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Showing papers by "University of the Witwatersrand published in 2020"


Journal ArticleDOI
TL;DR: These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay.
Abstract: Background World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). Methods We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. Results At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. Conclusions These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).

2,001 citations


Journal ArticleDOI
01 Oct 2020
TL;DR: The updated JBI guidance for scoping reviews includes additional guidance on several methodological issues, such as when a scoping review is (or is not) appropriate, and how to extract, analyze, and present results, and provides clarification for implications for practice and research.
Abstract: OBJECTIVE: The objective of this paper is to describe the updated methodological guidance for conducting a JBI scoping review, with a focus on new updates to the approach and development of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (the PRISMA-ScR). INTRODUCTION: Scoping reviews are an increasingly common approach to informing decision-making and research based on the identification and examination of the literature on a given topic or issue. Scoping reviews draw on evidence from any research methodology and may also include evidence from non-research sources, such as policy. In this manner, scoping reviews provide a comprehensive overview to address broader review questions than traditionally more specific systematic reviews of effectiveness or qualitative evidence. The increasing popularity of scoping reviews has been accompanied by the development of a reporting guideline: the PRISMA-ScR. In 2014, the JBI Scoping Review Methodology Group developed guidance for scoping reviews that received minor updates in 2017 and was most recently updated in 2020. The updates reflect ongoing and substantial developments in approaches to scoping review conduct and reporting. As such, the JBI Scoping Review Methodology Group recognized the need to revise the guidance to align with the current state of knowledge and reporting standards in evidence synthesis. METHODS: Between 2015 and 2020, the JBI Scoping Review Methodology Group expanded its membership; extensively reviewed the literature; engaged via annual face-to-face meetings, regular teleconferences, and email correspondence; sought advice from methodological experts; facilitated workshops; and presented at scientific conferences. This process led to updated guidance for scoping reviews published in the JBI Manual for Evidence Synthesis. The updated chapter was endorsed by JBI's International Scientific Committee in 2020. RESULTS: The updated JBI guidance for scoping reviews includes additional guidance on several methodological issues, such as when a scoping review is (or is not) appropriate, and how to extract, analyze, and present results, and provides clarification for implications for practice and research. Furthermore, it is aligned with the PRISMA-ScR to ensure consistent reporting. CONCLUSIONS: The latest JBI guidance for scoping reviews provides up-to-date guidance that can be used by authors when conducting a scoping review. Furthermore, it aligns with the PRISMA-ScR, which can be used to report the conduct of a scoping review. A series of ongoing and future methodological projects identified by the JBI Scoping Review Methodology Group to further refine the methodology are planned.

1,250 citations


Journal ArticleDOI
TL;DR: Survey shows that OTDs are fairly frequent in patients with SARS-CoV-2 infection and may precede the onset of full-blown clinical disease, which could explain the underlying pathogenetic mechanism of taste and olfactory disorders in SARS.
Abstract: To the Editor—We read with interest the article by Wang et al [1] describing the clinical features of 69 patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Wuhan, China. The authors provide a detailed description of major signs and symptoms of overt disease [2, 3], but fail to give an account of minor symptoms that may be present at earlier stages of the infection. After some patients admitted for coronavirus disease 2019 (COVID-19) at the Infectious Disease Department of L. Sacco Hospital in Milan, Italy, complained of olfactory and taste disorders (OTDs), we performed a cross-sectional survey of the prevalence of these alterations in the context of SARS-CoV-2 infection. On 19 March 2020, a simple questionnaire including questions about the presence or absence of OTDs, their type and time of onset respective to hospitalization were submitted through verbal interview to all SARS-CoV-2– positive hospitalized patients who were able to give informed consent. Of 88 hospitalized patients, 59 were able to be interviewed (29 were nonrespondents, of whom 4 had dementia, 2 had a linguistic barrier, and 23 were on noninvasive ventilation) (Table 1). Of these, 20 (33.9%) reported at least 1 taste or olfactory disorder and 11 (18.6%) both. Twelve patients (20.3%) presented the symptoms before the hospital admission, whereas 8 (13.5%) experienced the symptoms during the hospital stay. Taste alterations were more frequently (91%) before hospitalization, whereas after hospitalization taste and olfactory alteration appeared with equal frequency. Females reported OTDs more frequently than males (10/19 [52.6%] vs 10/40 [25%]; P = .036). Moreover, patients with at least 1 OTD were younger than those without (median, 56 years [interquartile range {IQR}, 47–60] vs 66 [IQR, 52–77]; P = .035). All patients reported the persistence of OTDs at the time of the interview. Olfactory and taste disorders are well known to be related with a wide range of viral infections [4, 5]. SARS-CoV has demonstrated in a mice model a transneural penetration through the olfactory bulb [6]. Moreover, angiotensinconverting enzyme 2 receptor, which is used by SARS-CoV-2 to bind and penetrate into the cell, is widely expressed on the epithelial cells of the mucosa of the oral cavity [7]. These findings could explain the underlying pathogenetic mechanism of taste and olfactory disorders in SARS-CoV-2 infection. Due to limitations related to the diffusivity of the disease and emergency contingencies, it was impossible to perform a more structured questionnaire associated with validated tests (ie, Pennsylvania smell identification test) [8]. However, our survey shows that OTDs are fairly frequent in patients with SARS-CoV-2 infection and may precede the onset of full-blown clinical disease. In a pandemic context, further investigations on nonhospitalized infected patients are required to ascertain if these symptoms, albeit unspecific, may represent a clinical screening tool to orientate testing of pauci-symptomatic individuals.

1,000 citations


Posted ContentDOI
22 Dec 2020-medRxiv
TL;DR: In this paper, the authors describe a new SARS-CoV-2 lineage (501Y.V2) characterised by eight lineage-defining mutations in the spike protein, including three at important residues in the receptor-binding domain (K417N, E484K and N501Y).
Abstract: Summary Continued uncontrolled transmission of the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in many parts of the world is creating the conditions for significant virus evolution. Here, we describe a new SARS-CoV-2 lineage (501Y.V2) characterised by eight lineage-defining mutations in the spike protein, including three at important residues in the receptor-binding domain (K417N, E484K and N501Y) that may have functional significance. This lineage emerged in South Africa after the first epidemic wave in a severely affected metropolitan area, Nelson Mandela Bay, located on the coast of the Eastern Cape Province. This lineage spread rapidly, becoming within weeks the dominant lineage in the Eastern Cape and Western Cape Provinces. Whilst the full significance of the mutations is yet to be determined, the genomic data, showing the rapid displacement of other lineages, suggest that this lineage may be associated with increased transmissibility.

980 citations


Journal ArticleDOI
Jens Kattge1, Gerhard Bönisch2, Sandra Díaz3, Sandra Lavorel  +751 moreInstitutions (314)
TL;DR: The extent of the trait data compiled in TRY is evaluated and emerging patterns of data coverage and representativeness are analyzed to 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.
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.

882 citations


Journal ArticleDOI
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

655 citations


Journal ArticleDOI
TL;DR: Reductions in low-density lipoprotein cholesterol levels of approximately 50% were obtained with inclisiran, administered subcutaneously every 6 months in patients with atherosclerotic cardiovascular disease and patients who had elevated LDL cholesterol levels despite receiving statin therapy at the maximum tolerated dose.
Abstract: Background Inclisiran inhibits hepatic synthesis of proprotein convertase subtilisin–kexin type 9. Previous studies suggest that inclisiran might provide sustained reductions in low-densit...

614 citations


Journal ArticleDOI
20 Jan 2020
TL;DR: In this article, the authors propose a set of four general principles that underlie high-quality knowledge co-production for sustainability research, and offer practical guidance on how to engage in meaningful co-productive practices, and how to evaluate their quality and success.
Abstract: Research practice, funding agencies and global science organizations suggest that research aimed at addressing sustainability challenges is most effective when ‘co-produced’ by academics and non-academics. Co-production promises to address the complex nature of contemporary sustainability challenges better than more traditional scientific approaches. But definitions of knowledge co-production are diverse and often contradictory. We propose a set of four general principles that underlie high-quality knowledge co-production for sustainability research. Using these principles, we offer practical guidance on how to engage in meaningful co-productive practices, and how to evaluate their quality and success.

607 citations


Journal ArticleDOI
TL;DR: This paper presents a meta-anatomy of the immune system and its role in the development and management of kidney disease andKidney Disease in China.

495 citations


Journal ArticleDOI
TL;DR: The use of community mitigation measures for the COVID-19 pandemic, plus influenza vaccination, are likely to be effective in reducing the incidence and impact of influenza, and some of these mitigation measures could have a role in preventing influenza in future seasons.
Abstract: After recognition of widespread community transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), by mid- to late February 2020, indicators of influenza activity began to decline in the Northern Hemisphere. These changes were attributed to both artifactual changes related to declines in routine health seeking for respiratory illness as well as real changes in influenza virus circulation because of widespread implementation of measures to mitigate transmission of SARS-CoV-2. Data from clinical laboratories in the United States indicated a 61% decrease in the number of specimens submitted (from a median of 49,696 per week during September 29, 2019-February 29, 2020, to 19,537 during March 1-May 16, 2020) and a 98% decrease in influenza activity as measured by percentage of submitted specimens testing positive (from a median of 19.34% to 0.33%). Interseasonal (i.e., summer) circulation of influenza in the United States (May 17-August 8, 2020) is currently at historical lows (median = 0.20% tests positive in 2020 versus 2.35% in 2019, 1.04% in 2018, and 2.36% in 2017). Influenza data reported to the World Health Organization's (WHO's) FluNet platform from three Southern Hemisphere countries that serve as robust sentinel sites for influenza from Oceania (Australia), South America (Chile), and Southern Africa (South Africa) showed very low influenza activity during June-August 2020, the months that constitute the typical Southern Hemisphere influenza season. In countries or jurisdictions where extensive community mitigation measures are maintained (e.g., face masks, social distancing, school closures, and teleworking), those locations might have little influenza circulation during the upcoming 2020-21 Northern Hemisphere influenza season. The use of community mitigation measures for the COVID-19 pandemic, plus influenza vaccination, are likely to be effective in reducing the incidence and impact of influenza, and some of these mitigation measures could have a role in preventing influenza in future seasons. However, given the novelty of the COVID-19 pandemic and the uncertainty of continued community mitigation measures, it is important to plan for seasonal influenza circulation in the United States this fall and winter. Influenza vaccination of all persons aged ≥6 months remains the best method for influenza prevention and is especially important this season when SARS-CoV-2 and influenza virus might cocirculate (1).

454 citations


Journal ArticleDOI
TL;DR: The combination of bedaquiline, pretomanid, and linezolid led to a favorable outcome at 6 months after the end of therapy in a high percentage of patients with highly drug-resistant forms of tuberculosis; some associated toxic effects were observed.
Abstract: Background Patients with highly drug-resistant forms of tuberculosis have limited treatment options and historically have had poor outcomes. Methods In an open-label, single-group study in...

Journal ArticleDOI
TL;DR: Those who received inclisiran had significantly lower levels of LDL cholesterol than those who received placebo, with an infrequent dosing regimen and an acceptable safety profile; there were robust reductions in LDL cholesterol levels in all genotypes of familial hypercholesterolemia.
Abstract: Background Familial hypercholesterolemia is characterized by an elevated level of low-density lipoprotein (LDL) cholesterol and an increased risk of premature atherosclerotic cardiovascula...

Journal ArticleDOI
TL;DR: In patients with homozygous familial hypercholesterolemia receiving maximum doses of lipid-lowering therapy, the reduction from baseline in the LDL cholesterol level in the evinacumab group, as compared with the small increase in the placebo group, resulted in a between-group difference of 49.0 percentage points at 24 weeks.
Abstract: Background Homozygous familial hypercholesterolemia is characterized by premature cardiovascular disease caused by markedly elevated levels of low-density lipoprotein (LDL) cholesterol. Th...

Journal ArticleDOI
TL;DR: The greatest challenge faced by the core group was trying to find a middle ground between those who think that PC is the relief of all suffering and those who believe that PC describes the care of those with a very limited remaining life span.

Journal ArticleDOI
Rafael Lozano1, Nancy Fullman1, John Everett Mumford1, Megan Knight1  +902 moreInstitutions (380)
TL;DR: To assess current trajectories towards the GPW13 UHC billion target—1 billion more people benefiting from UHC by 2023—the authors estimated additional population equivalents with UHC effective coverage from 2018 to 2023, and quantified frontiers of U HC effective coverage performance on the basis of pooled health spending per capita.

Journal ArticleDOI
TL;DR: The currently available literature on the epidemiology, etiology, vulnerability, preparedness and economic impact of COVID-19 in Africa, which could be useful and provide necessary information on ongoing CO VID-19 pandemics in the continent are collected and summarized.
Abstract: The recently emerged novel coronavirus, "severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)", caused a highly contagious disease called coronavirus disease 2019 (COVID-19). The virus was first reported from Wuhan city in China in December, 2019, which in less than three months spread throughout the globe and was declared a global pandemic by the World Health Organization (WHO) on 11th of March, 2020. So far, the ongoing pandemic severely damaged the world's most developed countries and is becoming a major threat for low- and middle-income countries. The poorest continent, Africa with the most vulnerable populations to infectious diseases, is predicted to be significantly affected by the ongoing COVID-19 outbreak. Therefore, in this review we collected and summarized the currently available literature on the epidemiology, etiology, vulnerability, preparedness and economic impact of COVID-19 in Africa, which could be useful and provide necessary information on ongoing COVID-19 pandemics in the continent. We also briefly summarized the concomitance of the COVID-19 pandemic and global warming.

Journal ArticleDOI
TL;DR: In this paper, the authors use advances made in kinematic restoration software in the last decade with a systematic reconstruction protocol for developing a more quantitative restoration of the Mediterranean region for the last 240 million years.

Journal ArticleDOI
TL;DR: There are multiple ways that international support and national commitment could help safeguard healthcare workers in Africa, essential for limiting the pandemic’s potentially devastating heath, socio-economic and security impacts on the continent.
Abstract: Medical staff caring for COVID-19 patients face mental stress, physical exhaustion, separation from families, stigma, and the pain of losing patients and colleagues. Many of them have acquired SARS-CoV-2 and some have died. In Africa, where the pandemic is escalating, there are major gaps in response capacity, especially in human resources and protective equipment. We examine these challenges and propose interventions to protect healthcare workers on the continent, drawing on articles identified on Medline (Pubmed) in a search on 24 March 2020. Global jostling means that supplies of personal protective equipment are limited in Africa. Even low-cost interventions such as facemasks for patients with a cough and water supplies for handwashing may be challenging, as is ‘physical distancing’ in overcrowded primary health care clinics. Without adequate protection, COVID-19 mortality may be high among healthcare workers and their family in Africa given limited critical care beds and difficulties in transporting ill healthcare workers from rural to urban care centres. Much can be done to protect healthcare workers, however. The continent has learnt invaluable lessons from Ebola and HIV control. HIV counselors and community healthcare workers are key resources, and could promote social distancing and related interventions, dispel myths, support healthcare workers, perform symptom screening and trace contacts. Staff motivation and retention may be enhanced through carefully managed risk ‘allowances’ or compensation. International support with personnel and protective equipment, especially from China, could turn the pandemic’s trajectory in Africa around. Telemedicine holds promise as it rationalises human resources and reduces patient contact and thus infection risks. Importantly, healthcare workers, using their authoritative voice, can promote effective COVID-19 policies and prioritization of their safety. Prioritizing healthcare workers for SARS-CoV-2 testing, hospital beds and targeted research, as well as ensuring that public figures and the population acknowledge the commitment of healthcare workers may help to maintain morale. Clearly there are multiple ways that international support and national commitment could help safeguard healthcare workers in Africa, essential for limiting the pandemic’s potentially devastating heath, socio-economic and security impacts on the continent.

Journal ArticleDOI
Georges Aad1, Brad Abbott2, Dale Charles Abbott3, Ovsat Abdinov4  +2934 moreInstitutions (199)
TL;DR: In this article, a search for the electroweak production of charginos and sleptons decaying into final states with two electrons or muons is presented, based on 139.fb$^{-1}$ of proton-proton collisions recorded by the ATLAS detector at the Large Hadron Collider at
Abstract: A search for the electroweak production of charginos and sleptons decaying into final states with two electrons or muons is presented. The analysis is based on 139 fb$^{-1}$ of proton–proton collisions recorded by the ATLAS detector at the Large Hadron Collider at $\sqrt{s}=13$ $\text {TeV}$. Three R-parity-conserving scenarios where the lightest neutralino is the lightest supersymmetric particle are considered: the production of chargino pairs with decays via either W bosons or sleptons, and the direct production of slepton pairs. The analysis is optimised for the first of these scenarios, but the results are also interpreted in the others. No significant deviations from the Standard Model expectations are observed and limits at 95% confidence level are set on the masses of relevant supersymmetric particles in each of the scenarios. For a massless lightest neutralino, masses up to 420 $\text {Ge}\text {V}$ are excluded for the production of the lightest-chargino pairs assuming W-boson-mediated decays and up to 1 $\text {TeV}$ for slepton-mediated decays, whereas for slepton-pair production masses up to 700 $\text {Ge}\text {V}$ are excluded assuming three generations of mass-degenerate sleptons.

Journal ArticleDOI
TL;DR: A single injection of nirsevimab resulted in fewer medically attended RSV-associated lower respiratory tract infections and hospitalizations than placebo throughout the RSV season in healthy preterm infants.
Abstract: Background Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants, and a need exists for prevention of RSV in healthy infants. Nirsevima...

Journal ArticleDOI
TL;DR: In this article, the authors investigated the forces that contributed to severe shortages in personal protective equipment in the US during the COVID-19 crisis and concluded that market prices are not appropriate mechanisms for rationing inputs to health because health is a public good.

Journal ArticleDOI
Marco Ajello1, R. Angioni2, R. Angioni3, Magnus Axelsson4  +149 moreInstitutions (42)
TL;DR: The 4LAC catalog of active galactic nuclei (AGNs) detected by the Fermi Gamma-ray Space Telescope Large Area Telescope (4LAC) between 2008 August 4 and 2016 August 2 contains 2863 objects located at high Galactic latitudes (|b|>10°deg}).
Abstract: The fourth catalog of active galactic nuclei (AGNs) detected by the Fermi Gamma-ray Space Telescope Large Area Telescope (4LAC) between 2008 August 4 and 2016 August 2 contains 2863 objects located at high Galactic latitudes (|b|>10{\deg}). It includes 85% more sources than the previous 3LAC catalog based on 4 years of data. AGNs represent at least 79% of the high-latitude sources in the fourth Fermi-Large Area Telescope Source Catalog (4FGL), which covers the energy range from 50 MeV to 1 TeV. In addition, 344 gamma-ray AGNs are found at low Galactic latitudes. Most of the 4LAC AGNs are blazars (98%), while the remainder are other types of AGNs. The blazar population consists of 24% Flat Spectrum Radio Quasars (FSRQs), 38% BL Lac-type objects (BL Lacs), and 38% blazar candidates of unknown types (BCUs). On average, FSRQs display softer spectra and stronger variability in the gamma-ray band than BL Lacs do, confirming previous findings. All AGNs detected by ground-based atmospheric Cherenkov telescopes are also found in the 4LAC.

Book ChapterDOI
01 Jan 2020
TL;DR: In this article, the intricate relationship between CO2 emission, global warming, and climate change was explicitly explained, and CO2 mitigation strategies in selected industrial sectors such as power, cement, iron, and steel as well as the petrochemical industry were presented.
Abstract: This chapter discusses the concepts of CO2 emission, global warming, and climate change with an emphasis on their environmental impacts. Specifically, the chapter reviews different sources of atmospheric CO2 emissions and recent advances in the implementation of carbon capture and storage (CCS) technology to mitigate greenhouse gas emissions. In this chapter, the intricate relationship between CO2 emission, global warming, and climate change was explicitly explained, and CO2 mitigation strategies in selected industrial sectors such as power, cement, iron, and steel as well as the petrochemical industry were presented. An overview of process integration concepts for energy minimization in environmental sustainability studies was highlighted. The current state of research in this field was reviewed, while future prospects in the application of process synthesis techniques to decrease the high energy and material requirement during CO2 capture were suggested. Finally, CO2 emission trend since the beginning of the first industrial revolution was discussed alongside current international treaties, limitations, and forecasts about greenhouse gas emission.

Journal ArticleDOI
TL;DR: RSV F protein nanoparticle vaccination in pregnant women did not meet the prespecified success criterion for efficacy against RSV-associated, medically significant lower respiratory tract infection in infants up to 90 days of life, and the suggestion of a possible benefit with respect to other end-point events involving RSv-associated respiratory disease in infants warrants further study.
Abstract: BACKGROUND: Respiratory syncytial virus (RSV) is the dominant cause of severe lower respiratory tract infection in infants, with the most severe cases concentrated among younger infants. METHODS: Healthy pregnant women, at 28 weeks 0 days through 36 weeks 0 days of gestation, with an expected delivery date near the start of the RSV season, were randomly assigned in an overall ratio of approximately 2:1 to receive a single intramuscular dose of RSV fusion (F) protein nanoparticle vaccine or placebo. Infants were followed for 180 days to assess outcomes related to lower respiratory tract infection and for 364 days to assess safety. The primary end point was RSV-associated, medically significant lower respiratory tract infection up to 90 days of life, and the primary analysis of vaccine efficacy against the primary end point was performed in the per-protocol population of infants (prespecified criterion for success, lower bound of the 97.52% confidence interval [CI] of ≥30%). RESULTS: A total of 4636 women underwent randomization, and there were 4579 live births. During the first 90 days of life, the percentage of infants with RSV-associated, medically significant lower respiratory tract infection was 1.5% in the vaccine group and 2.4% in the placebo group (vaccine efficacy, 39.4%; 97.52% CI, -1.0 to 63.7; 95% CI, 5.3 to 61.2). The corresponding percentages for RSV-associated lower respiratory tract infection with severe hypoxemia were 0.5% and 1.0% (vaccine efficacy, 48.3%; 95% CI, -8.2 to 75.3), and the percentages for hospitalization for RSV-associated lower respiratory tract infection were 2.1% and 3.7% (vaccine efficacy, 44.4%; 95% CI, 19.6 to 61.5). Local injection-site reactions among the women were more common with vaccine than with placebo (40.7% vs. 9.9%), but the percentages of participants who had other adverse events were similar in the two groups. CONCLUSIONS: RSV F protein nanoparticle vaccination in pregnant women did not meet the prespecified success criterion for efficacy against RSV-associated, medically significant lower respiratory tract infection in infants up to 90 days of life. The suggestion of a possible benefit with respect to other end-point events involving RSV-associated respiratory disease in infants warrants further study. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov NCT02624947.).

Journal ArticleDOI
TL;DR: The findings provide new and important evidence for maternal and paediatric influenza immunisation, and should inform future immunisation policy particularly in low-income and lower-middle-income countries.


Journal ArticleDOI
TL;DR: The NSOAP reflects a special commitment by state actors to make progress on global goals such as Universal Health Coverage and the United Nations Sustainable Development Goals and requires a continued global commitment involving genuine partnerships that embrace the collective strengths of both national and global actors.
Abstract: Efforts from the developed world to improve surgical, anesthesia and obstetric care in low- and middle-income countries have evolved from a primarily volunteer mission trip model to a sustainable health system strengthening approach as private and public stakeholders recognize the enormous health toll and financial burden of surgical disease. The National Surgical, Obstetric and Anesthesia Plan (NSOAP) has been developed as a policy strategy for countries to address, in part, the health burden of diseases amenable to surgical care, but these plans have not developed in isolation. The NSOAP has become a phenomenon of globalization as a broad range of partners – individuals and institutions – help in both NSOAP formulation, implementation and financing. As the nexus between policy and action in the field of global surgery, the NSOAP reflects a special commitment by state actors to make progress on global goals such as Universal Health Coverage and the United Nations Sustainable Development Goals. This requires a continued global commitment involving genuine partnerships that embrace the collective strengths of both national and global actors to deliver sustained, safe and affordable high-quality surgical care for all poor, rural and marginalized people.

Journal ArticleDOI
20 Nov 2020-Science
TL;DR: How changes in fire activity are threatening species with extinction across the globe are reviewed, forward-looking methods for predicting the combined effects of human drivers and fire on biodiversity are highlighted, and emerging actions and strategies that could revolutionize how society manages fire for biodiversity in the Anthropocene are foreshadowed.
Abstract: Fire has been a source of global biodiversity for millions of years. However, interactions with anthropogenic drivers such as climate change, land use, and invasive species are changing the nature of fire activity and its impacts. We review how such changes are threatening species with extinction and transforming terrestrial ecosystems. Conservation of Earth's biological diversity will be achieved only by recognizing and responding to the critical role of fire. In the Anthropocene, this requires that conservation planning explicitly includes the combined effects of human activities and fire regimes. Improved forecasts for biodiversity must also integrate the connections among people, fire, and ecosystems. Such integration provides an opportunity for new actions that could revolutionize how society sustains biodiversity in a time of changing fire activity.

Journal ArticleDOI
TL;DR: In this article, a metasurface-enhanced laser was proposed to produce high-purity OAM states with quantum numbers reaching l 1/ε 2/ε 3.
Abstract: Orbital angular momentum (OAM) from lasers holds promise for compact, at-source solutions for applications ranging from imaging to communications. However, conjugate symmetry between circular spin and opposite helicity OAM states (±l) from conventional spin–orbit approaches has meant that complete control of light’s angular momentum from lasers has remained elusive. Here, we report a metasurface-enhanced laser that overcomes this limitation. We demonstrate new high-purity OAM states with quantum numbers reaching l = 100 and non-symmetric vector vortex beams that lase simultaneously on independent OAM states as much as Δl = 90 apart, an extreme violation of previous symmetric spin–orbit lasing devices. Our laser conveniently outputs in the visible, producing new OAM states of light as well as all previously reported OAM modes from lasers, offering a compact and power-scalable source that harnesses intracavity structured matter for the creation of arbitrary chiral states of structured light. A metasurface laser generates orbital angular momentum states with quantum numbers reaching l = 100. Simultaneous output vortex beams, with Δl as great as 90, are demonstrated in the visible regime.

Journal ArticleDOI
Georges Aad1, Brad Abbott2, Dale Charles Abbott3, A. Abed Abud4  +2954 moreInstitutions (198)
TL;DR: In this paper, the trigger algorithms and selection were optimized to control the rates while retaining a high efficiency for physics analyses at the ATLAS experiment to cope with a fourfold increase of peak LHC luminosity from 2015 to 2018 (Run 2), and a similar increase in the number of interactions per beam-crossing to about 60.
Abstract: Electron and photon triggers covering transverse energies from 5 GeV to several TeV are essential for the ATLAS experiment to record signals for a wide variety of physics: from Standard Model processes to searches for new phenomena in both proton–proton and heavy-ion collisions. To cope with a fourfold increase of peak LHC luminosity from 2015 to 2018 (Run 2), to 2.1×1034cm-2s-1, and a similar increase in the number of interactions per beam-crossing to about 60, trigger algorithms and selections were optimised to control the rates while retaining a high efficiency for physics analyses. For proton–proton collisions, the single-electron trigger efficiency relative to a single-electron offline selection is at least 75% for an offline electron of 31 GeV, and rises to 96% at 60 GeV; the trigger efficiency of a 25 GeV leg of the primary diphoton trigger relative to a tight offline photon selection is more than 96% for an offline photon of 30 GeV. For heavy-ion collisions, the primary electron and photon trigger efficiencies relative to the corresponding standard offline selections are at least 84% and 95%, respectively, at 5 GeV above the corresponding trigger threshold.