Does a Drop-in and Case Management Model Improve Outcomes for Young Adults Experiencing Homelessness: A Case Study of YouthLink

This study used two approaches to examine YouthLink as an example of a drop-in and case management model for working with youth experiencing homelessness. These approaches investigated the same group of 1,229 unaccompanied youth, ages 16 to 24 and overwhelmingly Black, who voluntarily visited or received services from YouthLink in 2011. Both approaches looked at the same metrics of success over the same time period, 2011 to 2016. One approach—Study Aim 1—examined the drop-in and case management model overall, asking whether YouthLink's service model resulted in better outcomes. It compared a YouthLink cohort with a group of highly similar youth who did not visit YouthLink but may have received similar services elsewhere. A second approach—Study Aim 2—investigated within the YouthLink cohort the ways in which YouthLink's drop-in and case-management approach worked toward achieving the desired outcomes

Does a Drop-in and Case Management Model Improve Outcomes for Young Adults Experiencing Homelessness: A Case Study of YouthLink

This study used two approaches to examine YouthLink as an example of a drop-in and case management model for working with youth experiencing homelessness. These approaches investigated the same group of 1,229 unaccompanied youth, ages 16 to 24 and overwhelmingly Black, who voluntarily visited or received services from YouthLink in 2011. Both approaches looked at the same metrics of success over the same time period, 2011 to 2016. One approach—Study Aim 1—examined the drop-in and case management model overall, asking whether YouthLink’s service model resulted in better outcomes. It compared a YouthLink cohort with a group of highly similar youth who did not visit YouthLink but may have received similar services elsewhere. A second approach—Study Aim 2—investigated within the YouthLink cohort the ways in which YouthLink’s drop-in and case-management approach worked toward achieving the desired outcomes. The results and their implications were discussed.The Kresge Foundatio

A Total of 1,007 Percutaneous Coronary Interventions Without Onsite Cardiac Surgery Acute and Long-Term Outcomes

ObjectivesWe sought to compare clinical outcomes of elective percutaneous coronary intervention (PCI) and primary PCI for ST-segment elevation myocardial infarction (STEMI) at a community hospital without onsite cardiac surgery to those at a tertiary center with onsite cardiac surgery.BackgroundDisagreement exists about whether hospitals with cardiac catheterization laboratories, but without onsite cardiac surgery, should develop PCI programs. Primary PCI for STEMI at hospitals without onsite cardiac surgery have achieved satisfactory outcomes; however, elective PCI outcomes are not well defined.MethodsA total of 1,007 elective PCI and primary PCI procedures performed from March 1999 to August 2005 at the Immanuel St. Joseph’s Hospital–Mayo Health System (ISJ) in Mankato, Minnesota, were matched one-to-one with those performed at St. Mary’s Hospital (SMH) in Rochester, Minnesota. Strict protocols were followed for case selection and PCI program requirements. Clinical outcomes (in-hospital procedural success, death, any myocardial infarction, Q-wave myocardial infarction, and emergency coronary artery bypass surgery) and follow-up survival were compared between groups.ResultsAmong 722 elective PCIs, procedural success was 97% at ISJ compared with 95% at SMH (p = 0.046). Among 285 primary PCIs for STEMI, procedural success was 93% at ISJ and 96% at SMH (p = 0.085). No patients at ISJ undergoing PCI required emergent transfer for cardiac surgery. Survival at two years’ follow-up by treatment location was similar for patients with elective PCI and primary PCI.ConclusionsSimilar clinical outcomes for elective PCI and primary PCI were achieved at a community hospital without onsite cardiac surgery compared with those at a tertiary center with onsite cardiac surgery using a prospective, rigorous protocol for case selection and PCI program requirements

Uncovering a Massive z~7.65 Galaxy Hosting a Heavily Obscured Radio-Loud QSO Candidate in COSMOS-Web

In this letter, we report the discovery of the highest redshift, heavily obscured, radio-loud QSO candidate selected using JWST NIRCam/MIRI, mid-IR, sub-mm, and radio imaging in the COSMOS-Web field. Using multi-frequency radio observations and mid-IR photometry, we identify a powerful, radio-loud (RL), growing supermassive black hole (SMBH) with significant spectral steepening of the radio SED ($f_{1.32 \mathrm{GHz}} \sim 2$ mJy, $q_{24\mu m} = -1.1$, $\alpha_{1.32-3\mathrm{GHz}}=-1.2$, $\Delta \alpha = -0.4$). In conjunction with ALMA, deep ground-based observations, ancillary space-based data, and the unprecedented resolution and sensitivity of JWST, we find no evidence of QSO contribution to the UV/optical/NIR data and thus infer heavy amounts of obscuration (N$_{\mathrm{H}} > 10^{23}$ cm$^{-2}$). Using the wealth of deep UV to sub-mm photometric data, we report a singular solution photo-z of $z_\mathrm{phot}$ = 7.65$^{+0.4}_{-0.3}$ and estimate an extremely massive host-galaxy ($\log M_{\star} = 11.92 \pm 0.06\,\mathrm{M}_{\odot}$). This source represents the furthest known obscured RL QSO candidate, and its level of obscuration aligns with the most representative but observationally scarce population of QSOs at these epochs.Comment: Submitted to ApJL, Comments welcom

Mechanisms of Risk and Resilience in Military Families: Theoretical and Empirical Basis of a Family-Focused Resilience Enhancement Program

Recent studies have confirmed that repeated wartime deployment of a parent exacts a toll on military children and families and that the quality and functionality of familial relations is linked to force preservation and readiness. As a result, family-centered care has increasingly become a priority across the military health system. FOCUS (Families OverComing Under Stress), a family-centered, resilience-enhancing program developed by a team at UCLA and Harvard Schools of Medicine, is a primary initiative in this movement. In a large-scale implementation project initiated by the Bureau of Navy Medicine, FOCUS has been delivered to thousands of Navy, Marine, Navy Special Warfare, Army, and Air Force families since 2008. This article describes the theoretical and empirical foundation and rationale for FOCUS, which is rooted in a broad conception of family resilience. We review the literature on family resilience, noting that an important next step in building a clinically useful theory of family resilience is to move beyond developing broad “shopping lists” of risk indicators by proposing specific mechanisms of risk and resilience. Based on the literature, we propose five primary risk mechanisms for military families and common negative “chain reaction” pathways through which they undermine the resilience of families contending with wartime deployments and parental injury. In addition, we propose specific mechanisms that mobilize and enhance resilience in military families and that comprise central features of the FOCUS Program. We describe these resilience-enhancing mechanisms in detail, followed by a discussion of the ways in which evaluation data from the program’s first 2 years of operation supports the proposed model and the specified mechanisms of action

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P = 9.2 x 10(-20)), ER-negative BC (P = 1.1 x 10(-13)), BRCA1-associated BC (P = 7.7 x 10(-16)) and triple negative BC (P-diff = 2 x 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P = 2 x 10(-3)) and ABHD8 (PPeer reviewe

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