East African HIV care: depression and HIV outcomes.

Importance:Depression is a common co-morbidity for people living with HIV (PLWH) and is associated with elevated plasma HIV RNA levels. While depression correlates with deficits in antiretroviral (ARV) adherence, little data exist to inform the relationship between depression and HIV vial load more broadly. Objective:To examine the relationship between depression and viral load in the African Cohort Study (AFRICOS) independently of ARV adherence. Design:PLWH in Kenya, Uganda and Tanzania underwent screening for depression using the Center for Epidemiologic Studies Depression Scale (CESD) upon enrollment at AFRICOS HIV care sites. Setting:AFRICOS is an ongoing prospective longitudinal cohort study enrolling HIV-infected adults at HIV care centers including sites in Kenya, Tanzania and Uganda. These sites are administered by President's Emergency Plan For AIDS Relief programs. Participants:HIV+ individuals were eligible if they were at least 18 years old, receiving HIV care at the enrolling clinic and consented to data and specimen collection. Main outcome measure:CESD. Results:Among 2307 participants, 18-25% met the CESD threshold for depression. Depression was associated with decreased ARV adherence (OR 0.59, p =  0.01). Higher scores on three CESD items were significantly associated with 209-282% higher viral load, independently of ARV adherence among participants on ARVs ⩾6 months. Conclusions:PLWH had high prevalence of depression on the CESD. Diverse depression symptoms were independently associated with increases in viral load, underscoring the need for comprehensive treatment of depression

Synthetic Molecular Clouds from Supersonic MHD and Non-LTE Radiative Transfer Calculations

The dynamics of molecular clouds is characterized by supersonic random motions in the presence of a magnetic field. We study this situation using numerical solutions of the three-dimensional compressible magneto-hydrodynamic (MHD) equations in a regime of highly supersonic random motions. The non-LTE radiative transfer calculations are performed through the complex density and velocity fields obtained as solutions of the MHD equations, and more than 5x10^5 synthetic molecular spectra are obtained. We use a numerical flow without gravity or external forcing. The flow is super-Alfvenic and corresponds to model A of Padoan and Nordlund (1997). Synthetic data consist of sets of 90x90 synthetic spectra with 60 velocity channels, in five molecular transitions: J=1-0 and J=2-1 for 12CO and 13CO, and J=1-0 for CS. Though we do not consider the effects of stellar radiation, gravity, or mechanical energy input from discrete sources, our models do contain the basic physics of magneto-fluid dynamics and non-LTE radiation transfer and are therefore more realistic than previous calculations. As a result, these synthetic maps and spectra bear a remarkable resemblance to the corresponding observations of real clouds.Comment: 33 pages, 12 figures included, 5 jpeg figures not included (fig1a, fig1b, fig3, fig4 fig5), submitted to Ap

Overview of the Far Ultraviolet Spectroscopic Explorer Mission

The Far Ultraviolet Spectroscopic Explorer satellite observes light in the far-ultraviolet spectral region, 905 - 1187 A with high spectral resolution. The instrument consists of four coaligned prime-focus telescopes and Rowland spectrographs with microchannel plate detectors. Two of the telescope channels use Al:LiF coatings for optimum reflectivity from approximately 1000 to 1187 A and the other two use SiC coatings for optimized throughput between 905 and 1105 A. The gratings are holographically ruled to largely correct for astigmatism and to minimize scattered light. The microchannel plate detectors have KBr photocathodes and use photon counting to achieve good quantum efficiency with low background signal. The sensitivity is sufficient to examine reddened lines of sight within the Milky Way as well as active galactic nuclei and QSOs for absorption line studies of both Milky Way and extra-galactic gas clouds. This spectral region contains a number of key scientific diagnostics, including O VI, H I, D I and the strong electronic transitions of H2 and HD.Comment: To appear in FUSE special issue of the Astrophysical Journal Letters. 6 pages + 4 figure

Main Cause of the Poloidal Plasma Motion Inside a Magnetic Cloud Inferred from Multiple-Spacecraft Observations

Although the dynamical evolution of magnetic clouds (MCs) has been one of the foci of interplanetary physics for decades, only few studies focus on the internal properties of large-scale MCs. Recent work by Wang et al. (J. Geophys. Res.120, 1543, 2015) suggested the existence of the poloidal plasma motion in MCs. However, the main cause of this motion is not clear. In order to find it, we identify and reconstruct the MC observed by the Solar Terrestrial Relations Observatory (STEREO)-A, Wind, and STEREO-B spacecraft during 19 – 20 November 2007 with the aid of the velocity-modified cylindrical force-free flux-rope model. We analyze the plasma velocity in the plane perpendicular to the MC axis. It is found that there was evident poloidal motion at Wind and STEREO-B, but this was not clear at STEREO-A, which suggests a local cause rather than a global cause for the poloidal plasma motion inside the MC. The rotational directions of the solar wind and MC plasma at the two sides of the MC boundary are found to be consistent, and the values of the rotational speeds of the solar wind and MC plasma at the three spacecraft show a rough correlation. All of these results illustrate that the interaction with ambient solar wind through viscosity might be one of the local causes of the poloidal motion. Additionally, we propose another possible local cause: the existence of a pressure gradient in the MC. The significant difference in the total pressure at the three spacecraft suggests that this speculation is perhaps correct

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Harmonising and linking biomedical and clinical data across disparate data archives to enable integrative cross-biobank research

A wealth of biospecimen samples are stored in modern globally distributed biobanks. Biomedical researchers worldwide need to be able to combine the available resources to improve the power of large-scale studies. A prerequisite for this effort is to be able to search and access phenotypic, clinical and other information about samples that are currently stored at biobanks in an integrated manner. However, privacy issues together with heterogeneous information systems and the lack of agreed-upon vocabularies have made specimen searching across multiple biobanks extremely challenging. We describe three case studies where we have linked samples and sample descriptions in order to facilitate global searching of available samples for research. The use cases include the ENGAGE (European Network for Genetic and Genomic Epidemiology) consortium comprising at least 39 cohorts, the SUMMIT (surrogate markers for micro- and macro-vascular hard endpoints for innovative diabetes tools) consortium and a pilot for data integration between a Swedish clinical health registry and a biobank. We used the Sample avAILability (SAIL) method for data linking: first, created harmonised variables and then annotated and made searchable information on the number of specimens available in individual biobanks for various phenotypic categories. By operating on this categorised availability data we sidestep many obstacles related to privacy that arise when handling real values and show that harmonised and annotated records about data availability across disparate biomedical archives provide a key methodological advance in pre-analysis exchange of information between biobanks, that is, during the project planning phase

A meta-analysis of genome-wide association studies of epigenetic age acceleration

Funding: Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). Genotyping and DNA methylation profiling of the GS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” ((STRADL) Reference 104036/Z/14/Z)). Funding details for the cohorts included in the study by Lu et al. (2018) can be found in their publication. HCW is supported by a JMAS SIM fellowship from the Royal College of Physicians of Edinburgh and by an ESAT College Fellowship from the University of Edinburgh. AMM & HCW acknowledge the support of the Dr. Mortimer and Theresa Sackler Foundation. SH acknowledges support from grant 1U01AG060908-01. REM is supported by Alzheimer’s Research UK major project grant ARUK-PG2017B-10. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Data Availability: Summary statistics from the research reported in the manuscript will be made available immediately following publication on the Edinburgh Data Share portal with a permanent digital object identifier (DOI). According to the terms of consent for Generation Scotland participants, requests for access to the individual-level data must be reviewed by the GS Access Committee ([email protected]). Individual-level data are not immediately available, due to confidentiality considerations and our legal obligation to protect personal information. These data will, however, be made available upon request and after review by the GS access committee, once ethical and data governance concerns regarding personal data have been addressed by the receiving institution through a Data Transfer Agreement.Peer reviewedPublisher PD

Unexpected large eruptions from buoyant magma bodies within viscoelastic crust

Large volume effusive eruptions with relatively minor observed precursory signals are at odds with widely used models to interpret volcano deformation. Here we propose a new modelling framework that resolves this discrepancy by accounting for magma buoyancy, viscoelastic crustal properties, and sustained magma channels. At low magma accumulation rates, the stability of deep magma bodies is governed by the magma-host rock density contrast and the magma body thickness. During eruptions, inelastic processes including magma mush erosion and thermal effects, can form a sustained channel that supports magma flow, driven by the pressure difference between the magma body and surface vents. At failure onset, it may be difficult to forecast the final eruption volume; pressure in a magma body may drop well below the lithostatic load, create under-pressure and initiate a caldera collapse, despite only modest precursors