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The Office of Health Assessment and Translation: A Problem-Solving Resource for the National Toxicology Program

Environmental Health Perspectives (Impact Factor: 7.03). 05/2011; 119(5):A196-7. DOI: 10.1289/ehp.1103645
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    ABSTRACT: Systematic review methodologies provide objectivity and transparency to the process of collecting and synthesizing scientific evidence for reaching conclusions on specific research questions. There is increasing interest in applying these procedures to address environmental health questions. To develop a systematic review framework to address environmental health questions by extending approaches developed for clinical medicine to handle the breadth of data relevant to environmental health sciences (e.g., human, animal, and mechanistic studies). The Office of Health Assessment and Translation (OHAT) adapted guidance from systematic-review authorities and sought advice during development of the OHAT Approach through consultation with technical experts in systematic review and human health assessments as well as scientific advisory groups and the public. The method was refined by considering expert and public comments and through application to case studies. Presented here is a 7-step framework for systematic review and evidence integration for reaching hazard identification conclusions: problem formulation and protocol development, search for and select studies for inclusion, extract data from studies, assess the quality or risk of bias of individual studies, rate the confidence in the body of evidence, translate the confidence ratings into levels of evidence, and integrate the information from different evidence streams (human, animal, and "other relevant data" including mechanistic or in vitro studies) to develop hazard identification conclusions. The principles of systematic review can be successfully applied to environmental health questions to provide greater objectivity and transparency to the process of developing conclusions.
    Environmental Health Perspectives 04/2014; 122(7). DOI:10.1289/ehp.1307972 · 7.03 Impact Factor
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    Environmental Health Perspectives 04/2013; 121(4):a108-9. DOI:10.1289/ehp.1306711 · 7.03 Impact Factor
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    ABSTRACT: Background: Many studies have reported associations between air pollution particles with an aerodynamic diameter less than 2.5 microns (fine PM) and adverse cardiovascular effects. However there is increased concern that so-called ultrafine PM which comprises the smallest fraction of fine PM (aerodynamic diameter less than 0.1 micron) may be disproportionately toxic relative to the 0.1 to 2.5 micron fraction. Ultrafine PM is not routinely measured in state monitoring networks and is not homogenously dispersed throughout an airshed but rather located in hot spots such as near combustion sources (e.g.roads), making it difficult for epidemiology studies to associate exposure to ultrafine PM with adverse health effects.Methods and Results: Thirty four middle-aged individuals with metabolic syndrome were exposed for two hours while at rest in a randomized crossover design to clean air and concentrated ambient ultrafine particles (UCAPS) for two hours. To further define potential risk, study individuals carrying the null allele for GSTM1 (a prominent antioxidant gene) were identified by genotyping. Blood was obtained immediately prior to exposure, and at one hour and 20 hours afterward. Continuous Holter monitoring began immediately prior to exposure and continued for 24 hours. Based on changes we observed in previous CAPS studies, we hypothesized that ultrafine CAPS would cause changes in markers of blood inflammation and fibrinolysis as well as changes in heart rate variability and cardiac repolarization. GSTM1 null individuals had altered cardiac repolarization as seen by a change in QRS complexity following exposure to UCAPS and both the entire study population as well as GSTM1 null individuals had increased QT duration. Blood plasminogen and thrombomodulin were decreased in the whole population following UCAPS exposure, while C reactive protein and SAA were increased.Conclusions: This controlled human exposure study is the first to show that ambient ultrafine particles can cause cardiovascular changes in people with metabolic syndrome, which affects nearly a quarter of the U.S. adult population.
    Toxicological Sciences 04/2014; 140(1). DOI:10.1093/toxsci/kfu063 · 4.48 Impact Factor

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