Gastrointestinal disease and diet

Despite the large number of people affected by digestive diseases, gastroenterologists maintain a less than optimal course of treatment. The medical community has largely ignored the role that diet plays in treating and often curing gastrointestinal diseases. In this paper, I will explain, through my own experiences and through the work of those who have promoted a specific diet for the treatment of gastrointestinal diseases, how the medical community is oblivious to an important treatment for patients struggling with digestive disease

Geographic distribution of Show Me Healthy Women providers and breast cancer incidence and mortality in Missouri counties [abstract]

Breast cancer is the second most common cause of cancer death among US women. Regular mammography is the most effective method to reduce mortality. However, uninsured women face substantial barriers to receiving regular mammograms and paying for cancer treatment. The Show Me Healthy Women (SMHW) Program provides reimbursement to SMHW physicians for breast cancer screenings and treatment for their low-income patients.Enrollment in the SMHW program is voluntary. We describe the geographicdistribution of SMHW providers related to breast cancer incidence and mortality rates by county

Pathogenicity and selective constraint in the non-coding genome

Gene regulation plays a central role in evolution, organismal development, and disease. Despite the critical importance of gene regulation throughout development, there have been few genetic variants in regulatory elements with large effects that have been robustly associated to disease. In this work, my overarching aim was to gain a better understanding of the contribution of genetic variation in regulatory elements to Mendelian disorders and attempted to approach this problem from three different perspectives. I first sought to assess the contribution of regulatory variation to severe developmental disorders using sequence data from 8,000 affected individuals and their parents and to identify individual elements with a high probability of harbouring pathogenic regulatory elements. Next, I used population genetic models and data from more than 28,000 whole genome sequenced individuals to examine the forces of selection operating on non-coding elements genome-wide. Finally, I conducted a pilot experiment to assay >50,000 different non-coding variants across more than 700 different non-coding elements, including variants observed in patients with developmental disorders in a massively parallel reporter assay (MPRA) and collaborated on an assessment of the impact of patient mutations in eleven different enhancers using mouse transgenesis assays. A few key results from the work are summarised below: - I provide evidence that de novo SNVs in non-coding elements contribute to severe developmental disorders, and estimate that they contribute in 1-3% of cases not harbouring a likely diagnostic coding variant. - These de novo SNVs reside primarily in highly evolutionarily conserved regulatory elements and I estimate that a large fraction of conserved non-coding elements (50-70%) are acting as enhancers and a smaller subset (10-15%) have a function related to alternative splicing. - Statistical modelling of the distribution of variants in developmental disorder patients suggests that a small fraction of bases (maximum likelihood estimate of 3%) within a disease-associated non-coding element are likely pathogenic with high penetrance when mutated. - I develop a new genome-wide mutation rate model that accounts for a variety of germline features including recombination rate, replication timing, sequence context, and histone marks which greatly outperforms models based on sequence-context alone. - I find evidence for widespread purifying selection in the non-coding genome that is correlated with nucleotide-level evolutionary conservation, even when the conserved nucleotides lie within otherwise poorly conserved sequence. - I show that the selective constraint on small insertions and deletions is likely greater than the selective constraint on SNVs. - I present data from a pilot experiment assessing more than 50,000 different non-coding variants in a massively parallel reporter assay conducted in both HeLa and Neuroblastoma cells.Wellcome Trus

Abnormal wave reflections and left ventricular hypertrophy late after coarctation of the aorta repair

Patients with repaired coarctation of the aorta are thought to have increased afterload due to abnormalities in vessel structure and function. We have developed a novel cardiovascular magnetic resonance protocol that allows assessment of central hemodynamics, including central aortic systolic blood pressure, resistance, total arterial compliance, pulse wave velocity, and wave reflections. The main study aims were to (1) characterize group differences in central aortic systolic blood pressure and peripheral systolic blood pressure, (2) comprehensively evaluate afterload (including wave reflections) in the 2 groups, and (3) identify possible biomarkers among covariates associated with elevated left ventricular mass (LVM). Fifty adult patients with repaired coarctation and 25 age- and sex-matched controls were recruited. Ascending aorta area and flow waveforms were obtained using a high temporal-resolution spiral phase-contrast cardiovascular magnetic resonance flow sequence. These data were used to derive central hemodynamics and to perform wave intensity analysis noninvasively. Covariates associated with LVM were assessed using multivariable linear regression analysis. There were no significant group differences (P≥0.1) in brachial systolic, mean, or diastolic BP. However central aortic systolic blood pressure was significantly higher in patients compared with controls (113 versus 107 mm Hg, P=0.002). Patients had reduced total arterial compliance, increased pulse wave velocity, and larger backward compression waves compared with controls. LVM index was significantly higher in patients than controls (72 versus 59 g/m(2), P<0.0005). The magnitude of the backward compression waves was independently associated with variation in LVM (P=0.01). Using a novel, noninvasive hemodynamic assessment, we have shown abnormal conduit vessel function after coarctation of the aorta repair, including abnormal wave reflections that are associated with elevated LVM

Tumor Microenvironment RNA Expression Analysis in Human Xenograft Mice

While genomic analysis of tumor cells is a mainstay in cancer research, there is growing interest in the characterization of the tumor microenvironment, comprised of nearby healthy somatic cells, most notably fibroblasts and invading immune cells. Studying the RNA expression profile of the tumor microenvironment provides a way to analyze local response to tumor growth and ultimately to better characterize bodily response to different stages or genetic subsets of cancer. The purpose of this research was to develop a tool that efficiently separates tumor sequence data from human xenograft mice (mice with genetically human tumors) into separate microenvironment and tumor expression profiles. While this separation was previously done by physically excising healthy tissue under a microscope using laser capture microdissection, performing this separation in silico allows for rapid analysis of hundreds of samples. Further, using this tool, we can re-examine tumor expression profiles after filtering out ‘contaminating’ microenvironment sequence, resulting in a more accurate RNA expression profile.Bachelor of Scienc

York University: York Neighborhood Renewables

Our group aims to develop a solar installation model for the York University campus that takes into consideration the limitations of installing solar photovoltaic systems on all of the building rooftops across the campus. From this model we can determine which buildings receive the highest amounts of solar radiation for one year at York. This in turn will allow us to create a table showing each buildings ability for receiving solar energy. These maps are intended to provide beneficial information for governments and/or policy leaders, ultimately encouraging the development of a solar energy system at York University (Gastli & Charabi, 2010).York University: York Neighborhood Renewables - sponsored by professor Jose Etcheverry, York Universit

Examination of differential ratings of perceived exertion (dRPE) during bio-banded small-sided games.

The aims of the current study were to investigate the use of dRPE with academy soccer players to: 1) examine the effect of bio-banded and non-bio-banded maturity groups within SSG on players dRPE; 2) describe the multivariate relationships between dRPE measures investigating the sources of intra and inter-individual variation, and the effects of maturation and bio-banding. Using 32 highly trained under (U) 12 to U14 soccer players (mean (SD) age 12.9 (0.9) years, body mass 46.4 (8.5) kg and stature 158.2 (14.9) cm) academy soccer players from two English professional male soccer academies. Players were categorised according to somatic maturity status using estimated percentage of adult stature attainment, with players randomly assigned into teams to play 4v4 SSG. The study used a repeated measures design, whereby the selected players participated within 6 bio-banded (maturity matched [pre-PHV Vs pre-PHV and post-PHV vs post PHV] and miss-matched [pre-PHV vs post-PHV] and 6 mixed maturity SSG at their respective clubs. Using mixed and fixed effect regression models, it was established hat pre-PHV players exhibited higher dRPE compared with their post-PHV counterparts. Mixed bio-banded games reported higher dRPE outputs overall. Variation in dRPE measures across a series of bio-banded games are caused by both between and within sources of variation in relatively equal amounts. Across a series of bio-banded games, the four dRPE measures do not provide unique information, and between variation is best expressed by one or two highly correlated components, with within variation best explained by a single equally loaded component. Using a bio-banding SSG design study, we have shown that pre-PHV players report higher subjective measures of exertion than post-PHV players during. Additionally, when evenly mixing players based on measures of maturation, higher measures of perceived exertion were generally reported

Micro-ion Traps for Detection of (Pre)-Biotic Organic Compounds on Comets

Comets are currently believed to be a mixture of interstellar and nebular material. Many of the volatiles in comets are attributed to interstellar chemistry, because the same species of carbonaceous compounds are also observed in ices in interstellar molecular (ISM) clouds. Comets are thus likely to be a relatively pristine reservoir of primitive material and carbonaceous compounds in our solar system. They could be a major contributor to the delivery of prebiotic organic compounds, from which life emerged through impacts on early Earth. Mass spectrometers are very powerful tools to identify unknown chemicals, and much progress bas been made in miniaturizing mas spectrometers for space applications. Most miniatu rized mass spectrometers developed to date, however, are still relatively large, power hungry, complicated to assemble, and would have significant impact on space flight vehicle total payload and resource allocations

Evaluating a Proposed 20% National Renewable Portfolio Standard

This paper provides a preliminary analysis of the impacts of a proposed 20% national renewable portfolio standard (RPS) by 2021, which has been advanced in the U.S. Congress by Senator Jeff Bingaman of New Mexico. The paper was prepared before the America Recovery and Reinvestment Act was signed into law by President Barack Obama on February 17, 2009, and thus does not consider important changes in renewable energy (RE) policy that need to be addressed in follow-on analysis. We use NREL's Regional Energy Deployment System (ReEDS) model to evaluate the impacts of the RPS requirements on the energy sector and consider design issues associated with renewable energy certificate (REC) trading markets