NASA Human Research Wiki - An Online Collaboration Tool

In preparation for exploration-class missions, the Exploration Medical Capability (ExMC) element of NASA's Human Research Program (HRP) has compiled a large evidence base, which previously was available only to persons within the NASA community. The evidence base is comprised of several types of data, for example: information on more than 80 medical conditions which could occur during space flight, derived from several sources (including data on incidence and potential outcomes of these medical conditions, as captured in the Integrated Medical Model's Clinical Finding Forms). In addition, approximately 35 gap reports are included in the evidence base, identifying current understanding of the medical challenges for exploration, as well as any gaps in knowledge and/or technology that would need to be addressed in order to provide adequate medical support for these novel missions. In an effort to make the ExMC information available to the general public and increase collaboration with subject matter experts within and outside of NASA, ExMC has developed an online collaboration tool, very similar to a wiki, titled the NASA Human Research Wiki. The platform chosen for this data sharing, and the potential collaboration it could generate, is a MediaWiki-based application that would house the evidence, allow "read only" access to all visitors to the website, and editorial access to credentialed subject matter experts who have been approved by the Wiki's editorial board. Although traditional wikis allow users to edit information in real time, the NASA Human Research Wiki includes a peer review process to ensure quality and validity of information. The wiki is also intended to be a pathfinder project for other HRP elements that may want to use this type of web-based tool. The wiki website will be released with a subset of the data described and will continue to be populated throughout the year

Effects of aluminium chloride on some essential elements in pregnant rats and their offspring

Le but de notre étude est d’établir une relation de causalité entre l’injection intrapéritonéale d’AlCl3 et les variations plasmatiques et tissulaires des teneurs en calcium, magnésium, cuivre, zinc, phosphore et fer chez les rates gestantes et leurs foetus. Les rates gestantes sont injectées du 9ème au 13ème jour de la gestation par différentes doses d’AlCl3 (50, 100 et 200 mg/kg.j). Les éléments essentiels sont analysés dans le sang, les reins, le foie et l’intestin des animaux par spectrophotométrie d’absorption atomique. Les résultats montrent, après traitement par AlCl3, une augmentation des concentrations en calcium, fer et phosphore hépatique, aussi bien qu’en fer et phosphore au niveau rénal, et une diminution des concentrations en magnésium rénal et intestinal, en zinc hépatique, en cuivre hépatique et rénal, et en fer intestinal chez les rates gestantes et surtout pour les fortes doses. On a aussi noté une augmentation des concentrations en calcium, en phosphore et en zinc dans le plasma des rates gestantes et une diminution dans la concentration en magnésium dans le plasma des rates gestantes et leurs foetus pour les doses élevées d’AlCl3. Ces résultats prouvent que le passage de l’aluminium aux foetus suite au traitement des mères cause des perturbations dans le métabolisme des éléments essentiels

MidA is a putative methyltransferase that is required for mitochondrial complex I function

10 páginas, 6 figuras.-- et al.Dictyostelium and human MidA are homologous proteins that belong to a family of proteins of unknown function called DUF185. Using yeast two-hybrid screening and pull-down experiments, we showed that both proteins interact with the mitochondrial complex I subunit NDUFS2. Consistent with this, Dictyostelium cells lacking MidA showed a specific defect in complex I activity, and knockdown of human MidA in HEK293T cells resulted in reduced levels of assembled complex I. These results indicate a role for MidA in complex I assembly or stability. A structural bioinformatics analysis suggested the presence of a methyltransferase domain; this was further supported by site-directed mutagenesis of specific residues from the putative catalytic site. Interestingly, this complex I deficiency in a Dictyostelium midA- mutant causes a complex phenotypic outcome, which includes phototaxis and thermotaxis defects. We found that these aspects of the phenotype are mediated by a chronic activation of AMPK, revealing a possible role of AMPK signaling in complex I cytopathology.This work was supported by grants BMC2006-00394 and BMC2009-09050 to R.E. from the Spanish Ministerio de Ciencia e Innovación; to P.R.F. from the Thyne Reid Memorial Trusts and the Australian Research Council; to A.V. and O.G. from the Spanish National Bioinformatics Institute (www.inab.org), a platform of Genome Spain; to R.G. from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI070167) and from the Comunidad de Madrid (GEN-0269/2006). S.C. is supported by a research contract from Consejería de Educación de la Comunidad de Madrid y del Fondo Social Europeo (FSE).Peer Reviewe

Integrated Medical Model (IMM) Project Verification, Validation, and Credibility (VVandC)

The Integrated Medical Model (IMM) Project supports end user requests by employing the Integrated Medical Evidence Database (iMED) and IMM tools as well as subject matter expertise within the Project. The iMED houses data used by the IMM. The IMM is designed to forecast relative changes for a specified set of crew health and mission success risk metrics by using a probabilistic model based on historical data, cohort data, and subject matter expert opinion. A stochastic approach is taken because deterministic results would not appropriately reflect the uncertainty in the IMM inputs. Once the IMM was conceptualized, a plan was needed to rigorously assess input information, framework and code, and output results of the IMM, and ensure that end user requests and requirements were considered during all stages of model development and implementation, as well as lay the foundation for external review and application. METHODS: In 2008, the Project team developed a comprehensive verification and validation (VV) plan, which specified internal and external review criteria encompassing 1) verification of data and IMM structure to ensure proper implementation of the IMM, 2) several validation techniques to confirm that the simulation capability of the IMM appropriately represents occurrences and consequences of medical conditions during space missions, and 3) credibility processes to develop user confidence in the information derived from the IMM. When the NASA-STD-7009 (7009) [1] was published, the Project team updated their verification, validation, and credibility (VVC) project plan to meet 7009 requirements and include 7009 tools in reporting VVC status of the IMM. Construction of these tools included meeting documentation and evidence requirements sufficient to meet external review success criteria. RESULTS: IMM Project VVC updates are compiled recurrently and include updates to the 7009 Compliance and Credibility matrices. Reporting tools have evolved over the lifetime of the IMM Project to better communicate VVC status. This has included refining original 7009 methodology with augmentation from the HRP NASA-STD-7009 Guidance Document working group and the NASA-HDBK-7009 [2]. End user requests and requirements are being satisfied as evidenced by ISS Program acceptance of IMM risk forecasts, transition to an operational model and simulation tool, and completion of service requests from a broad end user consortium including operations, science and technology planning, and exploration planning. IMM v4.0 is slated for operational release in the FY015 and current VVC assessments illustrate the expected VVC status prior to the completion of customer lead external review efforts. CONCLUSIONS: The VVC approach established by the IMM Project of incorporating Project-specific recommended practices and guidelines for implementing the 7009 requirements is comprehensive and includes the involvement of end users at every stage in IMM evolution. Methods and techniques used to quantify the VVC status of the IMM Project represented a critical communication tool in providing clear and concise suitability assessments to IMM customers. These processes have not only received approval from the local NASA community but have also garnered recognition by other federal agencies seeking to develop similar guidelines in the medical modeling community