Cardiovascular health and particulate vehicular emissions: a critical evaluation of the evidence

A major public health goal is to determine linkages between specific pollution sources and adverse health outcomes. This paper provides an integrative evaluation of the database examining effects of vehicular emissions, such as black carbon (BC), carbonaceous gasses, and ultrafine PM, on cardiovascular (CV) morbidity and mortality. Less than a decade ago, few epidemiological studies had examined effects of traffic emissions specifically on these health endpoints. In 2002, the first of many studies emerged finding significantly higher risks of CV morbidity and mortality for people living in close proximity to major roadways, vs. those living further away. Abundant epidemiological studies now link exposure to vehicular emissions, characterized in many different ways, with CV health endpoints such as cardiopulmonary and ischemic heart disease and circulatory-disease-associated mortality; incidence of coronary artery disease; acute myocardial infarction; survival after heart failure; emergency CV hospital admissions; and markers of atherosclerosis. We identify numerous in vitro, in vivo, and human panel studies elucidating mechanisms which could explain many of these cardiovascular morbidity and mortality associations. These include: oxidative stress, inflammation, lipoperoxidation and atherosclerosis, change in heart rate variability (HRV), arrhythmias, ST-segment depression, and changes in vascular function (such as brachial arterial caliber and blood pressure). Panel studies with accurate exposure information, examining effects of ambient components of vehicular emissions on susceptible human subjects, appear to confirm these mechanisms. Together, this body of evidence supports biological mechanisms which can explain the various CV epidemiological findings. Based upon these studies, the research base suggests that vehicular emissions are a major environmental cause of cardiovascular mortality and morbidity in the United States. As a means to reduce the public health consequences of such emissions, it may be desirable to promulgate a black carbon (BC) PM2.5 standard under the National Ambient Air Quality Standards, which would apply to both on and off-road diesels. Two specific critical research needs are identified. One is to continue research on health effects of vehicular emissions, gaseous as well as particulate. The second is to utilize identical or nearly identical research designs in studies using accurate exposure metrics to determine whether other major PM pollutant sources and types may also underlie the specific health effects found in this evaluation for vehicular emissions

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

V/STOL model fan stage rig design report

A model single-stage fan with variable inlet guide vanes (VIGV) was designed to demonstrate efficient point operation while providing flow and pressure ratio modulation capability required for a V/STOL propulsion system. The fan stage incorporates a split-flap VIGV with an independently actuated ID flap to permit independent modulation of fan and core engine airstreams, a flow splitter integrally designed into the blade and vanes to completely segregate fan and core airstreams in order to maximize core stream supercharging for V/STOL operation, and an EGV with a variable leading edge fan flap for rig performance optimization. The stage was designed for a maximum flow size of 37.4 kg/s (82.3 lb/s) for compatibility with LeRC test facility requirements. Design values at maximum flow for blade tip velocity and stage pressure ratio are 472 m/s (1550 ft/s) and 1.68, respectively

Pulmonary clearance and inflammatory response in C3H/HeJ mice after intranasal exposure to Pseudomonas spp.

The environmental release of engineered microorganisms has caused health and environmental concerns. In this study, an animal model was used to examine health effects following pulmonary exposure to environmental and clinical isolates. In order to rule out the possibility that an adverse response was caused by endotoxin, 50% lethal doses (LD50) were determined, when possible, with endotoxin-sensitive (C3HeB/FeJ) and endotoxin-resistant (C3H/HeJ) mice by using both environmental isolates (Pseudomonas aeruginosa BC16, BC17, BC18, and AC869 and Pseudomonas maltophilia BC6) and clinical isolates (P. aeruginosa PAO1 and DG1). The LD50 of strains AC869, DG1, and PAO1 are 1.05 x 10(7), 6.56 x 10(6), and 1.02 x 10(7) CFU, respectively, in C3HeB/FeJ mice and 1.05 x 10(7), 1.00 x 10(7), and 2.75 x 10(6) CFU, respectively, in C3H/HeJ mice. Strains BC17 and BC18 were not lethal to the animals. On the basis of the LD50 data, an appropriate sublethal dose (approximately 10(6) CFU) was selected. Animals were challenged intranasally with microorganisms, and clearance from the lungs and nasal cavity was determined. Strains BC17, BC18, and AC869 were not detected in lungs or nasal washes 14 days following treatment. Strains BC6, BC16, and DG1 were recovered from the nasal cavities at the end of the experiment. Only strain PAO1 was detected in lungs and in nasal cavities 14 days after treatment. At selected intervals following treatment, the percentages of polymorphonuclear leukocytes and lymphocytes in bronchoalveolar lavage samples were determined. P. aeruginosa AC869, PAO1, and DG1 elicited a relatively strong inflammatory response which was indirectly related to lung clearance.(ABSTRACT TRUNCATED AT 250 WORDS