Showing papers by "Newcastle University 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
Novo Nordisk1, German Cancer Research Center2, University of Zurich3, University of Barcelona4, Newcastle University5, Medical University of Vienna6, University of Tübingen7, University Hospital Heidelberg8, Weizmann Institute of Science9, Max Planck Society10, Technische Universität München11, Heidelberg University12, Icahn School of Medicine at Mount Sinai13, National and Kapodistrian University of Athens14, University of Turin15, University of Cambridge16, University of Florence17, Paris Diderot University18, Humanitas University19, Hannover Medical School20, University of Hamburg21, University of Mainz22, University of Düsseldorf23, Cornell University24, Memorial Sloan Kettering Cancer Center25, Harvard University26, University of Cologne27, Leibniz Association28, University of Bern29, Mount Sinai Hospital30, University of Texas MD Anderson Cancer Center31, Kindai University32, Taipei Veterans General Hospital33, National Yang-Ming University34, University of Grenoble35, French Institute of Health and Medical Research36, Imperial College London37, Catalan Institution for Research and Advanced Studies38
TL;DR: The progressive accumulation of exhausted, unconventionally activated CD8+PD1+ T cells in NASH-affected livers provides a rationale for stratification of patients with HCC according to underlying aetiology in studies of immunotherapy as a primary or adjuvant treatment.
Abstract: Hepatocellular carcinoma (HCC) can have viral or non-viral causes1-5. Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need6,7. Here we report the progressive accumulation of exhausted, unconventionally activated CD8+PD1+ T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded activated CD8+PD1+ T cells within tumours but did not lead to tumour regression, which indicates that tumour immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASH-HCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8+PD1+CXCR6+, TOX+, and TNF+ T cells. The increase in HCC triggered by anti-PD1 treatment was prevented by depletion of CD8+ T cells or TNF neutralization, suggesting that CD8+ T cells help to induce NASH-HCC, rather than invigorating or executing immune surveillance. We found similar phenotypic and functional profiles in hepatic CD8+PD1+ T cells from humans with NAFLD or NASH. A meta-analysis of three randomized phase III clinical trials that tested inhibitors of PDL1 (programmed death-ligand 1) or PD1 in more than 1,600 patients with advanced HCC revealed that immune therapy did not improve survival in patients with non-viral HCC. In two additional cohorts, patients with NASH-driven HCC who received anti-PD1 or anti-PDL1 treatment showed reduced overall survival compared to patients with other aetiologies. Collectively, these data show that non-viral HCC, and particularly NASH-HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of patients with HCC according to underlying aetiology in studies of immunotherapy as a primary or adjuvant treatment.
526 citations
University of Oxford1, Wellcome Trust Sanger Institute2, University of Cambridge3, Public Health England4, Liverpool School of Tropical Medicine5, University of Sheffield6, Newcastle University7, Newcastle upon Tyne Hospitals NHS Foundation Trust8, University Hospital Southampton NHS Foundation Trust9, University of Southampton10, University Hospitals Bristol NHS Foundation Trust11, St George's, University of London12, University College London13, Guy's and St Thomas' NHS Foundation Trust14, University Hospitals Birmingham NHS Foundation Trust15, University of Glasgow16, North Bristol NHS Trust17, University College Hospital18, University of Hull19, Northwest University (China)20, Glasgow Dental Hospital and School21, Western General Hospital22, University of Nottingham23, Nottingham University Hospitals NHS Trust24, AstraZeneca25, Aneurin Bevan University Health Board26, Cardiff University27
TL;DR: A post-hoc analysis of the efficacy of the adenoviral vector vaccine, ChAdOx1 nCoV-19 (AZD1222), against B.1.7, emerged as the dominant cause of COVID-19 disease in the UK from November, 2020 as discussed by the authors.
521 citations
European Bioinformatics Institute1, Newcastle University2, Newcastle upon Tyne Hospitals NHS Foundation Trust3, Oregon Health & Science University4, University of Genoa5, Istituto Giannina Gaslini6, University of Western Australia7, King Edward Memorial Hospital8, American College of Medical Genetics9, Anschutz Medical Campus10, Johns Hopkins University11, Ludwig Maximilian University of Munich12, Children's Hospital of Philadelphia13, Austrian Academy of Sciences14, University of Connecticut15, French Institute of Health and Medical Research16, Lawrence Berkeley National Laboratory17, University of Michigan18, University of Freiburg19, University of Luxembourg20, Oregon State University21, Chestnut Hill College22, Medical University of Graz23, Queen Mary University of London24, Hebrew University of Jerusalem25, University of Pennsylvania26
TL;DR: Recent major extensions of the Human Phenotype Ontology for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas are presented and new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease are presented.
Abstract: The Human Phenotype Ontology (HPO, https://hpo.jax.org) was launched in 2008 to provide a comprehensive logical standard to describe and computationally analyze phenotypic abnormalities found in human disease. The HPO is now a worldwide standard for phenotype exchange. The HPO has grown steadily since its inception due to considerable contributions from clinical experts and researchers from a diverse range of disciplines. Here, we present recent major extensions of the HPO for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas. For example, the seizure subontology now reflects the International League Against Epilepsy (ILAE) guidelines and these enhancements have already shown clinical validity. We present new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease. These efforts will benefit software such as Exomiser by improving the accuracy and scope of cross-species phenotype matching. The computational modeling strategy used by the HPO to define disease entities and phenotypic features and distinguish between them is explained in detail.We also report on recent efforts to translate the HPO into indigenous languages. Finally, we summarize recent advances in the use of HPO in electronic health record systems.
503 citations
Niamh Mullins1, Andreas J. Forstner2, Andreas J. Forstner3, Andreas J. Forstner4 +396 more•Institutions (119)
TL;DR: The authors performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci, including genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics.
Abstract: Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
378 citations
Icahn School of Medicine at Mount Sinai1, Pontifical Catholic University of Chile2, VU University Medical Center3, Cedars-Sinai Medical Center4, Vita-Salute San Raffaele University5, University of Sydney6, Mayo Clinic7, Newcastle University8, Freeman Hospital9, National University of Singapore10, Radboud University Nijmegen11, Kolling Institute of Medical Research12, Macquarie University13, Royal North Shore Hospital14, Jagiellonian University Medical College15, University of Washington Medical Center16, University of Antioquia17, Vancouver General Hospital18, University of Cape Town19
TL;DR: In this paper, the authors presented the first effort of its kind to connect stakeholders, to ignite global awareness of sex-related and gender-related disparities in cardiovascular disease, and to provide a springboard for future research.
354 citations
Newcastle University1, University of Cambridge2, European Bioinformatics Institute3, Wellcome Trust Sanger Institute4, University College London5, Ludwig Maximilian University of Munich6, Newcastle upon Tyne Hospitals NHS Foundation Trust7, University College London Hospitals NHS Foundation Trust8, Royal Free Hospital9, UCL Institute of Child Health10, Harvard University11
TL;DR: In this article, the authors performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19.
Abstract: Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.
324 citations
TL;DR: In this paper, the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes were determined.
313 citations
TL;DR: It is recommended the establishment of a global research consortium to further study the natural history of OPMDs based on the classification and nomenclature proposed here, and link them to evidence-based interventions, to facilitate the prevention and management of lip and oral cavity cancer.
Abstract: Oral potentially malignant disorders (OPMDs) are associated with an increased risk of occurrence of cancers of the lip or oral cavity. This paper presents an updated report on the nomenclature and the classification of OPMDs, based predominantly on their clinical features, following discussions by an expert group at a workshop held by the World Health Organization (WHO) Collaborating Centre for Oral Cancer in the UK. The first workshop held in London in 2005 considered a wide spectrum of disorders under the term "potentially malignant disorders of the oral mucosa" (PMD) (now referred to as oral potentially malignant disorders: OPMD) including leukoplakia, erythroplakia, proliferative verrucous leukoplakia, oral lichen planus, oral submucous fibrosis, palatal lesions in reverse smokers, lupus erythematosus, epidermolysis bullosa, and dyskeratosis congenita. Any new evidence published in the intervening period was considered to make essential changes to the 2007 classification. In the current update, most entities were retained with minor changes to their definition. There is sufficient evidence for an increased risk of oral cancer among patients diagnosed with "oral lichenoid lesions" and among those diagnosed with oral manifestations of 'chronic graft-versus-host disease'. These have now been added to the list of OPMDs. There is, to date, insufficient evidence concerning the malignant potential of chronic hyperplastic candidosis and of oral exophytic verrucous hyperplasia to consider these conditions as OPMDs. Furthermore, due to lack of clear evidence of an OPMD in epidermolysis bullosa this was moved to the category with limited evidence. We recommend the establishment of a global research consortium to further study the natural history of OPMDs based on the classification and nomenclature proposed here. This will require multi-center longitudinal studies with uniform diagnostic criteria to improve the identification and cancer risk stratification of patients with OPMDs, link them to evidence-based interventions, with a goal to facilitate the prevention and management of lip and oral cavity cancer.
306 citations
TL;DR: In this article, the authors aimed to determine illness duration and characteristics in symptomatic UK school-aged children tested for SARS-CoV-2 using data from the COVID Symptom Study, one of the largest UK citizen participatory epidemiological studies to date.
268 citations
Katholieke Universiteit Leuven1, Sapienza University of Rome2, University of Paris3, University of Toulouse4, Harvard University5, Boston Children's Hospital6, University of California, Irvine7, University of Brescia8, Vita-Salute San Raffaele University9, Erasmus University Medical Center10, Hospital Clínico San Carlos11, Complutense University of Madrid12, Epsom and St Helier University Hospitals NHS Trust13, National Institutes of Health14, University of São Paulo15, University of Padua16, University of Naples Federico II17, Ghent University18, Nationwide Children's Hospital19, Marmara University20, Newcastle University21, University Hospital of Wales22, Universidad del Desarrollo23, Saint Louis University Hospital24, Ludwig Maximilian University of Munich25, Icahn School of Medicine at Mount Sinai26, University of Freiburg27, Children's Hospital of Philadelphia28, Garvan Institute of Medical Research29, University of New South Wales30
TL;DR: More than 30% of patients with IEI with SARS-CoV-2 infection had mild coronavirus disease 2019 (COVID-19) and risk factors predisposing to severe disease/mortality in the general population also seemed to affect patients withIEI, including more younger patients.
Abstract: Background There is uncertainty about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with rare inborn errors of immunity (IEI), a population at risk of developing severe coronavirus disease 2019. This is relevant not only for these patients but also for the general population, because studies of IEIs can unveil key requirements for host defense. Objective We sought to describe the presentation, manifestations, and outcome of SARS-CoV-2 infection in IEI to inform physicians and enhance understanding of host defense against SARS-CoV-2. Methods An invitation to participate in a retrospective study was distributed globally to scientific, medical, and patient societies involved in the care and advocacy for patients with IEI. Results We gathered information on 94 patients with IEI with SARS-CoV-2 infection. Their median age was 25 to 34 years. Fifty-three patients (56%) suffered from primary antibody deficiency, 9 (9.6%) had immune dysregulation syndrome, 6 (6.4%) a phagocyte defect, 7 (7.4%) an autoinflammatory disorder, 14 (15%) a combined immunodeficiency, 3 (3%) an innate immune defect, and 2 (2%) bone marrow failure. Ten were asymptomatic, 25 were treated as outpatients, 28 required admission without intensive care or ventilation, 13 required noninvasive ventilation or oxygen administration, 18 were admitted to intensive care units, 12 required invasive ventilation, and 3 required extracorporeal membrane oxygenation. Nine patients (7 adults and 2 children) died. Conclusions This study demonstrates that (1) more than 30% of patients with IEI had mild coronavirus disease 2019 (COVID-19) and (2) risk factors predisposing to severe disease/mortality in the general population also seemed to affect patients with IEI, including more younger patients. Further studies will identify pathways that are associated with increased risk of severe disease and are nonredundant or redundant for protection against SARS-CoV-2.
University of Fribourg1, Stellenbosch University2, University College London3, Zoological Society of London4, University of Lisbon5, Durham University6, University of Vienna7, International Union for Conservation of Nature and Natural Resources8, Lincoln University (New Zealand)9, Taizhou University10, University of Konstanz11, Helmholtz Centre for Environmental Research - UFZ12, Martin Luther University of Halle-Wittenberg13, Free University of Berlin14, Leibniz Association15, Czech University of Life Sciences Prague16, United States Forest Service17, Newcastle University18, Academy of Sciences of the Czech Republic19, Charles University in Prague20
TL;DR: These projections are the first quantitative projections of future trajectories of alien species numbers for seven major taxonomic groups in eight continents, accounting for variation in sampling intensity and uncertainty in projections.
Abstract: Biological invasions have steadily increased over recent centuries. However, we still lack a clear expectation about future trends in alien species numbers. In particular, we do not know whether alien species will continue to accumulate in regional floras and faunas, or whether the pace of accumulation will decrease due to the depletion of native source pools. Here, we apply a new model to simulate future numbers of alien species based on estimated sizes of source pools and dynamics of historical invasions, assuming a continuation of processes in the future as observed in the past (a business-as-usual scenario). We first validated performance of different model versions by conducting a back-casting approach, therefore fitting the model to alien species numbers until 1950 and validating predictions on trends from 1950 to 2005. In a second step, we selected the best performing model that provided the most robust predictions to project trajectories of alien species numbers until 2050. Altogether, this resulted in 3,790 stochastic simulation runs for 38 taxon-continent combinations. We provide the first quantitative projections of future trajectories of alien species numbers for seven major taxonomic groups in eight continents, accounting for variation in sampling intensity and uncertainty in projections. Overall, established alien species numbers per continent were predicted to increase from 2005 to 2050 by 36%. Particularly, strong increases were projected for Europe in absolute (+2,543 ± 237 alien species) and relative terms, followed by Temperate Asia (+1,597 ± 197), Northern America (1,484 ± 74) and Southern America (1,391 ± 258). Among individual taxonomic groups, especially strong increases were projected for invertebrates globally. Declining (but still positive) rates were projected only for Australasia. Our projections provide a first baseline for the assessment of future developments of biological invasions, which will help to inform policies to contain the spread of alien species.
University of Patras1, University of Bristol2, University of Copenhagen3, University of Mainz4, Autonomous University of Barcelona5, University of London6, Guy's and St Thomas' NHS Foundation Trust7, I.M. Sechenov First Moscow State Medical University8, Lund University9, University of Porto10, University of Nicosia11, Imperial College London12, University of Oslo13, Newcastle University14, Freeman Hospital15, Nova Southeastern University16, University of Liège17, Ghent University18, Uppsala University19, Mayo Clinic20, Inova Fairfax Hospital21, Erasmus University Rotterdam22
TL;DR: The European Society for Vascular Surgery (ESVS) 2021 Clinical Practice Guidelines on the Management of Venous Thrombosis as discussed by the authors have been published for the management of venous thrombotic vessels.
National Research Council1, University of Twente2, Nottingham Trent University3, Leibniz Association4, University of Piraeus5, Luleå University of Technology6, University of the Basque Country7, Technical University of Madrid8, University of Trento9, Frederick University10, Budapest University of Technology and Economics11, University of Tartu12, Umeå University13, Trinity College, Dublin14, Queen's University Belfast15, Kyushu University16, Academy of Sciences of the Czech Republic17, Aalborg University18, University of Reims Champagne-Ardenne19, Philippine Institute for Development Studies20, Newcastle University21
TL;DR: In this article, the authors present a comparative analysis of the mitigation targets of 327 European cities, as declared in their local climate plans, and analyze whether the type of plan, city size, membership of climate networks, and its regional location are associated with different levels of mitigation ambition.
Abstract: Cities across the globe recognise their role in climate mitigation and are acting to reduce carbon emissions. Knowing whether cities set ambitious climate and energy targets is critical for determining their contribution towards the global 1.5 °C target, partly because it helps to identify areas where further action is necessary. This paper presents a comparative analysis of the mitigation targets of 327 European cities, as declared in their local climate plans. The sample encompasses over 25% of the EU population and includes cities of all sizes across all Member States, plus the UK. The study analyses whether the type of plan, city size, membership of climate networks, and its regional location are associated with different levels of mitigation ambition. Results reveal that 78% of the cities have a GHG emissions reduction target. However, with an average target of 47%, European cities are not on track to reach the Paris Agreement: they need to roughly double their ambitions and efforts. Some cities are ambitious, e.g. 25% of our sample (81) aim to reach carbon neutrality, with the earliest target date being 2020.90% of these cities are members of the Climate Alliance and 75% of the Covenant of Mayors. City size is the strongest predictor for carbon neutrality, whilst climate network(s) membership, combining adaptation and mitigation into a single strategy, and local motivation also play a role. The methods, data, results and analysis of this study can serve as a reference and baseline for tracking climate mitigation ambitions across European and global cities.
University College London1, Francis Crick Institute2, Åbo Akademi University3, Goethe University Frankfurt4, Imperial College London5, Technion – Israel Institute of Technology6, University of Turku7, Newcastle University8, Max Planck Society9, Aix-Marseille University10, Instituto Gulbenkian de Ciência11
TL;DR: ZeroCostDL4Mic as discussed by the authors is an entry-level platform simplifying DL access by leveraging the free, cloud-based computational resources of Google Colab, which allows researchers with no coding expertise to train and apply key DL networks to perform tasks including segmentation, object detection, denoising, and image-to-image translation.
Abstract: Deep Learning (DL) methods are powerful analytical tools for microscopy and can outperform conventional image processing pipelines. Despite the enthusiasm and innovations fuelled by DL technology, the need to access powerful and compatible resources to train DL networks leads to an accessibility barrier that novice users often find difficult to overcome. Here, we present ZeroCostDL4Mic, an entry-level platform simplifying DL access by leveraging the free, cloud-based computational resources of Google Colab. ZeroCostDL4Mic allows researchers with no coding expertise to train and apply key DL networks to perform tasks including segmentation (using U-Net and StarDist), object detection (using YOLOv2), denoising (using CARE and Noise2Void), super-resolution microscopy (using Deep-STORM), and image-to-image translation (using Label-free prediction - fnet, pix2pix and CycleGAN). Importantly, we provide suitable quantitative tools for each network to evaluate model performance, allowing model optimisation. We demonstrate the application of the platform to study multiple biological processes.
Newcastle University1, University of Oxford2, University of Liverpool3, University of Birmingham4, University of Sheffield5, Public Health England6, Boston Children's Hospital7, University Hospitals Birmingham NHS Foundation Trust8, Mahidol University9, Imperial College London10, Newcastle upon Tyne Hospitals NHS Foundation Trust11
TL;DR: In this paper, an extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose, which showed that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T-cell response to the spike protein.
University of Calgary1, Cooperative Institute for Research in Environmental Sciences2, Swiss Federal Institute for Forest, Snow and Landscape Research3, ETH Zurich4, University of Washington5, University of Zurich6, University of Potsdam7, United States Geological Survey8, University of Minnesota9, University of Natural Resources and Life Sciences, Vienna10, University of Graz11, University of Toulouse12, University of Utah13, Heidelberg University14, University of Geneva15, University of Leeds16, Simon Fraser University17, Newcastle University18, University of Dayton19, University of Oslo20, Planetary Science Institute21, University of Alberta22, University of Grenoble23, University of Sheffield24, Indian Institute of Technology Indore25, University of Dundee26, UNESCO27, Jawaharlal Nehru University28, Stockholm International Water Institute29, University of British Columbia30, University of Exeter31, Kathmandu32, Wadia Institute of Himalayan Geology33, University of Kashmir34, University of Delhi35, Utrecht University36, International Centre for Integrated Mountain Development37, University of Chile38, Northumbria University39
TL;DR: In this paper, an analysis of satellite imagery, seismic records, numerical model results, and eyewitness videos reveals that ~27x106 m3 of rock and glacier ice collapsed from the steep north face of Ronti Peak.
Abstract: On 7 Feb 2021, a catastrophic mass flow descended the Ronti Gad, Rishiganga, and Dhauliganga valleys in Chamoli, Uttarakhand, India, causing widespread devastation and severely damaging two hydropower projects. Over 200 people were killed or are missing. Our analysis of satellite imagery, seismic records, numerical model results, and eyewitness videos reveals that ~27x106 m3 of rock and glacier ice collapsed from the steep north face of Ronti Peak. The rock and ice avalanche rapidly transformed into an extraordinarily large and mobile debris flow that transported boulders >20 m in diameter, and scoured the valley walls up to 220 m above the valley floor. The intersection of the hazard cascade with downvalley infrastructure resulted in a disaster, which highlights key questions about adequate monitoring and sustainable development in the Himalaya as well as other remote, high-mountain environments.
University of Barcelona1, Newcastle University2, Pontifical Catholic University of Chile3, University College London4, University of Paris5, University of Lisbon6, University of Florida7, University of Washington8, University of Antwerp9, University of Sydney10, Karolinska Institutet11, City University of New York12, King Fahd University Hospital13, University of California, San Diego14, University of California, Berkeley15, University Hospitals Birmingham NHS Foundation Trust16, College of Health Sciences, Bahrain17, Northwestern University18, The Graduate Center, CUNY19, University of Seville20, Royal Free Hospital21, University of Milan22, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico23, The Chinese University of Hong Kong24, Marmara University25, University of Haifa26
TL;DR: In this paper, a global Delphi study, a multidisciplinary group of experts developed consensus statements and recommendations, which a larger group of collaborators reviewed over three rounds until consensus was achieved.
Abstract: Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects approximately one-quarter of the global adult population, causing a substantial burden of ill health with wide-ranging social and economic implications. It is a multisystem disease and is considered the hepatic component of metabolic syndrome. Unlike other highly prevalent conditions, NAFLD has received little attention from the global public health community. Health system and public health responses to NAFLD have been weak and fragmented, and, despite its pervasiveness, NAFLD is largely unknown outside hepatology and gastroenterology. There is only a nascent global public health movement addressing NAFLD, and the disease is absent from nearly all national and international strategies and policies for non-communicable diseases, including obesity. In this global Delphi study, a multidisciplinary group of experts developed consensus statements and recommendations, which a larger group of collaborators reviewed over three rounds until consensus was achieved. The resulting consensus statements and recommendations address a broad range of topics - from epidemiology, awareness, care and treatment to public health policies and leadership - that have general relevance for policy-makers, health-care practitioners, civil society groups, research institutions and affected populations. These recommendations should provide a strong foundation for a comprehensive public health response to NAFLD.
TL;DR: This first national analysis of the impact of the COVID-19 pandemic on endoscopy services and endoscopic cancer diagnosis demonstrates the remarkable impact that the pandemic has had, which has resulted in a substantial and concerning reduction in cancer detection.
Abstract: Objective The COVID-19 pandemic has had a major global impact on endoscopic services. This reduced capacity, along with public reluctance to undergo endoscopy during the pandemic, might result in excess mortality from delayed cancer diagnosis. Using the UK’s National Endoscopy Database (NED), we performed the first national analysis of the impact of the pandemic on endoscopy services and endoscopic cancer diagnosis. Design We developed a NED COVID-19 module incorporating procedure-level data on all endoscopic procedures. Three periods were designated: pre-COVID (6 January 2020 to 15 March), transition (16–22 March) and COVID-impacted (23 March–31 May). National, regional and procedure-specific analyses were performed. The average weekly number of cancers, proportion of missing cancers and cancer detection rates were calculated. Results A weekly average of 35 478 endoscopy procedures were performed in the pre-COVID period. Activity in the COVID-impacted period reduced to 12% of pre-COVID levels; at its low point, activity was only 5%, recovering to 20% of pre-COVID activity by study end. Although more selective vetting significantly increased the per-procedure cancer detection rate (pre-COVID 1.91%; COVID-impacted 6.61%; p Conclusion This national analysis demonstrates the remarkable impact that the pandemic has had on endoscopic services, which has resulted in a substantial and concerning reduction in cancer detection. Major, urgent efforts are required to restore endoscopy capacity to prevent an impending cancer healthcare crisis.
01 Jan 2021
TL;DR: In this paper, material flow analysis is applied to understand current and future flows of cobalt embedded in electric vehicle batteries across the European Union, and four strategies are compared with four strategies: technology-driven substitution and technology driven reduction, new business models to stimulate battery reuse/recycling, policy-driven strategy to increase recycling, and new battery chemistry can help reduce the reliance on Co for electric vehicles.
Abstract: The wide adoption of lithium-ion batteries used in electric vehicles will require increased natural resources for the automotive industry. The expected rapid increase in batteries could result in new resource challenges and supply-chain risks. To strengthen the resilience and sustainability of automotive supply chains and reduce primary resource requirements, circular economy strategies are needed. Here we illustrate how these strategies can reduce the extraction of primary raw materials, that is, cobalt supplies. Material flow analysis is applied to understand current and future flows of cobalt embedded in electric vehicle batteries across the European Union. A reference scenario is presented and compared with four strategies: technology-driven substitution and technology-driven reduction of cobalt, new business models to stimulate battery reuse/recycling and policy-driven strategy to increase recycling. We find that new technologies provide the most promising strategies to reduce the reliance on cobalt substantially but could result in burden shifting such as an increase in nickel demand. To avoid the latter, technological developments should be combined with an efficient recycling system. We conclude that more-ambitious circular economy strategies, at both government and business levels, are urgently needed to address current and future resource challenges across the supply chain successfully. New battery chemistry can help reduce the reliance on Co for electric vehicles. However, to avoid burden shifting to other resources such as Ni, circular economy strategies with enhanced battery traceability and recycling could contribute substantially to the reduction of primary Co demand from the automotive industry.
TL;DR: In this paper, the transcriptomes of more than 500,000 single cells from developing human fetal skin, healthy adult skin, and adult skin with atopic dermatitis and psoriasis were compared across development, homeostasis, and disease.
Abstract: The skin confers biophysical and immunological protection through a complex cellular network established early in embryonic development. We profiled the transcriptomes of more than 500,000 single cells from developing human fetal skin, healthy adult skin, and adult skin with atopic dermatitis and psoriasis. We leveraged these datasets to compare cell states across development, homeostasis, and disease. Our analysis revealed an enrichment of innate immune cells in skin during the first trimester and clonal expansion of disease-associated lymphocytes in atopic dermatitis and psoriasis. We uncovered and validated in situ a reemergence of prenatal vascular endothelial cell and macrophage cellular programs in atopic dermatitis and psoriasis lesional skin. These data illustrate the dynamism of cutaneous immunity and provide opportunities for targeting pathological developmental programs in inflammatory skin diseases.
Newcastle University1, Royal Netherlands Meteorological Institute2, National Center for Atmospheric Research3, University of Adelaide4, University of Reading5, University of Innsbruck6, Swedish Meteorological and Hydrological Institute7, Ho Chi Minh City University of Agriculture and Forestry8, University of Michigan9, Jacobs University Bremen10, University of Copenhagen11, Met Office12, ETH Zurich13, University of New South Wales14, University of Iowa15, University of Melbourne16
TL;DR: In this paper, the authors examined evidence from observational, theoretical and modelling studies for the intensification of these rainfall extremes, the drivers and the impact on flash flooding and concluded that short-duration and long-duration (>1 day) rainfall extremes are intensifying with warming at a rate consistent with the increase in atmospheric moisture.
Abstract: Short-duration (1–3 h) rainfall extremes can cause serious damage to societies through rapidly developing (flash) flooding and are determined by complex, multifaceted processes that are altering as Earth’s climate warms. In this Review, we examine evidence from observational, theoretical and modelling studies for the intensification of these rainfall extremes, the drivers and the impact on flash flooding. Both short-duration and long-duration (>1 day) rainfall extremes are intensifying with warming at a rate consistent with the increase in atmospheric moisture (~7% K−1), while in some regions, increases in short-duration extreme rainfall intensities are stronger than expected from moisture increases alone. These stronger local increases are related to feedbacks in convective clouds, but their exact role is uncertain because of the very small scales involved. Future extreme rainfall intensification is also modulated by changes to temperature stratification and large-scale atmospheric circulation. The latter remains a major source of uncertainty. Intensification of short-duration extremes has likely increased the incidence of flash flooding at local scales, and this can further compound with an increase in storm spatial footprint to considerably increase total event rainfall. These findings call for urgent climate change adaptation measures to manage increasing flood risks. Short-duration rainfall extremes are determined by complex processes that are affected by the warming climate. This Review assesses the evidence for the intensification of short-duration rainfall extremes, the associated drivers and the implications for flood risks.
TL;DR: This paper aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available.
Abstract: Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
Wellcome Trust Sanger Institute1, Laboratory of Molecular Biology2, Queen Mary University of London3, University of Cambridge4, Newcastle University5, University College London6, Cambridge University Hospitals NHS Foundation Trust7, European Bioinformatics Institute8, University of Oxford9, John Radcliffe Hospital10, Garvan Institute of Medical Research11
TL;DR: The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures as discussed by the authors, using single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions of the developing and up to 11 distinct anatomical regions in the healthy human gut.
Abstract: The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung’s disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease. Cells from embryonic, fetal, paediatric and adult human intestinal tissue are analysed at different locations along the intestinal tract to construct a single-cell atlas of the developing and adult human intestinal tract, encompassing all cell lineages.
TL;DR: In this article, the authors highlight the advantages of these biomass-based carbon dots in terms of synthesis, properties, and applications in the biomedical field and highlight the future development of biomass derived quantum dots.
Abstract: Carbon dots have been considered as a solution to the challenges that semiconductor quantum dots have encountered because they are more biocompatible and can be synthesized from abundant and nontoxic materials such as biomass. This review will highlight the advantages of these biomass-based carbon dots in terms of synthesis, properties, and applications in the biomedical field. Furthermore, future applications especially in the biomedical field of biomass-based carbon dots as well as the challenges of semiconductor quantum dots such as biocompatibility, photobleaching, environmental challenges, toxicity, and poor solubility will be discussed in detail. Biomass-derived quantum dots, a subsection of carbon dots that are the most desirable for future research, will be focused upon including from synthesis to applications. Finally, the future development of biomass derived quantum dots in the biomedical field will be discussed and evaluated to unlock the potential for their applications.
TL;DR: The results demonstrate that interactivity, specifically, consumer-consumer interaction and consumer-seller interaction, positively affects social support, which in turn enhances consumers’ intention to co-create brand value.
TL;DR: In this paper, the efficacy of ivermectin treatment in reducing mortality, in secondary outcomes, and in chemoprophylaxis, among people with, or at high risk of, COVID-19 infection was assessed.
Abstract: Background Repurposed medicines may have a role against the SARS-CoV-2 virus. The antiparasitic ivermectin, with antiviral and anti-inflammatory properties, has now been tested in numerous clinical trials. Areas of uncertainty We assessed the efficacy of ivermectin treatment in reducing mortality, in secondary outcomes, and in chemoprophylaxis, among people with, or at high risk of, COVID-19 infection. Data sources We searched bibliographic databases up to April 25, 2021. Two review authors sifted for studies, extracted data, and assessed risk of bias. Meta-analyses were conducted and certainty of the evidence was assessed using the GRADE approach and additionally in trial sequential analyses for mortality. Twenty-four randomized controlled trials involving 3406 participants met review inclusion. Therapeutic advances Meta-analysis of 15 trials found that ivermectin reduced risk of death compared with no ivermectin (average risk ratio 0.38, 95% confidence interval 0.19-0.73; n = 2438; I2 = 49%; moderate-certainty evidence). This result was confirmed in a trial sequential analysis using the same DerSimonian-Laird method that underpinned the unadjusted analysis. This was also robust against a trial sequential analysis using the Biggerstaff-Tweedie method. Low-certainty evidence found that ivermectin prophylaxis reduced COVID-19 infection by an average 86% (95% confidence interval 79%-91%). Secondary outcomes provided less certain evidence. Low-certainty evidence suggested that there may be no benefit with ivermectin for "need for mechanical ventilation," whereas effect estimates for "improvement" and "deterioration" clearly favored ivermectin use. Severe adverse events were rare among treatment trials and evidence of no difference was assessed as low certainty. Evidence on other secondary outcomes was very low certainty. Conclusions Moderate-certainty evidence finds that large reductions in COVID-19 deaths are possible using ivermectin. Using ivermectin early in the clinical course may reduce numbers progressing to severe disease. The apparent safety and low cost suggest that ivermectin is likely to have a significant impact on the SARS-CoV-2 pandemic globally.
TL;DR: Dye-sensitized solar cells (DSCs) have experienced a renaissance as the best technology for several niche applications that take advantage of DSC's unique combination of properties: at low cost, they are composed of non-toxic materials, are colorful, transparent, and very efficient in low light conditions.
Abstract: Dye-sensitized solar cells (DSCs) are celebrating their 30th birthday and they are attracting a wealth of research efforts aimed at unleashing their full potential. In recent years, DSCs and dye-sensitized photoelectrochemical cells (DSPECs) have experienced a renaissance as the best technology for several niche applications that take advantage of DSCs' unique combination of properties: at low cost, they are composed of non-toxic materials, are colorful, transparent, and very efficient in low light conditions. This review summarizes the advancements in the field over the last decade, encompassing all aspects of the DSC technology: theoretical studies, characterization techniques, materials, applications as solar cells and as drivers for the synthesis of solar fuels, and commercialization efforts from various companies.
TL;DR: In this paper, the authors reviewed the technological and economical feasibilities as well as sustainable assessment of approaches (thermochemical and biochemical) applied for sustainable “drop-in” fuel production from lignocellulosic sources.
Abstract: This paper reviews the technological and economical feasibilities as well as sustainable assessment of approaches (thermochemical and biochemical) applied for sustainable “drop-in” fuel production from lignocellulosic sources. The challenges for each pathway to produce “drop-in” fuels are covered. Currently “drop-in” fuel production cost is approximately 2 times (~5–6$/gallon) higher than fossil fuels (3$/gallon), especially with the use of 2nd generation feedstocks. The primary sources of cost with “drop-in” fuel production are feedstock cost (40–60% of the total production cost), syngas cleaning and conditioning to meet Fischer-Tropsch synthesis requirement (12–15% of the total production cost) and bio oil upgrading (14–18% of the total production cost) in the case of pyrolysis and hydrothermal liquefaction (HTL). The most influential factors on the life cycle analysis (LCA) were biomass cultivation, harvesting, biomass pre-treatment, and transportation. Therefore, robust processes that can use local waste biomass are far more environmental and economically viable, especially as biofuel from second generation have a greater potential to reduce greenhouse gas emissions (50–100%) than first generation biofuels (50–90%) when land use changes are omitted in the LCA. The sustainability of biofuels is pre-dominantly dependant on the sustainability of the initial biomass, with 2nd generation feedstocks being more sustainable than 1st generation. Gasification-FTS is considered as the most promising technique for “drop-in” fuel production over pyrolysis and HTL due to its flexibility towards feedstock acceptance and the ability to produced high yields of liquid fuel together with other economically viable biofuels such as electricity and heat. Biochemical routes (i.e.fermentation) to “drop-in” fuels are still in their early development stages, and therefore require more studies and pilot-scale experiments in order to discover an economic and sustainable means of using these methods.