Deep HST Imaging of Sextans A I. The Spatially Resolved Recent Star Formation History

We have measured stellar photometry from deep Cycle 7 Hubble Space Telescope/WFPC2 imaging of the dwarf irregular galaxy Sextans A. The imaging was taken in three filters: F555W ($V$; 8 orbits), F814W ($I$; 16 orbits), and F656N (H$\alpha$; 1 orbit). Combining these data with Cycle 5 WFPC2 observations provides nearly complete coverage of the optically visible portion of the galaxy. The Cycle 7 observations are nearly 2 magnitudes more sensitive than the Cycle 5 observations, which provides unambiguous separation of the faint blue helium burning stars (BHeB stars) from contaminant populations. The depth of the photometry allows us to compare recent star formation histories recovered from both the main sequence (MS) stars and the BHeB stars for the last 300 Myr. The excellent agreement between these independent star formation rate (SFR) calculations is a resounding confirmation for the legitimacy of using the BHeB stars to calculate the recent SFR. Using the BHeB stars we have calculated the global star formation history over the past 700 Myr. The history calculated from the Cycle 7 data is remarkably identical to that calculated from the Cycle 5 data, implying that both halves of the galaxy formed stars in concert. We have also calculated the spatially resolved star formation history, combining the fields from the Cycle 5 and Cycle 7 data. Our interpretation of the pattern of star formation is that it is an orderly stochastic process.Comment: 27 pages, 14 figures, 2 mpeg movies, accepted in the Astronomical Journa

Asenapine versus placebo for schizophrenia

Background Background Schizophrenia is a highly prevalent and chronic disorder that comprises a wide range of symptomatology. Asenapine is a recently developed atypical antipsychotic that is approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia. Objectives Objectives To determine the clinical effects of asenapine for adults with schizophrenia or other schizophrenia-like disorders by comparing it with placebo. Search methods Search methods We searched the Cochrane Schizophrenia Group's Trials Register (July 04, 2014) which is based on regular searches of MEDLINE, EMBASE, CINAHL, BIOSIS, AMED, PubMed, PsycINFO, and registries of clinical trials. There are no language, date, document type, or publication status limitation for inclusion of records into the register. We inspected references of all included studies for further relevant studies. Selection criteria Selection criteria Our review includes randomised controlled trials (RCTs) comparing asenapine with placebo in adults (however defined) with schizophrenia or related disorders, including schizophreniform disorder, schizoaffective disorder and delusional disorder, again, by any means of diagnosis. Data collection and analysis Data collection and analysis We inspected citations from the searches and identified relevant abstracts, and extracted data from all included studies. For binary data we calculated risk ratio (RR) with 95% confidence intervals (CI), and for continuous data we calculated mean differences (MD). We used the GRADE approach to produce a 'Summary of findings' table which included our outcomes of interest, where possible. We used a fixed-effect model for our analyses. Main results Main results We obtained and scrutinised 41 potentially relevant records, and from these we could include only six trials (n = 1835). Five of the six trials had high risk of attrition bias and all trials were sponsored by pharmaceutical companies. Results showed a clinically important change in global state (1 RCT, n = 336, RR 0.81, 95% CI 0.68 to 0.97, low-quality evidence) and mental state (1 RCT, n = 336, RR 0.72, 95% CI 0.59 to 0.86, very low-quality evidence) at short-term amongst people receiving asenapine. People receiving asenapine demonstrated significant reductions in negative symptoms (1 RCT, n = 336, MD -1.10, 95% CI -2.29 to 0.09, very low-quality evidence) at short-term. Individuals receiving asenapine demonstrated significantly fewer incidents of serious adverse effects (1 RCT, n = 386, RR 0.29, 95% CI 0.14 to 0.63, very low-quality evidence) at medium-term. There was no clear difference in people discontinuing the study for any reason between asenapine and placebo at short-term (5 RCTs, n = 1046, RR 0.91, 95% CI 0.80 to 1.04, very low-quality evidence). No trial reported data for extrapyramidal symptoms or costs. Authors' conclusions Authors' conclusions There is some, albeit preliminary, evidence that asenapine provides an improvement in positive, negative, and depressive symptoms, whilst minimising the risk of adverse effects. However due to the low-quality and limited quantity of evidence, it remains difficult to recommend the use of asenapine for people with schizophrenia. We identify a need for large-scale, longer-term, better-designed and conducted randomised controlled trials investigating the clinical effects and safety of asenapine

The Star Formation History and Extended Structure of the Hercules Milky Way Satellite

We present imaging of the recently discovered Hercules Milky Way satellite and its surrounding regions to study its structure, star formation history and to thoroughly search for signs of disruption. We robustly determine the distance, luminosity, size and morphology of Hercules utilizing a bootstrap approach to characterize our uncertainties. We derive a distance to Hercules of $133 \pm 6$ kpc via a comparison to empirical and theoretical isochrones. As previous studies have found, Hercules is very elongated, with $\epsilon=0.67\pm0.03$ and a half light radius of $r_{h} \simeq 230$ pc. Using the color magnitude fitting package StarFISH, we determine that Hercules is old ($>12$ Gyr) and metal poor ($[Fe/H]\sim-2.0$), with a spread in metallicity, in agreement with previous spectroscopic work. We infer a total absolute magnitude of $M_V=-5.3\pm0.4$. Our innovative search for external Hercules structure both in the plane of the sky and along the line of sight yields some evidence that Hercules is embedded in a larger stream of stars. A clear stellar extension is seen to the Northwest with several additional candidate stellar overdensities along the position angle of Hercules out to $\sim$35' ($\sim$1.3 kpc). While the association of any of the individual stellar overdensities with Hercules is difficult to determine, we do show that the summed color magnitude diagram of all three is consistent with Hercules' stellar population. Finally, we estimate that any change in the distance to Hercules across its face is at most $\sim$6 kpc; and the data are consistent with Hercules being at the same distance throughout.Comment: 50 pages, 15 figures, submitted to the Astrophysical Journa

Effect of carbapenem resistance on outcomes of bloodstream infection caused by Enterobacteriaceae in low-income and middle-income countries (PANORAMA): a multinational prospective cohort study

Background Low-income and middle-income countries (LMICs) are under-represented in reports on the burden of antimicrobial resistance. We aimed to quantify the clinical effect of carbapenem resistance on mortality and length of hospital stay among inpatients in LMICs with a bloodstream infection due to Enterobacteriaceae. Methods The PANORAMA study was a multinational prospective cohort study at tertiary hospitals in Bangladesh, Colombia, Egypt, Ghana, India, Lebanon, Nepal, Nigeria, Pakistan, and Vietnam, recruiting consecutively diagnosed patients with carbapenem-susceptible Enterobacteriaceae (CSE) and carbapenem-resistant Entero-bacteriaceae (CRE) bloodstream infections. We excluded patients who had previously been enrolled in the study and those not treated with curative intent at the time of bloodstream infection onset. There were no age restrictions. Central laboratories in India and the UK did confirmatory testing and molecular characterisation, including strain typing. We applied proportional subdistribution hazard models with inverse probability weighting to estimate the effect of carbapenem resistance on probability of discharge alive and in-hospital death, and multistate modelling for excess length of stay in hospital. All patients were included in the analysis. Findings Between Aug 1, 2014, and June 30, 2015, we recruited 297 patients from 16 sites in ten countries: 174 with CSE bloodstream infection and 123 with CRE bloodstream infection. Median age was 46 years (IQR 15–61). Crude mortality was 20% (35 of 174 patients) for patients with CSE bloodstream infection and 35% (43 of 123 patients) for patients with CRE bloodstream infection. Carbapenem resistance was associated with an increased length of hospital stay (3·7 days, 95% CI 0·3–6·9), increased probability of in-hospital mortality (adjusted subdistribution hazard ratio 1·75, 95% CI 1·04–2·94), and decreased probability of discharge alive (0·61, 0·45–0·83). Multilocus sequence typing showed various clades, with marginal overlap between strains in the CRE and CSE clades. Interpretation Carbapenem resistance is associated with increased length of hospital stay and mortality in patients with bloodstream infections in LMICs. These data will inform global estimates of the burden of antimicrobial resistance and reinforce the need for better strategies to prevent, diagnose, and treat CRE infections in LMICs

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The Distance to IC 10 from Near-Infrared Observations of Cepheids

We have measured the distance to the Local Group dwarf irregular galaxy IC 10 from near-infrared JHK observations of Cepheids. The reddening-corrected distance modulus is 24:57 \Sigma 0:21 mag or 0:82 \Sigma 0:08 Mpc. This distance lies at the short end of the range of previous estimates, and is significantly more accurate than all prior determinations. At this distance, IC 10 is comparable in total mass to the Small Magellanic Cloud, but has much more vigorous star formation. Subject headings: Galaxies: individual (IC 10) -- Galaxies: distances -- Local Group -- Stars: Cepheids -- 3 -- 1. Introduction The nearby galaxy IC 10 is important for studies of the interstellar medium and star formation in dwarf irregular galaxies, because its unusually strong and blue-shifted CO lines (Becker 1990) make it relatively easy to trace the distribution of both molecular and atomic hydrogen in this galaxy. However, studies of this galaxy are hindered by the fact that its distance is very poorly d..