Showing papers on "Population published in 2021"

Cancer Statistics, 2021.

Abstract: Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers.

Post-acute COVID-19 syndrome.

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.

SARS-CoV-2 variants, spike mutations and immune escape.

Abstract: Although most mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about 11 months. Since late 2020, however, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations, in the context of ‘variants of concern’, that impact virus characteristics, including transmissibility and antigenicity, probably in response to the changing immune profile of the human population. There is emerging evidence of reduced neutralization of some SARS-CoV-2 variants by postvaccination serum; however, a greater understanding of correlates of protection is required to evaluate how this may impact vaccine effectiveness. Nonetheless, manufacturers are preparing platforms for a possible update of vaccine sequences, and it is crucial that surveillance of genetic and antigenic changes in the global virus population is done alongside experiments to elucidate the phenotypic impacts of mutations. In this Review, we summarize the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets. The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been characterized by the emergence of mutations and so-called variants of concern that impact virus characteristics, including transmissibility and antigenicity. In this Review, members of the COVID-19 Genomics UK (COG-UK) Consortium and colleagues summarize mutations of the SARS-CoV-2 spike protein, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets.

Coronavirus biology and replication: implications for SARS-CoV-2.

Abstract: The SARS-CoV-2 pandemic and its unprecedented global societal and economic disruptive impact has marked the third zoonotic introduction of a highly pathogenic coronavirus into the human population. Although the previous coronavirus SARS-CoV and MERS-CoV epidemics raised awareness of the need for clinically available therapeutic or preventive interventions, to date, no treatments with proven efficacy are available. The development of effective intervention strategies relies on the knowledge of molecular and cellular mechanisms of coronavirus infections, which highlights the significance of studying virus-host interactions at the molecular level to identify targets for antiviral intervention and to elucidate critical viral and host determinants that are decisive for the development of severe disease. In this Review, we summarize the first discoveries that shape our current understanding of SARS-CoV-2 infection throughout the intracellular viral life cycle and relate that to our knowledge of coronavirus biology. The elucidation of similarities and differences between SARS-CoV-2 and other coronaviruses will support future preparedness and strategies to combat coronavirus infections.

Cancer statistics for the year 2020: An overview

Abstract: Our study briefly reviews the data sources and methods used in compiling the International Agency for Research on Cancer (IARC) GLOBOCAN cancer statistics for the year 2020 and summarises the main results. National estimates were calculated based on the best available data on cancer incidence from population-based cancer registries (PBCR) and mortality from the World Health Organization mortality database. Cancer incidence and mortality rates for 2020 by sex and age groups were estimated for 38 cancer sites and 185 countries or territories worldwide. There were an estimated 19.3 million (95% uncertainty interval [UI]: 19.0-19.6 million) new cases of cancer (18.1 million excluding non-melanoma skin cancer) and almost 10.0 million (95% UI: 9.7-10.2 million) deaths from cancer (9.9 million excluding non-melanoma skin cancer) worldwide in 2020. The most commonly diagnosed cancers worldwide were female breast cancer (2.26 million cases), lung (2.21) and prostate cancers (1.41); the most common causes of cancer death were lung (1.79 million deaths), liver (830000) and stomach cancers (769000).

Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Abstract: Summary Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding Bill & Melinda Gates Foundation.

The Essential Guide to Doing Your Research Project

Abstract: PART ONE: TAKING THE LEAP INTO THE RESEARCH WORLD The challenge of tackling a research project So what is this thing called research and why do it? The need for research knowledge The potential of research knowledge Delving into the 'construct' of research Ontology and epistemology Competing positions The position of the reflexive researcher Getting help along the way The structure of the book How to get the most out of the book PART TWO: GETTING STARTED On your mark, get set, go! Navigating the process Understanding your programme Getting set up Getting the right advice Managing the workload Staying on course Finding a balance Dealing with 'crisis' PART THREE: STRIVING FOR INTEGRITY IN THE RESEARCH PROCESS Power, politics, ethics and research integrity Understanding the power game Credibility: Integrity in the production of knowledge Working with appropriate indicators Managing subjectivities Capturing 'truth' Approaching methods with consistency Making relevant and appropriate arguments Providing accurate and verifiable research accounts Ethics: Integrity and the 'researched' Legal obligations Moral obligations Ethical obligations Ethics approval processes Integrity indicators and checklist PART FOUR: DEVELOPING YOUR RESEARCH QUESTION The importance of good questions Defining your topic Curiosity and creativity Looking for inspiration Practicalities From interesting topics to researchable questions Narrowing in The need to redefine The hypothesis dilemma Hypothesis defined Appropriateness Characteristics of good questions PART FIVE: CRAFTING A RESEARCH PROPOSAL The role of the proposal Demonstrating merits of the research question Demonstrating merits of the proposed methods Demonstrating merits of the researcher Elements of the proposal Writing a winning proposal Following guidelines Writing purposively Drafting and redrafting Obstacles and challenges When your design doesn't fit proposal requirements When your design is emergent When want to or need to change direction/method PART SIX: WORKING WITH LITERATURE The importance of literature The role of literature Sourcing relevant literature Types of literature Calling on 'experts' Honing your search skills Managing the literature Assessing relevance Being systematic Annotating references Writing a the formal 'literature review' Purpose Coverage The writing process PART SEVEN: DESIGNING A RESEARCH PLAN Methodology, methods and tools The relationship between methodology and methods Moving from questions to answers Finding a path Hitting the target Getting down to the nitty gritty Fundamental questions Emergent methodological design PART EIGHT: UNDERSTANDING METHODOLOGIES: QUANTITATIVE, QUALITATIVE AND 'MIXED' APPROACHES Understanding the quantitative/ qualitative divide The quantitative tradition Scientific/ hypothetico-deductive methods Experimental design Exploring a population The qualitative tradition Credibility in qualitative studies Ethnography Phenomenology Ethnomethodology Understanding feminist approaches Mixed methodology Arguments for mixed methodology Perspectives and strategies Challenges and obstacles PART NINE: UNDERSTANDING METHODOLOGIES: EVALUATIVE, ACTION-ORIENTED AND EMANCIPATORY STRATEGIES Research that attempts to drive change Evaluation research Summative/outcome evaluation Formative/process evaluation The politics of evaluative research Negotiating real-world challenges of evaluative research Action research The scope of action research Key elements of action research Challenges associated with action research Emancipatory research Participatory action research Critical ethnography Issues in emancipatory research PART TEN: SEEKING 'RESPONDENTS' Who holds the answer? Samples: Selecting elements of a population Opportunities in working with a 'sample' Sample selection Random samples Non-random samples Key informants: Working with experts and insiders Opportunities in working with key informants Informant selection Cases: Delving into detail Opportunities in working with cases Case selection PART ELEVEN: DIRECT DATA COLLECTION - SURVEYS AND INTERVIEWS The challenge of getting data directly from the source Surveying Options and possibilities Issues and complexities The survey process The survey instrument Interviewing Options and possibilities Issues and complexities The interview process Conducting your interview PART TWELVE: INDIRECT DATA COLLECTION: WORKING WITH OBSERVATIONS AND EXISTING TEXT The challenge of gathering indirect data Observation Options and possibilities Issues and complexities The observation process Receiving, reflecting, recording, authenticating Working with existing 'text' Options and possibilities Issues and complexities The process of textual analysis Delving into documents, history, artefacts, and secondary data PART THIRTEEN: ANALYSING QUANTITATIVE DATA Moving from raw data to significant findings Keeping a sense of the overall project Doing statistical analysis Managing data and defining variables Data management Understanding variables - cause and effect Understanding variables - measurements scales Descriptive statistics Measuring central tendency Measuring dispersion Measuring the shape of the data Inferential statistics Questions suitable to inferential statistics Statistical significance Understanding and selecting the right statistical test Presenting quantitative data PART FOURTEEN: ANALYZING QUALITATIVE DATA The promise of qualitative analysis Keeping the bigger picture in focus From raw data to significant findings QDA software The logic of QDA Balancing creativity and focus Moving between inductive and deductive reasoning The methods of QDA Identifying biases/ noting impressions Reducing and coding into themes Looking for patterns and interconnections Mapping and building themes Developing theory Drawing conclusions Specific QDA strategies Presenting quantitative data PART FIFTEEN: THE CHALLENGE OF WRITING UP The writing challenge Research as communication Knowing and engaging your audience Finding an appropriate structure and style The writing process Writing as analysis Constructing your 'story' Developing each section/ chapter From first to final draft The need for exposure Attending conferences Giving presentations Writing and submitting articles The final word

Mobility network models of COVID-19 explain inequities and inform reopening.

Abstract: The coronavirus disease 2019 (COVID-19) pandemic markedly changed human mobility patterns, necessitating epidemiological models that can capture the effects of these changes in mobility on the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1. Here we introduce a metapopulation susceptible-exposed-infectious-removed (SEIR) model that integrates fine-grained, dynamic mobility networks to simulate the spread of SARS-CoV-2 in ten of the largest US metropolitan areas. Our mobility networks are derived from mobile phone data and map the hourly movements of 98 million people from neighbourhoods (or census block groups) to points of interest such as restaurants and religious establishments, connecting 56,945 census block groups to 552,758 points of interest with 5.4 billion hourly edges. We show that by integrating these networks, a relatively simple SEIR model can accurately fit the real case trajectory, despite substantial changes in the behaviour of the population over time. Our model predicts that a small minority of 'superspreader' points of interest account for a large majority of the infections, and that restricting the maximum occupancy at each point of interest is more effective than uniformly reducing mobility. Our model also correctly predicts higher infection rates among disadvantaged racial and socioeconomic groups2-8 solely as the result of differences in mobility: we find that disadvantaged groups have not been able to reduce their mobility as sharply, and that the points of interest that they visit are more crowded and are therefore associated with higher risk. By capturing who is infected at which locations, our model supports detailed analyses that can inform more-effective and equitable policy responses to COVID-19.

Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial.

Abstract: Summary Background With the unprecedented morbidity and mortality associated with the COVID-19 pandemic, a vaccine against COVID-19 is urgently needed. We investigated CoronaVac (Sinovac Life Sciences, Beijing, China), an inactivated vaccine candidate against COVID-19, containing inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for its safety, tolerability and immunogenicity. Methods In this randomised, double-blind, placebo-controlled, phase 1/2 clinical trial, healthy adults aged 18–59 years were recruited from the community in Suining County of Jiangsu province, China. Adults with SARS-CoV-2 exposure or infection history, with axillary temperature above 37·0°C, or an allergic reaction to any vaccine component were excluded. The experimental vaccine for the phase 1 trial was manufactured using a cell factory process (CellSTACK Cell Culture Chamber 10, Corning, Wujiang, China), whereas those for the phase 2 trial were produced through a bioreactor process (ReadyToProcess WAVE 25, GE, Umea, Sweden). The phase 1 trial was done in a dose-escalating manner. At screening, participants were initially separated (1:1), with no specific randomisation, into two vaccination schedule cohorts, the days 0 and 14 vaccination cohort and the days 0 and 28 vaccination cohort, and within each cohort the first 36 participants were assigned to block 1 (low dose CoronaVac [3 μg per 0·5 mL of aluminium hydroxide diluent per dose) then another 36 were assigned to block 2 (high-dose Coronavc [6 μg per 0·5 mL of aluminium hydroxide diluent per dse]). Within each block, participants were randomly assigned (2:1), using block randomisation with a block size of six, to either two doses of CoronaVac or two doses of placebo. In the phase 2 trial, at screening, participants were initially separated (1:1), with no specific randomisation, into the days 0 and 14 vaccination cohort and the days 0 and 28 vaccination cohort, and participants were randomly assigned (2:2:1), using block randomisation with a block size of five, to receive two doses of either low-dose CoronaVac, high-dose CoronaVac, or placebo. Participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was adverse reactions within 28 days after injection in all participants who were given at least one dose of study drug (safety population). The primary immunogenic outcome was seroconversion rates of neutralising antibodies to live SARS-CoV-2 at day 14 after the last dose in the days 0 and 14 cohort, and at day 28 after the last dose in the days 0 and 28 cohort in participants who completed their allocated two-dose vaccination schedule (per-protocol population). This trial is registered with ClinicalTrials.gov, NCT04352608, and is closed to accrual. Findings Between April 16 and April 25, 2020, 144 participants were enrolled in the phase 1 trial, and between May 3 and May 5, 2020, 600 participants were enrolled in the phase 2 trial. 743 participants received at least one dose of investigational product (n=143 for phase 1 and n=600 for phase 2; safety population). In the phase 1 trial, the incidence of adverse reactions for the days 0 and 14 cohort was seven (29%) of 24 participants in the 3 ug group, nine (38%) of 24 in the 6 μg group, and two (8%) of 24 in the placebo group, and for the days 0 and 28 cohort was three (13%) of 24 in the 3 μg group, four (17%) of 24 in the 6 μg group, and three (13%) of 23 in the placebo group. The seroconversion of neutralising antibodies on day 14 after the days 0 and 14 vaccination schedule was seen in 11 (46%) of 24 participants in the 3 μg group, 12 (50%) of 24 in the 6 μg group, and none (0%) of 24 in the placebo group; whereas at day 28 after the days 0 and 28 vaccination schedule, seroconversion was seen in 20 (83%) of 24 in the 3 μg group, 19 (79%) of 24 in the 6 μg group, and one (4%) of 24 in the placebo group. In the phase 2 trial, the incidence of adverse reactions for the days 0 and 14 cohort was 40 (33%) of 120 participants in the 3 μg group, 42 (35%) of 120 in the 6 μg group, and 13 (22%) of 60 in the placebo group, and for the days 0 and 28 cohort was 23 (19%) of 120 in the 3 μg group, 23 (19%) of 120 in the 6 μg group, and 11 (18%) of 60 for the placebo group. Seroconversion of neutralising antibodies was seen for 109 (92%) of 118 participants in the 3 μg group, 117 (98%) of 119 in the 6 μg group, and two (3%) of 60 in the placebo group at day 14 after the days 0 and 14 schedule; whereas at day 28 after the days 0 and 28 schedule, seroconversion was seen in 114 (97%) of 117 in the 3 μg group, 118 (100%) of 118 in the 6 μg group, and none (0%) of 59 in the placebo group. Interpretation Taking safety, immunogenicity, and production capacity into account, the 3 μg dose of CoronaVac is the suggested dose for efficacy assessment in future phase 3 trials. Funding Chinese National Key Research and Development Program and Beijing Science and Technology Program.

Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination.

Abstract: We report findings in five patients who presented with venous thrombosis and thrombocytopenia 7 to 10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against coronavirus disease 2019 (Covid-19). The patients were health care workers who were 32 to 54 years of age. All the patients had high levels of antibodies to platelet factor 4-polyanion complexes; however, they had had no previous exposure to heparin. Because the five cases occurred in a population of more than 130,000 vaccinated persons, we propose that they represent a rare vaccine-related variant of spontaneous heparin-induced thrombocytopenia that we refer to as vaccine-induced immune thrombotic thrombocytopenia.

GOT-10k: A Large High-Diversity Benchmark for Generic Object Tracking in the Wild

Abstract: We introduce here a large tracking database that offers an unprecedentedly wide coverage of common moving objects in the wild, called GOT-10k. Specifically, GOT-10k is built upon the backbone of WordNet structure [1] and it populates the majority of over 560 classes of moving objects and 87 motion patterns, magnitudes wider than the most recent similar-scale counterparts [19] , [20] , [23] , [26] . By releasing the large high-diversity database, we aim to provide a unified training and evaluation platform for the development of class-agnostic, generic purposed short-term trackers. The features of GOT-10k and the contributions of this article are summarized in the following. (1) GOT-10k offers over 10,000 video segments with more than 1.5 million manually labeled bounding boxes, enabling unified training and stable evaluation of deep trackers. (2) GOT-10k is by far the first video trajectory dataset that uses the semantic hierarchy of WordNet to guide class population, which ensures a comprehensive and relatively unbiased coverage of diverse moving objects. (3) For the first time, GOT-10k introduces the one-shot protocol for tracker evaluation, where the training and test classes are zero-overlapped . The protocol avoids biased evaluation results towards familiar objects and it promotes generalization in tracker development. (4) GOT-10k offers additional labels such as motion classes and object visible ratios, facilitating the development of motion-aware and occlusion-aware trackers. (5) We conduct extensive tracking experiments with 39 typical tracking algorithms and their variants on GOT-10k and analyze their results in this paper. (6) Finally, we develop a comprehensive platform for the tracking community that offers full-featured evaluation toolkits, an online evaluation server, and a responsive leaderboard. The annotations of GOT-10k’s test data are kept private to avoid tuning parameters on it.

Age-specific mortality and immunity patterns of SARS-CoV-2.

Abstract: Estimating the size of the coronavirus disease 2019 (COVID-19) pandemic and the infection severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is made challenging by inconsistencies in the available data. The number of deaths associated with COVID-19 is often used as a key indicator for the size of the epidemic, but the observed number of deaths represents only a minority of all infections1,2. In addition, the heterogeneous burdens in nursing homes and the variable reporting of deaths of older individuals can hinder direct comparisons of mortality rates and the underlying levels of transmission across countries3. Here we use age-specific COVID-19-associated death data from 45 countries and the results of 22 seroprevalence studies to investigate the consistency of infection and fatality patterns across multiple countries. We find that the age distribution of deaths in younger age groups (less than 65 years of age) is very consistent across different settings and demonstrate how these data can provide robust estimates of the share of the population that has been infected. We estimate that the infection fatality ratio is lowest among 5-9-year-old children, with a log-linear increase by age among individuals older than 30 years. Population age structures and heterogeneous burdens in nursing homes explain some but not all of the heterogeneity between countries in infection fatality ratios. Among the 45 countries included in our analysis, we estimate that approximately 5% of these populations had been infected by 1 September 2020, and that much higher transmission rates have probably occurred in a number of Latin American countries. This simple modelling framework can help countries to assess the progression of the pandemic and can be applied in any scenario for which reliable age-specific death data are available.

Mental health and well-being during the COVID-19 pandemic: longitudinal analyses of adults in the UK COVID-19 Mental Health & Wellbeing study.

Abstract: Background The effects of coronavirus disease 2019 (COVID-19) on the population's mental health and well-being are likely to be profound and long lasting. Aims To investigate the trajectory of mental health and well-being during the first 6 weeks of lockdown in adults in the UK. Method A quota survey design and a sampling frame that permitted recruitment of a national sample was employed. Findings for waves 1 (31 March to 9 April 2020), 2 (10 April to 27 April 2020) and 3 (28 April to 11 May 2020) are reported here. A range of mental health factors was assessed: pre-existing mental health problems, suicide attempts and self-harm, suicidal ideation, depression, anxiety, defeat, entrapment, mental well-being and loneliness. Results A total of 3077 adults in the UK completed the survey at wave 1. Suicidal ideation increased over time. Symptoms of anxiety, and levels of defeat and entrapment decreased across waves whereas levels of depressive symptoms did not change significantly. Positive well-being also increased. Levels of loneliness did not change significantly over waves. Subgroup analyses showed that women, young people (18–29 years), those from more socially disadvantaged backgrounds and those with pre-existing mental health problems have worse mental health outcomes during the pandemic across most factors. Conclusions The mental health and well-being of the UK adult population appears to have been affected in the initial phase of the COVID-19 pandemic. The increasing rates of suicidal thoughts across waves, especially among young adults, are concerning.

How Structural Racism Works - Racist Policies as a Root Cause of U.S. Racial Health Inequities.

Abstract: How Structural Racism Works As a legacy of African enslavement, structural racism affects both population and individual health in three interrelated domains: redlining and racialized residential s...

Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia.

Abstract: Background Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials. Methods In this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approximately one quarter of the participants received a second dose of tocilizumab or placebo 8 to 24 hours after the first dose. The primary outcome was clinical status at day 28 on an ordinal scale ranging from 1 (discharged or ready for discharge) to 7 (death) in the modified intention-to-treat population, which included all the patients who had received at least one dose of tocilizumab or placebo. Results Of the 452 patients who underwent randomization, 438 (294 in the tocilizumab group and 144 in the placebo group) were included in the primary and secondary analyses. The median value for clinical status on the ordinal scale at day 28 was 1.0 (95% confidence interval [CI], 1.0 to 1.0) in the tocilizumab group and 2.0 (non-ICU hospitalization without supplemental oxygen) (95% CI, 1.0 to 4.0) in the placebo group (between-group difference, -1.0; 95% CI, -2.5 to 0; P = 0.31 by the van Elteren test). In the safety population, serious adverse events occurred in 103 of 295 patients (34.9%) in the tocilizumab group and in 55 of 143 patients (38.5%) in the placebo group. Mortality at day 28 was 19.7% in the tocilizumab group and 19.4% in the placebo group (weighted difference, 0.3 percentage points (95% CI, -7.6 to 8.2; nominal P = 0.94). Conclusions In this randomized trial involving hospitalized patients with severe Covid-19 pneumonia, the use of tocilizumab did not result in significantly better clinical status or lower mortality than placebo at 28 days. (Funded by F. Hoffmann-La Roche and the Department of Health and Human Services; COVACTA ClinicalTrials.gov number, NCT04320615.).

Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults.

Abstract: Background Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness. Methods We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible. Results A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P = 0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed. Conclusions Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19. (Funded by the Bill and Melinda Gates Foundation and the Fundacion INFANT Pandemic Fund; Direccion de Sangre y Medicina Transfusional del Ministerio de Salud number, PAEPCC19, Plataforma de Registro Informatizado de Investigaciones en Salud number, 1421, and ClinicalTrials.gov number, NCT04479163.).

SARS-CoV-2 evolution during treatment of chronic infection.

Abstract: SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE21, and is a major antibody target. Here we report chronic SARS-CoV-2 with reduced sensitivity to neutralising antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences over 23 time points spanning 101 days. Little change was observed in the overall viral population structure following two courses of remdesivir over the first 57 days. However, following convalescent plasma therapy we observed large, dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and ΔH69/ΔV70 in the S1 N-terminal domain NTD of the Spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype diminished in frequency, before returning during a final, unsuccessful course of convalescent plasma. In vitro, the Spike escape double mutant bearing ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, whilst maintaining infectivity similar to wild type. D796H appeared to be the main contributor to decreased susceptibility but incurred an infectivity defect. The ΔH69/ΔV70 single mutant had two-fold higher infectivity compared to wild type, possibly compensating for the reduced infectivity of D796H. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy associated with emergence of viral variants with evidence of reduced susceptibility to neutralising antibodies.

COVID-19 Vaccination Hesitancy in the United States: A Rapid National Assessment.

Abstract: Given the results from early trials, COVID-19 vaccines will be available by 2021. However, little is known about what Americans think of getting immunized with a COVID-19 vaccine. Thus, the purpose of this study was to conduct a comprehensive and systematic national assessment of COVID-19 vaccine hesitancy in a community-based sample of the American adult population. A multi-item valid and reliable questionnaire was deployed online via mTurk and social media sites to recruit U.S. adults from the general population. A total of 1878 individuals participated in the study where the majority were: females (52%), Whites (74%), non-Hispanic (81%), married (56%), employed full time (68%), and with a bachelor's degree or higher (77%). The likelihood of getting a COVID-19 immunization in the study population was: very likely (52%), somewhat likely (27%), not likely (15%), definitely not (7%), with individuals who had lower education, income, or perceived threat of getting infected being more likely to report that they were not likely/definitely not going to get COVID-19 vaccine (i.e., vaccine hesitancy). In unadjusted group comparisons, compared to their counterparts, vaccine hesitancy was higher among African-Americans (34%), Hispanics (29%), those who had children at home (25%), rural dwellers (29%), people in the northeastern U.S. (25%), and those who identified as Republicans (29%). In multiple regression analyses, vaccine hesitancy was predicted significantly by sex, education, employment, income, having children at home, political affiliation, and the perceived threat of getting infected with COVID-19 in the next 1 year. Given the high prevalence of COVID-19 vaccine hesitancy, evidence-based communication, mass media strategies, and policy measures will have to be implemented across the U.S. to convert vaccines into vaccinations and mass immunization with special attention to the groups identified in this study.

Insect decline in the Anthropocene: Death by a thousand cuts

Abstract: Nature is under siege. In the last 10,000 y the human population has grown from 1 million to 7.8 billion. Much of Earth’s arable lands are already in agriculture (1), millions of acres of tropical forest are cleared each year (2, 3), atmospheric CO2 levels are at their highest concentrations in more than 3 million y (4), and climates are erratically and steadily changing from pole to pole, triggering unprecedented droughts, fires, and floods across continents. Indeed, most biologists agree that the world has entered its sixth mass extinction event, the first since the end of the Cretaceous Period 66 million y ago, when more than 80% of all species, including the nonavian dinosaurs, perished. Ongoing losses have been clearly demonstrated for better-studied groups of organisms. Terrestrial vertebrate population sizes and ranges have contracted by one-third, and many mammals have experienced range declines of at least 80% over the last century (5). A 2019 assessment suggests that half of all amphibians are imperiled (2.5% of which have recently gone extinct) (6). Bird numbers across North America have fallen by 2.9 billion since 1970 (7). Prospects for the world’s coral reefs, beyond the middle of this century, could scarcely be more dire (8). A 2020 United Nations report estimated that more than a million species are in danger of extinction over the next few decades (9), but also see the more bridled assessments in refs. 10 and 11. Although a flurry of reports has drawn attention to declines in insect abundance, biomass, species richness, and range sizes (e.g., refs. 12⇓⇓⇓⇓⇓–18; for reviews see refs. 19 and 20), whether the rates of declines for insects are on par with or exceed those for other groups remains unknown. There are still too … [↵][1]1To whom correspondence may be addressed. Email: david.wagner{at}uconn.edu. [1]: #xref-corresp-1-1