638 research outputs found

    A Prospective Controlled Trial of Routine Opt-Out HIV Testing in a Men's Jail

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    Approximately 10 million Americans enter jails annually. The Centers for Disease Control and Prevention now recommends routine opt-out HIV testing in these settings. The logistics for performing routine opt-out HIV testing within jails, however, remain controversial. The objective of this study was to evaluate the optimal time to routinely HIV test newly incarcerated jail detainees using an opt-out strategy.This prospective, controlled trial of routine opt-out HIV testing was conducted among 298 newly incarcerated male inmates in an urban men's jail in New Haven, Connecticut. 298 sequential entrants to the men's jail over a three week period in March and April 2008 were assigned to be offered routine opt-out HIV testing at one of three points after incarceration: immediate (same day, n = 103), early (next day, n = 98), or delayed (7 days, n = 97). The primary outcome was the proportion of men in each group consenting to testing.Routine opt-out HIV testing was significantly higher for the early (53%: AOR = 2.6; 95% CI = 1.5 to 4.7) and immediate (45%: AOR = 2.3; 95% CI = 1.3 to 4.0) testing groups compared to the delayed (33%) testing group. The immediate and early testing groups, however, did not significantly differ (p = 0.67). In multivariate analyses, factors significantly associated with routine opt-out HIV testing were assignment to the 'early' testing group (p = 0.0003) and low (bond > or = $5,000, immigration or federal charges or pre-sentencing > 30 days) likelihood of early release (p = 0.04). Two subjects received preliminary positive results and one of them was subsequently confirmed HIV seropositive.In this men's jail where attrition was high, routine opt-out HIV testing was not only feasible, but resulted in the highest rates of HIV testing when performed within 24 hours of incarceration.ClinicalTrials.gov NCT00624247

    Predicting Brain Age at Slice Level : Convolutional Neural Networks and Consequences for Interpretability

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    Funding Information: NE was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior— Brasil (CAPES)—Finance Code 001. MM was financed in part by the Conselho Nacional de Pesquisa—Brasil (CNPq). Funding Information: Conflict of Interest: BF had a research grant from Pfizer outside of this study.Peer reviewe

    Native and aspirin-triggered lipoxins control innate immunity by inducing proteasomal degradation of TRAF6

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    Innate immune signaling is critical for the development of protective immunity. Such signaling is, perforce, tightly controlled. Lipoxins (LXs) are eicosanoid mediators that play key counterregulatory roles during infection. The molecular mechanisms underlying LX-mediated control of innate immune signaling are of interest. In this study, we show that LX and aspirin (ASA)-triggered LX (ATL) inhibit innate immune signaling by inducing suppressor of cytokine signaling (SOCS) 2–dependent ubiquitinylation and proteasome-mediated degradation of TNF receptor–associated factor (TRAF) 2 and TRAF6, which are adaptor molecules that couple TNF and interleukin-1 receptor/Toll-like receptor family members to intracellular signaling events. LX-mediated degradation of TRAF6 inhibits proinflammatory cytokine production by dendritic cells. This restraint of innate immune signaling can be ablated by inhibition of proteasome function. In vivo, this leads to dysregulated immune responses, accompanied by increased mortality during infection. Proteasomal degradation of TRAF6 is a central mechanism underlying LX-driven immune counterregulation, and a hitherto unappreciated mechanism of action of ASA. These findings suggest a new molecular target for drug development for diseases marked by dysregulated inflammatory responses

    Novel CYP4F22 mutations associated with autosomal recessive congenital ichthyosis (ARCI). Study of the CYP4F22 c.1303C>T founder mutation

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    Mutations in CYP4F22 cause autosomal recessive congenital ichthyosis (ARCI). However, less than 10% of all ARCI patients carry a mutation in CYP4F22. In order to identify the molecular basis of ARCI among our patients (a cohort of ninety-two Spanish individuals) we performed a mutational analysis using direct Sanger sequencing in combination with a multigene targeted NGS panel. From these, eight ARCI families (three of them with Moroccan origin) were found to carry five different CYP4F22 mutations, of which two were novel. Computational analysis showed that the mutations found were present in highly conserved residues of the protein and may affect its structure and function. Seven of the eight families were carriers of a highly recurrent CYP4F22 variant, c.1303C>T; p.(His435Tyr). A 12Mb haplotype was reconstructed in all c.1303C>T carriers by genotyping ten microsatellite markers flanking the CYP4F22 gene. A prevalent 2.52Mb haplotype was observed among Spanish carrier patients suggesting a recent common ancestor. A smaller core haplotype of 1.2Mb was shared by Spanish and Moroccan families. Different approaches were applied to estimate the time to the most recent common ancestor (TMRCA) of carrier patients with Spanish origin. The age of the mutation was calculated by using DMLE and BDMC2. The algorithms estimated that the c.1303C>T variant arose approximately 2925 to 4925 years ago, while Spanish carrier families derived from a common ancestor who lived in the XIII century. The present study reports five CYP4F22 mutations, two of them novel, increasing the number of CYP4F22 mutations currently listed. Additionally, our results suggest that the recurrent c.1303C>T change has a founder effect in Spanish population and c.1303C>T carrier families originated from a single ancestor with probable African ancestry

    Small cells lung epidermoid carcinoma in a HTLV1-infected patient: case report and literature review

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    The human T cell lymphotropic virus type 1 (HTLV-1) is the first human retrovirus discovered. Since then, it has spread worldwide and is mainly associated with adult T cell leukemia/lymphoma (ATLL) and HTLV1-associated myelopathy (HAM). Its relationship, however, with other types of cancer is controversial. We describe the case of a patient presenting with small cells lung epidermoid carcinoma who had recently developed HAM, and a review of the literature related to these conditions. This is the first case of this type of lung cancer, the same of the first description in the literature, associated with HAM outside Japan

    Advancing Technologies for Climate Observation

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    Climate research needs Accurate global cloud ice measurements Cloud ice properties are fundamental controlling variables of radiative transfer and precipitation Cost-effective, sensitive instruments for diurnal and wide-swath coverage Mature technology for space remote sensing IceCube objectivesDevelop and validate a flight-qualified 883 GHz receiver for future use in ice cloud radiometer missions Raise TRL (57) of 883 GHz receiver technology Reduce instrument cost and risk by developing path to space for COTS sub-mm-wave receiver systems Enable remote sensing of global cloud ice with advanced technologies and technique

    Medication Complications in Extracorporeal Membrane Oxygenation.

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    The need for extracorporeal membrane oxygenation (ECMO) therapy is a marker of disease severity for which multiple medications are required. The therapy causes physiologic changes that impact drug pharmacokinetics. These changes can lead to exposure-driven decreases in efficacy or increased incidence of side effects. The pharmacokinetic changes are drug specific and largely undefined for most drugs. We review available drug dosing data and provide guidance for use in the ECMO patient population
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