Contrasting Inequalities: Comparing Correlates of Health in Canada and the United States

Comparative health studies consistently find that Canadians on average are healthier than Americans. Comparing health status within and between Canada and the United States provides key insights into the distribution of inequalities in these two countries. Canada’s universal health care insurance system contrasts with the mixed system of the United States: universal care for seniors, private health care insurance for many, and no or intermittent coverage for others. These countries are also notably different in the extent of income and racial/ethnic inequalities. It is within this context that this study compares the relative strength of the relationships between social, economic, and demographic factors (sex, age, marital status, income, education, country of birth, and race/ethnicity) and health status in Canada and the United States. Evidence drawn from the 2002-2003 Joint Canada/United States Survey of Health reveals that the correlations between these factors, above all country of birth and race/ethnicity, and health are relatively stronger in the United States, reflecting differences in health care access and racial/ethnic-based inequalities between the countries. The study findings are suggestive of the effects of universal access to health care and more equitable distribution of other social resources in protecting the health of the general population.self-reported health, United States, Canada, health insurance, income, race, ethnicity, age, sex

beadarrayFilter : an R package to filter beads

Microarrays enable the expression levels of thousands of genes to be measured simultaneously. However, only a small fraction of these genes are expected to be expressed under different experimental conditions. Nowadays, filtering has been introduced as a step in the microarray preprocessing pipeline. Gene filtering aims at reducing the dimensionality of data by filtering redundant features prior to the actual statistical analysis. Previous filtering methods focus on the Affymetrix platform and can not be easily ported to the Illumina platform. As such, we developed a filtering method for Illumina bead arrays. We developed an R package, beadarrayFilter, to implement the latter method. In this paper, the main functions in the package are highlighted and using many examples, we illustrate how beadarrayFilter can be used to filter bead arrays

NUMERICAL MODELLING OF THE COMBUSTION PROCESS AND EMISSIONS FORMATION OF KEROSENE AND ITS BLENDS IN DIESEL ENGINES

Ph.DDOCTOR OF PHILOSOPH

Ligand Selectivity in the Recognition of Protoberberine Alkaloids by Hybrid-2 Human Telomeric G-Quadruplex: Binding Free Energy Calculation, Fluorescence Binding, and NMR Experiments

The human telomeric G-quadruplex (G4) is an attractive target for developing anticancer drugs. Natural products protoberberine alkaloids are known to bind human telomeric G4 and inhibit telomerase. Among several structurally similar protoberberine alkaloids, epiberberine (EPI) shows the greatest specificity in recognizing the human telomeric G4 over duplex DNA and other G4s. Recently, NMR study revealed that EPI recognizes specifically the hybrid-2 form human telomeric G4 by inducing large rearrangements in the 50-flanking segment and loop regions to form a highly extensive four-layered binding pocket. Using the NMR structure of the EPI-human telomeric G4 complex, here we perform molecular dynamics free energy calculations to elucidate the ligand selectivity in the recognition of protoberberines by the human telomeric G4. The MM-PB(GB)SA (molecular mechanics-Poisson Boltzmann/Generalized Born) Surface Area) binding free energies calculated using the Amber force fields bsc0 and OL15 correlate well with the NMR titration and binding affinity measurements, with both calculations correctly identifying the EPI as the strongest binder to the hybrid-2 telomeric G4 wtTel26. The results demonstrated that accounting for the conformational flexibility of the DNA-ligand complexes is crucially important for explaining the ligand selectivity of the human telomeric G4. While the MD-simulated (molecular dynamics) structures of the G-quadruplex-alkaloid complexes help rationalize why the EPI-G4 interactions are optimal compared with the other protoberberines, structural deviations from the NMR structure near the binding site are observed in the MD simulations. We have also performed binding free energy calculation using the more rigorous double decoupling method (DDM); however, the results correlate less well with the experimental trend, likely due to the difficulty of adequately sampling the very large conformational reorganization in the G4 induced by the protoberberine binding

Asymptotic behaviour of a semilinear elliptic system with a large exponent

Consider the problem \begin{eqnarray*} -\Delta u &=& v^{\frac 2{N-2}},\quad v>0\quad {in}\quad \Omega, -\Delta v &=& u^{p},\:\:\:\quad u>0\quad {in}\quad \Omega, u&=&v\:\:=\:\:0 \quad {on}\quad \partial \Omega, \end{eqnarray*} where $\Omega$ is a bounded convex domain in $\R^N,$ $N>2,$ with smooth boundary $\partial \Omega.$ We study the asymptotic behaviour of the least energy solutions of this system as $p\to \infty.$ We show that the solution remain bounded for $p$ large and have one or two peaks away form the boundary. When one peak occurs we characterize its location.Comment: 16 pages, submmited for publicatio

Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia

Mitochondrial metabolism recently emerged as a critical dependency in acute myeloid leukemia (AML). The shape of mitochondria is tightly regulated by dynamin GTPase proteins, which drive opposing fusion and fission forces to consistently adapt bioenergetics to the cellular context. Here, we showed that targeting mitochondrial fusion was a new vulnerability of AML cells, when assayed in patient-derived xenograft (PDX) models. Genetic depletion of mitofusin 2 (MFN2) or optic atrophy 1 (OPA1) or pharmacological inhibition of OPA1 (MYLS22) blocked mitochondrial fusion and had significant anti-leukemic activity, while having limited impact on normal hematopoietic cells ex vivo and in vivo. Mechanistically, inhibition of mitochondrial fusion disrupted mitochondrial respiration and reactive oxygen species production, leading to cell cycle arrest at the G$_{0}$/G$_{1}$ transition. These results nominate the inhibition of mitochondrial fusion as a promising therapeutic approach for AML

Comparison of the properties of two fossil groups of galaxies with the normal group NGC 6034 based on multiband imaging and optical spectroscopy

We collected multiband imaging and spectroscopy for two fossil groups (RX J1119.7+2126 and 1RXS J235814.4+150524) and one normal group (NGC 6034). We computed photometric redshifts in the central zones of each group, combining previous data with the SDSS five-band data. For each group we investigated the red sequence (RS) of the color-magnitude relation and computed the luminosity functions, stellar population ages and distributions of the group members. Spectroscopy allowed us to investigate the large-scale surroundings of these groups and the substructure levels in 1RXS J235814.4+150524 and NGC 6034. The large-scale environment of 1RXS J235814.4+150524 is poor, though its galaxy density map shows a clear signature of the surrounding cosmic web. RX J1119.7+2126 appears to be very isolated, while the cosmic environment of NGC 6034 is very rich. At the group scale, 1RXS J235814.4+150524 shows no substructure. Galaxies with recent stellar populations seem preferentially located in the group outskirts. A RS is discernable for all three groups in a color-magnitude diagram. The luminosity functions based on photometric redshift selection and on statistical background subtraction have comparable shapes, and agree with the few points obtained from spectroscopic redshifts. These luminosity functions show the expected dip between first and second brightest galaxies for the fossil groups only. Their shape is also regular and relatively flat at faint magnitudes down to the completeness level for RX J1119.7+2126 and NGC 6034, while there is a clear lack of faint galaxies for 1RXS J235814.4+150524. RX J1119.7+2126 is definitely classified as a fossil group; 1RXS J235814.4+150524 also has properties very close to those of a fossil group, while we confirm that NGC 6034 is a normal group.Comment: Accepted in A&A, english-improved, 5 jpeg figures, and shortened abstrac

Predicting erythropoietin resistance in hemodialysis patients with type 2 diabetes

<p>Background: Resistance to ESAs (erythropoietin stimulating agents) is highly prevalent in hemodialysis patients with diabetes and associated with an increased mortality. The aim of this study was to identify predictors for ESA resistance and to develop a prediction model for the risk stratification in these patients.</p> <p>Methods: A post-hoc analysis was conducted of the 4D study, including 1015 patients with type 2 diabetes undergoing hemodialysis. Determinants of ESA resistance were identified by univariate logistic regression analyses. Subsequently, multivariate models were performed with stepwise inclusion of significant predictors from clinical parameters, routine laboratory and specific biomarkers.</p> <p>Results: In the model restricted to clinical parameters, male sex, shorter dialysis vintage, lower BMI, history of CHF, use of ACE-inhibitors and a higher heart rate were identified as independent predictors of ESA resistance. In regard to routine laboratory markers, lower albumin, lower iron saturation, higher creatinine and higher potassium levels were independently associated with ESA resistance. With respect to specific biomarkers, higher ADMA and CRP levels as well as lower Osteocalcin levels were predictors of ESA resistance.</p> <p>Conclusions: Easily obtainable clinical parameters and routine laboratory parameters can predict ESA resistance in diabetic hemodialysis patients with good discrimination. Specific biomarkers did not meaningfully further improve the risk prediction of ESA resistance. Routinely assessed data can be used in clinical practice to stratify patients according to the risk of ESA resistance, which may help to assign appropriate treatment strategies.</p&gt