157 research outputs found

    Enabling Space Exploration Medical System Development Using a Tool Ecosystem

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    The NASA Human Research Program's (HRP) Exploration Medical Capability (ExMC) Element is utilizing a Model Based Systems Engineering (MBSE) approach to enhance the development of systems engineering products that will be used to advance medical system designs for exploration missions beyond Low Earth Orbit. In support of future missions, the team is capturing content such as system behaviors, functional decompositions, architecture, system requirements and interfaces, and recommendations for clinical capabilities and resources in Systems Modeling Language (SysML) models. As these products mature, SysML models provide a way for ExMC to capture relationships among the various products, which includes supporting more integrated and multi-faceted views of future medical systems. In addition to using SysML models, HRP and ExMC are developing supplementary tools to support two key functions: 1) prioritizing current and future research activities for exploration missions in an objective manner; and 2) enabling risk-informed and evidence-based trade space analysis for future space vehicles, missions, and systems. This paper will discuss the long-term HRP and ExMC vision for the larger ecosystem of tools, which include dynamic Probabilistic Risk Assessment (PRA) capabilities, additional SysML models, a database of system component options, and data visualizations. It also includes a review of an initial Pilot Project focused on enabling medical system trade studies utilizing data that is coordinated across tools for consistent outputs (e.g., mission risk metrics that are associated with medical system mass values and medical conditions addressed). This first Pilot Project demonstrated successful operating procedures and integration across tools. Finally, the paper will also cover a second Pilot Project that utilizes tool enhancements such as medical system optimization capabilities, post-processing, and visualization of generated data for subject matter expert review, and increased integration amongst the tools themselves

    First Phase 1 Double-Blind, Placebo-Controlled, Randomized Rectal Microbicide Trial Using UC781 Gel with a Novel Index of Ex Vivo Efficacy

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    Objectives: Successful control of the HIV/AIDS pandemic requires reduction of HIV-1 transmission at sexually-exposed mucosae. No prevention studies of the higher-risk rectal compartment exist. We report the first-in-field Phase 1 trial of a rectally-applied, vaginally-formulated microbicide gel with the RT-inhibitor UC781 measuring clinical and mucosal safety, acceptability and plasma drug levels. A first-in-Phase 1 assessment of preliminary pharmacodynamics was included by measuring changes in ex vivo HIV-1 suppression in rectal biopsy tissue after exposure to product in vivo. Methods: HIV-1 seronegative, sexually-abstinent men and women (N = 36) were randomized in a double-blind, placebo-controlled trial comparing UC781 gel at two concentrations (0.1%, 0.25%) with placebo gel (1:1:1). Baseline, single-dose exposure and a separate, 7-day at-home dosing were assessed. Safety and acceptability were primary endpoints. Changes in colorectal mucosal markers and UC781 plasma drug levels were secondary endpoints; ex vivo biopsy infectibility was an ancillary endpoint. Results: All 36 subjects enrolled completed the 7-14 week trial (100% retention) including 3 flexible sigmoidoscopies, each with 28 biopsies (14 at 10 cm; 14 at 30 cm). There were 81 Grade 1 adverse events (AEs) and 8 Grade 2; no Grade 3, 4 or procedure-related AEs were reported. Acceptability was high, including likelihood of future use. No changes in mucosal immunoinflammatory markers were identified. Plasma levels of UC781 were not detected. Ex vivo infection of biopsies using two titers of HIV-1 BaL showed marked suppression of p24 in tissues exposed in vivo to 0.25% UC781; strong trends of suppression were seen with the lower 0.1% UC781 concentration. Conclusions: Single and 7-day topical rectal exposure to both concentrations of UC781 were safe with no significant AEs, high acceptability, no detected plasma drug levels and no significant mucosal changes. Ex vivo biopsy infections demonstrated marked suppression of HIV infectibility, identifying a potential early biomarker of efficacy. (Registered at ClinicalTrials.gov; #NCT00408538). © 2011 Anton et al

    The Effectiveness of Incarceration-Based Drug Treatment on Criminal Behavior: A Systematic Review

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    Many, if not most, incarcerated offenders have substance abuse problems. Without effective treatment, these substance-abusing offenders are likely to persist in non-drug offending. The period of incarceration offers an opportunity to intervene in the cycle of drug abuse and crime. Although many types of incarceration-based drug treatment programs are available (e.g., therapeutic communities and group counseling), the effectiveness of these programs is unclear. The objective of this research synthesis is to systematically review quasi-experimental and experimental (RCT) evaluations of the effectiveness of incarceration-based drug treatment programs in reducing post-release recidivism and drug relapse. A secondary objective of this synthesis is to examine variation in effectiveness by programmatic, sample, and methodological features. In this update of the original 2006 review (see Mitchell, Wilson, and MacKenzie, 2006), studies made available since the original review were included in an effort to keep current with emerging research. This synthesis of evaluations of incarceration-based drug treatment programs found that such programs are modestly effective in reducing recidivism. These findings most strongly support the effectiveness of therapeutic communities, as these programs produced relatively consistent reductions in recidivism and drug use. Both counseling and incarceration-based narcotic maintenance programs had mixed effects. Counseling programs were associated with reductions in recidivism but not drug use; whereas, incarceration-based narcotic maintenance programs were associated with reductions in drug use but not recidivism. Note that our findings regarding the effectiveness of incarceration-based narcotic maintenance programs differ from a larger review of community-based narcotic maintenance programs (see Egli, Pina, Christensen, Aebi, and Killias, 2009). Finally, boot camp programs for drug offenders had negligible effects on both recidivism and drug use

    Inverting the model of genomics data sharing with the NHGRI Genomic Data Science Analysis, Visualization, and Informatics Lab-space

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    The NHGRI Genomic Data Science Analysis, Visualization, and Informatics Lab-space (AnVIL; https://anvilproject.org) was developed to address a widespread community need for a unified computing environment for genomics data storage, management, and analysis. In this perspective, we present AnVIL, describe its ecosystem and interoperability with other platforms, and highlight how this platform and associated initiatives contribute to improved genomic data sharing efforts. The AnVIL is a federated cloud platform designed to manage and store genomics and related data, enable population-scale analysis, and facilitate collaboration through the sharing of data, code, and analysis results. By inverting the traditional model of data sharing, the AnVIL eliminates the need for data movement while also adding security measures for active threat detection and monitoring and provides scalable, shared computing resources for any researcher. We describe the core data management and analysis components of the AnVIL, which currently consists of Terra, Gen3, Galaxy, RStudio/Bioconductor, Dockstore, and Jupyter, and describe several flagship genomics datasets available within the AnVIL. We continue to extend and innovate the AnVIL ecosystem by implementing new capabilities, including mechanisms for interoperability and responsible data sharing, while streamlining access management. The AnVIL opens many new opportunities for analysis, collaboration, and data sharing that are needed to drive research and to make discoveries through the joint analysis of hundreds of thousands to millions of genomes along with associated clinical and molecular data types

    Education for Professiona

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