Comparison of antibodies that mediate HIV type 1 gp120 antibody-dependent cell-mediated cytotoxicity in asymptomatic HIV type 1-positive men and women

Recent studies suggest that HIV-specific antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies contribute to protective immunity against HIV. An important characteristic of future HIV vaccines will, therefore, be the ability to stimulate production of these antibodies in both men and women. Early studies suggest that men may have a better ADCC antibody response against HIV than women. Our objective was to determine whether men and women differ with respect to their ADCC response to HIV-1 gp120. HIV-positive, asymptomatic untreated men and women were matched for race, age, CD4(+) T cell number, HIV-1 viral load, and treatment and HIV-1 gp120 ADCC antibody titers were compared. A standard (51)Cr-release assay was used to determine HIV-1 gp120 ADCC antibody titers in HIV-1-seropositive individuals from the Multicenter AIDS Cohort Study (MACS; n=32) and the Women's Interagency HIV Study (WIHS; n=32). Both sexes had high ADCC titers against HIV-1 gp120: 34.4% (n=11) and 40.6% (n=13) of men and women, respectively, had titers of 10,000; 62.5% (n=20) and 56.3% (n=18) had titers of 100,000. Groups did not differ in percent specific release (% SR), lytic units (LU), correlations of titer to viral load, or titer to CD4(+) T cells in men or women. Both groups also had similar cross-clade ADCC antibody responses (p>0.5 for % SR and LU). Comparable groups of asymptomatic HIV-1-infected men and women had comparable HIV-1 gp120 ADCC antibodies. Both sexes had significant cross-clade reactivity. Differences between men and women may become evident as disease progresses; this should be evaluated at later stages of HIV-1 infection

The cost effectiveness and optimal configuration of HIV self-test distribution in South Africa: a model analysis.

BACKGROUND: HIV self-testing (HIVST) has been shown to be acceptable, feasible and effective in increasing HIV testing uptake. Novel testing strategies are critical to achieving the UNAIDS target of 95% HIV-positive diagnosis by 2025 in South Africa and globally. METHODS: We modelled the impact of six HIVST kit distribution modalities (community fixed-point, taxi ranks, workplace, partners of primary healthcare (PHC) antiretroviral therapy (ART) patients), partners of pregnant women, primary PHC distribution) in South Africa over 20 years (2020-2039), using data collected alongside the Self-Testing AfRica Initiative. We modelled two annual distribution scenarios: (A) 1 million HIVST kits (current) or (B) up to 6.7 million kits. Incremental economic costs (2019 US$) were estimated from the provider perspective; assumptions on uptake and screening positivity were based on surveys of a subset of kit recipients and modelled using the Thembisa model. Cost-effectiveness of each distribution modality compared with the status-quo distribution configuration was estimated as cost per life year saved (estimated from life years lost due to AIDS) and optimised using a fractional factorial design. RESULTS: The largest impact resulted from secondary HIVST distribution to partners of ART patients at PHC (life years saved (LYS): 119 000 (scenario A); 393 000 (scenario B)). However, it was one of the least cost-effective modalities (A:$1394/LYS; B: $4162/LYS). Workplace distribution was cost-saving ($52-$76 million) and predicted to have a moderate epidemic impact (A: 40 000 LYS; B: 156 000 LYS). An optimised scale-up to 6.7 million tests would result in an almost threefold increase in LYS compared with a scale-up of status-quo distribution (216 000 vs 75 000 LYS). CONCLUSION: Optimisation-informed distribution has the potential to vastly improve the impact of HIVST. Using this approach, HIVST can play a key role in improving the long-term health impact of investment in HIVST

Risk of infection and adverse outcomes among pregnant working women in selected occupational groups: A study in the Danish National Birth Cohort

<p>Abstract</p> <p>Background</p> <p>Exposure to infectious pathogens is a frequent occupational hazard for women who work with patients, children, animals or animal products. The purpose of the present study is to investigate if women working in occupations where exposure to infections agents is common have a high risk of infections and adverse pregnancy outcomes.</p> <p>Methods</p> <p>We used data from the Danish National Birth Cohort, a population-based cohort study and studied the risk of Infection and adverse outcomes in pregnant women working with patients, with children, with food products or with animals. The regression analysis were adjusted for the following covariates: maternal age, parity, history of miscarriage, socio-occupational status, pre-pregnancy body mass index, smoking habit, alcohol consumption.</p> <p>Results</p> <p>Pregnant women who worked with patients or children or food products had an excess risk of sick leave during pregnancy for more than three days. Most of negative reproductive outcomes were not increased in these occupations but the prevalence of congenital anomalies (CAs) was slightly higher in children of women who worked with patients. The prevalence of small for gestational age infants was higher among women who worked with food products. There was no association between occupation infections during pregnancy and the risk of reproductive failures in the exposed groups. However, the prevalence of CAs was slightly higher among children of women who suffered some infection during pregnancy but the numbers were small.</p> <p>Conclusion</p> <p>Despite preventive strategies, working in specific jobs during pregnancy may impose a higher risk of infections, and working in some of these occupations may impose a slightly higher risk of CAs in their offspring. Most other reproductive failures were not increased in these occupations.</p

Plasma and breast-milk selenium in HIV-infected Malawian mothers are positively associated with infant selenium status but are not associated with maternal supplementation: results of the Breastfeeding, Antiretrovirals, and Nutrition study

Background: Selenium is found in soils and is essential for human antioxidant defense and immune function. In Malawi, low soil selenium and dietary intakes coupled with low plasma selenium concentrations in HIV infection could have negative consequences for the health of HIV-infected mothers and their exclusively breastfed infants

Sulfide geochronology along the Endeavour Segment of the Juan de Fuca Ridge

Forty-nine hydrothermal sulfide-sulfate rock samples from the Endeavour Segment of the Juan de Fuca Ridge, northeastern Pacific Ocean, were dated by measuring the decay of 226Ra (half-life of 1600 years) in hydrothermal barite to provide a history of hydrothermal venting at the site over the past 6000 years. This dating method is effective for samples ranging in age from ∼200 to 20,000 years old and effectively bridges an age gap between shorter- and longer-lived U-series dating techniques for hydrothermal deposits. Results show that hydrothermal venting at the active High Rise, Sasquatch, and Main Endeavour fields began at least 850, 1450, and 2300 years ago, respectively. Barite ages of other inactive deposits on the axial valley floor are between ∼1200 and ∼2200 years old, indicating past widespread hydrothermal venting outside of the currently active vent fields. Samples from the half-graben on the eastern slope of the axial valley range in age from ∼1700 to ∼2925 years, and a single sample from outside the axial valley, near the westernmost valley fault scarp is ∼5850 ± 205 years old. The spatial relationship between hydrothermal venting and normal faulting suggests a temporal relationship, with progressive younging of sulfide deposits from the edges of the axial valley toward the center of the rift. These relationships are consistent with the inward migration of normal faulting toward the center of the valley over time and a minimum age of onset of hydrothermal activity in this region of 5850 years

Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages

Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration.We thank S. Lecher, S. Li and J. Zallet for technical support. Calculations were performed at the sciCORE scientific computing core facility at the University of Basel. This work was supported by the Swiss National Science Foundation (grants 310030_166687 (S.G.) and 320030_153442 (M.E.) and Swiss HIV Cohort Study grant 740 to L.F.), the European Research Council (309540-EVODRTB to S.G.), TB-PAN-NET (FP7-223681 to S.N.), PathoNgenTrace projects (FP7-278864-2 to S.N.), SystemsX.ch (S.G.), the German Center for Infection Research (DZIF; S.N.), the Novartis Foundation (S.G.), the Natural Science Foundation of China (91631301 to Q.G.), and the National Institute of Allergy and Infectious Diseases (5U01-AI069924-05) of the US National Institutes of Health (M.E.)

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts