Showing papers by "University of St Andrews published in 2021"
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
01 Jan 2021
TL;DR: Although SARS-CoV-2 RNA shedding in respiratory and stool samples can be prolonged, duration of viable virus is relatively short-lived.
Abstract: Summary Background Viral load kinetics and duration of viral shedding are important determinants for disease transmission. We aimed to characterise viral load dynamics, duration of viral RNA shedding, and viable virus shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in various body fluids, and to compare SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) viral dynamics. Methods In this systematic review and meta-analysis, we searched databases, including MEDLINE, Embase, Europe PubMed Central, medRxiv, and bioRxiv, and the grey literature, for research articles published between Jan 1, 2003, and June 6, 2020. We included case series (with five or more participants), cohort studies, and randomised controlled trials that reported SARS-CoV-2, SARS-CoV, or MERS-CoV infection, and reported viral load kinetics, duration of viral shedding, or viable virus. Two authors independently extracted data from published studies, or contacted authors to request data, and assessed study quality and risk of bias using the Joanna Briggs Institute Critical Appraisal Checklist tools. We calculated the mean duration of viral shedding and 95% CIs for every study included and applied the random-effects model to estimate a pooled effect size. We used a weighted meta-regression with an unrestricted maximum likelihood model to assess the effect of potential moderators on the pooled effect size. This study is registered with PROSPERO, CRD42020181914. Findings 79 studies (5340 individuals) on SARS-CoV-2, eight studies (1858 individuals) on SARS-CoV, and 11 studies (799 individuals) on MERS-CoV were included. Mean duration of SARS-CoV-2 RNA shedding was 17·0 days (95% CI 15·5–18·6; 43 studies, 3229 individuals) in upper respiratory tract, 14·6 days (9·3–20·0; seven studies, 260 individuals) in lower respiratory tract, 17·2 days (14·4–20·1; 13 studies, 586 individuals) in stool, and 16·6 days (3·6–29·7; two studies, 108 individuals) in serum samples. Maximum shedding duration was 83 days in the upper respiratory tract, 59 days in the lower respiratory tract, 126 days in stools, and 60 days in serum. Pooled mean SARS-CoV-2 shedding duration was positively associated with age (slope 0·304 [95% CI 0·115–0·493]; p=0·0016). No study detected live virus beyond day 9 of illness, despite persistently high viral loads, which were inferred from cycle threshold values. SARS-CoV-2 viral load in the upper respiratory tract appeared to peak in the first week of illness, whereas that of SARS-CoV peaked at days 10–14 and that of MERS-CoV peaked at days 7–10. Interpretation Although SARS-CoV-2 RNA shedding in respiratory and stool samples can be prolonged, duration of viable virus is relatively short-lived. SARS-CoV-2 titres in the upper respiratory tract peak in the first week of illness. Early case finding and isolation, and public education on the spectrum of illness and period of infectiousness are key to the effective containment of SARS-CoV-2. Funding None.
1,061 citations
National Institutes of Health1, University of Cambridge2, Wellcome Trust Sanger Institute3, Rockefeller University4, University of California, Davis5, Leibniz Association6, Seoul National University7, University of Southern California8, European Bioinformatics Institute9, Dresden University of Technology10, Max Planck Society11, Radboud University Nijmegen12, University of St Andrews13, University of Massachusetts Amherst14, University of Adelaide15, University of Missouri16, East Carolina University17, University of Queensland18, Clemson University19, University of Otago20, University of Arizona21, Natural History Museum22, Bangor University23, University of Konstanz24, Harvard University25, Northeastern University26, National Museum of Natural History27, University of Antwerp28, University of Graz29, University of Florida30, University of Basel31, University of California, Santa Cruz32, Zoological Society of San Diego33, Pacific Biosciences34, Pompeu Fabra University35, University of Maryland, College Park36, Harbin Institute of Technology37, University of Chicago38, Oregon Health & Science University39, Qatar Airways40, Monash University Malaysia Campus41, University of Milan42, Goethe University Frankfurt43, Pennsylvania State University44, University of Los Andes45, University of Copenhagen46, Norwegian University of Science and Technology47, Agency for Science, Technology and Research48, Royal Ontario Museum49, Smithsonian Institution50, Howard Hughes Medical Institute51, Walter Reed Army Institute of Research52, University of East Anglia53, University College Dublin54, University of Illinois at Urbana–Champaign55, La Trobe University56, University of California, San Diego57, Nova Southeastern University58
TL;DR: The Vertebrate Genomes Project (VGP) as mentioned in this paper is an international effort to generate high quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences.
Abstract: High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for only a few non-microbial species1-4. To address this issue, the international Genome 10K (G10K) consortium5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling highly accurate and nearly complete reference genomes. Here we present lessons learned from generating assemblies for 16 species that represent six major vertebrate lineages. We confirm that long-read sequencing technologies are essential for maximizing genome quality, and that unresolved complex repeats and haplotype heterozygosity are major sources of assembly error when not handled correctly. Our assemblies correct substantial errors, add missing sequence in some of the best historical reference genomes, and reveal biological discoveries. These include the identification of many false gene duplications, increases in gene sizes, chromosome rearrangements that are specific to lineages, a repeated independent chromosome breakpoint in bat genomes, and a canonical GC-rich pattern in protein-coding genes and their regulatory regions. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an international effort to generate high-quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences.
647 citations
University of Edinburgh1, Autonomous University of Madrid2, Pierre-and-Marie-Curie University3, University of Portsmouth4, University of Wisconsin-Madison5, University of Cape Town6, Moscow State University7, New Mexico 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, Consejo Nacional de Ciencia y Tecnología21, Universidad de Guanajuato22, 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.
575 citations
Innovations for Poverty Action1, Wageningen University and Research Centre2, Columbia University3, National Research University – Higher School of Economics4, Yale University5, University of Lagos6, Institute for Fiscal Studies7, Universidade Nova de Lisboa8, Lahore University of Management Sciences9, University of St Andrews10, Stockholm School of Economics11, Ghent University12, Alternatives13, Trinity College, Dublin14, University of Sierra Leone15, Kathmandu16, Cornell University17, University of Illinois at Chicago18, New York University Abu Dhabi19, Princeton University20, Stockholm University21, Tufts University22, University of Michigan23, Northwestern University24, London School of Economics and Political Science25
TL;DR: In this article, the authors analyzed COVID-19 vaccine acceptance across 15 survey samples covering 10 low and middle-income countries (LMICs) in Asia, Africa and South America, Russia (an upper-middle-income country) and the United States, including a total of 44,260 individuals.
Abstract: Widespread acceptance of COVID-19 vaccines is crucial for achieving sufficient immunization coverage to end the global pandemic, yet few studies have investigated COVID-19 vaccination attitudes in lower-income countries, where large-scale vaccination is just beginning. We analyze COVID-19 vaccine acceptance across 15 survey samples covering 10 low- and middle-income countries (LMICs) in Asia, Africa and South America, Russia (an upper-middle-income country) and the United States, including a total of 44,260 individuals. We find considerably higher willingness to take a COVID-19 vaccine in our LMIC samples (mean 80.3%; median 78%; range 30.1 percentage points) compared with the United States (mean 64.6%) and Russia (mean 30.4%). Vaccine acceptance in LMICs is primarily explained by an interest in personal protection against COVID-19, while concern about side effects is the most common reason for hesitancy. Health workers are the most trusted sources of guidance about COVID-19 vaccines. Evidence from this sample of LMICs suggests that prioritizing vaccine distribution to the Global South should yield high returns in advancing global immunization coverage. Vaccination campaigns should focus on translating the high levels of stated acceptance into actual uptake. Messages highlighting vaccine efficacy and safety, delivered by healthcare workers, could be effective for addressing any remaining hesitancy in the analyzed LMICs.
536 citations
TL;DR: In this article, the authors investigated the association between the mass roll-out of the first doses of these COVID-19 vaccines and hospital admissions for CoV-19 and found that the first dose of the BNT162b2 mRNA vaccine was associated with a vaccine effect of 91% (95% CI 85-94) for reduced COVID19 hospital admission at 28-34 days post-vaccination.
437 citations
TL;DR: This paper recommends a set of urgent policy actions that promote clean water, conserve watershed services, and restore freshwater ecosystems and their vital services.
Abstract: Freshwater ecosystems provide irreplaceable services for both nature and society. The quality and quantity of freshwater affect biogeochemical processes and ecological dynamics that determine biodiversity, ecosystem productivity, and human health and welfare at local, regional and global scales. Freshwater ecosystems and their associated riparian habitats are amongst the most biologically diverse on Earth, and have inestimable economic, health, cultural, scientific and educational values. Yet human impacts to lakes, rivers, streams, wetlands and groundwater are dramatically reducing biodiversity and robbing critical natural resources and services from current and future generations. Freshwater biodiversity is declining rapidly on every continent and in every major river basin on Earth, and this degradation is occurring more rapidly than in terrestrial ecosystems. Currently, about one third of all global freshwater discharges pass through human agricultural, industrial or urban infrastructure. About one fifth of the Earth's arable land is now already equipped for irrigation, including all the most productive lands, and this proportion is projected to surpass one third by midcentury to feed the rapidly expanding populations of humans and commensal species, especially poultry and ruminant livestock. Less than one fifth of the world's preindustrial freshwater wetlands remain, and this proportion is projected to decline to under one tenth by midcentury, with imminent threats from water transfer megaprojects in Brazil and India, and coastal wetland drainage megaprojects in China. The Living Planet Index for freshwater vertebrate populations has declined to just one third that of 1970, and is projected to sink below one fifth by midcentury. A linear model of global economic expansion yields the chilling prediction that human utilization of critical freshwater resources will approach one half of the Earth's total capacity by midcentury. Although the magnitude and growth of the human freshwater footprint are greater than is generally understood by policy makers, the news media, or the general public, slowing and reversing dramatic losses of freshwater species and ecosystems is still possible. We recommend a set of urgent policy actions that promote clean water, conserve watershed services, and restore freshwater ecosystems and their vital services. Effective management of freshwater resources and ecosystems must be ranked amongst humanity's highest priorities.
325 citations
Book•
01 Jan 2021TL;DR: The Project of Historiography as discussed by the authors ) is a project dedicated to the preservation and preservation of the history of the East and the West of the Middle Ages and the early modern world.
Abstract: Introduction: The Project of Historiography Section 1: Beginnings - East and West Introduction 1.1 Asian Historiography: Two Traditions 1.2 Historiography and Greek Self-Definition .3 Re-Reading the Roman Historians 1.4 The Historiography of Rural Labour 1.5 Towards Late-Antiquity Section 2: The Medieval World Introduction 2.1 The Historiography of the Medieval State 2.2 Saladin and the Third Crusade 2.3 Family and Household 2.4 The Medieval Nobility 2.5 Armies and Warfare 2.6 Popular Religion Section 3: Early-Modern Historiography Introduction 3.1 The Idea of Early Modern History 3.2 The Scientific Revolution 3.3 Intellectual History 3.4 The English Reformation 3.5 Popular Culture in the Early-Modern West 3.6 Revisionism in Britain Section 4: Reflecting on the Modern Age Introduction I: Revolution and Ideology 4.1 The French Revolution 4.2 The Soviet Revolution 4.3 National Socialism in Germany 4.4 Fascism and Beyond in Italy 4.5 Orientalism London: II Area Studies 4.6 China 4.7 Japan 4.8 India 4.9 Africa 4.10 North America 4.11 Latin America Section 5: Contexts for the Writing of History I: Hinterlands 5.1 History and Philosophy 5.2 History and Anthropology 5.3 History and Archaeology 5.4 History of Art II: Approaches 5.5 The Historical Narrative 5.6 The Annales School 5.7 Marxist Historiography 5.8 Women in Historiography 5.9 Comparative World History 5.10 Archives and Technology
302 citations
TL;DR: Efforts should be undertaken to diminish mixing in younger adults, particularly individuals aged 18–35 years, to mitigate the spread of the epidemic in the community.
Abstract: Funding: This work was supported by Award Number U54GM088558 from the National Institute of General Medical Sciences (ML, EG) and the US National Institutes of Health cooperative agreement U01 CA261277 (ML).
234 citations
03 Jun 2021
TL;DR: In this paper, the authors summarize the recent advances in the field of optical tweezers using structured light beams with customized phase, amplitude, and polarization in 3D optical trapping.
Abstract: Optical trapping describes the interaction between light and matter to manipulate micro-objects through momentum transfer. In the case of 3D trapping with a single beam, this is termed optical tweezers. Optical tweezers are a powerful and noninvasive tool for manipulating small objects, and have become indispensable in many fields, including physics, biology, soft condensed matter, among others. In the early days, optical trapping was typically accomplished with a single Gaussian beam. In recent years, we have witnessed rapid progress in the use of structured light beams with customized phase, amplitude, and polarization in optical trapping. Unusual beam properties, such as phase singularities on-axis and propagation invariant nature, have opened up novel capabilities to the study of micromanipulation in liquid, air, and vacuum. We summarize the recent advances in the field of optical trapping using structured light beams.
215 citations
TL;DR: The peptide hormone leptin regulates food intake, body mass, and reproductive function and plays a role in fetal growth, proinflammatory immune responses, angiogenesis and lipolysis.
Abstract: The peptide hormone leptin regulates food intake, body mass, and reproductive function and plays a role in fetal growth, proinflammatory immune responses, angiogenesis and lipolysis. Leptin is a product of the obese (ob) gene and, following synthesis and secretion from fat cells in white adipose tissue, binds to and activates its cognate receptor, the leptin receptor (LEP-R). LEP-R distribution facilitates leptin's pleiotropic effects, playing a crucial role in regulating body mass via a negative feedback mechanism between adipose tissue and the hypothalamus. Leptin resistance is characterized by reduced satiety, over-consumption of nutrients, and increased total body mass. Often this leads to obesity, which reduces the effectiveness of using exogenous leptin as a therapeutic agent. Thus, combining leptin therapies with leptin sensitizers may help overcome such resistance and, consequently, obesity. This review examines recent data obtained from human and animal studies related to leptin, its role in obesity, and its usefulness in obesity treatment.
TL;DR: Tissue-specific immunopathology occurs in COVID-19, implicating a significant component of the immune-mediated, virus-independent immunopathologic process as a primary mechanism in severe disease.
Abstract: Rationale: In life-threatening coronavirus disease (COVID-19), corticosteroids reduce mortality, suggesting that immune responses have a causal role in death. Whether this deleterious inflammation is primarily a direct reaction to the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or an independent immunopathologic process is unknown.Objectives: To determine SARS-CoV-2 organotropism and organ-specific inflammatory responses and the relationships among viral presence, inflammation, and organ injury.Methods: Tissue was acquired from 11 detailed postmortem examinations. SARS-CoV-2 organotropism was mapped by using multiplex PCR and sequencing, with cellular resolution achieved by in situ viral S (spike) protein detection. Histologic evidence of inflammation was quantified from 37 anatomic sites, and the pulmonary immune response was characterized by using multiplex immunofluorescence.Measurements and Main Results: Multiple aberrant immune responses in fatal COVID-19 were found, principally involving the lung and reticuloendothelial system, and these were not clearly topologically associated with the virus. Inflammation and organ dysfunction did not map to the tissue and cellular distribution of SARS-CoV-2 RNA and protein between or within tissues. An arteritis was identified in the lung, which was further characterized as a monocyte/myeloid-rich vasculitis, and occurred together with an influx of macrophage/monocyte-lineage cells into the pulmonary parenchyma. In addition, stereotyped abnormal reticuloendothelial responses, including excessive reactive plasmacytosis and iron-laden macrophages, were present and dissociated from viral presence in lymphoid tissues.Conclusions: Tissue-specific immunopathology occurs in COVID-19, implicating a significant component of the immune-mediated, virus-independent immunopathologic process as a primary mechanism in severe disease. Our data highlight novel immunopathologic mechanisms and validate ongoing and future efforts to therapeutically target aberrant macrophage and plasma-cell responses as well as promote pathogen tolerance in COVID-19.
TL;DR: HIV-positive status was associated with an increased risk of day-28 mortality among patients hospitalized for COVID-19 and the association persisted after adjusting for the other variables.
Abstract: BACKGROUND: Evidence is conflicting about how HIV modulates COVID-19. We compared the presentation characteristics and outcomes of adults with and without HIV who were hospitalized with COVID-19 at 207 centers across the United Kingdom and whose data were prospectively captured by the ISARIC WHO CCP study. METHODS: We used Kaplan-Meier methods and Cox regression to describe the association between HIV status and day-28 mortality, after separate adjustment for sex, ethnicity, age, hospital acquisition of COVID-19 (definite hospital acquisition excluded), presentation date, ten individual comorbidities, and disease severity at presentation (as defined by hypoxia or oxygen therapy). RESULTS: Among 47,592 patients, 122 (0.26%) had confirmed HIV infection and 112/122 (91.8%) had a record of antiretroviral therapy. At presentation, HIV-positive people were younger (median 56 versus 74 years; p<0.001) and had fewer comorbidities, more systemic symptoms and higher lymphocyte counts and C-reactive protein levels. The cumulative day-28 mortality was similar in the HIV-positive vs. HIV-negative groups (26.7% vs. 32.1%; p=0.16), but in those under 60 years of age HIV-positive status was associated with increased mortality (21.3% vs. 9.6%; p<0.001 [log-rank test]). Mortality was higher among people with HIV after adjusting for age (adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.01-2.14; p=0.05), and the association persisted after adjusting for the other variables (aHR 1.69; 95% CI 1.15-2.48; p=0.008) and when restricting the analysis to people aged <60 years (aHR 2.87; 95% CI 1.70-4.84; p<0.001). CONCLUSIONS: HIV-positive status was associated with an increased risk of day-28 mortality among patients hospitalized for COVID-19.
TL;DR: In this article, an association was found between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis.
Abstract: Reports of ChAdOx1 vaccine–associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0–27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41–13.83), with an estimated incidence of 1.13 (0.62–1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29–3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12–1.34) 0–27 d after vaccination, with an SCCS RR of 0.97 (0.93–1.02). For hemorrhagic events 0–27 d after vaccination, the aRR was 1.48 (1.12–1.96), with an SCCS RR of 0.95 (0.82–1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events. New data from the EAVE II cohort in Scotland suggests that a first dose of the ChAdOx1 nCoV-19 vaccine might be associated with a small increase in the risk of idiopathic thrombocytopenic purpura between 0 and 27 d after vaccination.
University of Oxford1, University of Edinburgh2, NHS Lothian3, Nottingham University Hospitals NHS Trust4, University of Glasgow5, NHS Greater Glasgow and Clyde6, National Institutes of Health7, I.M. Sechenov First Moscow State Medical University8, University of St Andrews9, Brighton and Sussex Medical School10, University of Liverpool11, North Manchester General Hospital12, Eaton Corporation13
TL;DR: In this article, the authors sought to establish the long-term effects of Covid-19 following hospitalisation, including new symptoms, disability, breathlessness, and quality of life (EQ5D-5L).
Abstract: Background This study sought to establish the long-term effects of Covid-19 following hospitalisation. Methods 327 hospitalised participants, with SARS-CoV-2 infection were recruited into a prospective multicentre cohort study at least 3 months post-discharge. The primary outcome was self-reported recovery at least ninety days after initial Covid-19 symptom onset. Secondary outcomes included new symptoms, disability (Washington group short scale), breathlessness (MRC Dyspnoea scale) and quality of life (EQ5D-5L). Findings 55% of participants reported not feeling fully recovered. 93% reported persistent symptoms, with fatigue the most common (83%), followed by breathlessness (54%). 47% reported an increase in MRC dyspnoea scale of at least one grade. New or worse disability was reported by 24% of participants. The EQ5D-5L summary index was significantly worse following acute illness (median difference 0.1 points on a scale of 0 to 1, IQR: -0.2 to 0.0). Females under the age of 50 years were five times less likely to report feeling recovered (adjusted OR 5.09, 95% CI 1.64 to 15.74), were more likely to have greater disability (adjusted OR 4.22, 95% CI 1.12 to 15.94), twice as likely to report worse fatigue (adjusted OR 2.06, 95% CI 0.81 to 3.31) and seven times more likely to become more breathless (adjusted OR 7.15, 95% CI 2.24 to 22.83) than men of the same age. Interpretation Survivors of Covid-19 experienced long-term symptoms, new disability, increased breathlessness, and reduced quality of life. These findings were present in young, previously healthy working age adults, and were most common in younger females. Funding National Institute for Health Research, UK Medical Research Council, Wellcome Trust, Department for International Development and the Bill and Melinda Gates Foundation.
14 Jan 2021
TL;DR: This Primer summarizes the basic principles of NMR as applied to the wide range of solid systems, and describes the most common MAS NMR experiments and data analysis approaches for investigating biological macromolecules, organic materials, and inorganic solids.
Abstract: Solid-state nuclear magnetic resonance (NMR) spectroscopy is an atomic-level method used to determine the chemical structure, three-dimensional structure, and dynamics of solids and semi-solids. This Primer summarizes the basic principles of NMR as applied to the wide range of solid systems. The fundamental nuclear spin interactions and the effects of magnetic fields and radiofrequency pulses on nuclear spins are the same as in liquid-state NMR. However, because of the anisotropy of the interactions in the solid state, the majority of high-resolution solid-state NMR spectra is measured under magic-angle spinning (MAS), which has profound effects on the types of radiofrequency pulse sequences required to extract structural and dynamical information. We describe the most common MAS NMR experiments and data analysis approaches for investigating biological macromolecules, organic materials, and inorganic solids. Continuing development of sensitivity-enhancement approaches, including 1H-detected fast MAS experiments, dynamic nuclear polarization, and experiments tailored to ultrahigh magnetic fields, is described. We highlight recent applications of solid-state NMR to biological and materials chemistry. The Primer ends with a discussion of current limitations of NMR to study solids, and points to future avenues of development to further enhance the capabilities of this sophisticated spectroscopy for new applications.
Texas A&M University1, University of Exeter2, University of Helsinki3, Université du Québec à Montréal4, Tanjungpura University5, University of Hawaii at Manoa6, University of Bristol7, Bowdoin College8, Chulalongkorn University9, University of California, Los Angeles10, Max Planck Society11, University of Nottingham12, University of Magallanes13, Oeschger Centre for Climate Change Research14, Université de Montréal15, Northeast Normal University16, Lehigh University17, Mount Holyoke College18, McGill University19, Stockholm University20, University of Leicester21, Katholieke Universiteit Leuven22, University of St Andrews23, Florida State University24, Aarhus University25, University of Toronto26, University of New Hampshire27, University of Łódź28, Centre national de la recherche scientifique29, Cranfield University30, University of Alberta31, Stockholm Environment Institute32, Lawrence Berkeley National Laboratory33, United States Geological Survey34, Texas A&M University at Galveston35, University of Victoria36, Adam Mickiewicz University in Poznań37, Finnish Meteorological Institute38, Royal Holloway, University of London39, University of Queensland40, Lamont–Doherty Earth Observatory41, National Park Service42, University of York43, Hope College44, University of Reading45, Uva Wellassa University46, Queen's University Belfast47, University of California, Berkeley48, Memorial University of Newfoundland49
TL;DR: In this article, the authors define and quantify the leading drivers of change that have impacted peatland carbon stocks during the Holocene and predict their effect during this century and in the far future.
Abstract: The carbon balance of peatlands is predicted to shift from a sink to a source this century. However, peatland ecosystems are still omitted from the main Earth system models that are used for future climate change projections, and they are not considered in integrated assessment models that are used in impact and mitigation studies. By using evidence synthesized from the literature and an expert elicitation, we define and quantify the leading drivers of change that have impacted peatland carbon stocks during the Holocene and predict their effect during this century and in the far future. We also identify uncertainties and knowledge gaps in the scientific community and provide insight towards better integration of peatlands into modelling frameworks. Given the importance of the contribution by peatlands to the global carbon cycle, this study shows that peatland science is a critical research area and that we still have a long way to go to fully understand the peatland–carbon–climate nexus. Peatlands are impacted by climate and land-use changes, with feedback to warming by acting as either sources or sinks of carbon. Expert elicitation combined with literature review reveals key drivers of change that alter peatland carbon dynamics, with implications for improving models.
TL;DR: In this paper, the authors provide public health guidance for increased surveillance and measures to reduce community transmission of SARS-CoV-2 genetic variants, such as B.1.7.
TL;DR: This work provides recommendations regarding definitions, detection, documentation, and follow-up to improve the identification and evaluation of people with persistently asymptomatic SARS-CoV-2 infection and their contacts and describes three methodological issues that hinder attempts to estimate this proportion.
Abstract: People with persistently asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection experience no symptoms throughout the course of infection, and pre-symptomatic individuals become infectious days before they report symptoms. Transmission of SARS-CoV-2 from individuals without symptoms contributes to pandemic spread, but the extent of transmission from persistently asymptomatic individuals remains unknown. We describe three methodological issues that hinder attempts to estimate this proportion. First, incomplete symptom assessment probably overestimates the asymptomatic fraction. Second, studies with inadequate follow-up misclassify pre-symptomatic individuals. Third, serological studies might identify people with previously unrecognised infection, but reliance on poorly defined antibody responses and retrospective symptom assessment might result in misclassification. We provide recommendations regarding definitions, detection, documentation, and follow-up to improve the identification and evaluation of people with persistently asymptomatic SARS-CoV-2 infection and their contacts. Accurate characterisation of the persistently asymptomatic fraction of infected individuals might shed light on COVID-19 pathogenesis and transmission dynamics, and inform public health responses.
Lamont–Doherty Earth Observatory1, University of St Andrews2, University of Arizona3, Naval Postgraduate School4, University of Texas at Austin5, University of California, Los Angeles6, Federal University of Paraná7, Pusan National University8, Bureau of Meteorology9, Indian Institute of Tropical Meteorology10, Ocean University of China11, Nanjing Normal University12, Stanford University13, University of Connecticut14, National Taiwan University15, University of Reading16, Sun Yat-sen University17, Chinese Academy of Sciences18
TL;DR: This article provided a review on past monsoon changes and their primary drivers, the projected future changes and key physical processes, and discuss challenges of the present and future modeling and outlooks.
Abstract: Monsoon rainfall has profound economic and societal impacts for more than two-thirds of the global population. Here we provide a review on past monsoon changes and their primary drivers, the projected future changes and key physical processes, and discuss challenges of the present and future modeling and outlooks. Continued global warming and urbanization over the past century has already caused a significant rise in the intensity and frequency of extreme rainfall events in all monsoon regions (high confidence). Observed changes in the mean monsoon rainfall vary by region with significant decadal variations. NH land monsoon rainfall as a whole declined from 1950 to 1980 and rebounded after the 1980s, due to the competing influences of internal climate variability and radiative forcing from GHGs and aerosol forcing (high confidence); however, it remains a challenge to quantify their relative contributions. The CMIP6 models simulate better global monsoon intensity and precipitation over CMIP5 models, but common biases and large intermodal spreads persist. Nevertheless, there is high confidence that the frequency and intensity of monsoon extreme rainfall events will increase, alongside an increasing risk of drought over some regions. Also, land monsoon rainfall will increase in South Asia and East Asia (high confidence) and northern Africa (medium confidence), and decrease in North America and unchanged in Southern Hemisphere. Over Asian-Australian monsoon region the rainfall variability is projected to increase on daily to decadal scales. The rainy season will likely be lengthened in the Northern Hemisphere due to late retreat (especially over East Asia), but shortened in the Southern Hemisphere due to delayed onset.
TL;DR: In this article, the zero-field muon spin relaxation (ZF-spin relaxation) was measured on strontium ruthenate samples under uniaxial stresses.
Abstract: Strontium ruthenate (Sr2RuO4) continues to present an important test of our understanding of unconventional superconductivity, because while its normal-state electronic structure is known with precision, its superconductivity remains unexplained. There is evidence that its order parameter is chiral, but reconciling this with recent observations of the spin part of the pairing requires an order parameter that is either finely tuned or implies a new form of pairing. Therefore, a definitive resolution of whether the superconductivity of Sr2RuO4 is chiral is important for the study of superconductivity. Here we report the measurement of zero-field muon spin relaxation—a probe sensitive to weak magnetism—on samples under uniaxial stresses. We observe stress-induced splitting between the onset temperatures of superconductivity and time-reversal symmetry breaking—consistent with the qualitative expectations for a chiral order parameter—and argue that this observation cannot be explained by conventional magnetism. In addition, we report the appearance of bulk magnetic order under higher uniaxial stress, above the critical pressure at which a Lifshitz transition occurs in Sr2RuO4. When strain is applied to strontium ruthenate, superconductivity emerges at a different temperature to the breaking of time-reversal symmetry. This indicates that the superconductivity could have a chiral d-wave order parameter.
TL;DR: This article reviewed and revised CO2 reconstructions from boron isotopes in carbonates and carbon carbonates, and found that CO2 exerted a fundamental control on environmental change throughout Earth's history.
Abstract: Throughout Earth's history, CO2 is thought to have exerted a fundamental control on environmental change. Here we review and revise CO2 reconstructions from boron isotopes in carbonates and carbon ...
TL;DR: In this article, a review of the potential of TADF compounds as photocatalysts is presented, and a discussion of the benefits of compounds showing TADFs for photocatalysis is presented.
Abstract: Organic compounds that show Thermally Activated Delayed Fluorescence (TADF) have become wildly popular as next-generation emitters in organic light emitting diodes (OLEDs). Since 2016, a subset of these have found increasing use as photocatalysts. This review comprehensively highlights their potential by documenting the diversity of the reactions where an organic TADF photocatalyst can be used in lieu of a noble metal complex photocatalyst. Beyond the small number of TADF photocatalysts that have been used to date, the analysis conducted within this review reveals the wider potential of organic donor–acceptor TADF compounds as photocatalysts. A discussion of the benefits of compounds showing TADF for photocatalysis is presented, which paints a picture of a very promising future for organic photocatalyst development.
Lea Berrang-Ford1, A. R. Siders2, Alexandra Lesnikowski3, Alexandra Paige Fischer4 +147 more•Institutions (87)
TL;DR: In this article, the authors present a systematic and comprehensive global stocktake of implemented human adaptation to climate change and identify eight priorities for global adaptation research: assess the effectiveness of adaptation responses, enhance the understanding of limits to adaptation, enable individuals and civil society to adapt, include missing places, scholars and scholarship, understand private sector responses, improve methods for synthesizing different forms of evidence, assess the adaptation at different temperature thresholds, and improve the inclusion of timescale and the dynamics of responses.
Abstract: Assessing global progress on human adaptation to climate change is an urgent priority. Although the literature on adaptation to climate change is rapidly expanding, little is known about the actual extent of implementation. We systematically screened >48,000 articles using machine learning methods and a global network of 126 researchers. Our synthesis of the resulting 1,682 articles presents a systematic and comprehensive global stocktake of implemented human adaptation to climate change. Documented adaptations were largely fragmented, local and incremental, with limited evidence of transformational adaptation and negligible evidence of risk reduction outcomes. We identify eight priorities for global adaptation research: assess the effectiveness of adaptation responses, enhance the understanding of limits to adaptation, enable individuals and civil society to adapt, include missing places, scholars and scholarship, understand private sector responses, improve methods for synthesizing different forms of evidence, assess the adaptation at different temperature thresholds, and improve the inclusion of timescale and the dynamics of responses. Determining progress in adaptation to climate change is challenging, yet critical as climate change impacts increase. A stocktake of the scientific literature on implemented adaptation now shows that adaptation is mostly fragmented and incremental, with evidence lacking for its impact on reducing risk.
King's College London1, University at Buffalo2, Goddard Space Flight Center3, University of Bremen4, University of Oslo5, University of Alaska Fairbanks6, Université libre de Bruxelles7, Utrecht University8, Bjerknes Centre for Climate Research9, California Institute of Technology10, University of Grenoble11, University of California, San Diego12, University of Edinburgh13, University of St Andrews14, University of Leeds15, International Institute for Applied Systems Analysis16, University of Tokyo17, University of Reading18, Met Office19, National Center for Atmospheric Research20, University of Bristol21, Université Paris-Saclay22, Goddard Institute for Space Studies23, Columbia University24, Potsdam Institute for Climate Impact Research25, Victoria University of Wellington26, Los Alamos National Laboratory27, Colorado State University28, Hokkaido University29, University of California, Irvine30, Universities Space Research Association31, University of Liège32, Nagoya University33, Australian Antarctic Division34, University of Tasmania35, University of Lapland36, Norwegian Polar Institute37, University of Tromsø38, Alfred Wegener Institute for Polar and Marine Research39, Swiss Federal Institute for Forest, Snow and Landscape Research40, ETH Zurich41, University of Fribourg42, Vrije Universiteit Brussel43, GNS Science44, Lawrence Berkeley National Laboratory45, University of Innsbruck46, University of Liverpool47, University of British Columbia48, Carnegie Mellon University49, Memorial University of Newfoundland50, Pennsylvania State University51, University of Potsdam52, Beijing Normal University53, CSC – IT Center for Science54
TL;DR: In this article, the authors estimate probability distributions for these projections under the new scenarios using statistical emulation of the ice sheet and glacier models, and find that limiting global warming to 1.5 degrees Celsius would halve the land ice contribution to twenty-first-century sea level rise, relative to current emissions pledges.
Abstract: The land ice contribution to global mean sea level rise has not yet been predicted1 using ice sheet and glacier models for the latest set of socio-economic scenarios, nor using coordinated exploration of uncertainties arising from the various computer models involved. Two recent international projects generated a large suite of projections using multiple models2,3,4,5,6,7,8, but primarily used previous-generation scenarios9 and climate models10, and could not fully explore known uncertainties. Here we estimate probability distributions for these projections under the new scenarios11,12 using statistical emulation of the ice sheet and glacier models. We find that limiting global warming to 1.5 degrees Celsius would halve the land ice contribution to twenty-first-century sea level rise, relative to current emissions pledges. The median decreases from 25 to 13 centimetres sea level equivalent (SLE) by 2100, with glaciers responsible for half the sea level contribution. The projected Antarctic contribution does not show a clear response to the emissions scenario, owing to uncertainties in the competing processes of increasing ice loss and snowfall accumulation in a warming climate. However, under risk-averse (pessimistic) assumptions, Antarctic ice loss could be five times higher, increasing the median land ice contribution to 42 centimetres SLE under current policies and pledges, with the 95th percentile projection exceeding half a metre even under 1.5 degrees Celsius warming. This would severely limit the possibility of mitigating future coastal flooding. Given this large range (between 13 centimetres SLE using the main projections under 1.5 degrees Celsius warming and 42 centimetres SLE using risk-averse projections under current pledges), adaptation planning for twenty-first-century sea level rise must account for a factor-of-three uncertainty in the land ice contribution until climate policies and the Antarctic response are further constrained.
TL;DR: In this paper, a review of the development of homogeneous catalysts in emerging applications of sustainable energy is presented, focusing mainly on hydrogen storage and methanol production, with a focus on the use of pincer complexes.
Abstract: As the world pledges to significantly cut carbon emissions, the demand for sustainable and clean energy has now become more important than ever. This includes both production and storage of energy carriers, a majority of which involve catalytic reactions. This article reviews recent developments of homogeneous catalysts in emerging applications of sustainable energy. The most important focus has been on hydrogen storage as several efficient homogeneous catalysts have been reported recently for (de)hydrogenative transformations promising to the hydrogen economy. Another direction that has been extensively covered in this review is that of the methanol economy. Homogeneous catalysts investigated for the production of methanol from CO2, CO, and HCOOH have been discussed in detail. Moreover, catalytic processes for the production of conventional fuels (higher alkanes such as diesel, wax) from biomass or lower alkanes have also been discussed. A section has also been dedicated to the production of ethylene glycol from CO and H2 using homogeneous catalysts. Well-defined transition metal complexes, in particular, pincer complexes, have been discussed in more detail due to their high activity and well-studied mechanisms.
TL;DR: It is argued that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission dynamics should inform policy decisions about mitigation strategies for targeted interventions according to the needs of the society by directing attention to the settings, activities, and socioeconomic factors associated with the highest risks of transmission.
Abstract: It is generally agreed that striking a balance between resuming economic and social activities and keeping the effective reproductive number (R0) below 1 using nonpharmaceutical interventions is an important goal until and even after effective vaccines become available. Therefore, the need remains to understand how the virus is transmitted in order to identify high-risk environments and activities that disproportionately contribute to its spread so that effective preventative measures could be put in place. Contact tracing and household studies, in particular, provide robust evidence about the parameters of transmission. In this Viewpoint, we discuss the available evidence from large-scale, well-conducted contact-tracing studies from across the world and argue that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission dynamics should inform policy decisions about mitigation strategies for targeted interventions according to the needs of the society by directing attention to the settings, activities, and socioeconomic factors associated with the highest risks of transmission.
TL;DR: In this paper, the authors demonstrate the use of photon avalanching at room temperature in single nanostructures and demonstrate their use in super-resolution imaging in near-infrared spectral windows of maximal biological transparency.
Abstract: Avalanche phenomena use steeply nonlinear dynamics to generate disproportionately large responses from small perturbations, and are found in a multitude of events and materials1. Photon avalanching enables technologies such as optical phase-conjugate imaging2, infrared quantum counting3 and efficient upconverted lasing4-6. However, the photon-avalanching mechanism underlying these optical applications has been observed only in bulk materials and aggregates6,7, limiting its utility and impact. Here we report the realization of photon avalanching at room temperature in single nanostructures-small, Tm3+-doped upconverting nanocrystals-and demonstrate their use in super-resolution imaging in near-infrared spectral windows of maximal biological transparency. Avalanching nanoparticles (ANPs) can be pumped by continuous-wave lasers, and exhibit all of the defining features of photon avalanching, including clear excitation-power thresholds, exceptionally long rise time at threshold, and a dominant excited-state absorption that is more than 10,000 times larger than ground-state absorption. Beyond the avalanching threshold, ANP emission scales nonlinearly with the 26th power of the pump intensity, owing to induced positive optical feedback in each nanocrystal. This enables the experimental realization of photon-avalanche single-beam super-resolution imaging7 with sub-70-nanometre spatial resolution, achieved by using only simple scanning confocal microscopy and without any computational analysis. Pairing their steep nonlinearity with existing super-resolution techniques and computational methods8-10, ANPs enable imaging with higher resolution and at excitation intensities about 100 times lower than other probes. The low photon-avalanching threshold and excellent photostability of ANPs also suggest their utility in a diverse array of applications, including sub-wavelength imaging7,11,12 and optical and environmental sensing13-15.
University of Wisconsin-Madison1, Arizona State University2, University College London3, United States Geological Survey4, University of Melbourne5, Westminster College (Utah)6, Curtin University7, Columbia University8, University of Edinburgh9, Lawrence Livermore National Laboratory10, New Mexico Institute of Mining and Technology11, University of Queensland12, University of Alaska Fairbanks13, Oregon State University14, University of Glasgow15, University of St Andrews16, Berkeley Geochronology Center17, University of California, Berkeley18, University of Florida19, Auburn University20, VU University Amsterdam21, Rutgers University22, Centre national de la recherche scientifique23, University of Vermont24, Geological Survey of Canada25, Japanese Ministry of Agriculture, Forestry and Fisheries26, Japan Agency for Marine-Earth Science and Technology27, Chinese Academy of Sciences28, Freiberg University of Mining and Technology29, China University of Geosciences (Wuhan)30
TL;DR: The 40Ar/39Ar dating method is among the most versatile of geochronometers, having the potential to date a broad variety of K-bearing materials spanning from the time of Earth's formation into the historical realm.
Abstract: The 40Ar/39Ar dating method is among the most versatile of geochronometers, having the potential to date a broad variety of K-bearing materials spanning from the time of Earth’s formation into the historical realm. Measurements using modern noble-gas mass spectrometers are now producing 40Ar/39Ar dates with analytical uncertainties of ~0.1%, thereby providing precise time constraints for a wide range of geologic and extraterrestrial processes. Analyses of increasingly smaller subsamples have revealed age dispersion in many materials, including some minerals used as neutron fluence monitors. Accordingly, interpretive strategies are evolving to address observed dispersion in dates from a single sample. Moreover, inferring a geologically meaningful “age” from a measured “date” or set of dates is dependent on the geological problem being addressed and the salient assumptions associated with each set of data. We highlight requirements for collateral information that will better constrain the interpretation of 40Ar/39Ar data sets, including those associated with single-crystal fusion analyses, incremental heating experiments, and in situ analyses of microsampled domains. To ensure the utility and viability of published results, we emphasize previous recommendations for reporting 40Ar/39Ar data and the related essential metadata, with the amendment that data conform to evolving standards of being findable, accessible, interoperable, and reusable (FAIR) by both humans and computers. Our examples provide guidance for the presentation and interpretation of 40Ar/39Ar dates to maximize their interdisciplinary usage, reproducibility, and longevity.