The C242T polymorphism of the NAD(P)H oxidase p22(phox) subunit is associated with an enhanced risk for cerebrovascular disease at a young age

Background and Purpose: Oxidative stress has been proposed as a major contributing factor for vascular disease, that acts independently from its participation in predisposing disorders such as diabetes and arterial hypertension. A functionally relevant C242T polymorphism of the CYBA gene encoding the NAD(P)H oxidase p22(phox) subunit, is supposed to lead to an abnormal reduction in the generation of reactive oxygen species in vascular smooth-muscle and endothelial cells. Methods: We investigated the p22(phox) C242T single-nucleotide polymorphism by polymerase chain reaction in consecutive patients with ischemic stroke or transient ischemic attack under the age of 50 (n = 161) and in population-based control subjects (n = 136). Results: Homozygosity for the T variant was associated with an enhanced risk for cerebral ischemia (odds ratio 3.85, confidence interval 1.39-10.64) after adjusting for classical risk factors. Risk for cerebral ischemia was not increased in heterozygous subjects. Conclusion: The p22(phox) C242T single-nucleotide polymorphism is associated with stroke risk. This finding supports the hypothesis that oxidative stress may contribute to stroke pathogenesis. Copyright (C) 2008 S. Karger AG, Basel

Information Acquisition and Adoption of Organic Farming Practices

This study offers an empirical framework for analyzing farmers' joint decisions to adopt organic farming practices and to seek technical (i.e., farming) information from various sources. To that end, a trivariate ordered probit model is specified and implemented in the case of organic land conversion in Crete, Greece. Findings suggest that the decisions of information acquisition and organic land conversion are indeed correlated, and different farming information sources play a complementary role. Structural policies improving the farmer's allocative ability are found to play an important role in encouraging organic farming adoption.Crete, Greece, information acquisition, organic farming, technology adoption, Farm Management,

‘Together … for only a moment’ British newspaper constructions of altruistic non-commercial surrogate motherhood

Objectives: To explore how national altruistic surrogacy is framed in a representative selection of the British press. Methods: A study of 90 British national newspaper articles was carried out using the Lexis-Nexis data base to search for articles on altruistic surrogacy. Content analysis of gain, loss, neutral frames and high or low alarm and vulnerability frames in the titles and the body of the text was carried out. The type of construction used in the article content was also analysed. Data were coded and consensus reached using a coding strategy specifically developed for the purposes of this study. Results: Titles and content were predominantly loss, high alarm and high vulnerability framed. The content was also gain framed, and written with a focus on the social and legal aspects differentially between the newspaper types. Discussion: The tabloid press emphasizes social issues, and the middle market and serious press focus on legal issues of altruistic surrogacy. Selectively framed and reinforced information provided by the different newspapers, reflect the different readership, with Tabloid readers likely to be, surrogates (mostly from lower socioeconomic strata) and serious/ middle-market readers likely to be commissioning parents (mostly professionals)

Non-Baryonic Dark Matter - Observational Evidence and Detection Methods

The evidence for the existence of dark matter in the universe is reviewed. A general picture emerges, where both baryonic and non-baryonic dark matter is needed to explain current observations. In particular, a wealth of observational information points to the existence of a non-baryonic component, contributing between around 20 and 40 percent of the critical mass density needed to make the universe geometrically flat on large scales. In addition, an even larger contribution from vacuum energy (or cosmological constant) is indicated by recent observations. To the theoretically favoured particle candidates for non-baryonic dark matter belong axions, supersymmetric particles, and of less importance, massive neutrinos. The theoretical foundation and experimental situation for each of these is reviewed. Direct and indirect methods for detection of supersymmetric dark matter are described in some detail. Present experiments are just reaching the required sensitivity to discover or rule out some of these candidates, and major improvements are planned over the coming years.Comment: Submitted to Reports on Progress in Physics, 59 pages, LaTeX, iopart macro, 14 embedded postscript figure

Neutralino-Nucleon Cross Section and Charge and Colour Breaking Constraints

We compute the neutralino-nucleon cross section in several supersymmetric scenarios, taking into account all kind of constraints. In particular, the constraints that the absence of dangerous charge and colour breaking minima imposes on the parameter space are studied in detail. In addition, the most recent experimental constraints, such as the lower bound on the Higgs mass, the $b\to s\gamma$ branching ratio, and the muon $g-2$ are considered. The astrophysical bounds on the dark matter density are also imposed on the theoretical computation of the relic neutralino density, assuming thermal production. This computation is relevant for the theoretical analysis of the direct detection of dark matter in current experiments. We consider first the supergravity scenario with universal soft terms and GUT scale. In this scenario the charge and colour breaking constraints turn out to be quite important, and \tan\beta\lsim 20 is forbidden. Larger values of $\tan\beta$ can also be forbidden, depending on the value of the trilinear parameter $A$. Finally, we study supergravity scenarios with an intermediate scale, and also with non-universal scalar and gaugino masses where the cross section can be very large.Comment: Final version to appear in JHE

Impact of Selection Bias on Estimation of Subsequent Event Risk

BACKGROUND: Studies of recurrent or subsequent disease events may be susceptible to bias caused by selection of subjects who both experience and survive the primary indexing event. Currently, the magnitude of any selection bias, particularly for subsequent time-to-event analysis in genetic association studies, is unknown. METHODS AND RESULTS: We used empirically inspired simulation studies to explore the impact of selection bias on the marginal hazard ratio for risk of subsequent events among those with established coronary heart disease. The extent of selection bias was determined by the magnitudes of genetic and nongenetic effects on the indexing (first) coronary heart disease event. Unless the genetic hazard ratio was unrealistically large (>1.6 per allele) and assuming the sum of all nongenetic hazard ratios was <10, bias was usually <10% (downward toward the null). Despite the low bias, the probability that a confidence interval included the true effect decreased (undercoverage) with increasing sample size because of increasing precision. Importantly, false-positive rates were not affected by selection bias. CONCLUSIONS: In most empirical settings, selection bias is expected to have a limited impact on genetic effect estimates of subsequent event risk. Nevertheless, because of undercoverage increasing with sample size, most confidence intervals will be over precise (not wide enough). When there is no effect modification by history of coronary heart disease, the false-positive rates of association tests will be close to nominal

Genome-wide analysis identifies novel susceptibility loci for myocardial infarction

AIMS: While most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation. METHODS AND RESULTS: We carried out a genome-wide association study for MI in the UK Biobank (n∼472 000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (n∼167 000). Multiple independent replication analyses and functional approaches were used to prioritize loci and evaluate positional candidate genes. Eight novel regions were identified for MI at the genome wide significance level, of which effect sizes at six loci were more robust for MI than for CAD without the presence of MI. Confirmatory evidence for association of a locus on chromosome 1p21.3 harbouring choline-like transporter 3 (SLC44A3) with MI in the context of CAD, but not with coronary atherosclerosis itself, was obtained in Biobank Japan (n∼165 000) and 16 independent angiography-based cohorts (n∼27 000). Follow-up analyses did not reveal association of the SLC44A3 locus with CAD risk factors, biomarkers of coagulation, other thrombotic diseases, or plasma levels of a broad array of metabolites, including choline, trimethylamine N-oxide, and betaine. However, aortic expression of SLC44A3 was increased in carriers of the MI risk allele at chromosome 1p21.3, increased in ischaemic (vs. non-diseased) coronary arteries, up-regulated in human aortic endothelial cells treated with interleukin-1β (vs. vehicle), and associated with smooth muscle cell migration in vitro. CONCLUSIONS: A large-scale analysis comprising ∼831 000 subjects revealed novel genetic determinants of MI and implicated SLC44A3 in the pathophysiology of vulnerable plaques

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

BACKGROUND: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. METHODS: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. FINDINGS: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14-1·83) and the presence of either LPA SNP (1·88, 1·40-2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81-1·11 and either LPA SNP 1·10, 0·92-1·31) or cardiovascular mortality (0·99, 0·81-1·2 and 1·13, 0·90-1·40, respectively) or in the validation studies. INTERPRETATION: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. FUNDING: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny