Dissecting the genetic heterogeneity of depression through age at onset.

Genome-wide studies in major depression have identified few replicated associations, potentially due to heterogeneity within the disorder. Several studies have suggested that age at onset (AAO) can distinguish sub-types of depression with specific heritable components. This paper investigates the role of AAO in the genetic susceptibility for depression using genome-wide association data on 2,746 cases and 1,594 screened controls from the RADIANT studies, with replication performed in 1,471 cases and 1,403 controls from two Munich studies. Three methods were used to analyze AAO: First a time-to-event analysis with controls censored, secondly comparing controls to case-subsets defined using AAO cut-offs, and lastly analyzing AAO as a quantitative trait. In the time-to-event analysis three SNPs reached suggestive significance (P < 5E-06), overlapping with the original case-control analysis of this study. In a case-control analysis using AAO thresholds, SNPs in 10 genomic regions showed suggestive association though again none reached genome-wide significance. Lastly, case-only analysis of AAO as a quantitative trait resulted in 5 SNPs reaching suggestive significance. Sex specific analysis was performed as a secondary analysis, yielding one SNP reaching genome-wide significance in early-onset males. No SNPs achieved significance in the replication study after correction for multiple testing. Analysis of AAO as a quantitative trait did suggest that, across all SNPs, common genetic variants explained a large proportion of the variance (51%, P = 0.04). This study provides the first focussed analysis of the genetic contribution to AAO in depression, and establishes a statistical framework that can be applied to a quantitative trait underlying any disorder. © 2012 Wiley Periodicals, Inc.

Design, synthesis and biological evaluation of a class of bioisosteric oximes of the novel dual peroxisome proliferator-activated receptor α/γ ligand LT175.

The effects resulting from the introduction of an oxime group in place of the distal aromatic ring of the diphenyl moiety of LT175, previously reported as a PPARα/γ dual agonist, have been investigated. This modification allowed the identification of new bioisosteric ligands with fairly good activity on PPARα and fine-tuned moderate activity on PPARγ. For the most interesting compound (S)-3, docking studies in PPARα and PPARγ provided a molecular explanation for its different behavior as full and partial agonist of the two receptor isotypes, respectively. A further investigation of this compound was carried out performing gene expression studies on HepaRG cells. The results obtained allowed to hypothesize a possible mechanism through which this ligand could be useful in the treatment of metabolic disorders. The higher induction of the expression of some genes, compared to selective agonists, seems to confirm the importance of a dual PPARα/γ activity which probably involves a synergistic effect on both receptor subtypes.

Complications et atteintes systémiques de la polyarthrite rhumatoïde [Complications and systemic manifestations of rheumatoid arthritis].

Rheumatoid arthritis (RA), in addition to the traditional joint damage can affect all organs as a systemic disease. Extra-articular manifestations of RA are highly variable ranging from rheumatoid nodules (most common) to rheumatoid vasculitis presenting a significant morbidity and mortality (49% at 5 years). With the new algorithms of treatment (earlier) and the use of biologics, the incidence of severe extra-articular manifestations decreases. Regarding the treatment of rheumatoid vasculitis, rituximab looks promising. RA also increases cardiovascular risk and the risk of osteoporosis. It is therefore important to identify these risks and, if appropriate, treat them. Collaboration with the general practitioner is essential in this situation.

[Archives de la Parole]. , Een liedje van de zee : neederlandsch lied / [Julius Röntgen, comp.] ; Hendrik Christiaan van Oort, baryton-basse ; accompagnement de piano. O kerstnacht, schooner dan de daegen : [kerstlied] / [Cornelis Padbrué ou Dirck Janszoon Sweeling, comp.] ; Hendrik Christiaan van Oort, baryton-basse

Néerlandais (flamand)

Exposition des oeuvres de Edouard Manet : catalogue / Ecole nationale des beaux-arts ; préface [et synthèse] de Emile Zola. [Discours prononcé par M. Antonin Proust sur la tombe de Manet]

[Exposition. Paris, Ecole nationale supérieure des Beaux Arts. 1884]

Oral rivaroxaban for symptomatic venous thromboembolism.

BACKGROUND: Rivaroxaban, an oral factor Xa inhibitor, may provide a simple, fixed-dose regimen for treating acute deep-vein thrombosis (DVT) and for continued treatment, without the need for laboratory monitoring. METHODS: We conducted an open-label, randomized, event-driven, noninferiority study that compared oral rivaroxaban alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with subcutaneous enoxaparin followed by a vitamin K antagonist (either warfarin or acenocoumarol) for 3, 6, or 12 months in patients with acute, symptomatic DVT. In parallel, we carried out a double-blind, randomized, event-driven superiority study that compared rivaroxaban alone (20 mg once daily) with placebo for an additional 6 or 12 months in patients who had completed 6 to 12 months of treatment for venous thromboembolism. The primary efficacy outcome for both studies was recurrent venous thromboembolism. The principal safety outcome was major bleeding or clinically relevant nonmajor bleeding in the initial-treatment study and major bleeding in the continued-treatment study. RESULTS: The study of rivaroxaban for acute DVT included 3449 patients: 1731 given rivaroxaban and 1718 given enoxaparin plus a vitamin K antagonist. Rivaroxaban had noninferior efficacy with respect to the primary outcome (36 events [2.1%], vs. 51 events with enoxaparin-vitamin K antagonist [3.0%]; hazard ratio, 0.68; 95% confidence interval [CI], 0.44 to 1.04; P<0.001). The principal safety outcome occurred in 8.1% of the patients in each group. In the continued-treatment study, which included 602 patients in the rivaroxaban group and 594 in the placebo group, rivaroxaban had superior efficacy (8 events [1.3%], vs. 42 with placebo [7.1%]; hazard ratio, 0.18; 95% CI, 0.09 to 0.39; P<0.001). Four patients in the rivaroxaban group had nonfatal major bleeding (0.7%), versus none in the placebo group (P=0.11). CONCLUSIONS: Rivaroxaban offers a simple, single-drug approach to the short-term and continued treatment of venous thrombosis that may improve the benefit-to-risk profile of anticoagulation. (Funded by Bayer Schering Pharma and Ortho-McNeil; ClinicalTrials.gov numbers, NCT00440193 and NCT00439725.).

Radiation doses in computed tomography: pitfalls in comparing CT to chest X-ray

Rapid response to : Madan M Rehani and Manorma Berry Radiation doses in computed tomography BMJ 2000; 320: 593-594

Dictionnaire françois-latin : auquel les mots françois, avec les manières d'user d'iceulx, sont tournez en latin... ([Reprod.]) / par maistre Iehan Thierry..

Collection : Archives de la linguistique française ; 376

Perheyrittäjyys:Mahdollisuuksia ja menetyksiä

Tutkielman tarkoituksena oli selvittää vähän tunnettua ilmiötä. Tavoitteena oli kartoittaa kokemuksia perheyrittäjyydestä perheyrityksen eri kehitysvaiheissa sekä tulevaisuutta ajatellen, ja nostaa täten esille perheyrityksissä vallitsevia haasteita, joita perheen, liiketoiminnan ja omistamisen yhteenkietoutuneet suhteet olivat aiheuttaneet. Casetutkimus toteutettiin teemahaastatteluilla, joista muodostettiin yksi kronologisesti etenevä tarina. Narratiivisen analyysin avulla tarinasta löydettiin keskeisiä teemoja. Tärkeimmiksi tutkimustuloksiksi osoittautuivat elämäntapayrittäjyys, työ- ja perheroolien sekoittuminen sekä perheen ja liiketoimien yhteensovittamisen ongelmat. Liiketoiminnan edut asetettiin liikaa perheen edelle, mikä johti lopulta yrittäjien avioeroon, liiketoiminnan voimakkaaseen supistamiseen ja uuden yrityksen perustamiseen toisen yrittäjän toimesta. Lisäksi aineistosta nousi esille psykologisen omistajuuden tunteita perheyritystä kohtaan sekä psykologisen omistajuuden varjopuolia.

Escuela, familia de origen inmigrante y participación

Las relaciones entre las familias y la escuela se inscriben en la articulación entre dos instituciones con asimetría de poder y en un contexto social y político que las sitúa en el debate entre intereses públicos y privados. Aunque deben considerarse espacios yuxtapuestos, a menudo lo que se percibe es la separación, la distancia, cuando no el conflicto, entre ambos. Y esto comporta que el territorio de la escuela y el de la familia se vigile, se controle, por la amenaza de invasión o intrusión. El artículo analiza la participación de los progenitores de origen inmigrante en la escuela en España.Realizando una breve referencia a la legislación, se centra en la situación organizativa confederal, federal y asociativa (utilizando como fuente de información datos propios obtenidos en cinco grupos de discusión organizados en los diferentes niveles organizativos) y, por último, se aproxima la realidad de las Asociaciones de Padres de Alumnos (a través de una encuesta a 594 presidentes de asociaciones).Además de constatar la baja participación general y, en particular, la de las familias de origen inmigrante (menor entre unos orígenes que entre otros) se evidencia la necesidad de trabajar para incorporarlos al movimiento de padres, hecho que se considera imprescindible para su desarrollo.

The career engagement scale : Development and validation of a measure of proactive career behaviors

Careers today increasingly require engagement in proactive career behaviors; however, there is a lack of validated measures assessing the general degree to which somebody is engaged in such career behaviors. We describe the results of six studies with six independent samples of German university students (total N = 2,854), working professionals (total N = 561), and university graduates (N = 141) that report the development and validation of the Career Engagement Scale - a measure of the degree to which somebody is proactively developing her or his career as expressed by diverse career behaviors. The studies provide support for measurement invariance across gender and time. In support of convergent and discriminant validity, we find that career engagement is more prevalent among working professionals than among university students and that this scale has incremental validity above several specific career behaviors regarding its relation to vocational identity clarity and career self-efficacy beliefs among students and to job and career satisfaction among employees. In support of incremental predictive validity, beyond the effects of several more specific career behaviors, career engagement while at university predicts higher job and career satisfaction several months later after beginning work.