HIV Surveillance in a Large, Community-Based Study: Results from the Pilot Study of Project Accept (HIV Prevention Trials Network 043)

<p>Abstract</p> <p>Background</p> <p>Project Accept is a community randomized, controlled trial to evaluate the efficacy of community mobilization, mobile testing, same-day results, and post-test support for the prevention of HIV infection in Thailand, Tanzania, Zimbabwe, and South Africa. We evaluated the accuracy of in-country HIV rapid testing and determined HIV prevalence in the Project Accept pilot study.</p> <p>Methods</p> <p>Two HIV rapid tests were performed in parallel in local laboratories. If the first two rapid tests were discordant (one reactive, one non-reactive), a third HIV rapid test or enzyme immunoassay was performed. Samples were designated HIV NEG if the first two tests were non-reactive, HIV DISC if the first two tests were discordant, and HIV POS if the first two tests were reactive. Samples were re-analyzed in the United States using a panel of laboratory tests.</p> <p>Results</p> <p>HIV infection status was correctly determined based on-in country testing for 2,236 (99.5%) of 2,247 participants [7 (0.37%) of 1,907 HIV NEG samples were HIV-positive; 2 (0.63%) of 317 HIV POS samples were HIV-negative; 2 (8.3%) of 24 HIV DISC samples were incorrectly identified as HIV-positive based on the in-country tie-breaker test]. HIV prevalence was: Thailand: 0.6%, Tanzania: 5.0%, Zimbabwe 14.7%, Soweto South Africa: 19.4%, Vulindlela, South Africa: 24.4%, (overall prevalence: 14.4%).</p> <p>Conclusions</p> <p>In-country testing based on two HIV rapid tests correctly identified the HIV infection status for 99.5% of study participants; most participants with discordant HIV rapid tests were not infected. HIV prevalence varied considerably across the study sites (range: 0.6% to 24.4%).</p> <p>Trial Registration</p> <p>ClinicalTrials.gov registry number <a href="http://www.clinicaltrials.gov/ct2/show/NCT00203749">NCT00203749</a>.</p

Galaxies Going Bananas: Inferring the 3D Geometry of High-Redshift Galaxies with JWST-CEERS

The 3D geometry of high-redshift galaxies remains poorly understood. We build a differentiable Bayesian model and use Hamiltonian Monte Carlo to efficiently and robustly infer the 3D shapes of star-forming galaxies in JWST-CEERS observations with $\log M_*/M_{\odot}=9.0-10.5$ at $z=0.5-8.0$. We reproduce previous results from HST-CANDELS in a fraction of the computing time and constrain the mean ellipticity, triaxiality, size and covariances with samples as small as $\sim50$ galaxies. We find high 3D ellipticities for all mass-redshift bins suggesting oblate (disky) or prolate (elongated) geometries. We break that degeneracy by constraining the mean triaxiality to be $\sim1$ for $\log M_*/M_{\odot}=9.0-9.5$ dwarfs at $z>1$ (favoring the prolate scenario), with significantly lower triaxialities for higher masses and lower redshifts indicating the emergence of disks. The prolate population traces out a ``banana'' in the projected $b/a-\log a$ diagram with an excess of low $b/a$, large $\log a$ galaxies. The dwarf prolate fraction rises from $\sim25\%$ at $z=0.5-1.0$ to $\sim50-80\%$ at $z=3-8$. If these are disks, they cannot be axisymmetric but instead must be unusually oval (triaxial) unlike local circular disks. We simultaneously constrain the 3D size-mass relation and its dependence on 3D geometry. High-probability prolate and oblate candidates show remarkably similar S\'ersic indices ($n\sim1$), non-parametric morphological properties and specific star formation rates. Both tend to be visually classified as disks or irregular but edge-on oblate candidates show more dust attenuation. We discuss selection effects, follow-up prospects and theoretical implications.Comment: Submitted to ApJ, main body is 35 pages of which ~half are full-page figures, comments welcom

VERITAS discovery of very high energy gamma-ray emission from S3 1227+25 and multiwavelength observations

We report the detection of very high energy gamma-ray emission from the blazar S3 1227+25 (VER J1230+253) with the Very Energetic Radiation Imaging Telescope Array System (VERITAS). VERITAS observations of the source were triggered by the detection of a hard-spectrum GeV flare on May 15, 2015 with the Fermi-Large Area Telescope (LAT). A combined five-hour VERITAS exposure on May 16th and May 18th resulted in a strong 13$\sigma$ detection with a differential photon spectral index, $\Gamma$ = 3.8 $\pm$ 0.4, and a flux level at 9% of the Crab Nebula above 120 GeV. This also triggered target of opportunity observations with Swift, optical photometry, polarimetry and radio measurements, also presented in this work, in addition to the VERITAS and Fermi-LAT data. A temporal analysis of the gamma-ray flux during this period finds evidence of a shortest variability timescale of $\tau_{obs}$ = 6.2 $\pm$ 0.9 hours, indicating emission from compact regions within the jet, and the combined gamma-ray spectrum shows no strong evidence of a spectral cut-off. An investigation into correlations between the multiwavelength observations found evidence of optical and gamma-ray correlations, suggesting a single-zone model of emission. Finally, the multiwavelength spectral energy distribution is well described by a simple one-zone leptonic synchrotron self-Compton radiation model.Comment: 18 pages, 6 figures. Accepted for publication in the Astrophysical Journal (ApJ

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

A Flexible System for Text Analysis with Semantic Network

The explosive growth of digital and digitized text creates opportunities for scholars and students to conduct new analyses and develop unique insights about our written culture and heritage. To effectively use large collections of textual data, scholars and students need flexible, easy to us

Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample.

BACKGROUND: We sought to determine whether clinical response or tolerance to the Selective Serotonin Reuptake Inhibitor (SSRI) citalopram is associated with genetic polymorphisms in potentially relevant pharmacokinetic enzymes. METHODOLOGY: We used a two-stage case-control study design in which we split the sample of 1,953 subjects from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial into a discovery (n = 831) and validation set (n = 1,046). Fifteen polymorphisms from five (CYP2D6, ABCB1, CYP2C19, CYP3A4, and CYP3A5) pharmacokinetic genes were genotyped. We examined the associations between these polymorphisms and citalopram response and tolerance. Significant associations were validated in the second stage for those polymorphism found to be statistically significant in the first stage. CONCLUSIONS: No genetic polymorphism in the pharmacokinetic genes examined was significantly associated with our response or tolerance phenotypes in both stages. For managing pharmacological treatment with citalopram, routine screening of the common pharmacokinetic DNA variants that we examined appears to be of limited clinical utility

Transparency of CHI Research Artifacts: Results of a Self-Reported Survey

Several fields of science are experiencing a ""replication crisis"" that has negatively impacted their credibility. Assessing the validity of a contribution via replicability of its experimental evidence and reproducibility of its analyses requires access to relevant study materials, data, and code. Failing to share them limits the ability to scrutinize or build-upon the research, ultimately hindering scientific progress.Understanding how the diverse research artifacts in HCI impact sharing can help produce informed recommendations for individual researchers and policy-makers in HCI. Therefore, we surveyed authors of CHI 2018-2019 papers, asking if they share their papers' research materials and data, how they share them, and why they do not. The results (34% response rate) show that sharing is uncommon, partly due to misunderstandings about the purpose of sharing and reliable hosting. We conclude with recommendations for fostering open research practices.This paper and all data and materials are freely available at https://osf.io/3bu6t

Foundations for Self-Determination in Early Childhood: An Inclusive Model for Children with Disabilities

This article introduces the Early Childhood Foundations Model for Self-Determination and provides a rationale for the need to consider the foundations of self-determination behavior that begin early in life. This model is based on the premise that young children with disabilities benefit from a collaborative partnership between important adults in the lives of children to provide a supportive, stimulating, and coordinated environment between inclusive classrooms and home settings. Within partnership, the Foundations Model establishes the proposition that the basic foundational skills for developing self-determination in later life require young children with disabilities to gain skills in (a) choice-making and problem solving, (b) self-regulation, and (c) engagement. In this position paper, the authors review literature related to these three foundational constructs and present a rationale for use of the Foundations Model as a guide to developing systematic interventions to start young students with disabilities on the road to building a foundation for self-determination