Changes in Bone Mineral Density During and After Lactation in Ugandan Women With HIV on Tenofovir-Based Antiretroviral Therapy.

Antiretroviral therapy (ART) in people living with human immunodeficiency virus (HIV) is associated with bone loss, but data are limited in lactation, when physiological bone mineral mobilization is occurring. This research charted changes in areal bone mineral density (aBMD) during and after lactation in Ugandan women with HIV (WWH) initiated onto ART in pregnancy, compared to women without HIV (REF). One-hundred WWH on tenofovir-based ART and 100 REF were enrolled in pregnancy. Lumbar spine (LS), total hip (TH), and whole-body-less-head (WBLH) aBMD were measured by dual-energy X-ray absorptiometry (DXA) at 2, 14, and 26 weeks of lactation, and at 3 months postlactation. The primary outcome was the difference between groups in mean percent change in LS aBMD between 2 and 14 weeks. Statistical analysis was performed in hierarchical repeated measures ANOVA models that corrected for multiple testing. Median age was 23.4 (IQR, 21.0 to 26.8) years. WWH had lower body weight. aBMD decreased in both groups during lactation, but WWH had greater decreases at TH (2-to-26 weeks: WWH [n = 63] -5.9% [95% CI, -6.4 to -5.4] versus REF [n = 64] -4.3% [95% CI, -4.8 to -3.8]; group*time point interaction p = .008). Decreases in LS aBMD were similar in WWH and REF (2-to-26 weeks: -2.0% [95% CI, -2.5 to -1.5]), although there was a tendency toward a smaller decrease in WWH between 2 and 14 weeks (WWH [n = 77] -1.8% [95% CI, -2.2 to -1.4] versus REF [n = 69] -2.9% [95% CI, -3.3 to -2.5]; group*time point interaction p = .08). Postlactation, LS aBMD was higher relative to week 2 in both groups. TH and WBLH aBMD did not return to week 2 values in WWH but did in REF (TH postlactation versus week 2: WWH [n = 61] -3.1% [95% CI, -3.6 to -2.6]; REF [n = 29] +0.1% [95% CI, -0.9 to +1.1]). These data show accentuated bone loss during lactation and only partial skeletal recovery by 3 months postlactation in Ugandan WWH on tenofovir-based ART. Studies are ongoing to understand longer-term consequences for bone health. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research

Triple-Antiretroviral Prophylaxis to Prevent Mother-To-Child HIV Transmission through Breastfeeding—The Kisumu Breastfeeding Study, Kenya: A Clinical Trial

Timothy Thomas and colleagues report the results of the Kisumu breastfeeding study (Kenya), a single-arm trial that assessed the feasibility and safety of a triple-antiretroviral regimen to suppress maternal HIV load in late pregnancy

The multi-country PROMOTE HIV antiretroviral treatment observational cohort in Sub-Saharan Africa: objectives, design, and baseline findings.

CAPRISA, 2018.Abstract available in pdf

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX collaboration

Extensive experimental data from high-energy nucleus-nucleus collisions were recorded using the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The comprehensive set of measurements from the first three years of RHIC operation includes charged particle multiplicities, transverse energy, yield ratios and spectra of identified hadrons in a wide range of transverse momenta (p_T), elliptic flow, two-particle correlations, non-statistical fluctuations, and suppression of particle production at high p_T. The results are examined with an emphasis on implications for the formation of a new state of dense matter. We find that the state of matter created at RHIC cannot be described in terms of ordinary color neutral hadrons.Comment: 510 authors, 127 pages text, 56 figures, 1 tables, LaTeX. Submitted to Nuclear Physics A as a regular article; v3 has minor changes in response to referee comments. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

HIV-1 Drug Resistance Emergence among Breastfeeding Infants Born to HIV-Infected Mothers during a Single-Arm Trial of Triple-Antiretroviral Prophylaxis for Prevention of Mother-To-Child Transmission: A Secondary Analysis

Analysis of a substudy of the Kisumu breastfeeding trial by Clement Zeh and colleagues reveals the emergence of HIV drug resistance in HIV-positive infants born to HIV-infected mothers treated with antiretroviral drugs

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Efficacy and safety of an extended nevirapine regimen in infant children of breastfeeding mothers with HIV-1 infection for prevention of postnatal HIV-1 transmission (HPTN 046): a randomised, double-blind, placebo-controlled trial.

Background. Nevirapine given once-daily for the first 6, 14, or 28 weeks of life to infants exposed to HIV-1 via breastfeeding reduces transmission through this route compared with single-dose nevirapine at birth or neonatally. We aimed to assess incremental safety and efficacy of extension of such prophylaxis to 6 months. Methods In our phase 3, randomised, double-blind, placebo-controlled HPTN 046 trial, we assessed the incremental benefit of extension of once-daily infant nevirapine from age 6 weeks to 6 months. We enrolled breastfeeding infants born to mothers with HIV-1 in four African countries within 7 days of birth. Following receipt of nevirapine from birth to 6 weeks, infants without HIV infection were randomly allocated (by use of a computer-generated permuted block algorithm with random block sizes and stratified by site and maternal antiretroviral treatment status) to receive extended nevirapine prophylaxis or placebo until 6 months or until breastfeeding cessation, whichever came first. The primary efficacy endpoint was HIV-1 infection in infants at 6 months and safety endpoints were adverse reactions in both groups. We used Kaplan-Meier analyses to compare differences in the primary outcome between groups. This study is registered with ClinicalTrials.gov, number NCT00074412. Findings. Between June 19, 2008, and March 12, 2010, we randomly allocated 1527 infants (762 nevirapine and 765 placebo); five of whom had HIV-1 infection at randomisation and were excluded from the primary analyses. In Kaplan-Meier analysis, 1·1% (95% CI 0·3–1·8) of infants who received extended nevirapine developed HIV-1 between 6 weeks and 6 months compared with 2·4% (1·3–3·6) of controls (difference 1·3%, 95% CI 0–2·6), equating to a 54% reduction in transmission (p=0·049). However, mortality (1·2% for nevirapine vs 1·1% for placebo; p=0·81) and combined HIV infection and mortality rates (2·3% vs 3·2%; p=0·27) did not differ between groups at 6 months. 125 (16%) of 758 infants given extended nevirapine and 116 (15%) of 761 controls had serious adverse events, but frequency of adverse events, serious adverse events, and deaths did not differ significantly between treatment groups. Interpretation. Nevirapine prophylaxis can safely be used to provide protection from mother-to-child transmission of HIV-1 via breastfeeding for infants up to 6 months of age