Development of a genotyping microarray for Usher syndrome

Usher syndrome, a combination of retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction, displays a high degree of clinical and genetic heterogeneity. Three clinical subtypes can be distinguished, based on the age of onset and severity of the hearing impairment, and the presence or absence of vestibular abnormalities. Thus far, eight genes have been implicated in the syndrome, together comprising 347 protein-coding exons.

Genome-wide association analysis identifies 13 new risk loci for schizophrenia

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

Genetic Markers Enhance Coronary Risk Prediction in Men: The MORGAM Prospective Cohorts

Background: More accurate coronary heart disease (CHD) prediction, specifically in middle-aged men, is needed to reduce the burden of disease more effectively. We hypothesised that a multilocus genetic risk score could refine CHD prediction beyond classic risk scores and obtain more precise risk estimates using a prospective cohort design.

Methods: Using data from nine prospective European cohorts, including 26,221 men, we selected in a case-cohort setting 4,818 healthy men at baseline, and used Cox proportional hazards models to examine associations between CHD and risk scores based on genetic variants representing 13 genomic regions. Over follow-up (range: 5-18 years), 1,736 incident CHD events occurred. Genetic risk scores were validated in men with at least 10 years of follow-up (632 cases, 1361 non-cases). Genetic risk score 1 (GRS1) combined 11 SNPs and two haplotypes, with effect estimates from previous genome-wide association studies. GRS2 combined 11 SNPs plus 4 SNPs from the haplotypes with coefficients estimated from these prospective cohorts using 10-fold cross-validation. Scores were added to a model adjusted for classic risk factors comprising the Framingham risk score and 10-year risks were derived.

Results: Both scores improved net reclassification (NRI) over the Framingham score (7.5%, p = 0.017 for GRS1, 6.5%, p = 0.044 for GRS2) but GRS2 also improved discrimination (c-index improvement 1.11%, p = 0.048). Subgroup analysis on men aged 50-59 (436 cases, 603 non-cases) improved net reclassification for GRS1 (13.8%) and GRS2 (12.5%). Net reclassification improvement remained significant for both scores when family history of CHD was added to the baseline model for this male subgroup improving prediction of early onset CHD events.

Conclusions: Genetic risk scores add precision to risk estimates for CHD and improve prediction beyond classic risk factors, particularly for middle aged men.

The role of adiposity in cardiometabolic traits:a Mendelian randomization analysis

The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.

External validation of the 2008 Framingham cardiovascular risk equation for CHD and stroke events in a European population of middle-aged men. The PRIME study

To test the applicability of the sex-specific 2008 Framingham general cardiovascular risk equation for coronary heart disease (CHD) and stroke in European middle-aged men from Ireland and France.

Large-scale association analysis identifies new risk loci for coronary artery disease

Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2)

Interacting supernovae from photoionization-confined shells around red supergiant stars

Betelgeuse, a nearby red supergiant, is a runaway star with a powerful stellar wind that drives a bow shock into its surroundings. This picture has been challenged by the discovery of a dense and almost static shell that is three times closer to the star than the bow shock and has been decelerated by some external force. The two physically distinct structures cannot both be formed by the hydrodynamic interaction of the wind with the interstellar medium. Here we report that a model in which Betelgeuse's wind is photoionized by radiation from external sources can explain the static shell without requiring a new understanding of the bow shock. Pressure from the photoionized wind generates a standing shock in the neutral part of the wind and forms an almost static, photoionization-confined shell. Other red supergiants should have significantly more massive shells than Betelgeuse, because the photoionization-confined shell traps up to 35 per cent of all mass lost during the red supergiant phase, confining this gas close to the star until it explodes. After the supernova explosion, massive shells dramatically affect the supernova lightcurve, providing a natural explanation for the many supernovae that have signatures of circumstellar interaction.

Fleuve glauque : les départements de la Seine, banlieue des romans « Spécial Police » de Frédéric Dard

This paper studies the representation of suburbs as a place of anguish in the “Special Police” novels (Fleuve Noir publisher, Paris) by Frédéric Dard. This anxiety, it is argued, is what lends this collection of 25 novels some of their essential qualities, their unhealthy climate and absolute darkness. Dard’s suburbs fit into the traditions of realism; but the atmosphere, characters and plots owe to the American hardboiled school and like in film noir, space is stylized and dramatized, and often used to express a judgment of moral nature. Spatial representations in these novels are part of a critique of civilization and constitute a comment on the social modernization and public intervention in the development of the French territory in the postwar period. The novels written by Frédéric Dard from the mid-1950s to mid-1960s offer a profoundly original representation of suburban angst and what was not yet known at the time as the suburban malaise. Avoiding clichés and excessively connoted referential spaces, Dard anchor these noir novels he called “novels of the night” in landscapes that are both biographical and intertextual. The West Suburbs of Paris and what was
to become the Yvelines department are at the centre of Dard’s novelistic geography, turning into a mythical and deadly space in which is negotiated an acculturation in France of the evil and ruined world described in American noir.

Frédéric Dard: Romans de la nuit

Préface et notices accompagant la republication de sept romans parus dans la collection Spécial Police dans les années 1950 et 1960. Ces romans de suspenses psychologiques à l'atmosphère sombre, inquiétante étaient parfois désignés par les initiés sous le nom de « Romans de la nuit ».
Cette anthologie regroupe sous ce titre sept oeuvres dont l'intrigue prend la forme d'un piège à la mécanique implacable, ainsi resituées dans leur contexte culturel

. Cette mort dont tu parlais
• C'est toi le venin
• Des yeux pour pleurer
• Le Monte-charge
• L'homme de l'avenue
• La Pelouse
• Une seconde de toute beauté