Background. Marked increases in Clostridium difficile infection (CDI) incidence, driven by epidemic strain spread, is a global phenomenon. Methods. The Clostridium difficile Ribotyping Network (CDRN) ...was established in 2007 as part of enhanced CDI surveillance in England, to facilitate the recognition and control of epidemic strains. We report on changes in CDI epidemiology in England in the first 3 years of CDRN. Results. CDRN received 12 603 fecal specimens, comprising significantly (P < .05) increasing numbers and proportions of national CDI cases in 2007–2008 (n = 2109, 3.8%), 2008–2009 (n = 4774, 13.2%), and 2009–2010 (n = 5720, 22.3%). The C. difficile recovery rate was 90%, yielding 11 294 isolates for ribotyping. Rates of 9 of the 10 most common ribotypes changed significantly (P < .05) during 2007–2010. Clostridium difficile ribotype 027 predominated, but decreased markedly from 55% to 36% and 21% in 2007–2008, 2008–2009, and 2009–2010, respectively. The largest regional variations in prevalence occurred for ribotypes 027, 002, 015, and 078. Cephalosporin and fluoroquinolone use in CDI cases was reported significantly (P < .05) less frequently during 2007–2010. Mortality data were subject to potential reporting bias, but there was a significant decrease in CDI-associated deaths during 2007–2010, which may have been due to multiple factors, including reduced prevalence of ribotype 027. Conclusions. Access to C. difficile ribotyping was associated with significant changes in the prevalence of epidemic strains, especially ribotype 027. These changes coincided with markedly reduced CDI incidence and related mortality in England. CDI control programs should include prospective access to C. difficile typing and analysis of risk factors for CDI and outcomes.
Protecting the world's freshwater resources requires diagnosing threats over a broad range of scales, from global to local. Here we present the first worldwide synthesis to jointly consider human and ...biodiversity perspectives on water security using a spatial framework that quantifies multiple stressors and accounts for downstream impacts. We find that nearly 80% of the world's population is exposed to high levels of threat to water security. Massive investment in water technology enables rich nations to offset high stressor levels without remedying their underlying causes, whereas less wealthy nations remain vulnerable. A similar lack of precautionary investment jeopardizes biodiversity, with habitats associated with 65% of continental discharge classified as moderately to highly threatened. The cumulative threat framework offers a tool for prioritizing policy and management responses to this crisis, and underscores the necessity of limiting threats at their source instead of through costly remediation of symptoms in order to assure global water security for both humans and freshwater biodiversity.
The global extent and distribution of forest trees is central to our understanding of the terrestrial biosphere. We provide the first spatially continuous map of forest tree density at a global ...scale. This map reveals that the global number of trees is approximately 3.04 trillion, an order of magnitude higher than the previous estimate. Of these trees, approximately 1.39 trillion exist in tropical and subtropical forests, with 0.74 trillion in boreal regions and 0.61 trillion in temperate regions. Biome-level trends in tree density demonstrate the importance of climate and topography in controlling local tree densities at finer scales, as well as the overwhelming effect of humans across most of the world. Based on our projected tree densities, we estimate that over 15 billion trees are cut down each year, and the global number of trees has fallen by approximately 46% since the start of human civilization.
The ocean carbon reservoir controls atmospheric carbon dioxide (CO2) on millennial timescales. Radiocarbon (14C) anomalies in eastern North Pacific sediments suggest a significant release of geologic ...14C‐free carbon at the end of the last ice age but without evidence of ocean acidification. Using inverse carbon cycle modeling optimized with reconstructed atmospheric CO2 and 14C/C, we develop first‐order constraints on geologic carbon and alkalinity release over the last 17.5 thousand years. We construct scenarios allowing the release of 850–2,400 Pg C, with a maximum release rate of 1.3 Pg C yr−1, all of which require an approximate equimolar alkalinity release. These neutralized carbon addition scenarios have minimal impacts on the simulated marine carbon cycle and atmospheric CO2, thereby demonstrating safe and effective ocean carbon storage. This deglacial phenomenon could serve as a natural analog to the successful implementation of gigaton‐scale ocean alkalinity enhancement, a promising marine carbon dioxide removal method.
Plain Language Summary
The ocean is the largest carbon reservoir on Earth's surface and, as such, it controls the concentration of the greenhouse gas carbon dioxide (CO2) in the atmosphere over long time periods. When CO2 was rising at the end of the last ice age, marine sediment evidence indicates a regional carbon release into the ocean, due to a distinct carbon isotope fingerprint left behind. Using a carbon cycle model and atmospheric data, we simulated different geologic carbon addition scenarios since the last ice age. We find that substantial carbon addition to the ocean could have occurred (up to 1.3 billion tons per year) without causing significant changes to the carbon cycle, but only if the carbon is neutralized by alkalinity in an approximate 1:1 ratio. This neutralized release is similar to an approach of carbon removal called ocean alkalinity enhancement (OAE), which aims to reduce atmospheric CO2 as a potential solution for climate change. These findings suggest that neutralized carbon addition—in the form of “neutralized” bicarbonate ion HCO3− $\left({\text{HCO}}_{3}^{-}\right)$ instead of “acidic” CO2—could explain the low levels of radiocarbon during the last deglaciation and shows that large‐scale OAE is feasible without causing major changes to the marine carbon cycle.
Key Points
Observed deglacial changes in atmospheric CO2 and 14C/C allow for up to 2,396 Pg of neutralized geologic carbon (i.e., bicarbonate) release
The global carbon cycle is essentially “blind” to neutralized carbon release, only constrained by 14C budget
This gigaton‐scale neutralized carbon release may be a natural analog to the marine CO2 removal method of ocean alkalinity enhancement
Here we provide global estimates of the seasonal flux of sediment, on a river-by-river basis, under modern and prehuman conditions. Humans have simultaneously increased the sediment transport by ...global rivers through soil erosion (by 2.3 ± 0.6 billion metric tons per year), yet reduced the flux of sediment reaching the world's coasts (by 1.4 ± 0.3 billion metric tons per year) because of retention within reservoirs. Over 100 billion metric tons of sediment and 1 to 3 billion metric tons of carbon are now sequestered in reservoirs constructed largely within the past 50 years. African and Asian rivers carry a greatly reduced sediment load; Indonesian rivers deliver much more sediment to coastal areas.
Protein-protein interactions are fundamental to many biological processes. Experimental screens have identified tens of thousands of interactions, and structural biology has provided detailed ...functional insight for select 3D protein complexes. An alternative rich source of information about protein interactions is the evolutionary sequence record. Building on earlier work, we show that analysis of correlated evolutionary sequence changes across proteins identifies residues that are close in space with sufficient accuracy to determine the three-dimensional structure of the protein complexes. We evaluate prediction performance in blinded tests on 76 complexes of known 3D structure, predict protein-protein contacts in 32 complexes of unknown structure, and demonstrate how evolutionary couplings can be used to distinguish between interacting and non-interacting protein pairs in a large complex. With the current growth of sequences, we expect that the method can be generalized to genome-wide elucidation of protein-protein interaction networks and used for interaction predictions at residue resolution.
Abstract
Background
The Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P) Epidemiology, Surveillance and Preparedness of the Novel SARS-CoV-2 Epidemic (RESPONSE) ...seroprevalence study conducted monthly cross-sectional testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in blood donors in 6 US metropolitan regions to estimate the extent of SARS-CoV-2 infections over time.
Methods
During March–August 2020, approximately ≥1000 serum specimens were collected monthly from each region and tested for SARS-CoV-2 antibodies using a well-validated algorithm. Regional seroprevalence estimates were weighted based on demographic differences compared with the general population. Seroprevalence was compared with reported coronavirus disease 2019 (COVID-19) case rates over time.
Results
For all regions, seroprevalence was <1.0% in March 2020. New York, New York, experienced the biggest increase (peak seroprevalence, 15.8% in May). All other regions experienced modest increases in seroprevalence (1%–2% in May–June to 2%–4% in July–August). Seroprevalence was higher in younger, non-Hispanic black, and Hispanic donors. Temporal increases in donor seroprevalence correlated with reported case rates in each region. In August, 1.3–5.6 estimated cumulative infections (based on seroprevalence data) per COVID-19 case were reported to the Centers for Disease Control and Prevention.
Conclusions
Increases in seroprevalence were found in all regions, with the largest increase in New York. Seroprevalence was higher in non-Hispanic black and Hispanic than in non-Hispanic white blood donors. SARS-CoV-2 antibody testing of blood donor samples can be used to estimate the seroprevalence in the general population by region and demographic group. The methods derived from the RESPONSE seroprevalence study served as the basis for expanding SARS-CoV-2 seroprevalence surveillance to all 50 states and Puerto Rico.
SARS-CoV-2 serosurveillance of blood donors in 6 US regions enabled population weighted seroprevalence estimates. Seroprevelance rates were higher in younger, non-Hispanic Black, and Hispanic donors and correlated with regional case rates. The study has expanded to a national serosurveillance program.
Tumor mutational burden (TMB) measurements aid in identifying patients who are likely to benefit from immunotherapy; however, there is empirical variability across panel assays and factors ...contributing to this variability have not been comprehensively investigated. Identifying sources of variability can help facilitate comparability across different panel assays, which may aid in broader adoption of panel assays and development of clinical applications.
Twenty-nine tumor samples and 10 human-derived cell lines were processed and distributed to 16 laboratories; each used their own bioinformatics pipelines to calculate TMB and compare to whole exome results. Additionally, theoretical positive percent agreement (PPA) and negative percent agreement (NPA) of TMB were estimated. The impact of filtering pathogenic and germline variants on TMB estimates was assessed. Calibration curves specific to each panel assay were developed to facilitate translation of panel TMB values to whole exome sequencing (WES) TMB values.
Panel sizes >667 Kb are necessary to maintain adequate PPA and NPA for calling TMB high versus TMB low across the range of cut-offs used in practice. Failure to filter out pathogenic variants when estimating panel TMB resulted in overestimating TMB relative to WES for all assays. Filtering out potential germline variants at >0% population minor allele frequency resulted in the strongest correlation to WES TMB. Application of a calibration approach derived from The Cancer Genome Atlas data, tailored to each panel assay, reduced the spread of panel TMB values around the WES TMB as reflected in lower root mean squared error (RMSE) for 26/29 (90%) of the clinical samples.
Estimation of TMB varies across different panels, with panel size, gene content, and bioinformatics pipelines contributing to empirical variability. Statistical calibration can achieve more consistent results across panels and allows for comparison of TMB values across various panel assays. To promote reproducibility and comparability across assays, a software tool was developed and made publicly available.
•Estimation of TMB varies across different panels, with panel size, gene content and bioinformatics pipelines contributing to empirical variability.•Panel sizes greater than 667Kb are necessary to maintain adequate PPA and NPA for calling TMB high versus TMB low across the range of cutoffs used in practice.•Statistical calibration can achieve more consistent results across panels and allows for comparison of TMB values across various panel assays.
Transgender healthcare is a rapidly evolving interdisciplinary field. In the last decade, there has been an unprecedented increase in the number and visibility of transgender and gender diverse (TGD) ...people seeking support and gender-affirming medical treatment in parallel with a significant rise in the scientific literature in this area. The World Professional Association for Transgender Health (WPATH) is an international, multidisciplinary, professional association whose mission is to promote evidence-based care, education, research, public policy, and respect in transgender health. One of the main functions of WPATH is to promote the highest standards of health care for TGD people through the Standards of Care (SOC). The SOC was initially developed in 1979 and the last version (SOC-7) was published in 2012. In view of the increasing scientific evidence, WPATH commissioned a new version of the Standards of Care, the SOC-8.
The overall goal of SOC-8 is to provide health care professionals (HCPs) with clinical guidance to assist TGD people in accessing safe and effective pathways to achieving lasting personal comfort with their gendered selves with the aim of optimizing their overall physical health, psychological well-being, and self-fulfillment.
The SOC-8 is based on the best available science and expert professional consensus in transgender health. International professionals and stakeholders were selected to serve on the SOC-8 committee. Recommendation statements were developed based on data derived from independent systematic literature reviews, where available, background reviews and expert opinions. Grading of recommendations was based on the available evidence supporting interventions, a discussion of risks and harms, as well as the feasibility and acceptability within different contexts and country settings.
A total of 18 chapters were developed as part of the SOC-8. They contain recommendations for health care professionals who provide care and treatment for TGD people. Each of the recommendations is followed by explanatory text with relevant references. General areas related to transgender health are covered in the chapters Terminology, Global Applicability, Population Estimates, and Education. The chapters developed for the diverse population of TGD people include Assessment of Adults, Adolescents, Children, Nonbinary, Eunuchs, and Intersex Individuals, and people living in Institutional Environments. Finally, the chapters related to gender-affirming treatment are Hormone Therapy, Surgery and Postoperative Care, Voice and Communication, Primary Care, Reproductive Health, Sexual Health, and Mental Health.
The SOC-8 guidelines are intended to be flexible to meet the diverse health care needs of TGD people globally. While adaptable, they offer standards for promoting optimal health care and guidance for the treatment of people experiencing gender incongruence. As in all previous versions of the SOC, the criteria set forth in this document for gender-affirming medical interventions are clinical guidelines; individual health care professionals and programs may modify these in consultation with the TGD person.
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