Near-highway pollutants in motor vehicle exhaust: A review of epidemiologic evidence of cardiac and pulmonary health risks

There is growing evidence of a distinct set of freshly-emitted air pollutants downwind from major highways, motorways, and freeways that include elevated levels of ultrafine particulates (UFP), black carbon (BC), oxides of nitrogen (NOx), and carbon monoxide (CO). People living or otherwise spending substantial time within about 200 m of highways are exposed to these pollutants more so than persons living at a greater distance, even compared to living on busy urban streets. Evidence of the health hazards of these pollutants arises from studies that assess proximity to highways, actual exposure to the pollutants, or both. Taken as a whole, the health studies show elevated risk for development of asthma and reduced lung function in children who live near major highways. Studies of particulate matter (PM) that show associations with cardiac and pulmonary mortality also appear to indicate increasing risk as smaller geographic areas are studied, suggesting localized sources that likely include major highways. Although less work has tested the association between lung cancer and highways, the existing studies suggest an association as well. While the evidence is substantial for a link between near-highway exposures and adverse health outcomes, considerable work remains to understand the exact nature and magnitude of the risks

IL23R (Interleukin 23 Receptor) variants protective against inflammatory bowel diseases (IBD) display loss of functiondue to impaired protein stability and intracellular trafficking

Genome-wide association studies as well as murine models have shown that the interleukin 23 receptor (IL23R) pathway plays a pivotal role in chronic inflammatory diseases such as Crohn disease (CD), ulcerative colitis, psoriasis, and type 1 diabetes. Genome-wide association studies and targeted re-sequencing studies have revealed the presence of multiple potentially causal variants of the IL23R. Specifically the G149R, V362I, and R381Q IL23R chain variants are linked to protection against the development of Crohn disease and ulcerative colitis in humans. Moreover, the exact mechanism of action of these receptor variants has not been elucidated. We show that all three of these IL23R variants cause a reduction in IL23 receptor activation-mediated phosphorylation of the signaltransducing activator of transcription 3 (STAT3) and phosphorylation of signal transducing activator of transcription 4 (STAT4). The reduction in signaling is due to lower levels of cell surface receptor expression. For G149R, the receptor retention in the endoplasmic reticulum is due to an impairment of receptor maturation, whereas the R381Q and V362I variants have reduced protein stability. Finally, we demonstrate that the endogenous expression of IL23R protein from V362I and R381Q variants in human lymphoblastoid cell lines exhibited lower expression levels relative to susceptibility alleles. Our results suggest a convergent cause of IL23R variant protection against chronic inflammatory disease

Lessons learned from 104 years of mobile observatories [poster]

Poster session IN13B-1211 presented 10 December 2007 at the AGU Fall Meeting, 10–14 December 2007, San Francisco, CA, USAAs the oceanographic community ventures into a new era of integrated observatories, it may be helpful to look back on the era of "mobile observatories" to see what Cyberinfrastructure lessons might be learned. For example, SIO has been operating research vessels for 104 years, supporting a wide range of disciplines: marine geology and geophysics, physical oceanography, geochemistry, biology, seismology, ecology, fisheries, and acoustics. In the last 6 years progress has been made with diverse data types, formats and media, resulting in a fully-searchable online SIOExplorer Digital Library of more than 800 cruises (http://SIOExplorer.ucsd.edu). Public access to SIOExplorer is considerable, with 795,351 files (206 GB) downloaded last year. During the last 3 years the efforts have been extended to WHOI, with a "Multi-Institution Testbed for Scalable Digital Archiving" funded by the Library of Congress and NSF (IIS 0455998). The project has created a prototype digital library of data from both institutions, including cruises, Alvin submersible dives, and ROVs. In the process, the team encountered technical and cultural issues that will be facing the observatory community in the near future. Technological Lessons Learned: Shipboard data from multiple institutions are extraordinarily diverse, and provide a good training ground for observatories. Data are gathered from a wide range of authorities, laboratories, servers and media, with little documentation. Conflicting versions exist, generated by alternative processes. Domain- and institution-specific issues were addressed during initial staging. Data files were categorized and metadata harvested with automated procedures. With our second-generation approach to staging, we achieve higher levels of automation with greater use of controlled vocabularies. Database and XML- based procedures deal with the diversity of raw metadata values and map them to agreed-upon standard values, in collaboration with the Marine Metadata Interoperability (MMI) community. All objects are tagged with an expert level, thus serving an educational audience, as well as research users. After staging, publication into the digital library is completely automated. The technical challenges have been largely overcome, thanks to a scalable, federated digital library architecture from the San Diego Supercomputer Center, implemented at SIO, WHOI and other sites. The metadata design is flexible, supporting modular blocks of metadata tailored to the needs of instruments, samples, documents, derived products, cruises or dives, as appropriate. Controlled metadata vocabularies, with content and definitions negotiated by all parties, are critical. Metadata may be mapped to required external standards and formats, as needed. Cultural Lessons Learned: The cultural challenges have been more formidable than expected. They became most apparent during attempts to categorize and stage digital data objects across two institutions, each with their own naming conventions and practices, generally undocumented, and evolving across decades. Whether the questions concerned data ownership, collection techniques, data diversity or institutional practices, the solution involved a joint discussion with scientists, data managers, technicians and archivists, working together. Because metadata discussions go on endlessly, significant benefit comes from dictionaries with definitions of all community-authorized metadata values.Funding provided by the Library of Congress and NSF (IIS 0455998

Exploring the use of a participative design in the early development of a predictive test : the importance of physician involvement

In this study, we contribute to the personalized medicine and health care management literature by developing and testing a new participative design approach. We propose that involving gastroenterologists in the development of a predictive test to assist them in their clinical decision-making process for the treatment of inflammatory bowel diseases will increase the likelihood of their acceptance of the innovation. Based on data obtained from 6 focus groups across Canada from a total of 28 physicians, analyses reveal that current tools do not enable discriminating between treatment options to find the best fit for each patient. Physicians expect a new predictive tool to have the capability of showing clear reliability and significant benefits for the patient, while being accessible in a timely manner that facilitates clinical decisions. Physicians also insist on their key role in the implementation process, hence confirming the relevance and importance of participative designs in personalized medicine

A transcriptome-based approach to identify functional modules within and across primary human immune cells

Genome-wide transcriptomic analyses have provided valuable insight into fundamental biology and disease pathophysiology. Many studies have taken advantage of the correlation in the expression patterns of the transcriptome to infer a potential biologic function of uncharacterized genes, and multiple groups have examined the relationship between co-expression, co-regulation, and gene function on a broader scale. Given the unique characteristics of immune cells circulating in the blood, we were interested in determining whether it was possible to identify functional co-expression modules in human immune cells. Specifically, we sequenced the transcriptome of nine immune cell types from peripheral blood cells of healthy donors and, using a combination of global and targeted analyses of genes within co-expression modules, we were able to determine functions for these modules that were cell lineagespecific or shared among multiple cell lineages. In addition, our analyses identified transcription factors likely important for immune cell lineage commitment and/or maintenance

Patients’ perception of their involvement in shared treatment decision making : key factors in the treatment of inflammatory bowel disease

Objectives This study aims to characterize the relationships between the quality of the information given by the physician, the involvement of the patient in shared decision making (SDM), and outcomes in terms of satisfaction and anxiety pertaining to the treatment of inflammatory bowel disease (IBD). Methods A Web survey was conducted among 200 Canadian patients affected with IBD. The theoretical model of SDM was adjusted using path analysis. SAS software was used for all statistical analyses. Results The quality of the knowledge transfer between the physician and the patient is significantly associated with the components of SDM: information comprehension, patient involvement and decision certainty about the chosen treatment. In return, patient involvement in SDM is significantly associated with higher satisfaction and, as a result, lower anxiety as regards treatment selection. Conclusions This study demonstrates the importance of involving patients in shared treatment decision making in the context of IBD. Practice implications Understanding shared decision making may motivate patients to be more active in understanding the relevant information for treatment selection, as it is related to their level of satisfaction, anxiety and adherence to treatment. This relationship should encourage physicians to promote shared decision making

Phenotypes associated with genetic determinants of type I interferon regulation in the UK Biobank:a protocol

BACKGROUND: Type I interferons are cytokines involved in innate immunity against viruses. Genetic disorders of type I interferon regulation are associated with a range of autoimmune and cerebrovascular phenotypes. Carriers of pathogenic variants involved in genetic disorders of type I interferons are generally considered asymptomatic. Preliminary data suggests, however, that genetically determined dysregulation of type I interferon responses is associated with autoimmunity, and may also be relevant to sporadic cerebrovascular disease and dementia. We aim to determine whether functional variants in genes involved in type I interferon regulation and signalling are associated with the risk of autoimmunity, stroke, and dementia in a population cohort.METHODS: We will perform a hypothesis-driven candidate pathway association study of type I interferon-related genes using rare variants in the UK Biobank (UKB). We will manually curate type I interferon regulation and signalling genes from a literature review and Gene Ontology, followed by clinical and functional filtering. Variants of interest will be included based on pre-defined clinical relevance and functional annotations (using LOFTEE, M-CAP and a minor allele frequency &lt;0.1%). The association of variants with 15 clinical and three neuroradiological phenotypes will be assessed with a rare variant genetic risk score and gene-level tests, using a Bonferroni-corrected p-value threshold from the number of genetic units and phenotypes tested. We will explore the association of significant genetic units with 196 additional health-related outcomes to help interpret their relevance and explore the clinical spectrum of genetic perturbations of type I interferon.ETHICS AND DISSEMINATION: The UKB has received ethical approval from the North West Multicentre Research Ethics Committee, and all participants provided written informed consent at recruitment. This research will be conducted using the UKB Resource under application number 93160. We expect to disseminate our results in a peer-reviewed journal and at an international cardiovascular conference.</p