Genome-wide association study to identify common variants associated with brachial circumference: a meta-analysis of 14 cohorts.

Brachial circumference (BC), also known as upper arm or mid arm circumference, can be used as an indicator of muscle mass and fat tissue, which are distributed differently in men and women. Analysis of anthropometric measures of peripheral fat distribution such as BC could help in understanding the complex pathophysiology behind overweight and obesity. The purpose of this study is to identify genetic variants associated with BC through a large-scale genome-wide association scan (GWAS) meta-analysis. We used fixed-effects meta-analysis to synthesise summary results across 14 GWAS discovery and 4 replication cohorts comprising overall 22,376 individuals (12,031 women and 10,345 men) of European ancestry. Individual analyses were carried out for men, women, and combined across sexes using linear regression and an additive genetic model: adjusted for age and adjusted for age and BMI. We prioritised signals for follow-up in two-stages. We did not detect any signals reaching genome-wide significance. The FTO rs9939609 SNP showed nominal evidence for association (p<0.05) in the age-adjusted strata for men and across both sexes. In this first GWAS meta-analysis for BC to date, we have not identified any genome-wide significant signals and do not observe robust association of previously established obesity loci with BC. Large-scale collaborations will be necessary to achieve higher power to detect loci underlying BC.

Caractéristiques de la clientèle des structures à bas seuil d'accès pour toxicomanes mettant à disposition du matériel d'injection stérile en Suisse [Characteristics of attenders of low threshold syringe-exchange centers providing sterile syringes in Switzerland].

BACKGROUND: The objectives of the present study were to evaluate Aids prevention in drug users attending low threshold centres providing sterile injection equipment in Switzerland, to identify the characteristics of these users, and to monitor the progress of indicators of drug-related harm. METHODS: This paper presents results from a cross-sectional survey carried out in 1994. RESULTS: The mean age of attenders was 28 years, and women represented 27% of the sample. 75% of attenders used a combination of hard drugs (heroin and cocaine). Mean duration of heroin consumption was 8 years, and of cocaine 7 years; 76% of attenders had a fixed abode, but only 34% had stable employment; 45% were being treated with methadone; 9% had shared their injection material in the last 6 months; 24% always used condoms in the case of a stable relationship, and 71% in casual relationships. In a cluster analysis constructed on the basis of multiple correspondence analysis, two distinct profiles of users emerge: highly marginalised users with a high level of consumption (21%); irregular users, better integrated socially, of which the majority are under methadone treatment (79%). CONCLUSION: Theses centres play a major role in Aids prevention. Nevertheless, efforts to improve the hygiene conditions of drug injection in Switzerland should be pursued and extended. At the same time, prevention of HIV sexual transmissions should be reinforced.

Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations.

High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10(-8)) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability.

A methodology for the classification of convective structures using meteorological radar: Application to heavy rainfall events on the Mediterranean coast of the Iberian Peninsula

During the period 1996-2000, forty-three heavy rainfall events have been detected in the Internal Basins of Catalonia (Northeastern of Spain). Most of these events caused floods and serious damage. This high number leads to the need for a methodology to classify them, on the basis of their surface rainfall distribution, their internal organization and their physical features. The aim of this paper is to show a methodology to analyze systematically the convective structures responsible of those heavy rainfall events on the basis of the information supplied by the meteorological radar. The proposed methodology is as follows. Firstly, the rainfall intensity and the surface rainfall pattern are analyzed on the basis of the raingauge data. Secondly, the convective structures at the lowest level are identified and characterized by using a 2-D algorithm, and the convective cells are identified by using a 3-D procedure that looks for the reflectivity cores in every radar volume. Thirdly, the convective cells (3-D) are associated with the 2-D structures (convective rainfall areas). This methodology has been applied to the 43 heavy rainfall events using the meteorological radar located near Barcelona and the SAIH automatic raingauge network.

Expression of common acute lymphoblastic leukemia antigen (CALLA) on human malignant melanoma cell lines.

Fifteen human melanoma cells lines were tested by an antibody-binding radioimmunoassay using a monoclonal antibody (A12) directed against the common acute lymphoblastic leukemia antigen (CALLA). Cells from six melanoma lines were found to react with this antibody. The level of antigen and the percentage of positive cells in these six melanoma lines showed wide variation, as demonstrated by analysis in the fluorescence-activated cell sorter (FACS). Immunoprecipitation of solubilized 125I-labeled membrane proteins from CALLA positive melanoma cells with A12 monoclonal antibody revealed a major polypeptide chain with an apparent m.w. of 100,000 daltons, characteristic for CALLA as determined on SDS-polyacrylamide gel electrophoresis. The expression of CALLA on MP-6 melanoma cells was modulated when the cells were cultured in the presence of A12 antibody. Reexpression of CALLA on these cells occurred within 5 days after transfer of the modulated cells into medium devoid of monoclonal antibody.

Precarious Work: Agenda and Implications for Corporate Social Responsibility

Precarious work, in contrast to regular, permanent wage work, is commonly associated to insecure and unstable, and often poor quality jobs. The concept of precarious work relates either to a socioeconomic group which allows one to refer it to a "class in itself," or as - pursued more recently - to the precarization process which results in a growing fragmentation of societal structures. Common to both conceptions is that they refer to the exposition of workers to employment instability, limited access to legal and union protection, socially irresponsible and discriminating employment practices, and social and economic vulnerability in general. The present contribution provides an overview of some key issues and future directions of research on precarious work relevant to CSR researchers, policy-makers, and social scientists.

Leaf senescence of common bean plants as affected by soil phosphorus supply

Responses of leaf senescence to P supply could constitute adaptive mechanisms for plant growth under P-limiting conditions. The aim of this study was to evaluate the effects of soil P supply on leaf senescence of common bean (Phaseolus vulgaris L.). Eight P levels, ranging from 5 to 640 mg kg-1 P, were applied to pots containing four bean plants of cultivar Carioca in 10 kg of an Oxic Haplustult soil. Attached leaves were counted weekly, abscised leaves were collected every other day, and seeds were harvested at maturity. The number of live leaves increased until 48 days after emergence (DAE) and decreased afterwards, irrespective of applied P levels. At lower applied P levels, the initial increase and the final decrease of leaf number was weak, whereas at higher applied P levels the leaf number increased intensively at the beginning of the growth cycle and decreased strongly after 48 DAE. Dry matter and P accumulated in senesced leaves increased as soil P levels increased until 61 DAE, but differences between P treatments narrowed thereafter. The greatest amounts of dry mass and P deposited by senesced leaves were observed at 48-54 DAE for high P levels, at 62-68 DAE for intermediate P levels and at 69-76 DAE for low P levels. These results indicate that soil P supply did not affect the stage of maximal leaf number and the beginning of leaf senescence of common bean plants, but the stage of greatest deposition of senesced leaves occurred earlier in the growth cycle as the soil P supply was raised.

Microsatellite markers reveal shallow genetic differentiation between cohorts of the common sea urchin Paracentrotus lividus (Lamarck) in northwest Mediterranean

Temporal variability was studied in the common sea urchin Paracentrotus lividus through the analysis of the genetic composition of three yearly cohorts sampled over two consecutive springs in a locality in northwestern Mediterranean. Individuals were aged using growth ring patterns observed in tests and samples were genotyped for five microsatellite loci. No reduction of genetic diversity was observed relative to a sample of the adult population from the same location or within cohorts across years. FST and amova results indicated that the differentiation between cohorts is rather shallow and not significant, as most variability is found within cohorts and within individuals. This mild differentiation translated into estimates of effective population size of 90100 individuals. When the observed excess of homozygotes was taken into account, the estimate of the average number of breeders increased to c. 300 individuals. Given our restricted sampling area and the known small-scale heterogeneity in recruitment in this species, our results suggest that at stretches of a few kilometres of shoreline, large numbers of progenitors are likely to contribute to the larval pool at each reproduction event. Intercohort variation in our samples is six times smaller than spatial variation between adults of four localities in the western Mediterranean. Our results indicate that, notwithstanding the stochastic events that take place during the long planktonic phase and during the settlement and recruitment processes, reproductive success in this species is high enough to produce cohorts genetically diverse and with little differentiation between them. Further research is needed before the link between genetic structure and underlying physical and biological processes can be well established.

Relationships between grain yield and accumulation of biomass, nitrogen and phosphorus in common bean cultivars

Shoot biomass is considered a relevant component for crop yield, but relationships between biological productivity and grain yield in legume crops are usually difficult to establish. Two field experiments were carried out to investigate the relationships between grain yield, biomass production and N and P accumulation at reproductive stages of common bean (Phaseolus vulgaris) cultivars. Nine and 18 cultivars were grown on 16 m² plots in 1998 and 1999, respectively, with four replications. Crop biomass was sampled at four growth stages (flowering R6, pod setting R7, beginning of pod filling R8, and mid-pod filling R8.5), grain yield was measured at maturity, and N and P concentrations were determined in plant tissues. In both years, bean cultivars differed in grain yield, in root mass at R6 and R7 stages, and in shoot mass at R6 and R8.5, whereas at R7 and R8 differences in shoot mass were significant in 1998 only. In both years, grain yield did not correlate with shoot mass at R6 and R7 and with root mass at R6. Grain yield correlated with shoot mass at R8 in 1999 but not in 1998, with shoot mass at R8.5 and with root mass at R7 in both years. Path coefficient analysis indicated that shoot mass at R8.5 had a direct effect on grain yield in both years, that root mass at R7 had a direct effect on grain yield in 1998, and that in 1999 the amounts of N and P in shoots at R8.5 had indirect effects on grain yield via shoot mass at R8.5. A combined analysis of both experiments revealed that biomass accumulation, N and P in shoots at R6 and R7 as well as root mass at R6 were similar in both years. In 1998 however bean accumulated more root mass at R7 and more biomass and N and P in shoots at R8 and R8.5, resulting in a 57 % higher grain yield in 1998. This indicates that grain yield of different common bean cultivars is not intrinsically associated with vegetative vigor at flowering and that mechanisms during pod filling can strongly influence the final crop yield. The establishment of a profuse root system during pod setting, associated with the continuous N and P acquisition during early pod filling, seems to be relevant for higher grain yields of common bean.

Common variants in the ATP2B1 gene are associated with susceptibility to hypertension: the Japanese Millennium Genome Project.

Hypertension is one of the most common complex genetic disorders. We have described previously 38 single nucleotide polymorphisms (SNPs) with suggestive association with hypertension in Japanese individuals. In this study we extend our previous findings by analyzing a large sample of Japanese individuals (n=14 105) for the most associated SNPs. We also conducted replication analyses in Japanese of susceptibility loci for hypertension identified recently from genome-wide association studies of European ancestries. Association analysis revealed significant association of the ATP2B1 rs2070759 polymorphism with hypertension (P=5.3×10(-5); allelic odds ratio: 1.17 [95% CI: 1.09 to 1.26]). Additional SNPs in ATP2B1 were subsequently genotyped, and the most significant association was with rs11105378 (odds ratio: 1.31 [95% CI: 1.21 to 1.42]; P=4.1×10(-11)). Association of rs11105378 with hypertension was cross-validated by replication analysis with the Global Blood Pressure Genetics consortium data set (odds ratio: 1.13 [95% CI: 1.05 to 1.21]; P=5.9×10(-4)). Mean adjusted systolic blood pressure was highly significantly associated with the same SNP in a meta-analysis with individuals of European descent (P=1.4×10(-18)). ATP2B1 mRNA expression levels in umbilical artery smooth muscle cells were found to be significantly different among rs11105378 genotypes. Seven SNPs discovered in published genome-wide association studies were also genotyped in the Japanese population. In the combined analysis with replicated 3 genes, FGF5 rs1458038, CYP17A1, rs1004467, and CSK rs1378942, odds ratio of the highest risk group was 2.27 (95% CI: 1.65 to 3.12; P=4.6×10(-7)) compared with the lower risk group. In summary, this study confirmed common genetic variation in ATP2B1, as well as FGF5, CYP17A1, and CSK, to be associated with blood pressure levels and risk of hypertension.

Testing for multicointegration in panel data with common factors

The paper addresses the concept of multicointegration in panel data frame- work. The proposal builds upon the panel data cointegration procedures developed in Pedroni (2004), for which we compute the moments of the parametric statistics. When individuals are either cross-section independent or cross-section dependence can be re- moved by cross-section demeaning, our approach can be applied to the wider framework of mixed I(2) and I(1) stochastic processes analysis. The paper also deals with the issue of cross-section dependence using approximate common factor models. Finite sample performance is investigated through Monte Carlo simulations. Finally, we illustrate the use of the procedure investigating inventories, sales and production relationship for a panel of US industries.

Efectos regionales de la política monetaria : implicaciones para los países de la zona euro

De acuerdo con la teoría de las áreas monetàrias óptimas,los shocks asimétricos tienen un papel fundamental en la determinación de los beneficios y los costes derivados del establecimiento de una área monetaria. En este sentido, diferentes estudios recientes señalan una importante reducción del grado de asimetría de los shocks en términos reales a lo largo de los últimos años entre los países europeos como consecuencia de la mayor coordinación de las políticas económicas y de la aproximación de las estructuras productivas. De todas maneras, una de las cuestiones clave en el nuevo entorno económico, y que no ha sido demasiado considerada a la literatura reciente, es el posible papel desestabilitzador de la política monetaria común como consecuencia de las diferencias en los mecanismos de transmisión de la política monetaria en los distintos países y regiones de la Zona Euro. En este trabajo se considera la mencionada cuestión desde un punto de vista teórico y se analiza empíricamente la existencia de diferencias regionales en los efectos de la política monetaria llevada a término en España a lo largo de los últimos años con la finalidad d identificar los principales determinantes de esta asimetría en el ámbito europeo

Unipolar transport and shot noise in metal-semiconductor-metal structures

We carry out a self-consistent analytical theory of unipolar current and noise properties of metal-semiconductor-metal structures made of highly resistive semiconductors in the presence of an applied bias of arbitrary strength. By including the effects of the diffusion current we succeed in studying the whole range of carrier injection conditions going from low level injection, where the structure behaves as a linear resistor, to high level injection, where the structure behaves as a space charge limited diode. We show that these structures display shot noise at the highest voltages. Remarkably the crossover from Nyquist noise to shot noise exhibits a complicated behavior with increasing current where an initial square root dependence (double thermal noise) is followed by a cubic power law.