Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and ≥50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52–96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF

X-Ray Scaling Relations of Early-type Galaxies

X-ray luminosity, temperature, gas mass, total mass, and their scaling relations are derived for 94 early-type galaxies (ETGs) using archival Chandra X-ray Observatory observations. Consistent with earlier studies, the scaling relations, L X ∝ T 4.5±0.2, M ∝ T 2.4±0.2, and L X ∝ M 2.8±0.3, are significantly steeper than expected from self-similarity. This steepening indicates that their atmospheres are heated above the level expected from gravitational infall alone. Energetic feedback from nuclear black holes and supernova explosions are likely heating agents. The tight L X –T correlation for low-luminosity systems (i.e., below 1040 erg s−1) are at variance with hydrodynamical simulations, which generally predict higher temperatures for low-luminosity galaxies. We also investigate the relationship between total mass and pressure, Y X = M g × T, finding $M\propto {Y}_{X}^{0.45\pm 0.04}$. We explore the gas mass to total mass fraction in ETGs and find a range of 0.1%–1.0%. We find no correlation between the gas-to-total mass fraction with temperature or total mass. Higher stellar velocity dispersions and higher metallicities are found in hotter, brighter, and more massive atmospheres. X-ray core radii derived from β-model fitting are used to characterize the degree of core and cuspiness of hot atmospheres

The Origin of Molecular Clouds in Central Galaxies

We present an analysis of 55 central galaxies in clusters and groups with molecular gas masses and star formation rates lying between ${10}^{8}\,\mathrm{and}\,{10}^{11}\ {M}_{\odot }$ and 0.5 and 270 ${M}_{\odot }\ {\mathrm{yr}}^{-1}$, respectively. Molecular gas mass is correlated with star formation rate, Hα line luminosity, and central atmospheric gas density. Molecular gas is detected only when the central cooling time or entropy index of the hot atmosphere falls below ~1 Gyr or ~35 keV cm2, respectively, at a (resolved) radius of 10 kpc. These correlations indicate that the molecular gas condensed from hot atmospheres surrounding the central galaxies. We explore the origins of thermally unstable cooling by evaluating whether molecular gas becomes prevalent when the minimum of the cooling to free-fall time ratio (${t}_{\mathrm{cool}}/{t}_{\mathrm{ff}}$) falls below ~10. We find that (1) molecular gas-rich systems instead lie between $10\lt \min ({t}_{\mathrm{cool}}/{t}_{\mathrm{ff}})\lt 25$, where ${t}_{\mathrm{cool}}/{t}_{\mathrm{ff}}=25$ corresponds approximately to cooling time and entropy thresholds of 1 Gyr and $35\,\mathrm{keV}\,{\mathrm{cm}}^{2}$, respectively; (2) $\min ({t}_{\mathrm{cool}}/{t}_{\mathrm{ff}}$) is uncorrelated with molecular gas mass and jet power; and (3) the narrow range $10\lt \min ({t}_{\mathrm{cool}}/{t}_{\mathrm{ff}})\lt 25$ can be explained by an observational selection effect, although a real physical effect cannot be excluded. These results and the absence of isentropic cores in cluster atmospheres are in tension with models that assume thermal instability ensues from linear density perturbations in hot atmospheres when ${t}_{\mathrm{cool}}/{t}_{\mathrm{ff}}\lesssim 10$. Some of the molecular gas may instead have condensed from atmospheric gas lifted outward by buoyantly rising X-ray bubbles or by dynamically induced uplift (e.g., mergers, sloshing)

The Onset of Thermally Unstable Cooling from the Hot Atmospheres of Giant Galaxies in Clusters: Constraints on Feedback Models

We present accurate mass and thermodynamic profiles for 57 galaxy clusters observed with the Chandra X-ray Observatory. We investigate the effects of local gravitational acceleration in central cluster galaxies, and explore the role of the local free-fall time (${t}_{\mathrm{ff}}$) in thermally unstable cooling. We find that the radially averaged cooling time (${t}_{\mathrm{cool}}$) is as effective an indicator of cold gas, traced through its nebular emission, as the ratio ${t}_{\mathrm{cool}}$/${t}_{\mathrm{ff}}$. Therefore, ${t}_{\mathrm{cool}}$ primarily governs the onset of thermally unstable cooling in hot atmospheres. The location of the minimum ${t}_{\mathrm{cool}}$/${t}_{\mathrm{ff}}$, a thermodynamic parameter that many simulations suggest is key in driving thermal instability, is unresolved in most systems. Consequently, selection effects bias the value and reduce the observed range in measured ${t}_{\mathrm{cool}}$/${t}_{\mathrm{ff}}$ minima. The entropy profiles of cool-core clusters are characterized by broken power laws down to our resolution limit, with no indication of isentropic cores. We show, for the first time, that mass isothermality and the $K\propto {r}^{2/3}$ entropy profile slope imply a floor in ${t}_{\mathrm{cool}}$/${t}_{\mathrm{ff}}$ profiles within central galaxies. No significant departures of ${t}_{\mathrm{cool}}$/${t}_{\mathrm{ff}}$ below 10 are found. This is inconsistent with models that assume thermally unstable cooling ensues from linear perturbations at or near this threshold. We find that the inner cooling times of cluster atmospheres are resilient to active galactic nucleus (AGN)-driven change, suggesting gentle coupling between radio jets and atmospheric gas. Our analysis is consistent with models in which nonlinear perturbations, perhaps seeded by AGN-driven uplift of partially cooled material, lead to cold gas condensation

Human immunodeficiency virus continuum of care in 11 european union countries at the end of 2016 overall and by key population: Have we made progress?

Background. High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region. Methods. A CoC with the following 4 stages was constructed: number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit. Results. We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were: 86%, 93%, 93%, 74%; for people who inject drugs: 94%, 88%, 85%, 70%; and for heterosexuals: 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries. Conclusions. The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science. © The Author(s) 2019. Published by Oxford University Press