Association study of genes associated to asthma in a specific environment, in an asthma familial collection located in a rural area influenced by different industries

Eight candidate genes selected in this study were previously associated with gene-environment interactions in asthma in an urban area. These genes were analyzed in a familial collection from a founder and remote population (Saguenay–Lac-Saint-Jean; SLSJ) located in an area with low air levels of ozone but with localized areas of relatively high air pollutant levels, such as sulphur dioxide, when compared to many urban areas. Polymorphisms (SNPs) were extracted from the genome-wide association study (GWAS) performed on the SLSJ familial collection. A transmission disequilibrium test (TDT) was performed using the entire family sample (1,428 individuals in 254 nuclear families). Stratification according to the proximity of aluminium, pulp and paper industries was also analyzed. Two genes were associated with asthma in the entire sample before correction (CAT and NQO1) and one was associated after correction for multiple analyses (CAT). Two genes were associated when subjects were stratified according to the proximity of aluminium industries (CAT and NQO1) and one according to the proximity of pulp and paper industries (GSTP1). However, none of them resisted correction for multiple analyses. Given that the spatial pattern of environmental exposures can be complex and inadequately represented by a few stationary monitors and that exposures can also come from sources other than the standard outdoor air pollution (e.g., indoor air, occupation, residential wood smoke), a new approach and new tools are required to measure specific and individual pollutant exposures in order to estimate the real impact of gene-environment interactions on respiratory health

Reanalysis-driven climate simulation over CORDEX North America domain using the Canadian Regional Climate Model, version 5: model performance evaluation

The performance of reanalysis-driven Canadian Regional Climate Model, version 5 (CRCM5) in reproducing the present climate over the North American COordinated Regional climate Downscaling EXperiment domain for the 1989–2008 period has been assessed in comparison with several observation-based datasets. The model reproduces satisfactorily the near-surface temperature and precipitation characteristics over most part of North America. Coastal and mountainous zones remain problematic: a cold bias (2–6 °C) prevails over Rocky Mountains in summertime and all year-round over Mexico; winter precipitation in mountainous coastal regions is overestimated. The precipitation patterns related to the North American Monsoon are well reproduced, except on its northern limit. The spatial and temporal structure of the Great Plains Low-Level Jet is well reproduced by the model; however, the night-time precipitation maximum in the jet area is underestimated. The performance of CRCM5 was assessed against earlier CRCM versions and other RCMs. CRCM5 is shown to have been substantially improved compared to CRCM3 and CRCM4 in terms of seasonal mean statistics, and to be comparable to other modern RCMs

A global numerical study of radon-222 and lead-210 in the atmosphere using the AES and York University CDT General Circulation Model (AYCG)

The Canadian Climate Center (CCC) GCM has been modified to allow its use for studies in atmospheric chemistry. The initial experiments reported here have been run to test and allow sensitivity studies of the new transport module. The impact of different types of parameterization for the convective mixing have been studied based on the large scale evolution of Rn-222 and Pb-210. Preliminary results have shown that the use of a scheme, which mixes unstable columns over a very short time scale, produces a global distribution of lead that agrees in some aspects with observations. The local impact of different mixing schemes on a short lived tracer like the radon is very important

Analysis of streamflow characteristics over Northeastern Canada in a changing climate

An analysis of streamflow characteristics (i.e. mean annual and seasonal flows and extreme high and low flows) in current and future climates for 21 watersheds of north-east Canada covering mainly the province of Quebec is presented in this article. For the analysis, streamflows are derived from a 10-member ensemble of Canadian Regional Climate Model (CRCM) simulations, driven by the Canadian Global Climate Model simulations, of which five correspond to current 1970–1999 period, while the other five correspond to future 2041–2070 period. For developing projected changes of streamflow characteristics from current to future periods, two different approaches are used: one based on the concept of ensemble averaging while the other approach is based on merged samples of current and similarly future simulations following multiple comparison tests. Verification of the CRCM simulated streamflow characteristics for the 1970–1999 period suggests that the model simulated mean hydrographs and high flow characteristics compare well with those observed, while the model tends to underestimate low flow extremes. Results of projected changes to mean annual streamflow suggest statistically significant increases nearly all over the study domain, while those for seasonal streamflow show increases/decreases depending on the season. Two- and 5-year return levels of 15-day low flows are projected to increase significantly over most part of the study domain, though the changes are small in absolute terms. Based on the ensemble averaging approach, changes to 10- and 30-year return levels of high flows are not generally found significant. However, when a similar analysis is performed using longer samples, significant increases to high flow return levels are found mainly for northernmost watersheds. This study highlights the need for longer samples, particularly for extreme events in the development of robust projections

Polar mesoscale cyclones in the northeast Atlantic: Comparing climatologies from ERA-40 and satellite imagery

Polar mesoscale cyclones over the subarctic are thought to be an important component of the coupled atmosphere–ocean climate system. However, the relatively small scale of these features presents some concern as to their representation in the meteorological reanalysis datasets that are commonly used to drive ocean models. Here polar mesocyclones are detected in the 40-Year European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis dataset (ERA-40) in mean sea level pressure and 500-hPa geopotential height, using an automated cyclone detection algorithm. The results are compared to polar mesocyclones detected in satellite imagery over the northeast Atlantic, for the period October 1993–September 1995. Similar trends in monthly cyclone numbers and a similar spatial distribution are found. However, there is a bias in the size of cyclones detected in the reanalysis. Up to 80% of cyclones larger than 500 km are detected in MSL pressure, but this hit rate decreases, approximately linearly, to ∼40% for 250-km-scale cyclones and to ∼20% for 100-km-scale cyclones. Consequently a substantial component of the associated air–sea fluxes may be missing from the reanalysis, presenting a serious shortcoming when using such reanalysis data for ocean modeling simulations. Eight maxima in cyclone density are apparent in the mean sea level pressure, clustered around synoptic observing stations in the northeast Atlantic. They are likely spurious, and a result of unidentified shortcomings in the ERA-40 data assimilation procedure

Universality of Level Spacing Distributions in Classical Chaos

We suggest that random matrix theory applied to a classical action matrix can be used in classical physics to distinguish chaotic from non-chaotic behavior. We consider the 2-D stadium billiard system as well as the 2-D anharmonic and harmonic oscillator. By unfolding of the spectrum of such matrix we compute the level spacing distribution, the spectral auto-correlation and spectral rigidity. We observe Poissonian behavior in the integrable case and Wignerian behavior in the chaotic case. We present numerical evidence that the action matrix of the stadium billiard displays GOE behavior and give an explanation for it. The findings present evidence for universality of level fluctuations - known from quantum chaos - also to hold in classical physics

Reanalysis-driven climate simulation over CORDEX North America domain using the Canadian Regional Climate Model, version 5: model performance evaluation

The performance of reanalysis-driven Canadian Regional Climate Model, version 5 (CRCM5) in reproducing the present climate over the North American COordinated Regional climate Downscaling EXperiment domain for the 1989-2008 period has been assessed in comparison with several observation-based datasets. The model reproduces satisfactorily the near-surface temperature and precipitation characteristics over most part of North America. Coastal and mountainous zones remain problematic: a cold bias (2-6°C) prevails over Rocky Mountains in summertime and all year-round over Mexico; winter precipitation in mountainous coastal regions is overestimated. The precipitation patterns related to the North American Monsoon are well reproduced, except on its northern limit. The spatial and temporal structure of the Great Plains Low-Level Jet is well reproduced by the model; however, the night-time precipitation maximum in the jet area is underestimated. The performance of CRCM5 was assessed against earlier CRCM versions and other RCMs. CRCM5 is shown to have been substantially improved compared to CRCM3 and CRCM4 in terms of seasonal mean statistics, and to be comparable to other modern RCM

Increased autophagy-related 5 gene expression is associated with collagen expression in the airways of refractory asthmatics

Background: Fibrosis, particularly excessive collagen deposition, presents a challenge for treating asthmatic individuals. At present, no drugs can remove or reduce excessive collagen in asthmatic airways. Hence, the identification of pathways involved in collagen deposition would help to generate therapeutic targets to interfere with the airway remodeling process. Autophagy, a cellular degradation process, has been shown to be dysregulated in various fibrotic diseases, and genetic association studies in independent human populations have identified autophagy-related 5 (ATG5) to be associated with asthma pathogenesis. Hence, the dysregulation of autophagy may contribute to fibrosis in asthmatic airways. Objective: This study aimed to determine if (1) collagen deposition in asthmatic airways is associated with ATG5 expression and (2) ATG5 protein expression is associated with asthma per se and severity. Methods: Gene expression of transforming growth factor beta 1, various asthma-related collagen types [collagen, type I, alpha 1; collagen, type II, alpha 1; collagen, type III, alpha 1; collagen, type V, alpha 1 (COL5A1) and collagen, type V, alpha 2], and ATG5 were measured using mRNA isolated from bronchial biopsies of refractory asthmatic subjects and assessed for pairwise associations. Protein expression of ATG5 in the airways was measured and associations were assessed for asthma per se, severity, and lung function. Main results: In refractory asthmatic individuals, gene expression of ATG5 was positively associated with COL5A1 in the airways. No association was detected between ATG5 protein expression and asthma per se, severity, and lung function. Conclusion and clinical relevance: Positive correlation between the gene expression patterns of ATG5 and COL5A1 suggests that dysregulated autophagy may contribute to subepithelial fibrosis in the airways of refractory asthmatic individuals. This finding highlights the therapeutic potential of ATG5 in ameliorating airway remodeling in the difficult-to-treat refractory asthmatic individuals