Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study.

BACKGROUND Understanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention. METHODS AND FINDINGS The InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a cohort of 340,234 European participants with 3.99 million person-years of follow-up. We studied the combined effects of an additive genetic T2D risk score and modifiable and non-modifiable risk factors using Prentice-weighted Cox regression and random effects meta-analysis methods. The effect of the genetic score was significantly greater in younger individuals (p for interaction  = 1.20×10-4). Relative genetic risk (per standard deviation [4.4 risk alleles]) was also larger in participants who were leaner, both in terms of body mass index (p for interaction  = 1.50×10-3) and waist circumference (p for interaction  = 7.49×10-9). Examination of absolute risks by strata showed the importance of obesity for T2D risk. The 10-y cumulative incidence of T2D rose from 0.25% to 0.89% across extreme quartiles of the genetic score in normal weight individuals, compared to 4.22% to 7.99% in obese individuals. We detected no significant interactions between the genetic score and sex, diabetes family history, physical activity, or dietary habits assessed by a Mediterranean diet score. CONCLUSIONS The relative effect of a T2D genetic risk score is greater in younger and leaner participants. However, this sub-group is at low absolute risk and would not be a logical target for preventive interventions. The high absolute risk associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention.

Introduction aux réseaux neuronaux : de la synapse à la psyché

TABLE DES MATIERES - Préface - Avant-propos - Architecture des réseaux neuronaux - Développement des réseaux neuronaux du système nerveux central - Microcircuits, plasticité et computation - Réseaux neuronaux en fonctionnement - Vulnérabilité des réseaux neuronaux biologiques et artificiels - Conclusion générale - Glossaire - Bibliographie - Index des notions - Index des noms

HIV-1 coreceptor usage and CXCR4-specific viral load predict clinical disease progression during combination antiretroviral therapy

Background: Although combination antiretroviral therapy (cART) dramatically reduces rates of AIDS and death, a minority of patients experience clinical disease progression during treatment. <p>Objective: To investigate whether detection of CXCR4(X4)-specific strains or quantification of X4-specific HIV-1 load predict clinical outcome. Methods: From the Swiss HIV Cohort Study, 96 participants who initiated cART yet subsequently progressed to AIDS or death were compared with 84 contemporaneous, treated nonprogressors. A sensitive heteroduplex tracking assay was developed to quantify plasma X4 and CCR5 variants and resolve HIV-1 load into coreceptor-specific components. Measurements were analyzed as cofactors of progression in multivariable Cox models adjusted for concurrent CD4 cell count and total viral load, applying inverse probability weights to adjust for sampling bias. Results: Patients with X4 variants at baseline displayed reduced CD4 cell responses compared with those without X4 strains (40 versus 82 cells/mu l; P= 0.012). The adjusted multivariable hazard ratio (HR) for clinical progression was 4.8 [95% confidence interval (Cl) 2.3-10.0] for those demonstrating X4 strains at baseline. The X4-specific HIV-1 load was a similarly independent predictor, with HR values of 3.7(95%Cl, 1.2-11.3) and 5.9 (95% Cl, 2.2-15.0) for baseline loads of 2.2-4.3 and > 4.3 log(10)copies/ml, respectively, compared with < 2.2 log(10)copies/ml. Conclusions: HIV-1 coreceptor usage and X4-specific viral loads strongly predicted disease progression during cART, independent of and in addition to CD4 cell count or total viral load. Detection and quantification of X4 strains promise to be clinically useful biomarkers to guide patient management and study HIV-1 pathogenesis.

Exploring the environmental diversity of kinetoplastid flagellates in the high-throughput DNA sequencing era

The class Kinetoplastea encompasses both free-living and parasitic species from a wide range of hosts. Several representatives of this group are responsible for severe human diseases and for economic losses in agriculture and livestock. While this group encompasses over 30 genera, most of the available information has been derived from the vertebrate pathogenic genera Leishmaniaand Trypanosoma. Recent studies of the previously neglected groups of Kinetoplastea indicated that the actual diversity is much higher than previously thought. This article discusses the known segment of kinetoplastid diversity and how gene-directed Sanger sequencing and next-generation sequencing methods can help to deepen our knowledge of these interesting protists.

Recueil de Peiresc, principalement relatif aux langues orientales.

Donné en 1770 par Begon, intendant de la Marine à Dunkerque; cf. Delisle, Cab. des mss., I, 438 et III, 372

S. Jérôme, sur Isaïe.

N° 80 des mss envoyés à Paris par Maugerard en octobre 1802; cf. B.n.F., département des Manuscrits, Archives Modernes 497; — abbaye d'Echternach (dioc. de Trèves), cf. titre "Continet" et cote "B 5"; 1789. Le patrimoine libéré, 152 et n° 96; — note de Gilbert Ouy: "Ce volume a lontemps porté à la suite d'une erreur la cote 9525, sa véritable cote lui a été restituée en 1958" (f. de garde)

Documents relatifs à la canonisation de la reine Jeanne de Valois.

Acquis le 11 décembre 1830 de M. de Montmerqué de Paris par échange; cf. B.n.F., département des Manuscrits, registre des acquisitions 1828-1833, n° 78 "il a donné les procès verbaux et autres pièces originales, relatifs à la canonisation de la reine Jeanne de France de la branche de Valois fille de Louis XI et femme de Louis XII, contre quinze signatures anciennes"; — note autographe "(...) ces pièces ont été préservées de la destruction par le soussigné. Il prie messieurs les bibliothéquaires et conservateurs de la Bibliothèque du roi d'en agréer l'offre et de les réunir aux manuscrits qui concernent l'histoire de France. A Paris le 11 décembre 1830. Montmerqué, conseiller à la C. royale de Paris" (1)

Thébaïde et Achilléïde de Stace.

N° 5 des mss envoyés à Paris par Maugerard en octobre 1802; cf. B.n.F., département des Manuscrits, Archives Modernes 497; — abbaye d'Echternach (dioc. de Trèves), cf. titre "Continet"; 1789. Le patrimoine libéré, 152 et n° 96

[Petri de Riga Aurora].

Acquis le 8-12 floréal an VIII (28 avril-2 mai 1804), envoyé de la ville de Sens et remis au département des Manuscrits par le conservateur Millin, et placé dans le grenier du Levant à la suite des mss. venus de Compiègne; cf. B.n.F., département des Manuscrits, Archives Modernes 492, registre des acquisitions du département des Manuscrits an II-an XIV (1793-1805), f. 107 "Biblia sacra metrica a Petro de Riga, cod. memb. s. XIV exaratus in fol."; Delisle, Cab. des mss., II, 15; — ne provient pas de l'abbaye d'Orval (dioc. de Trèves), contrairement à l'avis de Delisle qui a confondu ce ms. et le latin 9749, cf. Cab. des mss., II, 389; A.-C. Fraeijs de Veubeke, Scriptorium, 31, 1977, 348 et 27, 1973, 106 (catalogue des mss. subsistants d'Orval) mais de l'abbaye de Vaux-Luisant, cf. latin 9562

Fragments de divers manuscrits.

Contient : I ; II

Cicéron, Songe de Scipion, avec le commentaire de Macrobe.

N° 26 des mss envoyés à Paris par Maugerard en octobre 1802; cf. B.n.F., département des Manuscrits, Archives Modernes 497; — abbaye d'Echternach (dioc. de Trèves), cf. titre "Continet"; 1789. Le patrimoine libéré, 152 et n° 96

"Comment. Boetii in periermenias librum Aristotelis.

N° 22 des mss envoyés à Paris par Maugerard en octobre 1802; cf. B.n.F., département des Manuscrits, Archives Modernes 497; — abbaye d'Echternach (dioc. de Trèves), cf. titre "Continet"; 1789. Le patrimoine libéré, 152 et n° 96