR: In this paper, the authors compare the performance of R-squared and SMAPE with respect to the distribution of ground truth elements, and show that the coefficient of determination is more informative and truthful than SMAPE, and does not have the interpretability limitations of MSE, RMSE, MAE and MAPE.
Abstract: Regression analysis makes up a large part of supervised machine learning, and consists of the prediction of a continuous independent target from a set of other predictor variables. The difference between binary classification and regression is in the target range: in binary classification, the target can have only two values (usually encoded as 0 and 1), while in regression the target can have multiple values. Even if regression analysis has been employed in a huge number of machine learning studies, no consensus has been reached on a single, unified, standard metric to assess the results of the regression itself. Many studies employ the mean square error (MSE) and its rooted variant (RMSE), or the mean absolute error (MAE) and its percentage variant (MAPE). Although useful, these rates share a common drawback: since their values can range between zero and +infinity, a single value of them does not say much about the performance of the regression with respect to the distribution of the ground truth elements. In this study, we focus on two rates that actually generate a high score only if the majority of the elements of a ground truth group has been correctly predicted: the coefficient of determination (also known as R-squared or R 2) and the symmetric mean absolute percentage error (SMAPE). After showing their mathematical properties, we report a comparison between R 2 and SMAPE in several use cases and in two real medical scenarios. Our results demonstrate that the coefficient of determination (R-squared) is more informative and truthful than SMAPE, and does not have the interpretability limitations of MSE, RMSE, MAE and MAPE. We therefore suggest the usage of R-squared as standard metric to evaluate regression analyses in any scientific domain.
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...
King's College London1, University of Padua2, Karolinska Institutet3, University of Ferrara4, University of Pavia5, Hospital General Universitario Gregorio Marañón6, Yonsei University7, University College London8, University of Cambridge9, National Health Service10, Deakin University11, University of Toronto12
TL;DR: In this article, the authors conducted a systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015).
Abstract: Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset of any mental disorders before the ages of 14, 18, 25 were 34.6%, 48.4%, 62.5%, and peak age was 14.5 years (k = 14, median = 18, interquartile range (IQR) = 11-34). For diagnostic blocks, the proportion of individuals with onset of disorder before the age of 14, 18, 25 and peak age were as follows: neurodevelopmental disorders: 61.5%, 83.2%, 95.8%, 5.5 years (k = 21, median=12, IQR = 7-16), anxiety/fear-related disorders: 38.1%, 51.8%, 73.3%, 5.5 years (k = 73, median = 17, IQR = 9-25), obsessive-compulsive/related disorders: 24.6%, 45.1%, 64.0%, 14.5 years (k = 20, median = 19, IQR = 14-29), feeding/eating disorders/problems: 15.8%, 48.1%, 82.4%, 15.5 years (k = 11, median = 18, IQR = 15-23), conditions specifically associated with stress disorders: 16.9%, 27.6%, 43.1%, 15.5 years (k = 16, median = 30, IQR = 17-48), substance use disorders/addictive behaviours: 2.9%, 15.2%, 48.8%, 19.5 years (k = 58, median = 25, IQR = 20-41), schizophrenia-spectrum disorders/primary psychotic states: 3%, 12.3%, 47.8%, 20.5 years (k = 36, median = 25, IQR = 20-34), personality disorders/related traits: 1.9%, 9.6%, 47.7%, 20.5 years (k = 6, median = 25, IQR = 20-33), and mood disorders: 2.5%, 11.5%, 34.5%, 20.5 years (k = 79, median = 31, IQR = 21-46). No significant difference emerged by sex, or definition of age of onset. Median age at onset for specific mental disorders mapped on a time continuum, from phobias/separation anxiety/autism spectrum disorder/attention deficit hyperactivity disorder/social anxiety (8-13 years) to anorexia nervosa/bulimia nervosa/obsessive-compulsive/binge eating/cannabis use disorders (17-22 years), followed by schizophrenia, personality, panic and alcohol use disorders (25-27 years), and finally post-traumatic/depressive/generalized anxiety/bipolar/acute and transient psychotic disorders (30-35 years), with overlap among groups and no significant clustering. These results inform the timing of good mental health promotion/preventive/early intervention, updating the current mental health system structured around a child/adult service schism at age 18.
Ontario Institute for Cancer Research1, St. John's University2, Federal University of Paraná3, European Bioinformatics Institute4, Medical University of Vienna5, Protein Sciences6, Chongqing University of Posts and Telecommunications7, Oregon Health & Science University8, University of Toronto9, Harvard University10
TL;DR: The Reactome Knowledgebase as mentioned in this paper provides manually curated molecular details across a broad range of physiological and pathological biological processes in humans, including both hereditary and acquired disease processes, annotated as an ordered network of molecular transformations in a single consistent data model.
Abstract: The Reactome Knowledgebase (https://reactome.org), an Elixir core resource, provides manually curated molecular details across a broad range of physiological and pathological biological processes in humans, including both hereditary and acquired disease processes. The processes are annotated as an ordered network of molecular transformations in a single consistent data model. Reactome thus functions both as a digital archive of manually curated human biological processes and as a tool for discovering functional relationships in data such as gene expression profiles or somatic mutation catalogs from tumor cells. Recent curation work has expanded our annotations of normal and disease-associated signaling processes and of the drugs that target them, in particular infections caused by the SARS-CoV-1 and SARS-CoV-2 coronaviruses and the host response to infection. New tools support better simultaneous analysis of high-throughput data from multiple sources and the placement of understudied ('dark') proteins from analyzed datasets in the context of Reactome's manually curated pathways.
Guy's and St Thomas' NHS Foundation Trust1, University College London2, University of Bristol3, University Hospitals Bristol NHS Foundation Trust4, University of Paris5, Hebrew University of Jerusalem6, Turku University Hospital7, Ghent University8, Utrecht University9, University of Malaya10, Imperial College London11, University of Oxford12, Harvard University13, Medanta14, Regeneron15, Université Paris-Saclay16, Ministry of Health (Malaysia)17, Genentech18, University Medical Center Groningen19, University of Chicago20, The Queen's Medical Center21, Karolinska University Hospital22, University of Córdoba (Spain)23, Genzyme24, Albert Schweitzer Hospital25, University of British Columbia26, World Health Organization27, University of Toronto28
TL;DR: In this article, a prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.
Abstract: Importance Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm. Objective To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes. Data Sources Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts. Study Selection Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria. Data Extraction and Synthesis In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using theI2statistic. The primary analysis was an inverse variance–weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality. Main Outcomes and Measures The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days. Results A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95];P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92;P Conclusions and Relevance In this prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality. Trial Registration PROSPERO Identifier:CRD42021230155
Centre for Mental Health1, Swansea University2, University of Sydney3, University of Manchester4, Griffith University5, University College Cork6, Stellenbosch University7, Sao Paulo State University8, University of Zagreb9, University of Rochester Medical Center10, University of Udine11, National Taiwan University12, Innsbruck Medical University13, Yale University14, Johns Hopkins University15, Australian National University16, Brigham and Women's Hospital17, University of Auckland18, Hobart Corporation19, Columbia University Medical Center20, University of Oxford21, National Institute for Health Research22, Aga Khan University23, Katholieke Universiteit Leuven24, University of Bristol25, University of Peradeniya26, World Health Organization27, Karolinska Institutet28, First Pavlov State Medical University of St. Peterburg29, Medical University of Vienna30, University of Nottingham31, University of Glasgow32, University of Edinburgh33, Shanghai Jiao Tong University34, Columbia University35, University of Ulm36, University of Oslo37, Goethe University Frankfurt38, Saint Petersburg State University39, University of Toronto40, Sunnybrook Health Sciences Centre41, Waseda University42, Rajarata University of Sri Lanka43, Tel Aviv University44, University Hospitals Bristol NHS Foundation Trust45
TL;DR: In this article, the early effect of the COVID-19 pandemic on suicide rates around the world was assessed using real-time suicide data from countries or areas within countries through a systematic internet search and recourse to our networks and the published literature.
TL;DR: In this paper, the prevalence and associated factors of antibiotic prescribing in patients with SARS-CoV-2 infection were estimated in a randomized controlled trial with 30,623 patients.
TL;DR: 3D variability analysis (3DVA) as discussed by the authors fits a linear subspace model of conformational change to cryo-EM data at high resolution, enabling the resolution and visualization of detailed molecular motions of both large and small proteins.
University of Siena1, University of Göttingen2, UCL Institute of Neurology3, City College of New York4, National Institutes of Health5, Brown University6, University of Toronto7, Università Campus Bio-Medico8, Beth Israel Deaconess Medical Center9, Medical University of South Carolina10, Cincinnati Children's Hospital Medical Center11, Aristotle University of Thessaloniki12, Aalto University13, Paris 12 Val de Marne University14, Vita-Salute San Raffaele University15, University of Trento16, Ludwig Maximilian University of Munich17, Harvard University18, Duke University19, University of Messina20, Copenhagen University Hospital21, Fukushima Medical University22, Ben-Gurion University of the Negev23, University of Tübingen24
TL;DR: New operational guidelines are provided for safety in planning future trials based on traditional and patterned TMS protocols, as well as a summary of the minimal training requirements for operators, and a note on ethics of neuroenhancement.
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 quantum-confined semiconductor nanostructures, electrons exhibit distinctive behavior compared with that in bulk solids as mentioned in this paper, which enables the design of materials with tunable chemical, physical, electrical, and optical properties.
Abstract: In quantum-confined semiconductor nanostructures, electrons exhibit distinctive behavior compared with that in bulk solids. This enables the design of materials with tunable chemical, physical, electrical, and optical properties. Zero-dimensional semiconductor quantum dots (QDs) offer strong light absorption and bright narrowband emission across the visible and infrared wavelengths and have been engineered to exhibit optical gain and lasing. These properties are of interest for imaging, solar energy harvesting, displays, and communications. Here, we offer an overview of advances in the synthesis and understanding of QD nanomaterials, with a focus on colloidal QDs, and discuss their prospects in technologies such as displays and lighting, lasers, sensing, electronics, solar energy conversion, photocatalysis, and quantum information.
TL;DR: This paper aims to demonstrate the efforts towards in-situ applicability of EMMARM, which aims to provide real-time information about the physical and emotional impacts of age-related illness and disability on individuals and society.
Abstract: 1School of Social Work, Bar Ilan University, Ramat Gan, Israel. 2Department of Psychology, University of Toronto, Ontario, Canada. 3Department of Human Development and Family Studies, Colorado State University, Fort Collins. 4Social and Behavioral Sciences Department, Yale School of Public Health, New Haven, Connecticut. 5Department of Psychology, North Carolina State University, Raleigh. 6Department of Psychology, Friedrich-Schiller-University Jena, Germany. 7German Centre of Gerontology, Berlin, Germany. 8Network of Aging Research, Heidelberg University, Germany.
TL;DR: Aghanim et al. as mentioned in this paper used the same data set to derive a 95% upper bound of 0.020 using the principal component analysis (PCA) model and uniform priors on the PCA mode amplitudes.
Abstract: Author(s): Aghanim, N; Akrami, Y; Ashdown, M; Aumont, J; Baccigalupi, C; Ballardini, M; Banday, AJ; Barreiro, RB; Bartolo, N; Basak, S; Battye, R; Benabed, K; Bernard, JP; Bersanelli, M; Bielewicz, P; Bock, JJ; Bond, JR; Borrill, J; Bouchet, FR; Boulanger, F; Bucher, M; Burigana, C; Butler, RC; Calabrese, E; Cardoso, JF; Carron, J; Challinor, A; Chiang, HC; Chluba, J; Colombo, LPL; Combet, C; Contreras, D; Crill, BP; Cuttaia, F; De Bernardis, P; De Zotti, G; Delabrouille, J; Delouis, JM; DI Valentino, E; DIego, JM; Dore, O; Douspis, M; Ducout, A; Dupac, X; Dusini, S; Efstathiou, G; Elsner, F; Enslin, TA; Eriksen, HK; Fantaye, Y; Farhang, M; Fergusson, J; Fernandez-Cobos, R; Finelli, F; Forastieri, F; Frailis, M; Fraisse, AA; Franceschi, E; Frolov, A; Galeotta, S; Galli, S; Ganga, K; Genova-Santos, RT; Gerbino, M; Ghosh, T; Gonzalez-Nuevo, J; Gorski, KM; Gratton, S; Gruppuso, A; Gudmundsson, JE; Hamann, J; Handley, W; Hansen, FK; Herranz, D; Hildebrandt, SR; Hivon, E; Huang, Z; Jaffe, AH; Jones, WC; Karakci, A; Keihanen, E; Keskitalo, R; Kiiveri, K; Kim, J; Kisner, TS | Abstract: In the original version, the bounds given in Eqs. (87a) and (87b) on the contribution to the early-time optical depth, (15,30), contained a numerical error in deriving the 95th percentile from the Monte Carlo samples. The corrected 95% upper bounds are: τ(15,30) l 0:018 (lowE, flat τ(15, 30), FlexKnot), (1) τ(15, 30) l 0:023 (lowE, flat knot, FlexKnot): (2) These bounds are a factor of 3 larger than the originally reported results. Consequently, the new bounds do not significantly improve upon previous results from Planck data presented in Millea a Bouchet (2018) as was stated, but are instead comparable. Equations (1) and (2) give results that are now similar to those of Heinrich a Hu (2021), who used the same Planck 2018 data to derive a 95% upper bound of 0.020 using the principal component analysis (PCA) model and uniform priors on the PCA mode amplitudes.
TL;DR: Results reveal unanticipated risks of 6PPD antioxidants to an aquatic species and imply toxicological relevance for dissipated tire rubber residues, and identify a highly toxic quinone transformation product of N-(1,3-dimethylbutyl)-N′-phenyl-p- Phenylenediamine (6PPD), a globally ubiquitous tire rubber antioxidant.
Abstract: In U.S. Pacific Northwest coho salmon (Oncorhynchus kisutch), stormwater exposure annually causes unexplained acute mortality when adult salmon migrate to urban creeks to reproduce. By investigating this phenomenon, we identified a highly toxic quinone transformation product of N-(1,3-dimethylbutyl)-N9-phenyl-p-phenylenediamine) (6PPD), a globally ubiquitous tire rubber antioxidant. Retrospective analysis of representative roadway runoff and stormwater-impacted creeks of the U.S. West Coast indicated widespread occurrence of 6PPD-quinone (
TL;DR: In this article, the authors use an interrupted time series to study the political effect of the enforcement of a strict confinement policy in response to the COVID-19 pandemic, and find that lockdowns have increased vote intentions for the party of the prime minister/president, trust in government and satisfaction with democracy.
Abstract: Major crises can act as critical junctures or reinforce the political status quo, depending on how citizens view the performance of central institutions. We use an interrupted time series to study the political effect of the enforcement of a strict confinement policy in response to the COVID-19 pandemic. Specifically, we take advantage of a unique representative web-based survey that was fielded in March and April 2020 in Western Europe to compare the political support of those who took the survey right before and right after the start of the lockdown in their country. We find that lockdowns have increased vote intentions for the party of the Prime Minister/President, trust in government and satisfaction with democracy. Furthermore, we find that, while rallying individuals around current leaders and institutions, they have had no effect on traditional left–right attitudes.