Showing papers by "University of Leicester published in 2020"
Maastricht University1, University of Bologna2, University of Melbourne3, University of Leicester4, Federation University Australia5, University of British Columbia6, Imperial College London7, University of London8, Public Health Foundation of India9, University of Western Australia10, Baker IDI Heart and Diabetes Institute11, National and Kapodistrian University of Athens12, University of Manchester13, Manchester Academic Health Science Centre14, Boston University15, University College London16, University of New South Wales17, North-West University18, The George Institute for Global Health19
TL;DR: Document reviewers: Hind Beheiry (Sudan), Irina Chazova (Russia), Albertino Damasceno (Mozambique), Anna Dominiczak (UK), Stephen Harrap (Australia), Hiroshi Itoh (Japan), Tazeen Jafar (Singapore), Marc Jaffe (USA), Patricio Jaramillo-Lopez (Colombia), Kazuomi Kario (Japan).
Abstract: Document reviewers: Hind Beheiry (Sudan), Irina Chazova (Russia), Albertino Damasceno (Mozambique), Anna Dominiczak (UK), Anastase Dzudie (Cameroon), Stephen Harrap (Australia), Hiroshi Itoh (Japan), Tazeen Jafar (Singapore), Marc Jaffe (USA), Patricio Jaramillo-Lopez (Colombia), Kazuomi Kario (Japan), Giuseppe Mancia (Italy), Ana Mocumbi (Mozambique), Sanjeevi N.Narasingan (India), Elijah Ogola (Kenya), Srinath Reddy (India), Ernesto Schiffrin (Canada), Ann Soenarta (Indonesia), Rhian Touyz (UK), Yudah Turana (Indonesia), Michael Weber (USA), Paul Whelton (USA), Xin Hua Zhang, (Australia), Yuqing Zhang (China).
1,657 citations
University of Leicester1, Leicester General Hospital2, Duke University3, National Institutes of Health4, Yale University5, Katholieke Universiteit Leuven6, King's College London7, The Catholic University of America8, Steno Diabetes Center9, University of Copenhagen10, Harvard University11, University of North Carolina at Chapel Hill12
TL;DR: A panel to update the prior position statements on the management of type 2 diabetes in adults includes additional focus on lifestyle management and diabetes self-management education and support and efforts targeting weight loss.
Abstract: The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the literature since 2014 informed new recommendations. These include additional focus on lifestyle management and diabetes self-management education and support. For those with obesity, efforts targeting weight loss, including lifestyle, medication and surgical interventions, are recommended. With regards to medication management, for patients with clinical cardiovascular disease, a sodium–glucose cotransporter-2 (SGLT2) inhibitor or a glucagon-like peptide-1 (GLP-1) receptor agonist with proven cardiovascular benefit is recommended. For patients with chronic kidney disease or clinical heart failure and atherosclerotic cardiovascular disease, an SGLT2 inhibitor with proven benefit is recommended. GLP-1 receptor agonists are generally recommended as the first injectable medication.
1,192 citations
Université Paris-Saclay1, Commonwealth Scientific and Industrial Research Organisation2, Goddard Space Flight Center3, Stanford University4, Yale University5, National Oceanic and Atmospheric Administration6, Netherlands Institute for Space Research7, VU University Amsterdam8, Chiba University9, Japan Agency for Marine-Earth Science and Technology10, Linköping University11, University of California, Irvine12, National Institute of Water and Atmospheric Research13, New York University14, Seconda Università degli Studi di Napoli15, École Polytechnique16, Stockholm University17, Skidmore College18, University of Victoria19, Babeș-Bolyai University20, National Institute of Geophysics and Volcanology21, California Institute of Technology22, Met Office23, University of Reading24, International Institute for Applied Systems Analysis25, National Institute for Environmental Studies26, City University of New York27, University of Bern28, Max Planck Society29, Purdue University30, European Centre for Medium-Range Weather Forecasts31, Lund University32, University of Bristol33, Geophysical Fluid Dynamics Laboratory34, University of Leicester35, Université du Québec à Montréal36, Peking University37, Massachusetts Institute of Technology38, Lawrence Berkeley National Laboratory39, Southern Cross University40, Auburn University41, Joint Global Change Research Institute42, Food and Agriculture Organization43, Finnish Meteorological Institute44, Technical University of Crete45, Imperial College London46, University of Rochester47, Royal Netherlands Meteorological Institute48, Scripps Institution of Oceanography49, University of Toronto50, University of Maryland, College Park51, Hohai University52
TL;DR: The second version of the living review paper dedicated to the decadal methane budget, integrating results of top-down studies (atmospheric observations within an atmospheric inverse-modeling framework) and bottom-up estimates (including process-based models for estimating land surface emissions and atmospheric chemistry, inventories of anthropogenic emissions, and data-driven extrapolations) as discussed by the authors.
Abstract: Understanding and quantifying the global methane (CH4) budget is important for assessing realistic pathways to mitigate climate change. Atmospheric emissions and concentrations of CH4 continue to increase, making CH4 the second most important human-influenced greenhouse gas in terms of climate forcing, after carbon dioxide (CO2). The relative importance of CH4 compared to CO2 depends on its shorter atmospheric lifetime, stronger warming potential, and variations in atmospheric growth rate over the past decade, the causes of which are still debated. Two major challenges in reducing uncertainties in the atmospheric growth rate arise from the variety of geographically overlapping CH4 sources and from the destruction of CH4 by short-lived hydroxyl radicals (OH). To address these challenges, we have established a consortium of multidisciplinary scientists under the umbrella of the Global Carbon Project to synthesize and stimulate new research aimed at improving and regularly updating the global methane budget. Following Saunois et al. (2016), we present here the second version of the living review paper dedicated to the decadal methane budget, integrating results of top-down studies (atmospheric observations within an atmospheric inverse-modelling framework) and bottom-up estimates (including process-based models for estimating land surface emissions and atmospheric chemistry, inventories of anthropogenic emissions, and data-driven extrapolations).
For the 2008–2017 decade, global methane emissions are estimated by atmospheric inversions (a top-down approach) to be 576 Tg CH4 yr−1 (range 550–594, corresponding to the minimum and maximum estimates of the model ensemble). Of this total, 359 Tg CH4 yr−1 or ∼ 60 % is attributed to anthropogenic sources, that is emissions caused by direct human activity (i.e. anthropogenic emissions; range 336–376 Tg CH4 yr−1 or 50 %–65 %). The mean annual total emission for the new decade (2008–2017) is 29 Tg CH4 yr−1 larger than our estimate for the previous decade (2000–2009), and 24 Tg CH4 yr−1 larger than the one reported in the previous budget for 2003–2012 (Saunois et al., 2016). Since 2012, global CH4 emissions have been tracking the warmest scenarios assessed by the Intergovernmental Panel on Climate Change. Bottom-up methods suggest almost 30 % larger global emissions (737 Tg CH4 yr−1, range 594–881) than top-down inversion methods. Indeed, bottom-up estimates for natural sources such as natural wetlands, other inland water systems, and geological sources are higher than top-down estimates. The atmospheric constraints on the top-down budget suggest that at least some of these bottom-up emissions are overestimated. The latitudinal distribution of atmospheric observation-based emissions indicates a predominance of tropical emissions (∼ 65 % of the global budget, < 30∘ N) compared to mid-latitudes (∼ 30 %, 30–60∘ N) and high northern latitudes (∼ 4 %, 60–90∘ N). The most important source of uncertainty in the methane budget is attributable to natural emissions, especially those from wetlands and other inland waters.
Some of our global source estimates are smaller than those in previously published budgets (Saunois et al., 2016; Kirschke et al., 2013). In particular wetland emissions are about 35 Tg CH4 yr−1 lower due to improved partition wetlands and other inland waters. Emissions from geological sources and wild animals are also found to be smaller by 7 Tg CH4 yr−1 by 8 Tg CH4 yr−1, respectively. However, the overall discrepancy between bottom-up and top-down estimates has been reduced by only 5 % compared to Saunois et al. (2016), due to a higher estimate of emissions from inland waters, highlighting the need for more detailed research on emissions factors. Priorities for improving the methane budget include (i) a global, high-resolution map of water-saturated soils and inundated areas emitting methane based on a robust classification of different types of emitting habitats; (ii) further development of process-based models for inland-water emissions; (iii) intensification of methane observations at local scales (e.g., FLUXNET-CH4 measurements) and urban-scale monitoring to constrain bottom-up land surface models, and at regional scales (surface networks and satellites) to constrain atmospheric inversions; (iv) improvements of transport models and the representation of photochemical sinks in top-down inversions; and (v) development of a 3D variational inversion system using isotopic and/or co-emitted species such as ethane to improve source partitioning.
1,047 citations
Queensland University of Technology1, University of Leicester2, Pennsylvania State University3, Delft University of Technology4, University of Cassino5, Chinese Academy of Sciences6, Edinburgh Napier University7, University of Cambridge8, ICM Partners9, Lund University10, Cooperative Institute for Research in Environmental Sciences11, Tallinn University of Technology12, University of Hong Kong13, Eindhoven University of Technology14, University of New South Wales15, Virginia Tech16, Polytechnic University of Milan17, Technical University of Denmark18, University of Colorado Boulder19, University of Maryland, College Park20, University of California, Berkeley21, Aalborg University22, University of Leeds23, Yale University24, Spanish National Research Council25, National University of Singapore26, Aalto University27, McGill University28, Peking University29
TL;DR: It is argued that existing evidence is sufficiently strong to warrant engineering controls targeting airborne transmission as part of an overall strategy to limit infection risk indoors, and that the use of engineering controls in public buildings would be an additional important measure globally to reduce the likelihood of transmission.
924 citations
TL;DR: The extent of the trait data compiled in TRY is evaluated and emerging patterns of data coverage and representativeness are analyzed to conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements.
Abstract: Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
882 citations
University of Oxford1, Nottingham University Hospitals NHS Trust2, University of Leicester3, North Manchester General Hospital4, Northampton General Hospital5, North Tees and Hartlepool NHS Foundation Trust6, University Hospitals Birmingham NHS Foundation Trust7, University of Manchester8, James Cook University Hospital9, Cardiff and Vale University Health Board10, King's College London11, University Hospital Southampton NHS Foundation Trust12, University of Cambridge13, University of Nottingham14, University of Edinburgh15
TL;DR: In patients hospitalized with COVID-19, dexamethasone reduced 28-day mortality among those receiving invasive mechanical ventilation or oxygen at randomization, but not among patients not receiving respiratory support.
Abstract: Background: Coronavirus disease 2019 (COVID-19) is associated with diffuse lung damage Corticosteroids may modulate immune-mediated lung injury and reducing progression to respiratory failure and death
Methods: The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, adaptive, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19 We report the preliminary results for the comparison of dexamethasone 6 mg given once daily for up to ten days vs usual care alone The primary outcome was 28-day mortality
Results: 2104 patients randomly allocated to receive dexamethasone were compared with 4321 patients concurrently allocated to usual care Overall, 454 (216%) patients allocated dexamethasone and 1065 (246%) patients allocated usual care died within 28 days (age-adjusted rate ratio [RR] 083; 95% confidence interval [CI] 074 to 092; P<0001) The proportional and absolute mortality rate reductions varied significantly depending on level of respiratory support at randomization (test for trend p<0001): Dexamethasone reduced deaths by one-third in patients receiving invasive mechanical ventilation (290% vs 407%, RR 065 [95% CI 051 to 082]; p<0001), by one-fifth in patients receiving oxygen without invasive mechanical ventilation (215% vs 250%, RR 080 [95% CI 070 to 092]; p=0002), but did not reduce mortality in patients not receiving respiratory support at randomization (170% vs 132%, RR 122 [95% CI 093 to 161]; p=014)
Conclusions: In patients hospitalized with COVID-19, dexamethasone reduced 28-day mortality among those receiving invasive mechanical ventilation or oxygen at randomization, but not among patients not receiving respiratory support
798 citations
King's College London1, University of Cambridge2, University of Leicester3, Catholic University of the Sacred Heart4, HealthPartners5, Tan Tock Seng Hospital6, Nanyang Technological University7, University of Southampton8, University of Miami9, University of Amsterdam10, Centre national de la recherche scientifique11, Anschutz Medical Campus12, Monash University13, Imperial College London14, State University of Campinas15, The Chinese University of Hong Kong16, Peking University17
TL;DR: An international panel of experts in the field of diabetes and endocrinology is formed to provide some guidance and practical recommendations for the management of diabetes during the COVID-19 pandemic.
659 citations
TL;DR: Gaia Early Data Release 3 contains astrometry and photometry results for about 1.8 billion sources based on observations collected by the ESA Gaia satellite during the first 34 months of operations as discussed by the authors.
Abstract: Gaia Early Data Release 3 contains astrometry and photometry results for about 1.8 billion sources based on observations collected by the ESA Gaia satellite during the first 34 months of operations. This paper focuses on the photometric content, describing the input data, the algorithms, the processing, and the validation of the results. Particular attention is given to the quality of the data and to a number of features that users may need to take into account to make the best use of the EDR3 catalogue. The treatment of the BP and RP background has been updated to include a better estimation of the local background, and the detection of crowding effects has been used to exclude affected data from the calibrations. The photometric calibration models have also been updated to account for flux loss over the whole magnitude range. Significant improvements in the modelling and calibration of the point and line spread functions have also helped to reduce a number of instrumental effects that were still present in DR2. EDR3 contains 1.806 billion sources with G-band photometry and 1.540 billion sources with BP and RP photometry. The median uncertainty in the G-band photometry, as measured from the standard deviation of the internally calibrated mean photometry for a given source, is 0.2 mmag at magnitude G=10 to 14, 0.8 mmag at G=17, and 2.6 mmag at G=19. The significant magnitude term found in the Gaia DR2 photometry is no longer visible, and overall there are no trends larger than 1 mmag/mag. Using one passband over the whole colour and magnitude range leaves no systematics above the 1% level in magnitude in any of the bands, and a larger systematic is present for a very small sample of bright and blue sources. A detailed description of the residual systematic effects is provided. Overall the quality of the calibrated mean photometry in EDR3 is superior with respect to DR2 for all bands.
625 citations
King's College London1, Monash University2, Imperial College London3, Dresden University of Technology4, Anschutz Medical Campus5, Agostino Gemelli University Polyclinic6, Nanyang Technological University7, University of Pisa8, Peking University9, HealthPartners10, University of Michigan11, University of Leicester12, University of Yaoundé13, University of Montpellier14
TL;DR: A large number of patients with or at risk of diabetes and metabolic complications of preexisting diabetes, including diabetic ketoacidosis and h...
Abstract: Diabetes and Covid-19 Diabetes is associated with an increased risk of severe Covid-19. New-onset diabetes and metabolic complications of preexisting diabetes, including diabetic ketoacidosis and h...
578 citations
16 Jan 2020
TL;DR: This Primer by Lord and colleagues reviews the epidemiology, mechanisms, clinical detection and treatment of autism and identifies the long-term needs of people with autism.
Abstract: Autism spectrum disorder is a construct used to describe individuals with a specific combination of impairments in social communication and repetitive behaviours, highly restricted interests and/or sensory behaviours beginning early in life. The worldwide prevalence of autism is just under 1%, but estimates are higher in high-income countries. Although gross brain pathology is not characteristic of autism, subtle anatomical and functional differences have been observed in post-mortem, neuroimaging and electrophysiological studies. Initially, it was hoped that accurate measurement of behavioural phenotypes would lead to specific genetic subtypes, but genetic findings have mainly applied to heterogeneous groups that are not specific to autism. Psychosocial interventions in children can improve specific behaviours, such as joint attention, language and social engagement, that may affect further development and could reduce symptom severity. However, further research is necessary to identify the long-term needs of people with autism, and treatments and the mechanisms behind them that could result in improved independence and quality of life over time. Families are often the major source of support for people with autism throughout much of life and need to be considered, along with the perspectives of autistic individuals, in both research and practice.
574 citations
University of Tübingen1, University of Pavia2, Charité3, University of Leicester4, University of Barcelona5, University of Graz6, Istanbul University7, Paris Diderot University8, University of Birmingham9, Norfolk and Norwich University Hospital10, Instituto de Medicina Molecular11, Peking Union Medical College Hospital12, University of Iceland13, University of East Anglia14, University of Oxford15
TL;DR: The recommendations for the management of LVV have been updated to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.
Abstract: BACKGROUND
Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations.
METHODS
Using EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations.
RESULTS
Three overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40-60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons.
CONCLUSIONS
We have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.
University of Nottingham1, University of London2, University of Edinburgh3, University College London4, University of Oxford5, University of Leicester6, University of Cambridge7, NHS England8, Swansea University9, Queen Mary University of London10, University of Liverpool11, Queen's University Belfast12
TL;DR: The QCOVID population based risk algorithm performed well, showing very high levels of discrimination for deaths and hospital admissions due to covid-19, and has the potential to be dynamically updated as the pandemic evolves.
Abstract: OBJECTIVE: To derive and validate a risk prediction algorithm to estimate hospital admission and mortality outcomes from coronavirus disease 2019 (covid-19) in adults. DESIGN: Population based cohort study. SETTING AND PARTICIPANTS: QResearch database, comprising 1205 general practices in England with linkage to covid-19 test results, Hospital Episode Statistics, and death registry data. 6.08 million adults aged 19-100 years were included in the derivation dataset and 2.17 million in the validation dataset. The derivation and first validation cohort period was 24 January 2020 to 30 April 2020. The second temporal validation cohort covered the period 1 May 2020 to 30 June 2020. MAIN OUTCOME MEASURES: The primary outcome was time to death from covid-19, defined as death due to confirmed or suspected covid-19 as per the death certification or death occurring in a person with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the period 24 January to 30 April 2020. The secondary outcome was time to hospital admission with confirmed SARS-CoV-2 infection. Models were fitted in the derivation cohort to derive risk equations using a range of predictor variables. Performance, including measures of discrimination and calibration, was evaluated in each validation time period. RESULTS: 4384 deaths from covid-19 occurred in the derivation cohort during follow-up and 1722 in the first validation cohort period and 621 in the second validation cohort period. The final risk algorithms included age, ethnicity, deprivation, body mass index, and a range of comorbidities. The algorithm had good calibration in the first validation cohort. For deaths from covid-19 in men, it explained 73.1% (95% confidence interval 71.9% to 74.3%) of the variation in time to death (R2); the D statistic was 3.37 (95% confidence interval 3.27 to 3.47), and Harrell's C was 0.928 (0.919 to 0.938). Similar results were obtained for women, for both outcomes, and in both time periods. In the top 5% of patients with the highest predicted risks of death, the sensitivity for identifying deaths within 97 days was 75.7%. People in the top 20% of predicted risk of death accounted for 94% of all deaths from covid-19. CONCLUSION: The QCOVID population based risk algorithm performed well, showing very high levels of discrimination for deaths and hospital admissions due to covid-19. The absolute risks presented, however, will change over time in line with the prevailing SARS-C0V-2 infection rate and the extent of social distancing measures in place, so they should be interpreted with caution. The model can be recalibrated for different time periods, however, and has the potential to be dynamically updated as the pandemic evolves.
TL;DR: Individuals from Black and Asian ethnicities are at increased risk of COVID-19 infection compared to White individuals; Asians may be at higher risk of ITU admission and death.
TL;DR: Emerging data from the grey literature and preprint articles suggest BAME individuals are at an increased risk of acquiring SARS-CoV-2 infection compared to White individuals and also worse clinical outcomes from COVID-19.
Lund University1, Dresden University of Technology2, European Space Agency3, Heidelberg University4, University of Barcelona5, University of Edinburgh6, INAF7, University of Paris8, Max Planck Society9, University of Maryland, Baltimore County10, Goddard Space Flight Center11, Leiden University12, University of Turin13, Centre national de la recherche scientifique14, Leibniz Institute for Astrophysics Potsdam15, Netherlands Institute for Space Research16, Las Cumbres Observatory Global Telescope Network17, Liverpool John Moores University18, University of Leicester19, Princeton University20, Université de Namur21
TL;DR: Gaia Early Data Release 3 (Gaia EDR3) as discussed by the authors contains results for 1.812 billion sources in the magnitude range G = 3 to 21 based on observations collected by the European Space Agency Gaia satellite during the first 34 months of its operational phase.
Abstract: Gaia Early Data Release 3 (Gaia EDR3) contains results for 1.812 billion sources in the magnitude range G = 3 to 21 based on observations collected by the European Space Agency Gaia satellite during the first 34 months of its operational phase. We describe the input data, the models, and the processing used for the astrometric content of Gaia EDR3, as well as the validation of these results performed within the astrometry task. The processing broadly followed the same procedures as for Gaia DR2, but with significant improvements to the modelling of observations. For the first time in the Gaia data processing, colour-dependent calibrations of the line- and point-spread functions have been used for sources with well-determined colours from DR2. In the astrometric processing these sources obtained five-parameter solutions, whereas other sources were processed using a special calibration that allowed a pseudocolour to be estimated as the sixth astrometric parameter. Compared with DR2, the astrometric calibration models have been extended, and the spin-related distortion model includes a self-consistent determination of basic-angle variations, improving the global parallax zero point. Gaia EDR3 gives full astrometric data (positions at epoch J2016.0, parallaxes, and proper motions) for 1.468 billion sources (585 million with five-parameter solutions, 882 million with six parameters), and mean positions at J2016.0 for an additional 344 million. Solutions with five parameters are generally more accurate than six-parameter solutions, and are available for 93% of the sources brighter than G = 17 mag. The median uncertainty in parallax and annual proper motion is 0.02-0.03 mas at magnitude G = 9 to 14, and around 0.5 mas at G = 20. Extensive characterisation of the statistical properties of the solutions is provided, including the estimated angular power spectrum of parallax bias from the quasars.
TL;DR: Preliminary signals must be explored urgently and further studies are needed to confirm the presence of non-volatile volcanic material in the Caspian Sea and assess its importance in the search for dinosaurs.
Abstract: Preliminary signals must be explored urgently
TL;DR: A digital learning package that outlines the actions that team leaders can take to provide psychologically safe spaces for staff, together with guidance on communication and reducing social stigma, peer and family support, and encouragement of self-care and help-seeking behaviour is developed and evaluated.
Abstract: The coronavirus pandemic (COVID-19) will undoubtedly have psychological impacts for healthcare workers, which could be sustained; frontline workers will be particularly at risk. Actions are needed to mitigate the impacts of COVID-19 on mental health by protecting and promoting the psychological wellbeing of healthcare workers during and after the outbreak. We developed and evaluated a digital learning package using Agile methodology within the first three weeks of UK outbreak. This e-package includes evidence-based guidance, support and signposting relating to psychological wellbeing for all UK healthcare employees. A three-step rapid development process included public involvement activities (PPIs) (STEP 1), content and technical development with iterative peer review (STEP 2), and delivery and evaluation (STEP 3). The package outlines the actions that team leaders can take to provide psychologically safe spaces for staff, together with guidance on communication and reducing social stigma, peer and family support, signposting others through psychological first aid (PFA), self-care strategies (e.g., rest, work breaks, sleep, shift work, fatigue, healthy lifestyle behaviours), and managing emotions (e.g., moral injury, coping, guilt, grief, fear, anxiety, depression, preventing burnout and psychological trauma). The e-package includes advice from experts in mental wellbeing as well as those with direct pandemic experiences from the frontline, as well as signposting to public mental health guidance. Rapid delivery in STEP 3 was achieved via direct emails through professional networks and social media. Evaluation included assessment of fidelity and implementation qualities. Essential content was identified through PPIs (n = 97) and peer review (n = 10) in STEPS 1 and 2. The most important messages to convey were deemed to be normalisation of psychological responses during a crisis, and encouragement of self-care and help-seeking behaviour. Within 7 days of completion, the package had been accessed 17,633 times, and healthcare providers had confirmed immediate adoption within their health and wellbeing provisions. Evaluation (STEP 3, n = 55) indicated high user satisfaction with content, usability and utility. Assessment of implementation qualities indicated that the package was perceived to be usable, practical, low cost and low burden. Our digital support package on 'psychological wellbeing for healthcare workers' is free to use, has been positively evaluated and was highly accessed within one week of release. It is available here: Supplementary Materials. This package was deemed to be appropriate, meaningful and useful for the needs of UK healthcare workers. We recommend provision of this e-package to healthcare workers alongside wider strategies to support their psychological wellbeing during and after the COVID-19 pandemic.
TL;DR: Women with a history of GDM appear to have a nearly 10-fold higher risk of developing type 2 diabetes mellitus than those with a normoglycaemic pregnancy, particularly in the early years after pregnancy.
Abstract: Objective To estimate and compare progression rates to type 2 diabetes mellitus (T2DM) in women with gestational diabetes mellitus (GDM) and healthy controls. Design Systematic review and meta-analysis. Data sources Medline and Embase between January 2000 and December 2019, studies published in English and conducted on humans. Eligibility criteria for selecting studies Observational studies investigating progression to T2DM. Inclusion criteria were postpartum follow-up for at least 12 months, incident physician based diagnosis of diabetes, T2DM reported as a separate outcome rather than combined with impaired fasting glucose or impaired glucose tolerance, and studies with both a group of patients with GDM and a control group. Results This meta-analysis of 20 studies assessed a total of 1 332 373 individuals (67 956 women with GDM and 1 264 417 controls). Data were pooled by random effects meta-analysis models, and heterogeneity was assessed by use of the I2 statistic. The pooled relative risk for the incidence of T2DM between participants with GDM and controls was estimated. Reasons for heterogeneity between studies were investigated by prespecified subgroup and meta-regression analyses. Publication bias was assessed by funnel plots and, overall, studies were deemed to have a low risk of bias (P=0.58 and P=0.90). The overall relative risk for T2DM was almost 10 times higher in women with previous GDM than in healthy controls (9.51, 95% confidence interval 7.14 to 12.67, P Conclusions Women with a history of GDM appear to have a nearly 10-fold higher risk of developing T2DM than those with a normoglycaemic pregnancy. The magnitude of this risk highlights the importance of intervening to prevent the onset of T2DM, particularly in the early years after pregnancy. Systematic review registration PROSPERO CRD42019123079.
TL;DR: In this article, the authors measured ACE2 concentrations in 1485 men and 537 women with heart failure (index cohort) and found that the strongest predictor of elevated concentrations of ACE2 in both cohorts was male sex.
Abstract: AIMS: The current pandemic coronavirus SARS-CoV-2 infects a wide age group but predominantly elderly individuals, especially men and those with cardiovascular disease. Recent reports suggest an association with use of renin-angiotensin-aldosterone system (RAAS) inhibitors. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for coronaviruses. Higher ACE2 concentrations might lead to increased vulnerability to SARS-CoV-2 in patients on RAAS inhibitors. METHODS AND RESULTS: We measured ACE2 concentrations in 1485 men and 537 women with heart failure (index cohort). Results were validated in 1123 men and 575 women (validation cohort).The median age was 69 years for men and 75 years for women. The strongest predictor of elevated concentrations of ACE2 in both cohorts was male sex (estimate = 0.26, P < 0.001; and 0.19, P < 0.001, respectively). In the index cohort, use of ACE inhibitors, angiotensin receptor blockers (ARBs), or mineralocorticoid receptor antagonists (MRAs) was not an independent predictor of plasma ACE2. In the validation cohort, ACE inhibitor (estimate = -0.17, P = 0.002) and ARB use (estimate = -0.15, P = 0.03) were independent predictors of lower plasma ACE2, while use of an MRA (estimate = 0.11, P = 0.04) was an independent predictor of higher plasma ACE2 concentrations. CONCLUSION: In two independent cohorts of patients with heart failure, plasma concentrations of ACE2 were higher in men than in women, but use of neither an ACE inhibitor nor an ARB was associated with higher plasma ACE2 concentrations. These data might explain the higher incidence and fatality rate of COVID-19 in men, but do not support previous reports suggesting that ACE inhibitors or ARBs increase the vulnerability for COVID-19 through increased plasma ACE2 concentrations.
TL;DR: Striking differences between Chinese and Italian mortality indicate ethnicity might affect disease outcome, but there is little to no data to support or refute this.
University of Colorado Denver1, University of South Florida2, National Institutes of Health3, University of Leicester4, Federal University of Paraná5, Monash University6, Emory University7, University of Rochester8, University of Newcastle9, McMaster University10, Wake Forest University11, Cochrane Collaboration12, University of Bern13, University of Arizona14, Laval University15, University of California, San Francisco16, Washington University in St. Louis17, University of Southampton18, Boston Children's Hospital19, University of Wisconsin-Madison20, Hokkaido University21, Zhejiang University22, University of Pittsburgh23
TL;DR: Clinical recommendations for the management of severe asthma are provided and the use of novel therapies for severe asthma, specifically biologicals for type 2 high asthma, and antimuscarinic agents and macrolides, as well as on biomarkers for predicting treatment response are made.
Abstract: This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the European Respiratory Society/American Thoracic Society Task Force9s questions. The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of asthma experts, who made specific recommendations on six specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations: 1) suggest using anti-interleukin (IL)-5 and anti-IL-5 receptor α for severe uncontrolled adult eosinophilic asthma phenotypes; 2) suggest using a blood eosinophil cut-point ≥150 μL−1 to guide anti-IL-5 initiation in adult patients with severe asthma; 3) suggest considering specific eosinophil (≥260 μL−1) and exhaled nitric oxide fraction (≥19.5 ppb) cut-offs to identify adolescents or adults with the greatest likelihood of response to anti-IgE therapy; 4) suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite Global Initiative for Asthma (GINA) step 4–5 or National Asthma Education and Prevention Program (NAEPP) step 5 therapies; 5) suggest a trial of chronic macrolide therapy to reduce asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype; and 6) suggest using anti-IL-4/13 for adult patients with severe eosinophilic asthma and for those with severe corticosteroid-dependent asthma regardless of blood eosinophil levels. These recommendations should be reconsidered as new evidence becomes available.
TL;DR: It is important routine care continues in spite of the pandemic, to avoid a rise in non-COVID-19-related morbidity and mortality.
Abstract: Routine care for chronic disease is an ongoing major challenge We aimed to evaluate the global impact of COVID-19 on routine care for chronic diseases An online survey was posted 31 March to 23 April 2020 targeted at healthcare professionals 202 from 47 countries responded Most reported change in routine care to virtual communication Diabetes, chronic obstructive pulmonary disease, and hypertension were the most impacted conditions due to reduction in access to care 80% reported the mental health of their patients worsened during COVID-19 It is important routine care continues in spite of the pandemic, to avoid a rise in non-COVID-19-related morbidity and mortality
TL;DR: Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension.
Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
TL;DR: To assess current trajectories towards the GPW13 UHC billion target—1 billion more people benefiting from UHC by 2023—the authors estimated additional population equivalents with UHC effective coverage from 2018 to 2023, and quantified frontiers of U HC effective coverage performance on the basis of pooled health spending per capita.
TL;DR: To estimate the prevalence of both cardiometabolic and other co‐morbidities in patients with COVID‐19, and to estimate the increased risk of severity of disease and mortality in people with co‐Morbidities.
Abstract: Background: COVID-19 is a global pandemic and with current knowledge about the virus rapidly evolving, systematic reviews are needed to assess those most at ris
TL;DR: Space-borne observations of vegetation greenness show a large increase with time over this study period, supporting the timing and increase in the land carbon sink over these afforestation regions.
Abstract: Limiting the rise in global mean temperatures relies on reducing carbon dioxide (CO2) emissions and on the removal of CO2 by land carbon sinks. China is currently the single largest emitter of CO2, responsible for approximately 27 per cent (2.67 petagrams of carbon per year) of global fossil fuel emissions in 20171. Understanding of Chinese land biosphere fluxes has been hampered by sparse data coverage2–4, which has resulted in a wide range of a posteriori estimates of flux. Here we present recently available data on the atmospheric mole fraction of CO2, measured from six sites across China during 2009 to 2016. Using these data, we estimate a mean Chinese land biosphere sink of −1.11 ± 0.38 petagrams of carbon per year during 2010 to 2016, equivalent to about 45 per cent of our estimate of annual Chinese anthropogenic emissions over that period. Our estimate reflects a previously underestimated land carbon sink over southwest China (Yunnan, Guizhou and Guangxi provinces) throughout the year, and over northeast China (especially Heilongjiang and Jilin provinces) during summer months. These provinces have established a pattern of rapid afforestation of progressively larger regions5,6, with provincial forest areas increasing by between 0.04 million and 0.44 million hectares per year over the past 10 to 15 years. These large-scale changes reflect the expansion of fast-growing plantation forests that contribute to timber exports and the domestic production of paper7. Space-borne observations of vegetation greenness show a large increase with time over this study period, supporting the timing and increase in the land carbon sink over these afforestation regions. Newly available atmospheric carbon dioxide measurements from six sites across China during 2009 to 2016 indicate a larger land carbon sink than previously thought, reflecting increased afforestation.
TL;DR: This multinational task force recommends early, bedside rehabilitation for patients affected by severe COVID-19 and advocates for assessment of oxygen needs at discharge and more comprehensive assessment of rehabilitation needs, including physical as well as mental aspects 6–8 weeks after discharge.
Abstract: Background Patients with COVID-19 or post-COVID-19 will most probably have a need for rehabilitation during and directly after the hospitalisation. Data on safety and efficacy are lacking. Healthcare professionals cannot wait for published randomised controlled trials before they can start these rehabilitative interventions in daily clinical practice, as the number of post-COVID-19 patients increases rapidly. The Convergence of Opinion on Recommendations and Evidence process was used to make interim recommendation for the rehabilitation in the hospital and post-hospital phase in COVID-19 and post-COVID-19 patients, respectively. Methods 93 experts were asked to fill out 13 multiple choice questions. Agreement of directionality was tabulated for each question. At least 70% agreement on directionality was necessary to make consensus suggestions. Results 76 experts (82%) reached consensus on all questions based upon indirect evidence and clinical experience on the need for early rehabilitation during the hospital admission, the screening for treatable traits with rehabilitation in all patients at discharge and 6–8 weeks after discharge, and around the content of rehabilitation for these patients. It advocates for assessment of oxygen needs at discharge and more comprehensive assessment of rehabilitation needs including physical as well as mental aspects 6–8 weeks after discharge. Based on the deficits identified multidisciplinary rehabilitation should be offered with attention for skeletal muscle and functional as well as mental restoration. Conclusions This multinational task force recommends early, bedside rehabilitation for patients affected by severe COVID-19. The model of pulmonary rehabilitation may suit as a framework, particularly in a subset of patients with long term respiratory consequences.
TL;DR: This work proposes two different DL techniques to assess the considered problem, and implements a fusion of handcrafted and learned features in the MAN to improve classification accuracy during lung cancer assessment.
TL;DR: This work shows that a segment within the CTCF N terminus interacts with the SA2–SCC1 subunits of human cohesin, and reveals the molecular basis of the cohes in–CTCF interaction that enables the dynamic regulation of chromatin folding.
Abstract: Cohesin catalyses the folding of the genome into loops that are anchored by CTCF1. The molecular mechanism of how cohesin and CTCF structure the 3D genome has remained unclear. Here we show that a segment within the CTCF N terminus interacts with the SA2–SCC1 subunits of human cohesin. We report a crystal structure of SA2–SCC1 in complex with CTCF at a resolution of 2.7 A, which reveals the molecular basis of the interaction. We demonstrate that this interaction is specifically required for CTCF-anchored loops and contributes to the positioning of cohesin at CTCF binding sites. A similar motif is present in a number of established and newly identified cohesin ligands, including the cohesin release factor WAPL2,3. Our data suggest that CTCF enables the formation of chromatin loops by protecting cohesin against loop release. These results provide fundamental insights into the molecular mechanism that enables the dynamic regulation of chromatin folding by cohesin and CTCF. The crystal structure of the SA2–SCC1 subunits of human cohesin in complex with CTCF reveals the molecular basis of the cohesin–CTCF interaction that enables the dynamic regulation of chromatin folding.