65 research outputs found

    A Snapshot of How Latino Heterosexual Men Promote Sexual Health Within Their Social Networks: Process Evaluation Findings from an Efficacious Community-Level Intervention

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    HoMBReS was a community-level social network intervention designed to increase sexual health among Latino heterosexual men who were members of a multi-county soccer league

    Predictors of Heavy Episodic Drinking and Weekly Drunkenness Among Immigrant Latinos in North Carolina

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    Few studies have examined correlates of heavy drinking among rural immigrant Latino men. This analysis identified correlates of typical week drunkenness and past 30-day heavy episodic drinking, within a sample of immigrant Latino men in rural North Carolina (n = 258). In the bivariate analyses, Mexican birth, entering the United States as an adult, and year-round employment were associated with increased odds of typical week drunkenness, and higher acculturation and affiliation with a religion with strict prohibitions against drinking alcohol were associated with lower odds of typical week drunkenness. Being older, Mexican birth, and entering the United States as an adult were associated with increased odds of heavy episodic drinking, and affiliation with a religion with strict prohibitions against drinking alcohol was associated with decreased odds of heavy episodic drinking. In multivariable modeling, only religious affiliation was associated with typical week drunkenness. Mexican birth, entering the United States as an adult and were associated with increased odds of heavy episodic drinking, and affiliation with a religion with strict prohibitions against drinking alcohol and completing high school was associated with lower odds of heavy episodic drinking. The health of minority men in the United States has been neglected, and immigrant Latino men comprise a particularly vulnerable population. This analysis provides initial data on some factors associated with heavy drinking within a population about whom little is known. Future studies should examine moderating or mediating factors between age, acculturation, religiosity, and heavy drinking that might be targets for behavioral interventions

    Depressive Symptoms Among Immigrant Latino Sexual Minorities

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    To estimate the prevalence and identify correlates of depressive symptoms among immigrant Latino sexual minorities

    Comprehensive molecular and clinical characterization of NUP98 fusions in pediatric acute myeloid leukemia

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    NUP98 fusions comprise a family of rare recurrent alterations in AML, associated with adverse outcomes. In order to define the underlying biology and clinical implications of this family of fusions, we performed comprehensive transcriptome, epigenome, and immunophenotypic profiling of 2,235 children and young adults with AML and identified 160 NUP98 rearrangements (7.2%), including 108 NUP98-NSD1 (4.8%), 32 NUP98-KDM5A (1.4%) and 20 NUP98-X cases (0.9%) with 13 different fusion partners. Fusion partners defined disease characteristics and biology; patients with NUP98-NSD1 or NUP98-KDM5A had distinct immunophenotypic, transcriptomic, and epigenomic profiles. Unlike the two most prevalent NUP98 fusions, NUP98-X variants are typically not cryptic. Furthermore, NUP98-X cases are associated with WT1 mutations, and have epigenomic profiles that resemble either NUP98-NSD1 or NUP98-KDM5A. Cooperating FLT3-ITD and WT1 mutations define NUP98-NSD1, and chromosome 13 aberrations are highly enriched in NUP98-KDM5A. Importantly, we demonstrate that NUP98 fusions portend dismal overall survival, with the noteworthy exception of patients bearing abnormal chromosome 13 (clinicaltrials gov. Identifiers: NCT00002798, NCT00070174, NCT00372593, NCT01371981).</p

    Comparative genomics reveals insights into avian genome evolution and adaptation

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    Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits

    Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

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    Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≄1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

    Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

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    Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≄ II, EF ≀35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

    ???ORganics Exposure in Orbit (OREOcube) experiment on the International Space Station: Preliminary studies

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    Organic compounds that survive in uncommon space environments are an important focus in astrobiology. The ORganics Exposure in Orbit (OREOcube) experiment will investigate, in real time, chemical changes in organic compounds exposed to low Earth orbit radiation conditions on an external platform on International Space Station (ISS). OREOcube is packaged as an identical pair of 10-cm cube instruments, each weighing < 2 kg and containing a highly capable UV-visible-NIR spectrometer, a 24-sample carousel, and integral optics enabling use of the Sun as a light source for spectroscopy, along with the electronics, microcontroller, and data storage to make each cube an autonomous stand-alone instrument package requiring only a standard power and data interface. In our preliminary laboratory investigation, three thin-film organics were studied: tryptophan (an amino acid), adenine (a nucleobase) and anthrarufin (a quinone). The organics were deposited on thin films of hematite (Fe2O3) and magnetite (Fe3O4) to examine the role that iron oxide minerals may play in the alteration of organics on Mars. In the laboratory, our samples were prepared on optical windows and then contained in hermetically sealed reaction cells. The reaction cells were filled with CO2 (g), which is the primary component of the martian atmosphere. The objective of OREOcube is to investigate the influence of mineralogically relevant inorganic materials on the stability, modification, and degradation of the organic molecules during long-duration radiation exposure on the ISS. The results of our laboratory experiments will be used as the basis for the selection of samples for further investigations on the OREOcube ISS experiment
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