Showing papers by "University of Glasgow published in 2020"
TL;DR: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates, and there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries.
5,802 citations
Karolinska Institutet1, Uppsala University2, University of Glasgow3, University College London4, University of Oxford5, King's College London6, University of Exeter7, Black Dog Institute8, University of California, Irvine9, University of Cambridge10, Swansea University11, Guy's and St Thomas' NHS Foundation Trust12, UCL Institute of Child Health13, St George's, University of London14, Emory University15, University of Bristol16, Academy of Medical Sciences, United Kingdom17
TL;DR: There is an urgent need for research to address how mental health consequences for vulnerable groups can be mitigated under pandemic conditions, and on the impact of repeated media consumption and health messaging around COVID-19.
3,909 citations
Book•
23 Feb 2020
TL;DR: The ATLAS detector as installed in its experimental cavern at point 1 at CERN is described in this paper, where a brief overview of the expected performance of the detector when the Large Hadron Collider begins operation is also presented.
Abstract: The ATLAS detector as installed in its experimental cavern at point 1 at CERN is described in this paper. A brief overview of the expected performance of the detector when the Large Hadron Collider begins operation is also presented.
3,111 citations
Christopher J L Murray1, Christopher J L Murray2, Christopher J L Murray3, Aleksandr Y. Aravkin3 +2269 more•Institutions (286)
TL;DR: The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure.
3,059 citations
Queen's University Belfast1, University of St Andrews2, Aix-Marseille University3, Historic England4, University of Sheffield5, University of Oxford6, Alfred Wegener Institute for Polar and Marine Research7, Xi'an Jiaotong University8, University of Minnesota9, Nanjing Normal University10, University of Hohenheim11, University of Kiel12, University of California, Santa Cruz13, Lawrence Livermore National Laboratory14, ETH Zurich15, University of Waikato16, Woods Hole Oceanographic Institution17, Heidelberg University18, Cornell University19, Lund University20, University of New South Wales21, University of Arizona22, University of Groningen23, University of Bristol24, University of Glasgow25, University of California, Irvine26, University of Bern27, Aarhus University28, Nagoya University29, Swiss Federal Institute for Forest, Snow and Landscape Research30, National Museum of Japanese History31, University of Bologna32
TL;DR: In this article, the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP.
Abstract: Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.
2,800 citations
TL;DR: In study participants, mortality was high, independent risk factors were increasing age, male sex, and chronic comorbidity, including obesity, and the importance of pandemic preparedness and the need to maintain readiness to launch research studies in response to outbreaks is shown.
Abstract: Objective To characterise the clinical features of patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United Kingdom during the growth phase of the first wave of this outbreak who were enrolled in the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study, and to explore risk factors associated with mortality in hospital. Design Prospective observational cohort study with rapid data gathering and near real time analysis. Setting 208 acute care hospitals in England, Wales, and Scotland between 6 February and 19 April 2020. A case report form developed by ISARIC and WHO was used to collect clinical data. A minimal follow-up time of two weeks (to 3 May 2020) allowed most patients to complete their hospital admission. Participants 20 133 hospital inpatients with covid-19. Main outcome measures Admission to critical care (high dependency unit or intensive care unit) and mortality in hospital. Results The median age of patients admitted to hospital with covid-19, or with a diagnosis of covid-19 made in hospital, was 73 years (interquartile range 58-82, range 0-104). More men were admitted than women (men 60%, n=12 068; women 40%, n=8065). The median duration of symptoms before admission was 4 days (interquartile range 1-8). The commonest comorbidities were chronic cardiac disease (31%, 5469/17 702), uncomplicated diabetes (21%, 3650/17 599), non-asthmatic chronic pulmonary disease (18%, 3128/17 634), and chronic kidney disease (16%, 2830/17 506); 23% (4161/18 525) had no reported major comorbidity. Overall, 41% (8199/20 133) of patients were discharged alive, 26% (5165/20 133) died, and 34% (6769/20 133) continued to receive care at the reporting date. 17% (3001/18 183) required admission to high dependency or intensive care units; of these, 28% (826/3001) were discharged alive, 32% (958/3001) died, and 41% (1217/3001) continued to receive care at the reporting date. Of those receiving mechanical ventilation, 17% (276/1658) were discharged alive, 37% (618/1658) died, and 46% (764/1658) remained in hospital. Increasing age, male sex, and comorbidities including chronic cardiac disease, non-asthmatic chronic pulmonary disease, chronic kidney disease, liver disease and obesity were associated with higher mortality in hospital. Conclusions ISARIC WHO CCP-UK is a large prospective cohort study of patients in hospital with covid-19. The study continues to enrol at the time of this report. In study participants, mortality was high, independent risk factors were increasing age, male sex, and chronic comorbidity, including obesity. This study has shown the importance of pandemic preparedness and the need to maintain readiness to launch research studies in response to outbreaks. Study registration ISRCTN66726260.
2,459 citations
TL;DR: The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.
Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18.
1,600 citations
TL;DR: The only way to tackle air pollution is through public awareness coupled with a multidisciplinary approach by scientific experts; national and international organizations must address the emergence of this threat and propose sustainable solutions.
Abstract: One of our era's greatest scourges is air pollution, on account not only of its impact on climate change but also its impact on public and individual health due to increasing morbidity and mortality. There are many pollutants that are major factors in disease in humans. Among them, Particulate Matter (PM), particles of variable but very small diameter, penetrate the respiratory system via inhalation, causing respiratory and cardiovascular diseases, reproductive and central nervous system dysfunctions, and cancer. Despite the fact that ozone in the stratosphere plays a protective role against ultraviolet irradiation, it is harmful when in high concentration at ground level, also affecting the respiratory and cardiovascular system. Furthermore, nitrogen oxide, sulfur dioxide, Volatile Organic Compounds (VOCs), dioxins, and polycyclic aromatic hydrocarbons (PAHs) are all considered air pollutants that are harmful to humans. Carbon monoxide can even provoke direct poisoning when breathed in at high levels. Heavy metals such as lead, when absorbed into the human body, can lead to direct poisoning or chronic intoxication, depending on exposure. Diseases occurring from the aforementioned substances include principally respiratory problems such as Chronic Obstructive Pulmonary Disease (COPD), asthma, bronchiolitis, and also lung cancer, cardiovascular events, central nervous system dysfunctions, and cutaneous diseases. Last but not least, climate change resulting from environmental pollution affects the geographical distribution of many infectious diseases, as do natural disasters. The only way to tackle this problem is through public awareness coupled with a multidisciplinary approach by scientific experts; national and international organizations must address the emergence of this threat and propose sustainable solutions.
1,499 citations
TL;DR: The development of theSWiM guideline for the synthesis of quantitative data of intervention effects is described and the nine SWiM reporting items with accompanying explanations and examples are presented.
Abstract: In systematic reviews that lack data amenable to meta-analysis, alternative synthesis methods are commonly used, but these methods are rarely reported. This lack of transparency in the methods can cast doubt on the validity of the review findings. The Synthesis Without Meta-analysis (SWiM) guideline has been developed to guide clear reporting in reviews of interventions in which alternative synthesis methods to meta-analysis of effect estimates are used. This article describes the development of the SWiM guideline for the synthesis of quantitative data of intervention effects and presents the nine SWiM reporting items with accompanying explanations and examples.
1,275 citations
TL;DR: In 2019, the LIGO Livingston detector observed a compact binary coalescence with signal-to-noise ratio 12.9 and the Virgo detector was also taking data that did not contribute to detection due to a low SINR but were used for subsequent parameter estimation as discussed by the authors.
Abstract: On 2019 April 25, the LIGO Livingston detector observed a compact binary coalescence with signal-to-noise ratio 12.9. The Virgo detector was also taking data that did not contribute to detection due to a low signal-to-noise ratio, but were used for subsequent parameter estimation. The 90% credible intervals for the component masses range from to if we restrict the dimensionless component spin magnitudes to be smaller than 0.05). These mass parameters are consistent with the individual binary components being neutron stars. However, both the source-frame chirp mass and the total mass of this system are significantly larger than those of any other known binary neutron star (BNS) system. The possibility that one or both binary components of the system are black holes cannot be ruled out from gravitational-wave data. We discuss possible origins of the system based on its inconsistency with the known Galactic BNS population. Under the assumption that the signal was produced by a BNS coalescence, the local rate of neutron star mergers is updated to 250-2810.
1,189 citations
University of Glasgow1, Jagiellonian University2, Queen Mary University of London3, Vanderbilt University Medical Center4, University of Manchester5, University of Naples Federico II6, University of Roehampton7, University of Texas at Austin8, Jagiellonian University Medical College9, Humboldt University of Berlin10, Huazhong University of Science and Technology11, Catholic University of the Sacred Heart12
TL;DR: While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis, Hence, patients should not discontinue their use.
Abstract: The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.
University Hospitals Bristol NHS Foundation Trust1, National Institute for Health Research2, University College Cork3, Warneford Hospital4, Swansea University5, Aga Khan University6, University of Glasgow7, Centre for Mental Health8, University of Bristol9, University of Peradeniya10, University of Oslo11, Medical University of Vienna12, University of Sydney13, Rafsanjan University of Medical Sciences14, University of Toronto15, University of Nottingham16, University of Hong Kong17
TL;DR: The promise of targeting the inflammation pathway in the management of this challenging condition is today somewhat weaker, but this might not be the last word on the potential role of anti-inflammatory drugs in the treatment of bipolar depression.
TL;DR: Surprisingly, recent data demonstrate that besides eliciting caspase activation, MOMP engages various pro-inflammatory signalling functions, suggesting that mitochondria-derived signalling downstream of pro-apoptotic cues may also have non-lethal functions.
Abstract: Through their many and varied metabolic functions, mitochondria power life. Paradoxically, mitochondria also have a central role in apoptotic cell death. Upon induction of mitochondrial apoptosis, mitochondrial outer membrane permeabilization (MOMP) usually commits a cell to die. Apoptotic signalling downstream of MOMP involves cytochrome c release from mitochondria and subsequent caspase activation. As such, targeting MOMP in order to manipulate cell death holds tremendous therapeutic potential across different diseases, including neurodegenerative diseases, autoimmune disorders and cancer. In this Review, we discuss new insights into how mitochondria regulate apoptotic cell death. Surprisingly, recent data demonstrate that besides eliciting caspase activation, MOMP engages various pro-inflammatory signalling functions. As we highlight, together with new findings demonstrating cell survival following MOMP, this pro-inflammatory role suggests that mitochondria-derived signalling downstream of pro-apoptotic cues may also have non-lethal functions. Finally, we discuss the importance and roles of mitochondria in other forms of regulated cell death, including necroptosis, ferroptosis and pyroptosis. Collectively, these new findings offer exciting, unexplored opportunities to target mitochondrial regulation of cell death for clinical benefit.
TL;DR: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEi/ARB nonusers, and it is unlikely that in-hospital use ofACEI/ARB wasassociated with an increased mortality risk.
Abstract: Rationale: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in pati...
Ikerbasque1, University of the Basque Country2, Carlos III Health Institute3, University of Salamanca4, University of Manchester5, National Health Service6, Imperial College London7, Mayo Clinic8, Sapienza University of Rome9, University of Copenhagen10, University of Glasgow11, University of Regensburg12, Yale University13, University of Padua14, University of Edinburgh15, University of Minnesota16, Marche Polytechnic University17, University of Rennes18, University of Paris19, University of Florence20, University of Milano-Bicocca21, University of Zurich22, Erasmus University Rotterdam23, University of Barcelona24
TL;DR: This expert Consensus Statement, endorsed by the ENS-CCA, summarizes the latest advances in CCA, including classification, genetics and treatment, and provides recommendations for CCA management and priorities across basic, translational and clinical research.
Abstract: Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point of the biliary tree Their incidence is increasing globally, currently accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies The silent presentation of these tumours combined with their highly aggressive nature and refractoriness to chemotherapy contribute to their alarming mortality, representing ~2% of all cancer-related deaths worldwide yearly The current diagnosis of CCA by non-invasive approaches is not accurate enough, and histological confirmation is necessary Furthermore, the high heterogeneity of CCAs at the genomic, epigenetic and molecular levels severely compromises the efficacy of the available therapies In the past decade, increasing efforts have been made to understand the complexity of these tumours and to develop new diagnostic tools and therapies that might help to improve patient outcomes In this expert Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we aim to summarize and critically discuss the latest advances in CCA, mostly focusing on classification, cells of origin, genetic and epigenetic abnormalities, molecular alterations, biomarker discovery and treatments Furthermore, the horizon of CCA for the next decade from 2020 onwards is highlighted
TL;DR: In this paper, the authors reported the observation of a compact binary coalescence involving a 222 −243 M ⊙ black hole and a compact object with a mass of 250 −267 M ⋆ (all measurements quoted at the 90% credible level) The gravitational-wave signal, GW190814, was observed during LIGO's and Virgo's third observing run on 2019 August 14 at 21:10:39 UTC and has a signal-to-noise ratio of 25 in the three-detector network.
Abstract: We report the observation of a compact binary coalescence involving a 222–243 M ⊙ black hole and a compact object with a mass of 250–267 M ⊙ (all measurements quoted at the 90% credible level) The gravitational-wave signal, GW190814, was observed during LIGO's and Virgo's third observing run on 2019 August 14 at 21:10:39 UTC and has a signal-to-noise ratio of 25 in the three-detector network The source was localized to 185 deg2 at a distance of ${241}_{-45}^{+41}$ Mpc; no electromagnetic counterpart has been confirmed to date The source has the most unequal mass ratio yet measured with gravitational waves, ${0112}_{-0009}^{+0008}$, and its secondary component is either the lightest black hole or the heaviest neutron star ever discovered in a double compact-object system The dimensionless spin of the primary black hole is tightly constrained to ≤007 Tests of general relativity reveal no measurable deviations from the theory, and its prediction of higher-multipole emission is confirmed at high confidence We estimate a merger rate density of 1–23 Gpc−3 yr−1 for the new class of binary coalescence sources that GW190814 represents Astrophysical models predict that binaries with mass ratios similar to this event can form through several channels, but are unlikely to have formed in globular clusters However, the combination of mass ratio, component masses, and the inferred merger rate for this event challenges all current models of the formation and mass distribution of compact-object binaries
TL;DR: It is inferred that the primary black hole mass lies within the gap produced by (pulsational) pair-instability supernova processes, with only a 0.32% probability of being below 65 M⊙, which can be considered an intermediate mass black hole (IMBH).
Abstract: On May 21, 2019 at 03:02:29 UTC Advanced LIGO and Advanced Virgo observed a short duration gravitational-wave signal, GW190521, with a three-detector network signal-to-noise ratio of 14.7, and an estimated false-alarm rate of 1 in 4900 yr using a search sensitive to generic transients. If GW190521 is from a quasicircular binary inspiral, then the detected signal is consistent with the merger of two black holes with masses of 85_{-14}^{+21} M_{⊙} and 66_{-18}^{+17} M_{⊙} (90% credible intervals). We infer that the primary black hole mass lies within the gap produced by (pulsational) pair-instability supernova processes, with only a 0.32% probability of being below 65 M_{⊙}. We calculate the mass of the remnant to be 142_{-16}^{+28} M_{⊙}, which can be considered an intermediate mass black hole (IMBH). The luminosity distance of the source is 5.3_{-2.6}^{+2.4} Gpc, corresponding to a redshift of 0.82_{-0.34}^{+0.28}. The inferred rate of mergers similar to GW190521 is 0.13_{-0.11}^{+0.30} Gpc^{-3} yr^{-1}.
TL;DR: Using a transmission model, a basic reproductive number is estimated for Wuhan coronavirus (2019-nCoV) and it is estimated that 58-76% of transmissions must be prevented to stop increasing.
Abstract: Since first identified, the epidemic scale of the recently emerged novel coronavirus (2019-nCoV) in Wuhan, China, has increased rapidly, with cases arising across China and other countries and regions. using a transmission model, we estimate a basic reproductive number of 3.11 (95%CI, 2.39-4.13); 58-76% of transmissions must be prevented to stop increasing; Wuhan case ascertainment of 5.0% (3.6-7.4); 21022 (11090-33490) total infections in Wuhan 1 to 22 January.
TL;DR: The current status of the Standard Model calculation of the anomalous magnetic moment of the muon is reviewed in this paper, where the authors present a detailed account of recent efforts to improve the calculation of these two contributions with either a data-driven, dispersive approach, or a first-principle, lattice approach.
TL;DR: The 4C Mortality Score outperformed existing scores, showed utility to directly inform clinical decision making, and can be used to stratify patients admitted to hospital with covid-19 into different management groups.
Abstract: OBJECTIVE:To develop and validate a pragmatic risk score to predict mortality in patients admitted to hospital with coronavirus disease 2019 (covid-19). DESIGN:Prospective observational cohort study. SETTING:International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study (performed by the ISARIC Coronavirus Clinical Characterisation Consortium-ISARIC-4C) in 260 hospitals across England, Scotland, and Wales. Model training was performed on a cohort of patients recruited between 6 February and 20 May 2020, with validation conducted on a second cohort of patients recruited after model development between 21 May and 29 June 2020. PARTICIPANTS: Adults (age ≥18 years) admitted to hospital with covid-19 at least four weeks before final data extraction. MAIN OUTCOME MEASURE:In-hospital mortality. RESULTS:35 463 patients were included in the derivation dataset (mortality rate 32.2%) and 22 361 in the validation dataset (mortality rate 30.1%). The final 4C Mortality Score included eight variables readily available at initial hospital assessment: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein (score range 0-21 points). The 4C Score showed high discrimination for mortality (derivation cohort: area under the receiver operating characteristic curve 0.79, 95% confidence interval 0.78 to 0.79; validation cohort: 0.77, 0.76 to 0.77) with excellent calibration (validation: calibration-in-the-large=0, slope=1.0). Patients with a score of at least 15 (n=4158, 19%) had a 62% mortality (positive predictive value 62%) compared with 1% mortality for those with a score of 3 or less (n=1650, 7%; negative predictive value 99%). Discriminatory performance was higher than 15 pre-existing risk stratification scores (area under the receiver operating characteristic curve range 0.61-0.76), with scores developed in other covid-19 cohorts often performing poorly (range 0.63-0.73). CONCLUSIONS:An easy-to-use risk stratification score has been developed and validated based on commonly available parameters at hospital presentation. The 4C Mortality Score outperformed existing scores, showed utility to directly inform clinical decision making, and can be used to stratify patients admitted to hospital with covid-19 into different management groups. The score should be further validated to determine its applicability in other populations. STUDY REGISTRATION:ISRCTN66726260.
TL;DR: Several mechanisms through which the pandemic response is likely to affect health are summarised: economic effects, social isolation, family relationships, health related behaviours, disruption to essential services, disrupted education, transport and green space, social disorder, and psychosocial effects.
Abstract: Countries worldwide have implemented strict controls on movement in response to the covid-19 pandemic. The aim is to cut transmission by reducing close contact (box 1), but the measures have profound consequences. Several sectors are seeing steep reductions in business, and there has been panic buying in shops. Social, economic, and health consequences are inevitable.
Box 1
### Social distancing measuresRETURN TO TEXT
The health benefits of social distancing measures are obvious, with a slower spread of infection reducing the risk that health services will be overwhelmed. But they may also prolong the pandemic and the restrictions adopted to mitigate it.1 Policy makers need to balance these considerations while paying attention to broader effects on health and health equity.
Several groups may be particularly vulnerable to the effects of both the pandemic and the social distancing measures (box 2). Table 1 summarises several mechanisms through which the pandemic response is likely to affect health: economic effects, social isolation, family relationships, health related behaviours, disruption to essential services, disrupted education, transport and green space, social disorder, and psychosocial effects. Figure 1 shows the complexity of the pathways through which these effects may arise. Below we expand on the first three mechanisms, using Scotland as an example. The appendix on bmj.com provides further details of mechanisms, effects, and mitigation measures.
Box 2
### Groups at particular risk from responses to covid-19RETURN TO TEXT
TL;DR: SARS-CoV-2 itself is not a recombinant of any sarbecoviruses detected to date, and its receptor-binding motif appears to be an ancestral trait shared with bat viruses and not one acquired recently via recombination.
Abstract: There are outstanding evolutionary questions on the recent emergence of human coronavirus SARS-CoV-2 including the role of reservoir species, the role of recombination and its time of divergence from animal viruses. We find that the sarbecoviruses—the viral subgenus containing SARS-CoV and SARS-CoV-2—undergo frequent recombination and exhibit spatially structured genetic diversity on a regional scale in China. SARS-CoV-2 itself is not a recombinant of any sarbecoviruses detected to date, and its receptor-binding motif, important for specificity to human ACE2 receptors, appears to be an ancestral trait shared with bat viruses and not one acquired recently via recombination. To employ phylogenetic dating methods, recombinant regions of a 68-genome sarbecovirus alignment were removed with three independent methods. Bayesian evolutionary rate and divergence date estimates were shown to be consistent for these three approaches and for two different prior specifications of evolutionary rates based on HCoV-OC43 and MERS-CoV. Divergence dates between SARS-CoV-2 and the bat sarbecovirus reservoir were estimated as 1948 (95% highest posterior density (HPD): 1879–1999), 1969 (95% HPD: 1930–2000) and 1982 (95% HPD: 1948–2009), indicating that the lineage giving rise to SARS-CoV-2 has been circulating unnoticed in bats for decades. In this manuscript, the authors address evolutionary questions on the emergence of SARS-CoV-2. They find that SARS-CoV-2 is not a recombinant of any sarbecoviruses detected to date, and that the bat and pangolin sequences most closely related to SARS-CoV-2 probably diverged several decades ago or possibly earlier from human SARS-CoV-2 samples.
TL;DR: NLR is an independent risk factor of the in-hospital mortality for COVID-19 patients especially for male, and assessment of NLR may help identify high risk individuals with CO VID-19.
TL;DR: The results of this nationwide analysis in England show that type 1 and type 2 diabetes were both independently associated with a significant death with COVID-19, and the effects were attenuated to ORs of 2·86 (2·58–3·18) for type 1 diabetes and 1·80 (1·75–1·86) fortype 2 diabetes when also adjusted for previous hospital admissions with coronary heart disease, cerebrovascular disease, or heart failure.
Sahlgrenska University Hospital1, National Institutes of Health2, University of Paris3, Children's Hospital Oakland Research Institute4, University of Glasgow5, Centro Nacional de Investigaciones Cardiovasculares6, Aarhus University7, Medical University of Vienna8, University of Amsterdam9, University of California, Los Angeles10, University of Western Ontario11, Monash University12, University of Copenhagen13, University of Western Australia14, Royal Perth Hospital15, French Institute of Health and Medical Research16, Oregon Health & Science University17, University of Cambridge18, University of Bristol19, Trinity College, Dublin20, University of Texas Southwestern Medical Center21, Charité22, Utrecht University23, University of the Witwatersrand24, Imperial College London25, Technische Universität München26, University of Helsinki27, University of Groningen28, Hacettepe University29, University of Milan30, Columbia University31
TL;DR: In this paper, the authors proposed a method to solve the problem of the problem: this paper ] of "uniformity" of the distribution of data points in the data set.
Abstract: Abstract
TL;DR: Male sex, older age, renal impairment, non-white ethnicity, socioeconomic deprivation, and previous stroke and heart failure were associated with increased COVID-19-related mortality in both type 1 and type 2 diabetes.
TL;DR: This research presents a case study of parenting in a time of COVID-19, which aims to provide a guide for parents to consider their children's needs during this crucial period of transition.
European Bioinformatics Institute1, Wellcome Trust Sanger Institute2, Francis Crick Institute3, Broad Institute4, University of Oxford5, University of Cambridge6, University of Toronto7, Oregon Health & Science University8, University of Texas MD Anderson Cancer Center9, Heidelberg University10, German Cancer Research Center11, University of Ljubljana12, NorthShore University HealthSystem13, Vancouver Prostate Centre14, Simon Fraser University15, Walter and Eliza Hall Institute of Medical Research16, University of Melbourne17, Katholieke Universiteit Leuven18, Cornell University19, University of California, Santa Cruz20, Ontario Institute for Cancer Research21, University of California, Los Angeles22, Peter MacCallum Cancer Centre23, Harvard University24, Indiana University25, University of Chicago26, University of Cologne27, University of Helsinki28, University of Glasgow29
TL;DR: Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.
Abstract: Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection.
TL;DR: It is suggested obesity or excess ectopic fat deposition may be a unifying risk factor for severe COVID-19 infection, reducing protective cardiorespiratory reserve as well as potentiating the immune dysregulation that appears to mediate the progression to critical illness and organ failure in a proportion of patients with CO VID-19.
Abstract: Circulation. 2020;142:4–6. DOI: 10.1161/CIRCULATIONAHA.120.047659 4 Naveed Sattar , MD Iain B. McInnes, MD John J.V. McMurray, MD T he coronavirus disease 2019 (COVID-19) pandemic has led to worldwide research efforts to identify people at greatest risk of developing critical illness and dying. Initial data pointed toward older individuals being particularly vulnerable, as well as those with diabetes mellitus or cardiovascular (including hypertension), respiratory, or kidney disease. These problems are often concentrated in certain racial groups (eg, African Americans and Asians), which also appear to be more prone to worse COVID-19 outcomes.1 Increasing numbers of reports have linked obesity to more severe COVID-19 illness and death.1–3 In a French study, the risk for invasive mechanical ventilation in patients with COVID-19 infection admitted to the intensive treatment unit was more than 7-fold higher for those with body mass index (BMI) >35 compared with BMI <25 kg/m2.2 Among individuals with COVID-19 who were <60 years of age in New York City, those with a BMI between 30 to 34 kg/m2 and >35 kg/m2 were 1.8 times and 3.6 times more likely to be admitted to critical care, respectively, than individuals with a BMI <30 kg/m2.3 We suggest obesity or excess ectopic fat deposition may be a unifying risk factor for severe COVID-19 infection, reducing protective cardiorespiratory reserve as well as potentiating the immune dysregulation that appears, at least in part, to mediate the progression to critical illness and organ failure in a proportion of patients with COVID-19 (Figure). Whether obesity is an independent risk factor for susceptibility to infection requires further research. From a cardiovascular perspective, trial and genetic evidence conclusively show that obesity (and excess fat mass) are causally related to hypertension, diabetes mellitus, coronary heart disease, stroke, atrial fibrillation, renal disease, and heart failure. Obesity potentiates multiple cardiovascular risk factors, the premature development of cardiovascular disease, and adverse cardiorenal outcomes. There is also a metabolic concern. In individuals with diabetes mellitus, or at high risk of diabetes mellitus, obesity and excess ectopic fat lead to impairment of insulin resistance and reduced β-cell function. Both the latter limit ability to evoke an appropriate metabolic response on immunologic challenge, leading some patients with diabetes mellitus to require substantial amounts of insulin during severe infections. Overall, the integrated regulation of metabolism required for the complex cellular interactions, and for effective host defense, is lost, leading to functional immunologic deficit. COVID-19 may also directly disrupt pancreatic β-cell function through an interaction with angiotensin-converting enzyme 2. Furthermore, obesity enhances thrombosis, which is relevant given the association between severe COVID-19 and prothrombotic disseminated intravascular coagulation and high rates of venous thromboembolism. Beyond cardiometabolic and thrombotic consequences, obesity has detrimental effects on lung function, diminishing forced expiratory volume and forced vital capacity (Figure). Higher relative fat mass is also linked to such adverse changes, perhaps relevant to emerging reports of greater critical illness from COVID-19 in © 2020 American Heart Association, Inc. ON MY MIND
TL;DR: The vision of 5G is extended to more ambitious scenarios in a more distant future and speculates on the visionary technologies that could provide the step changes needed for enabling 6G.
Abstract: While 5G is being tested worldwide and anticipated to be rolled out gradually in 2019, researchers around the world are beginning to turn their attention to what 6G might be in 10+ years time, and there are already initiatives in various countries focusing on the research of possible 6G technologies. This article aims to extend the vision of 5G to more ambitious scenarios in a more distant future and speculates on the visionary technologies that could provide the step changes needed for enabling 6G.