Showing papers by "University College London 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
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
TL;DR: The B.617.1.2 variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Coronavirus disease 2019 (Covid-19), has contributed to the development of the disease.
Abstract: Background The B.1.617.2 (delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), has contributed to ...
2,032 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
TL;DR: In this paper, the authors analyzed data from 4,182 incident cases of COVID-19 in which individuals self-reported their symptoms prospectively in the COVID Symptom Study app.
Abstract: Reports of long-lasting coronavirus disease 2019 (COVID-19) symptoms, the so-called 'long COVID', are rising but little is known about prevalence, risk factors or whether it is possible to predict a protracted course early in the disease. We analyzed data from 4,182 incident cases of COVID-19 in which individuals self-reported their symptoms prospectively in the COVID Symptom Study app1. A total of 558 (13.3%) participants reported symptoms lasting ≥28 days, 189 (4.5%) for ≥8 weeks and 95 (2.3%) for ≥12 weeks. Long COVID was characterized by symptoms of fatigue, headache, dyspnea and anosmia and was more likely with increasing age and body mass index and female sex. Experiencing more than five symptoms during the first week of illness was associated with long COVID (odds ratio = 3.53 (2.76-4.50)). A simple model to distinguish between short COVID and long COVID at 7 days (total sample size, n = 2,149) showed an area under the curve of the receiver operating characteristic curve of 76%, with replication in an independent sample of 2,472 individuals who were positive for severe acute respiratory syndrome coronavirus 2. This model could be used to identify individuals at risk of long COVID for trials of prevention or treatment and to plan education and rehabilitation services.
1,222 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
TL;DR: The status of InterPro (version 81.0) in its 20th year of operation, and its associated software, is reported, including updates to database content, the release of a new website and REST API, and performance improvements in InterProScan.
Abstract: The InterPro database (https://www.ebi.ac.uk/interpro/) provides an integrative classification of protein sequences into families, and identifies functionally important domains and conserved sites. InterProScan is the underlying software that allows protein and nucleic acid sequences to be searched against InterPro's signatures. Signatures are predictive models which describe protein families, domains or sites, and are provided by multiple databases. InterPro combines signatures representing equivalent families, domains or sites, and provides additional information such as descriptions, literature references and Gene Ontology (GO) terms, to produce a comprehensive resource for protein classification. Founded in 1999, InterPro has become one of the most widely used resources for protein family annotation. Here, we report the status of InterPro (version 81.0) in its 20th year of operation, and its associated software, including updates to database content, the release of a new website and REST API, and performance improvements in InterProScan.
1,108 citations
TL;DR: In this paper, the authors conducted an online survey of people with confirmed and confirmed COVID-19, distributed via COVID19 support groups and social media (e.g. Body Politic, Long COVID Support Group, Long Haul COVID Fighters).
996 citations
Erola Pairo-Castineira1, Erola Pairo-Castineira2, Sara Clohisey1, Lucija Klaric2 +1446 more•Institutions (27)
TL;DR: The GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2244 critically ill Covid-19 patients from 208 UK intensive care units is reported, finding evidence in support of a causal link from low expression of IFNAR2, and high expression of TYK2, to life-threatening disease.
Abstract: Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10−8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10−8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 × 10−12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10−8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte–macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice. A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.
941 citations
University College London1, International Institute for Applied Systems Analysis2, University of Reading3, United Nations University4, University of London5, University of Colorado Boulder6, Umeå University7, Tsinghua University8, World Health Organization9, Cardiff University10, University of Geneva11, University of New England (United States)12, University of Birmingham13, Yale University14, University of Washington15, Northeastern University16, Virginia Tech17, University of Oxford18, University of York19, International Livestock Research Institute20, Cayetano Heredia University21, Harvard University22, Boston University23, University of Sussex24, Nelson Marlborough Institute of Technology25, Emory University26, Columbia University27, Autonomous University of Barcelona28, Technische Universität München29, University of Melbourne30, Iran University of Medical Sciences31, University of Exeter32, Imperial College London33, University of Sheffield34, European Centre for Disease Prevention and Control35, Universiti Malaysia Terengganu36, University of Santiago de Compostela37
TL;DR: TRANSLATIONS For the Chinese, French, German, and Spanish translations of the abstract see Supplementary Materials section.
TL;DR: In this paper, the authors showed that adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 24 mg as an anesthetic drug.
Abstract: Background Obesity is a global health challenge with few pharmacologic options Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 24 mg as an a
University of Cambridge1, University College London2, National Centre for Disease Control3, Laboratory of Molecular Biology4, Institute of Genomics and Integrative Biology5, Imperial College London6, Medical Research Council7, Apollo Hospital, Indraprastha8, Hiroshima University9, University of Tokyo10, University of Copenhagen11, University of Oxford12
TL;DR: The B.617.1.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike as discussed by the authors.
Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.
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.
Université Paris-Saclay1, Autonomous University of Barcelona2, University of Cambridge3, National Institute for Occupational Safety and Health4, University of Bonn5, German Center for Neurodegenerative Diseases6, Harvard University7, University of Lausanne8, University of Padua9, National Research Council10, Heidelberg University11, Salk Institute for Biological Studies12, University of Minnesota13, Pasteur Institute14, Tel Aviv University15, Johns Hopkins University16, University of Portsmouth17, Katholieke Universiteit Leuven18, PSL Research University19, Trinity College, Dublin20, Baylor College of Medicine21, University College London22, University of Edinburgh23, Oregon Health & Science University24, National Institutes of Health25, Columbia University26, University of Copenhagen27, University of Rochester28, Ludwig Maximilian University of Munich29, University of Málaga30, Tufts University31, University of Freiburg32, Utrecht University33, Nihon University34, Max Delbrück Center for Molecular Medicine35, University of California, Los Angeles36, University of Yamanashi37, New York University38, University of British Columbia39, King Abdullah University of Science and Technology40, University of Wisconsin-Madison41, University of California, San Francisco42, McGill University43, University of Kentucky44, Kyushu University45, University of Bordeaux46, Polytechnic Institute of Cávado and Ave47, University of Minho48, University of Alabama at Birmingham49, University of Gothenburg50, University of Poitiers51, Cajal Institute52, King's College London53, University of Strasbourg54, Virginia Tech55, University of Düsseldorf56, I.M. Sechenov First Moscow State Medical University57, Russian Academy of Sciences58, University of Seville59, Georgia Institute of Technology60, University of Texas Health Science Center at Houston61, University of California, San Diego62, Universidade Federal do Rio Grande do Sul63, University of Ljubljana64, Ikerbasque65, University of Manchester66
TL;DR: In this article, the authors point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic vs-neuroprotective or A1-vs.A2.
Abstract: Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions.
TL;DR: This article found that those resistant to a COVID-19 vaccine were less likely to obtain information about the pandemic from traditional and authoritative sources and had similar levels of mistrust in these sources compared to vaccine accepting respondents.
Abstract: Identifying and understanding COVID-19 vaccine hesitancy within distinct populations may aid future public health messaging. Using nationally representative data from the general adult populations of Ireland (N = 1041) and the United Kingdom (UK; N = 2025), we found that vaccine hesitancy/resistance was evident for 35% and 31% of these populations respectively. Vaccine hesitant/resistant respondents in Ireland and the UK differed on a number of sociodemographic and health-related variables but were similar across a broad array of psychological constructs. In both populations, those resistant to a COVID-19 vaccine were less likely to obtain information about the pandemic from traditional and authoritative sources and had similar levels of mistrust in these sources compared to vaccine accepting respondents. Given the geographical proximity and socio-economic similarity of the populations studied, it is not possible to generalize findings to other populations, however, the methodology employed here may be useful to those wishing to understand COVID-19 vaccine hesitancy elsewhere.
TL;DR: There is preliminary evidence that children and adolescents have lower susceptibility to SARS-CoV-2, with the pooled odds ratio of 0.56 for being an infected contact compared with adults, although seroprevalence in adolescents appeared similar to adults.
Abstract: Importance The degree to which children and adolescents are infected by and transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. The role of children and adolescents in transmission of SARS-CoV-2 is dependent on susceptibility, symptoms, viral load, social contact patterns, and behavior. Objective To systematically review the susceptibility to and transmission of SARS-CoV-2 among children and adolescents compared with adults. Data Sources PubMed and medRxiv were searched from database inception to July 28, 2020, and a total of 13 926 studies were identified, with additional studies identified through hand searching of cited references and professional contacts. Study Selection Studies that provided data on the prevalence of SARS-CoV-2 in children and adolescents (younger than 20 years) compared with adults (20 years and older) derived from contact tracing or population screening were included. Single-household studies were excluded. Data Extraction and Synthesis PRISMA guidelines for abstracting data were followed, which was performed independently by 2 reviewers. Quality was assessed using a critical appraisal checklist for prevalence studies. Random-effects meta-analysis was undertaken. Main Outcomes and Measures Secondary infection rate (contact-tracing studies) or prevalence or seroprevalence (population screening studies) among children and adolescents compared with adults. Results A total of 32 studies comprising 41 640 children and adolescents and 268 945 adults met inclusion criteria, including 18 contact-tracing studies and 14 population screening studies. The pooled odds ratio of being an infected contact in children compared with adults was 0.56 (95% CI, 0.37-0.85), with substantial heterogeneity (I2 = 94.6%). Three school-based contact-tracing studies found minimal transmission from child or teacher index cases. Findings from population screening studies were heterogenous and were not suitable for meta-analysis. Most studies were consistent with lower seroprevalence in children compared with adults, although seroprevalence in adolescents appeared similar to adults. Conclusions and Relevance In this meta-analysis, there is preliminary evidence that children and adolescents have lower susceptibility to SARS-CoV-2, with an odds ratio of 0.56 for being an infected contact compared with adults. There is weak evidence that children and adolescents play a lesser role than adults in transmission of SARS-CoV-2 at a population level. This study provides no information on the infectivity of children.
Cornell University1, National University of Singapore2, University of New South Wales3, University of Lausanne4, University of Michigan5, Erasmus University Rotterdam6, Tel Aviv University7, University of Melbourne8, Singapore Management University9, University of Maryland, College Park10, University of Pennsylvania11, Eindhoven University of Technology12, Stanford University13, Concordia University14, London Business School15, Baylor University16, University College London17, California State University, Sacramento18, INSEAD19, Saint Louis University20, Nanyang Technological University21, University of Minnesota22, Harvard University23, University of Arkansas24, VU University Amsterdam25
TL;DR: A broad-scope overview provides an integrative approach for considering the implications of COVID-19 for work, workers, and organizations while also identifying issues for future research and insights to inform solutions.
Abstract: The impacts of COVID-19 on workers and workplaces across the globe have been dramatic. This broad review of prior research rooted in work and organizational psychology, and related fields, is intended to make sense of the implications for employees, teams, and work organizations. This review and preview of relevant literatures focuses on (a) emergent changes in work practices (e.g., working from home, virtual teamwork) and (b) emergent changes for workers (e.g., social distancing, stress, and unemployment). In addition, potential moderating factors (demographic characteristics, individual differences, and organizational norms) are examined given the likelihood that COVID-19 will generate disparate effects. This broad-scope overview provides an integrative approach for considering the implications of COVID-19 for work, workers, and organizations while also identifying issues for future research and insights to inform solutions. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
TL;DR: In this paper, the authors report chronic SARS-CoV-2 with reduced sensitivity to neutralizing antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences over 23 time points spanning 101 days.
Abstract: SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE21, and is a major antibody target. Here we report chronic SARS-CoV-2 with reduced sensitivity to neutralising antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences over 23 time points spanning 101 days. Little change was observed in the overall viral population structure following two courses of remdesivir over the first 57 days. However, following convalescent plasma therapy we observed large, dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and ΔH69/ΔV70 in the S1 N-terminal domain NTD of the Spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype diminished in frequency, before returning during a final, unsuccessful course of convalescent plasma. In vitro, the Spike escape double mutant bearing ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, whilst maintaining infectivity similar to wild type. D796H appeared to be the main contributor to decreased susceptibility but incurred an infectivity defect. The ΔH69/ΔV70 single mutant had two-fold higher infectivity compared to wild type, possibly compensating for the reduced infectivity of D796H. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy associated with emergence of viral variants with evidence of reduced susceptibility to neutralising antibodies.
01 Feb 2021
TL;DR: Amongst vaccine attitudes, intermediate to high levels of mistrust of vaccine benefit and concerns about future unforeseen side effects were the most important determinants of both uncertainty and unwillingness to vaccinate against COVID-19.
Abstract: Background: Negative attitudes towards vaccines and an uncertainty or unwillingness to receive vaccinations are major barriers to managing the COVID-19 pandemic in the long-term. We estimate predictors of four domains of negative attitudes towards vaccines and identify groups most at risk of uncertainty and unwillingness to receive a COVID-19 vaccine in a large sample of UK adults. Methods: Data were cross-sectional and from 32,361 adults in the UCL COVID-19 Social Study. Ordinary least squares regression analyses examined the impact of socio-demographic and COVID-19 related factors on four types of negative vaccine attitudes: mistrust of vaccine benefit, worries about unforeseen effects, concerns about commercial profiteering, and preference for natural immunity. Multinomial regression examined the impact of socio-demographic and COVID-19 related factors, negative vaccine attitudes, and prior vaccine behaviour on uncertainty and unwillingness to be vaccinated for COVID-19. Findings: 16% of respondents displayed high levels of mistrust about vaccines across one or more domains. Distrustful attitudes towards vaccination were higher amongst individuals from ethnic minority backgrounds, with lower levels of education, lower annual income, poor knowledge of COVID-19, and poor compliance with government COVID-19 guidelines. Overall, 14% of respondents reported unwillingness to receive a vaccine for COVID-19, whilst 23% were unsure. The largest predictors of both COVID-19 vaccine uncertainty and refusal were low-income groups (< 16,000, a year), having not received a flu vaccine last year, poor adherence to COVID-19 government guidelines, female gender, and living with children. Amongst vaccine attitudes, intermediate to high levels of mistrust of vaccine benefit and concerns about future unforeseen side effects were the most important determinants of both uncertainty and unwillingness to vaccinate against COVID-19. Interpretation: Negative attitudes towards vaccines are a major public health concern in the UK. General mistrust in vaccines and concerns about future side effects in particular will be barriers to achieving population immunity to COVID-19 through vaccination. Public health messaging should be tailored to address these concerns and specifically to women, ethnic minorities, and people with lower levels of education and incomes. Funding: The Nuffield Foundation [WEL/FR-000022583], the MARCH Mental Health Network funded by the Cross-Disciplinary Mental Health Network Plus initiative supported by UK Research and Innovation [ES/S002588/1], and the Wellcome Trust [221400/Z/20/Z and 205407/Z/16/Z].
TL;DR: The findings emphasise the importance of supporting individuals in the lead-up to future lockdowns to try to reduce distress, and highlight that groups already at risk for poor mental health before the pandemic have remained at risk throughout lockdown and its aftermath.
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: In this article, the authors evaluated the relationship between efficacy and in vitro neutralizing and binding antibodies of 7 vaccines for which sufficient data have been generated, and they found a robust correlation was seen between neutralizing titer and efficacy.
Innsbruck Medical University1, The Catholic University of America2, First Faculty of Medicine, Charles University in Prague3, Copenhagen University Hospital4, University of Cologne5, University College London6, Leiden University Medical Center7, Institut Gustave Roussy8, Agostino Gemelli University Polyclinic9, Imperial College London10, University of Navarra11, Johannes Kepler University of Linz12, Erasmus University Rotterdam13, Humboldt University of Berlin14, Medical University of Vienna15, The Royal Marsden NHS Foundation Trust16, University of Amsterdam17, Dresden University of Technology18, European Institute of Oncology19
TL;DR: A European consensus conference on endometrial carcinoma was held in 2014 to produce multi-disciplinary evidence-based guidelines on selected questions as mentioned in this paper, and the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy and Oncologies (ESTRO), and the EPSP jointly decided to update these evidence-base guidelines and to cover new topics in order to improve the quality of care for women with endometrium carcinoma across Europe and worldwide.
Abstract: A European consensus conference on endometrial carcinoma was held in 2014 to produce multi-disciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide.
TL;DR: The SIREN study as discussed by the authors showed that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults in the UK.
University of Edinburgh1, Autonomous University of Madrid2, Pierre-and-Marie-Curie University3, University of Portsmouth4, University of Wisconsin-Madison5, University of Cape Town6, 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 article, the authors assessed the immune responses of individuals after vaccination with the mRNA-based vaccine BNT162b22.1.7 and found that the emergence of the E484K substitution in a B.1, 1.1., 1.7 background represents a threat to the efficacy of the BNT 162b2 vaccine.
Abstract: Transmission of SARS-CoV-2 is uncontrolled in many parts of the world; control is compounded in some areas by the higher transmission potential of the B.1.1.7 variant1, which has now been reported in 94 countries. It is unclear whether the response of the virus to vaccines against SARS-CoV-2 on the basis of the prototypic strain will be affected by the mutations found in B.1.1.7. Here we assess the immune responses of individuals after vaccination with the mRNA-based vaccine BNT162b22. We measured neutralizing antibody responses after the first and second immunizations using pseudoviruses that expressed the wild-type spike protein or a mutated spike protein that contained the eight amino acid changes found in the B.1.1.7 variant. The sera from individuals who received the vaccine exhibited a broad range of neutralizing titres against the wild-type pseudoviruses that were modestly reduced against the B.1.1.7 variant. This reduction was also evident in sera from some patients who had recovered from COVID-19. Decreased neutralization of the B.1.1.7 variant was also observed for monoclonal antibodies that target the N-terminal domain (9 out of 10) and the receptor-binding motif (5 out of 31), but not for monoclonal antibodies that recognize the receptor-binding domain that bind outside the receptor-binding motif. Introduction of the mutation that encodes the E484K substitution in the B.1.1.7 background to reflect a newly emerged variant of concern (VOC 202102/02) led to a more-substantial loss of neutralizing activity by vaccine-elicited antibodies and monoclonal antibodies (19 out of 31) compared with the loss of neutralizing activity conferred by the mutations in B.1.1.7 alone. The emergence of the E484K substitution in a B.1.1.7 background represents a threat to the efficacy of the BNT162b2 vaccine.
Guy's and St Thomas' NHS Foundation Trust1, Changi General Hospital2, Government Medical College, Srinagar3, University of California, Los Angeles4, Rabin Medical Center5, Tel Aviv University6, The Chinese University of Hong Kong7, Guy's Hospital8, King's College London9, Swansea University10, Belfast Health and Social Care Trust11, Aga Khan University12, Harefield Hospital13, Shanghai University14, University College London15, Hospital Clínico San Carlos16, Università Campus Bio-Medico17, Indiana University18, Kasturba Medical College, Manipal19
TL;DR: In order to maintain relevance and continue upholding good reporting quality among observational studies in surgery, this paper aimed to update STROCSS 2019 guidelines, which were developed in 2017 and updated in 2019.
TL;DR: Transthyretin amyloidosis (ATTR) is a life-threatening disease characterized by progressive accumulation of misfolded transthyrein (TTR) protein in tissus as mentioned in this paper.
Abstract: Background Transthyretin amyloidosis, also called ATTR amyloidosis, is a life-threatening disease characterized by progressive accumulation of misfolded transthyretin (TTR) protein in tiss...
TL;DR: The crucial role of diagnostic tests during the first global wave of coronavirus disease 2019 (COVID-19) and the technical and implementation problems encountered during the early phase of the pandemic are explored and future directions for the progressive and better use of diagnostics during a possible resurgence of CO VID-19 in future global waves or regional outbreaks are defined.
Abstract: During the early phase of the coronavirus disease 2019 (COVID-19) pandemic, design, development, validation, verification and implementation of diagnostic tests were actively addressed by a large number of diagnostic test manufacturers. Hundreds of molecular tests and immunoassays were rapidly developed, albeit many still await clinical validation and formal approval. In this Review, we summarize the crucial role of diagnostic tests during the first global wave of COVID-19. We explore the technical and implementation problems encountered during this early phase in the pandemic, and try to define future directions for the progressive and better use of (syndromic) diagnostics during a possible resurgence of COVID-19 in future global waves or regional outbreaks. Continuous global improvement in diagnostic test preparedness is essential for more rapid detection of patients, possibly at the point of care, and for optimized prevention and treatment, in both industrialized countries and low-resource settings.