Showing papers by "University of Melbourne published in 2020"

The ATLAS Experiment at the CERN Large Hadron Collider

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.

Mental Health, Substance Use, and Suicidal Ideation During the COVID-19 Pandemic - United States, June 24-30, 2020.

Abstract: The coronavirus disease 2019 (COVID-19) pandemic has been associated with mental health challenges related to the morbidity and mortality caused by the disease and to mitigation activities, including the impact of physical distancing and stay-at-home orders.* Symptoms of anxiety disorder and depressive disorder increased considerably in the United States during April-June of 2020, compared with the same period in 2019 (1,2). To assess mental health, substance use, and suicidal ideation during the pandemic, representative panel surveys were conducted among adults aged ≥18 years across the United States during June 24-30, 2020. Overall, 40.9% of respondents reported at least one adverse mental or behavioral health condition, including symptoms of anxiety disorder or depressive disorder (30.9%), symptoms of a trauma- and stressor-related disorder (TSRD) related to the pandemic† (26.3%), and having started or increased substance use to cope with stress or emotions related to COVID-19 (13.3%). The percentage of respondents who reported having seriously considered suicide in the 30 days before completing the survey (10.7%) was significantly higher among respondents aged 18-24 years (25.5%), minority racial/ethnic groups (Hispanic respondents [18.6%], non-Hispanic black [black] respondents [15.1%]), self-reported unpaid caregivers for adults§ (30.7%), and essential workers¶ (21.7%). Community-level intervention and prevention efforts, including health communication strategies, designed to reach these groups could help address various mental health conditions associated with the COVID-19 pandemic.

2020 International Society of Hypertension global hypertension practice guidelines

Abstract: Document reviewers: Hind Beheiry (Sudan), Irina Chazova (Russia), Albertino Damasceno (Mozambique), Anna Dominiczak (UK), Anastase Dzudie (Cameroon), Stephen Harrap (Australia), Hiroshi Itoh (Japan), Tazeen Jafar (Singapore), Marc Jaffe (USA), Patricio Jaramillo-Lopez (Colombia), Kazuomi Kario (Japan), Giuseppe Mancia (Italy), Ana Mocumbi (Mozambique), Sanjeevi N.Narasingan (India), Elijah Ogola (Kenya), Srinath Reddy (India), Ernesto Schiffrin (Canada), Ann Soenarta (Indonesia), Rhian Touyz (UK), Yudah Turana (Indonesia), Michael Weber (USA), Paul Whelton (USA), Xin Hua Zhang, (Australia), Yuqing Zhang (China).

A serological assay to detect SARS-CoV-2 seroconversion in humans.

Abstract: Here, we describe a serological enzyme-linked immunosorbent assay for the screening and identification of human SARS-CoV-2 seroconverters. This assay does not require the handling of infectious virus, can be adjusted to detect different antibody types in serum and plasma and is amenable to scaling. Serological assays are of critical importance to help define previous exposure to SARS-CoV-2 in populations, identify highly reactive human donors for convalescent plasma therapy and investigate correlates of protection.

Pan-cancer analysis of whole genomes

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.

The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises.

Abstract: The current International Association for the Study of Pain (IASP) definition of pain as "An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage" was recommended by the Subcommittee on Taxonomy and adopted by the IASP Council in 1979. This definition has become accepted widely by health care professionals and researchers in the pain field and adopted by several professional, governmental, and nongovernmental organizations, including the World Health Organization. In recent years, some in the field have reasoned that advances in our understanding of pain warrant a reevaluation of the definition and have proposed modifications. Therefore, in 2018, the IASP formed a 14-member, multinational Presidential Task Force comprising individuals with broad expertise in clinical and basic science related to pain, to evaluate the current definition and accompanying note and recommend whether they should be retained or changed. This review provides a synopsis of the critical concepts, the analysis of comments from the IASP membership and public, and the committee's final recommendations for revisions to the definition and notes, which were discussed over a 2-year period. The task force ultimately recommended that the definition of pain be revised to "An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage," and that the accompanying notes be updated to a bulleted list that included the etymology. The revised definition and notes were unanimously accepted by the IASP Council early this year.

Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium

Abstract: BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.

GW190425: Observation of a Compact Binary Coalescence with Total Mass ∼ 3.4 M O

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.

Opportunities and challenges in long-read sequencing data analysis.

Abstract: Long-read technologies are overcoming early limitations in accuracy and throughput, broadening their application domains in genomics. Dedicated analysis tools that take into account the characteristics of long-read data are thus required, but the fast pace of development of such tools can be overwhelming. To assist in the design and analysis of long-read sequencing projects, we review the current landscape of available tools and present an online interactive database, long-read-tools.org, to facilitate their browsing. We further focus on the principles of error correction, base modification detection, and long-read transcriptomics analysis and highlight the challenges that remain.

Delay or Avoidance of Medical Care Because of COVID-19-Related Concerns - United States, June 2020.

Abstract: Temporary disruptions in routine and nonemergency medical care access and delivery have been observed during periods of considerable community transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). However, medical care delay or avoidance might increase morbidity and mortality risk associated with treatable and preventable health conditions and might contribute to reported excess deaths directly or indirectly related to COVID-19 (2). To assess delay or avoidance of urgent or emergency and routine medical care because of concerns about COVID-19, a web-based survey was administered by Qualtrics, LLC, during June 24-30, 2020, to a nationwide representative sample of U.S. adults aged ≥18 years. Overall, an estimated 40.9% of U.S. adults have avoided medical care during the pandemic because of concerns about COVID-19, including 12.0% who avoided urgent or emergency care and 31.5% who avoided routine care. The estimated prevalence of urgent or emergency care avoidance was significantly higher among the following groups: unpaid caregivers for adults* versus noncaregivers (adjusted prevalence ratio [aPR] = 2.9); persons with two or more selected underlying medical conditions† versus those without those conditions (aPR = 1.9); persons with health insurance versus those without health insurance (aPR = 1.8); non-Hispanic Black (Black) adults (aPR = 1.6) and Hispanic or Latino (Hispanic) adults (aPR = 1.5) versus non-Hispanic White (White) adults; young adults aged 18-24 years versus adults aged 25-44 years (aPR = 1.5); and persons with disabilities§ versus those without disabilities (aPR = 1.3). Given this widespread reporting of medical care avoidance because of COVID-19 concerns, especially among persons at increased risk for severe COVID-19, urgent efforts are warranted to ensure delivery of services that, if deferred, could result in patient harm. Even during the COVID-19 pandemic, persons experiencing a medical emergency should seek and be provided care without delay (3).

GW190814: Gravitational Waves from the Coalescence of a 23 Solar Mass Black Hole with a 2.6 Solar Mass Compact Object

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

Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19.

Abstract: To the Editor — We report the kinetics of immune responses in relation to clinical and virological features of a patient with mild-to-moderate coronavirus disease 2019 (COVID-19) that required hospitalization. Increased antibody-secreting cells (ASCs), follicular helper T cells (TFH cells), activated CD4+ T cells and CD8+ T cells and immunoglobulin M (IgM) and IgG antibodies that bound the COVID-19causing coronavirus SARS-CoV-2 were detected in blood before symptomatic recovery. These immunological changes persisted for at least 7 d following full resolution of symptoms. A 47-year-old woman from Wuhan, Hubei province, China, presented to an emergency department in Melbourne, Australia. Her symptoms commenced 4 d earlier with lethargy, sore throat, dry cough, pleuritic chest pain, mild dyspnea and subjective fevers (Fig. 1a). She traveled from Wuhan to Australia 11 d before presentation. She had no contact with the Huanan seafood market or with known COVID-19 cases. She was otherwise healthy and was a non-smoker taking no medications. Clinical examination revealed a temperature of 38.5 °C, a pulse rate of 120 beats per minute, a blood pressure of 140/80 mm Hg, a respiratory rate of 22 breaths per minute, and oxygen saturation 98% while breathing ambient air. Lung auscultation revealed bi-basal rhonchi. At presentation on day 4, SARS-CoV-2 was detected in a nasopharyngeal swab specimen by real-time reverse-transcriptase PCR. SARS-CoV-2 was again detected at days 5–6 in nasopharyngeal, sputum and fecal samples, but was undetectable from day 7 (Fig. 1a). Blood C-reactive protein was elevated at 83.2, with normal counts of lymphocytes (4.3 × 109 cells per liter (range, 4.0 × 109 to 12.0 × 109 cells per liter)) and neutrophils (6.3 × 109 cells per liter (range, 2.0 × 109 to 8.0 × 109 × 109 cells per liter)). No other respiratory pathogens were detected. Her management was intravenous fluid rehydration without supplemental oxygenation. No antibiotics, steroids or antiviral agents were administered. Chest radiography demonstrated bi-basal infiltrates at day 5 that cleared on day 10 (Fig. 1b). She was discharged to home isolation on day 11. Her symptoms resolved completely by day 13, and she remained well at day 20, with progressive increases in plasma SARS-CoV-2-binding IgM and IgG antibodies from day 7 until day 20 (Fig. 1c and Extended Data Fig. 1). The patient was enrolled through the Sentinel Travelers Research Preparedness Platform for Emerging Infectious Diseases novel coronavirus substudy (SETREP-ID-coV) and provided written informed consent before the study. Patient care and research were conducted in compliance with the Case Report guidelines and the Declaration of Helsinki. Experiments were performed with ethics approvals HREC/17/MH/53, HREC/15/MonH/64/2016.196 and UoM#1442952.1/#1443389.4. We analyzed the kinetics and breadth of immune responses associated with clinical resolution of COVID-19. As ASCs are key for the rapid production of antibodies following infection with Ebola virus1,2 and infection with and vaccination against influenza virus2,3, and activated circulating TFH cells (cTFH cells) are concomitantly induced following vaccination against influenza virus3, we defined the frequency of CD3–CD19+CD27hiCD38hi ASC and CD4+CXCR5+ICOS+PD-1+ cTFH cell responses before symptomatic recovery. ASCs appeared in the blood at the time of viral clearance (day 7; 1.48%) and peaked on day 8 (6.91%). The emergence of cTFH cells occurred concurrently in blood at day 7 (1.98%), increasing on day 8 (3.25%) and day 9 (4.46%) (Fig. 1d). The peak of both ASCs and cTFH cells was markedly higher in the patient with COVID-19 than in healthy control participants (0.61% ± 0.40% and 1.83% ± 0.77%, respectively (average ± s.d.); n = 5). Both ASCs and cTFH cells were prominently present during convalescence (day 20) (4.54% and 7.14%, respectively; Fig. 1d). Thus, our study provides evidence on the recruitment of both ASCs and cTFH cells in this patient’s blood while she was still unwell and 3 d before the resolution of symptoms. Since co-expression of CD38 and HLA-DR is the key phenotype of the activation of CD8+ T cells in response to viral infections, we analyzed co-expression of CD38 and HLA-DR. As per reports for Ebola and influenza1,4, co-expression of CD38 and HLA-DR on CD8+ T cells (assessed as the frequency of CD38+HLA-DR+ CD8+ T cells) rapidly increased in this patient from day 7 (3.57%) to day 8 (5.32%) and day 9 (11.8%), then decreased at day 20 (7.05%) (Fig. 1e). Furthermore, the frequency of CD38+HLA-DR+ CD8+ T cells was much higher in this patient than in healthy individuals (1.47% ± 0.50%; n = 5). CD38+HLA-DR+ T cells were also recently documented in a patient with COVID-19 at one time point5. Similarly, co-expression of CD38 and HLA-DR on CD4+ T cells (assessed as the frequency of CD38+HLA-DR+ CD4+ T cells) increased between day 7 (0.55%) and day 9 (3.33%) in this patient, relative to that of healthy donors (0.63% ± 0.28%; n = 5), although at lower levels than that of CD8+ T cells. CD38+HLA-DR+ T cells, especially CD8+ T cells, produced larger amounts of granzymes A and B and perforin (~34–54% higher) than did their parent cells (CD8+ or CD4+ populations; Fig. 1e). Thus, the emergence and rapid increase in activated CD38+HLA-DR+ T cells, especially CD8+ T cells, at days 7–9 preceded the resolution of symptoms. Details on data reproducibility are in the Life Sciences Reporting Summary. Analysis of CD16+CD14+ monocytes, which are related to immunopathology, showed lower frequencies of CD16+CD14+ monocytes in the blood of this patient at days 7, 8 and 9 (1.29%, 0.43% and 1.47%, respectively) than in that of healthy control donors (9.03% ± 4.39%; n = 5) (Fig. 1f), possibly indicative of the efflux of CD16+CD14+ monocytes from the blood to the site of infection. No differences in activated HLA-DR+CD3–CD56+ natural killer cells were found. As pro-inflammatory cytokines and chemokines are predictive of severe clinical outcomes for influenza6, we quantified 17 pro-inflammatory cytokines and chemokines in plasma. We found low levels of the chemokine MCP-1 (CCL2) in the patient’s plasma (Extended Data Fig. 2a), although this was comparable to results obtained for healthy donors (22.15 ± 13.81; n = 5), patients infected with influenza A virus or influenza B, assessed at days 7–9

TRY plant trait database : Enhanced coverage and open access

Abstract: Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.

GW190521: A Binary Black Hole Merger with a Total Mass of 150 M

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}.

Coronavirus Infections in Children Including COVID-19: An Overview of the Epidemiology, Clinical Features, Diagnosis, Treatment and Prevention Options in Children.

Abstract: Coronaviruses (CoVs) are a large family of enveloped, single-stranded, zoonotic RNA viruses. Four CoVs commonly circulate among humans: HCoV2-229E, -HKU1, -NL63 and -OC43. However, CoVs can rapidly mutate and recombine leading to novel CoVs that can spread from animals to humans. The novel CoVs severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. The 2019 novel coronavirus (SARS-CoV-2) is currently causing a severe outbreak of disease (termed COVID-19) in China and multiple other countries, threatening to cause a global pandemic. In humans, CoVs mostly cause respiratory and gastrointestinal symptoms. Clinical manifestations range from a common cold to more severe disease such as bronchitis, pneumonia, severe acute respiratory distress syndrome, multi-organ failure and even death. SARS-CoV, MERS-CoV and SARS-CoV-2 seem to less commonly affect children and to cause fewer symptoms and less severe disease in this age group compared with adults, and are associated with much lower case-fatality rates. Preliminary evidence suggests children are just as likely as adults to become infected with SARS-CoV-2 but are less likely to be symptomatic or develop severe symptoms. However, the importance of children in transmitting the virus remains uncertain. Children more often have gastrointestinal symptoms compared with adults. Most children with SARS-CoV present with fever, but this is not the case for the other novel CoVs. Many children affected by MERS-CoV are asymptomatic. The majority of children infected by novel CoVs have a documented household contact, often showing symptoms before them. In contrast, adults more often have a nosocomial exposure. In this review, we summarize epidemiologic, clinical and diagnostic findings, as well as treatment and prevention options for common circulating and novel CoVs infections in humans with a focus on infections in children.

The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data

Abstract: The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.

Eleven grand challenges in single-cell data science

Abstract: The recent boom in microfluidics and combinatorial indexing strategies, combined with low sequencing costs, has empowered single-cell sequencing technology. Thousands-or even millions-of cells analyzed in a single experiment amount to a data revolution in single-cell biology and pose unique data science problems. Here, we outline eleven challenges that will be central to bringing this emerging field of single-cell data science forward. For each challenge, we highlight motivating research questions, review prior work, and formulate open problems. This compendium is for established researchers, newcomers, and students alike, highlighting interesting and rewarding problems for the coming years.

The evolutionary history of 2,658 cancers

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.

Tropical Cyclones and Climate Change Assessment: Part II: Projected Response to Anthropogenic Warming

Abstract: Model projections of tropical cyclone (TC) activity response to anthropogenic warming in climate models are assessed. Observations, theory, and models, with increasing robustness, indicate ...

Immediate and long-term impact of the COVID-19 pandemic on delivery of surgical services.

Abstract: BACKGROUND: The ongoing pandemic is having a collateral health effect on delivery of surgical care to millions of patients. Very little is known about pandemic management and effects on other services, including delivery of surgery. METHODS: This was a scoping review of all available literature pertaining to COVID-19 and surgery, using electronic databases, society websites, webinars and preprint repositories. RESULTS: Several perioperative guidelines have been issued within a short time. Many suggestions are contradictory and based on anecdotal data at best. As regions with the highest volume of operations per capita are being hit, an unprecedented number of operations are being cancelled or deferred. No major stakeholder seems to have considered how a pandemic deprives patients with a surgical condition of resources, with patients disproportionally affected owing to the nature of treatment (use of anaesthesia, operating rooms, protective equipment, physical invasion and need for perioperative care). No recommendations exist regarding how to reopen surgical delivery. The postpandemic evaluation and future planning should involve surgical services as an essential part to maintain appropriate surgical care for the population during an outbreak. Surgical delivery, owing to its cross-cutting nature and synergistic effects on health systems at large, needs to be built into the WHO agenda for national health planning. CONCLUSION: Patients are being deprived of surgical access, with uncertain loss of function and risk of adverse prognosis as a collateral effect of the pandemic. Surgical services need a contingency plan for maintaining surgical care in an ongoing or postpandemic phase.

The characterisation of subjective cognitive decline

Abstract: A growing awareness about brain health and Alzheimer's disease in the general population is leading to an increasing number of cognitively unimpaired individuals, who are concerned that they have reduced cognitive function, to approach the medical system for help. The term subjective cognitive decline (SCD) was conceived in 2014 to describe this condition. Epidemiological data provide evidence that the risk for mild cognitive impairment and dementia is increased in individuals with SCD. However, the majority of individuals with SCD will not show progressive cognitive decline. An individually tailored diagnostic process might be reasonable to identify or exclude underlying medical conditions in an individual with SCD who actively seeks medical help. An increasing number of studies are investigating the link between SCD and the very early stages of Alzheimer's disease and other neurodegenerative diseases.

BERTweet: A pre-trained language model for English Tweets

Abstract: We present BERTweet, the first public large-scale pre-trained language model for English Tweets. Our BERTweet, having the same architecture as BERT-base (Devlin et al., 2019), is trained using the RoBERTa pre-training procedure (Liu et al., 2019). Experiments show that BERTweet outperforms strong baselines RoBERTa-base and XLM-R-base (Conneau et al., 2020), producing better performance results than the previous state-of-the-art models on three Tweet NLP tasks: Part-of-speech tagging, Named-entity recognition and text classification. We release BERTweet under the MIT License to facilitate future research and applications on Tweet data. Our BERTweet is available at https://github.com/VinAIResearch/BERTweet

GW190412: Observation of a binary-black-hole coalescence with asymmetric masses

Abstract: We report the observation of gravitational waves from a binary-black-hole coalescence during the first two weeks of LIGO’s and Virgo’s third observing run. The signal was recorded on April 12, 2019 at 05∶30∶44 UTC with a network signal-to-noise ratio of 19. The binary is different from observations during the first two observing runs most notably due to its asymmetric masses: a ∼30 M⊙ black hole merged with a ∼8 M⊙ black hole companion. The more massive black hole rotated with a dimensionless spin magnitude between 0.22 and 0.60 (90% probability). Asymmetric systems are predicted to emit gravitational waves with stronger contributions from higher multipoles, and indeed we find strong evidence for gravitational radiation beyond the leading quadrupolar order in the observed signal. A suite of tests performed on GW190412 indicates consistency with Einstein’s general theory of relativity. While the mass ratio of this system differs from all previous detections, we show that it is consistent with the population model of stellar binary black holes inferred from the first two observing runs.

Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies.

Abstract: Antibody-based drugs and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being expedited through preclinical and clinical development. Data from the study of SARS-CoV and other respiratory viruses suggest that anti-SARS-CoV-2 antibodies could exacerbate COVID-19 through antibody-dependent enhancement (ADE). Previous respiratory syncytial virus and dengue virus vaccine studies revealed human clinical safety risks related to ADE, resulting in failed vaccine trials. Here, we describe key ADE mechanisms and discuss mitigation strategies for SARS-CoV-2 vaccines and therapies in development. We also outline recently published data to evaluate the risks and opportunities for antibody-based protection against SARS-CoV-2.