FEMALE RETENTION IN THE U.S. NAVY SUPPLY CORPS

Our research uses a quantitative and survey-based approach to study gender disparities in retention among Navy Supply Corps officers. Our work offers a clear assessment of retention and separation rates over the course of one officer life cycle, from the end of their first term of service to the last promotion milestone (15 years) before retirement eligibility to help provide a focal point for retention efforts. Using individual data from the Defense Manpower Data Center on Navy officers who commissioned from 2006 to 2021, we find that the female Supply Corps officers separate at higher rates than males and are less likely to be married or have children. These gender differences are statistically significant. Supply Corps female retention and separation patterns, across gender and children, align to Medical Corps. Married female Supply Corps officers' retention and separation patterns fall between SW and Medical Corps, but align more closely to SW. Our survey respondents noted family support, work-life balance, and career-enhancing opportunities as retention incentives. In comparison, they noted a lack of family support and work-life balance as primary separation drivers. Bonuses and lack of transparency around detailing were also mentioned as additional separation drivers.Lieutenant Commander, United States NavyLieutenant Commander, United States NavyApproved for public release. Distribution is unlimited

Female Retention in the U.S. Navy Supply Corps

Symposium Student Poster ShowThe purpose of our research is to identify gender disparities in retention amongst Navy Supply Corps Officers. Our goal is to provide a clear assessment of retention of gender diversity across time and rank in the Supply Corps community. We will also identify factors leading to female retention among Navy Supply Corps Officers compared to female officers Navy-wide.Approved for public release; distribution is unlimited

Localized precipitation and runoff on Mars

We use the Mars Regional Atmospheric Modeling System (MRAMS) to simulate lake storms on Mars, finding that intense localized precipitation will occur for lake size >=10^3 km^2. Mars has a low-density atmosphere, so deep convection can be triggered by small amounts of latent heat release. In our reference simulation, the buoyant plume lifts vapor above condensation level, forming a 20km-high optically-thick cloud. Ice grains grow to 200 microns radius and fall near (or in) the lake at mean rates up to 1.5 mm/hr water equivalent (maximum rates up to 6 mm/hr water equivalent). Because atmospheric temperatures outside the surface layer are always well below 273K, supersaturation and condensation begin at low altitudes above lakes on Mars. In contrast to Earth lake-effect storms, lake storms on Mars involve continuous precipitation, and their vertical velocities and plume heights exceed those of tropical thunderstorms on Earth. Convection does not reach above the planetary boundary layer for lakes O(10^2) mbar. Instead, vapor is advected downwind with little cloud formation. Precipitation occurs as snow, and the daytime radiative forcing at the land surface due to plume vapor and storm clouds is too small to melt snow directly (<+10 W/m^2). However, if orbital conditions are favorable, then the snow may be seasonally unstable to melting and produce runoff to form channels. We calculate the probability of melting by running thermal models over all possible orbital conditions and weighting their outcomes by probabilities given by Laskar et al., 2004. We determine that for an equatorial vapor source, sunlight 15% fainter than at present, and snowpack with albedo 0.28 (0.35), melting may occur with 4%(0.1%) probability. This rises to 56%(12%) if the ancient greenhouse effect was modestly (6K) greater than today.Comment: Submitted to JGR Planet

In situ detection of boron by ChemCam on Mars

We report the first in situ detection of boron on Mars. Boron has been detected in Gale crater at levels Curiosity rover ChemCam instrument in calcium-sulfate-filled fractures, which formed in a late-stage groundwater circulating mainly in phyllosilicate-rich bedrock interpreted as lacustrine in origin. We consider two main groundwater-driven hypotheses to explain the presence of boron in the veins: leaching of borates out of bedrock or the redistribution of borate by dissolution of borate-bearing evaporite deposits. Our results suggest that an evaporation mechanism is most likely, implying that Gale groundwaters were mildly alkaline. On Earth, boron may be a necessary component for the origin of life; on Mars, its presence suggests that subsurface groundwater conditions could have supported prebiotic chemical reactions if organics were also present and provides additional support for the past habitability of Gale crater

Selection for Forage and Avoidance of Risk by Woodland Caribou (Rangifer Tarandus Caribou) at Coarse andLocal Scales

The relationship between selection at coarse and fine spatiotemporal spatial scales is still poorly understood. Some authors claim that, to accommodate different needs at different scales, individuals should have contrasting selection patterns at different scales of selection, while others claim that coarse scale selection patterns should reflect fine scale selection decisions. Here we examine site selection by 110 woodland caribou equipped with GPS radio‐collars with respect to forage availability and predation risk across a broad gradient in availability of both variables in boreal forests of Northern Ontario. We tested whether caribou selection for forage and avoidance of risk was consistent between coarse (seasonal home range) and fine scales of selection. We found that local selection patterns predicted coarse scale selection patterns, indicating a close relationship between the drivers of selection at both spatial scales

OXA1L mutations cause mitochondrial encephalopathy and a combined oxidative phosphorylation defect

OXA1, the mitochondrial member of the YidC/Alb3/Oxa1 membrane protein insertase family, is required for the assembly of oxidative phosphorylation complexes IV and V in yeast. However, depletion of human OXA1 (OXA1L) was previously reported to impair assembly of complexes I and V only. We report a patient presenting with severe encephalopathy, hypotonia and developmental delay who died at 5 years showing complex IV deficiency in skeletal muscle. Whole exome sequencing identified biallelic OXA1L variants (c.500507dup, p.(Ser170Glnfs*18) and c.620G>T, p.(Cys207Phe)) that segregated with disease. Patient muscle and fibroblasts showed decreased OXA1L and subunits of complexes IV and V. Crucially, expression of wild-type human OXA1L in patient fibroblasts rescued the complex IV and V defects. Targeted depletion of OXA1L in human cells or Drosophila melanogaster caused defects in the assembly of complexes I, IV and V, consistent with patient data. Immunoprecipitation of OXA1L revealed the enrichment of mtDNA-encoded subunits of complexes I, IV and V. Our data verify the pathogenicity of these OXA1L variants and demonstrate that OXA1L is required for the assembly of multiple respiratory chain complexes.Peer reviewe

Intestinal Microbial Diversity during Early-Life Colonization Shapes Long-Term IgE Levels

Microbial exposure following birth profoundly impacts mammalian immune system development. Microbiota alterations are associated with increased incidence of allergic and autoimmune disorders with elevated serum IgE as a hallmark. The previously reported abnormally high serum IgE levels in germ-free mice suggests that immunoregulatory signals from microbiota are required to control basal IgE levels. We report that germ-free mice and those with low-diversity microbiota develop elevated serum IgE levels in early life. B cells in neonatal germ-free mice undergo isotype switching to IgE at mucosal sites in a CD4 T-cell- and IL-4-dependent manner. A critical level of microbial diversity following birth is required in order to inhibit IgE induction. Elevated IgE levels in germ-free mice lead to increased mast-cell-surface-bound IgE and exaggerated oral-induced systemic anaphylaxis. Thus, appropriate intestinal microbial stimuli during early life are critical for inducing an immunoregulatory network that protects from induction of IgE at mucosal sites

The ECOUTER methodology for stakeholder engagement in translational research.

BACKGROUND: Because no single person or group holds knowledge about all aspects of research, mechanisms are needed to support knowledge exchange and engagement. Expertise in the research setting necessarily includes scientific and methodological expertise, but also expertise gained through the experience of participating in research and/or being a recipient of research outcomes (as a patient or member of the public). Engagement is, by its nature, reciprocal and relational: the process of engaging research participants, patients, citizens and others (the many 'publics' of engagement) brings them closer to the research but also brings the research closer to them. When translating research into practice, engaging the public and other stakeholders is explicitly intended to make the outcomes of translation relevant to its constituency of users. METHODS: In practice, engagement faces numerous challenges and is often time-consuming, expensive and 'thorny' work. We explore the epistemic and ontological considerations and implications of four common critiques of engagement methodologies that contest: representativeness, communication and articulation, impacts and outcome, and democracy. The ECOUTER (Employing COnceptUal schema for policy and Translation Engagement in Research) methodology addresses problems of representation and epistemic foundationalism using a methodology that asks, "How could it be otherwise?" ECOUTER affords the possibility of engagement where spatial and temporal constraints are present, relying on saturation as a method of 'keeping open' the possible considerations that might emerge and including reflexive use of qualitative analytic methods. RESULTS: This paper describes the ECOUTER process, focusing on one worked example and detailing lessons learned from four other pilots. ECOUTER uses mind-mapping techniques to 'open up' engagement, iteratively and organically. ECOUTER aims to balance the breadth, accessibility and user-determination of the scope of engagement. An ECOUTER exercise comprises four stages: (1) engagement and knowledge exchange; (2) analysis of mindmap contributions; (3) development of a conceptual schema (i.e. a map of concepts and their relationship); and (4) feedback, refinement and development of recommendations. CONCLUSION: ECOUTER refuses fixed truths but also refuses a fixed nature. Its promise lies in its flexibility, adaptability and openness. ECOUTER will be formed and re-formed by the needs and creativity of those who use it

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

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