Différences selon le sexe dans l’âge d’apparition, la symptomatologie et l’évolution de la schizophrénie

Les différences selon le sexe dans l'âge d'apparition, la symptomatologie et l'évolution de la schizophrénie sont examinées par une analyse de cas dûment enregistrés et par une enquête directe à partir d'un échantillon représentatif de patients hospitalisés pour la première fois. La découverte centrale que les hommes deviennent schizophrènes à un âge plus précoce que les femmes se confirme après avoir écarté d'autres interprétations dues à des distorsions d'échantillonnage, à des différences d'intervalle entre l'apparition effective de la maladie et la première admission à l'hôpital, à des différences par sexe dans le développement des symptômes ou à d'autres facteurs confondants. Si l'on cherche les causes de ces différences entre hommes et femmes, il semble que les perturbations du début du développement social doivent être comprises alors comme les conséquences d'une schizophrénie débutante plutôt que comme ses conditions d'apparition. Il en ressort le besoin de modèles expliI catifs qui permettent de tester empiriquement les hypothèses sur le développement spécifique de la schizophrénie dans l'un et l'autre sexe.Gender differences in age at onset, symptomatology and course of schizophrenia are examined by analyzing case register data and by direct investigation of a representative sample of first-admitted patients. The main finding that males fall ill at an earlier age than females can be confirmed even after ruling out other interpretations due to sample bias, different time span between real onset and first hospital admission, gender differences in symptom development or other confounding factors. When looking for causes of these gender differences it seems that disturbances in early social development must be understood as a consequence of beginning schizophrenia rather than a prerequisite. The need for explanatory models is stressed that allow for the empirical testing of hypotheses concerning gender specific development of schizophrenia

"Stopping before you start" : reducing and preventing initiation of tobacco use in the ACT

Tobacco is the leading cause of preventable death in Australia and contributes to 5.4% of disease burden in the Australian Capital Territory. Initiation of tobacco use is most likely to occur during adolescence and young adulthood (at less than 20 years). Prevention of tobacco initiation involves a combination of regulatory, educational and health promotion interventions including restrictions on the sale of tobacco products. This paper reports on the development and use of an agent-based model to explore the impact of modifying three hypothetical regulatory and health promotion interventions: 1) increasing the minimum purchasing age for tobacco products, 2) reducing retail sales of tobacco products to persons under the minimum purchasing age and 3) reducing secondary sharing of tobacco products to persons under the minimum purchasing age using health promotion messaging. The model was built using a participatory approach that engaged policy officers, health promotion officers, epidemiologists, biostatisticians and computer scientists. The structure of the model included interacting state chart representations of smoking and level of concern about tobacco use (engagement status) and a pro-smoking score, which defined the hazard rate of initiation, cessation, and relapse. The pro-smoking score was a function of several risk factors including engagement, social effect of having more or fewer smoking peers, addiction and withdrawal levels and access to tobacco products. Parameterisation of the model drew on a range of data sources with local data being prioritised where it was available. A series of scenarios comparing the impact of the interventions on smoking prevalence rates and age of initiation are reported. Of the three interventions simulated, increasing the minimum purchasing age from 18 to 21 years had the greatest impact on smoking prevalence across the population, reducing the prevalence of smoking from 8.5% (95% CI 7.8, 9.2) to 6.9% (95% CI 6.4, 7.4) five years post-intervention and 4.1% (95% CI 3.8, 4.3) 20 years post intervention (Figure 1). The interventions aimed to reduce the sale of tobacco products to minors and reduce secondary sharing produced small reductions on their own. However, when implemented in combination with increasing the minimum purchasing age, they significantly increased the impact of this intervention from ten years post-implementation, ultimately resulting in a prevalence rate of 2.8% (95% CI 2.6, 3.0) 20 years post-implementation. Given the challenges associated with ceasing tobacco use, these in silico experiments demonstrate the importance of regulatory public health interventions to delay, and therefore potentially prevent initiation

The Regulatory Role of MicroRNA in Hepatitis-B Virus-Associated Hepatocellular Carcinoma (HBV-HCC) Pathogenesis.

The incidence and mortality of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HBV-HCC) is an intractable public health problem in developing countries that is compounded by limited early detection and therapeutic options. Despite the early promise of utilizing the regulatory role of miRNA in liver cancer, this field remains largely in the work-in-progress phase. This exploratory review paper adopts a broad focus in order to collate evidence of the regulatory role of miRNA in each stage of the HBV-HCC continuum. This includes the regulatory role of miRNA in early HBV infection, chronic inflammation, fibrosis/cirrhosis, and the onset of HCC. The paper specifically investigates HBV dysregulated miRNA that influence the expression of the host/HBV genome in HBV-HCC pathogenesis and fully acknowledges that this does not cover the full spectrum of dysregulated miRNA. The sheer number of dysregulated miRNA in each phase support a hypothesis that future therapeutic interventions will need to consider incorporating multiple miRNA panels

Old World megadroughts and pluvials during the Common Era

Climate model projections suggest widespread drying in the Mediterranean Basin and wetting in Fennoscandia in the coming decades largely as a consequence of greenhouse gas forcing of climate. To place these and other “Old World” climate projections into historical perspective based on more complete estimates of natural hydroclimatic variability, we have developed the “Old World Drought Atlas” (OWDA), a set of year-to-year maps of tree-ring reconstructed summer wetness and dryness over Europe and the Mediterranean Basin during the Common Era. The OWDA matches historical accounts of severe drought and wetness with a spatial completeness not previously available. In addition, megadroughts reconstructed over north-central Europe in the 11th and mid-15th centuries reinforce other evidence from North America and Asia that droughts were more severe, extensive, and prolonged over Northern Hemisphere land areas before the 20th century, with an inadequate understanding of their causes. The OWDA provides new data to determine the causes of Old World drought and wetness and attribute past climate variability to forced and/or internal variability

Detection of Fusarium oxysporum f.sp. lactucae race 1 and 4 via race-specific real-time PCR and target enrichment

Fusarium oxysporum f.sp. lactucae (Fol) causes a vascular disease in lettuce that results in significant yield losses. Race-specific and sensitive real-time PCR assays were developed for Fol races 1 and 4, which are prevalent in Europe. Using genotyping-by-sequencing, unique DNA loci specific to each race were identified and subsequently used for the design of primers and hydrolysis probes. Two assays per race were developed to ensure specificity. The two assays of each race could be run in duplex format, while still giving a sensitivity of 100 fg genomic DNA for all assays. Sample preparation methods were developed for plant tissue, soil, and surfaces, with an extra enrichment step when additional sensitivity was required. By controlling the incubation conditions during the enrichment step, the real-time PCR signal could be matched to the number of spore equivalents in the original sample. When enriching naturally infested soil, down to six conidiospore equivalents L-1 soil could be detected. As enrichment ensures sensitive detection and focuses on living Fol propagules, it facilitates the evaluation of control measures. The developed detection methods for soil and surfaces were applied to samples from commercial lettuce farms and confirmed the prevalence of Fol race 4 in Belgium. Monitoring of soil disinfestation events revealed that despite a dramatic decrease in quantity, the pathogen could still be detected either immediately after sheet steaming or after harvesting the first new crop. The detection method for plant tissue was successfully used to quantify Fol in lettuce inoculated with race 1, race 4 or a combination of both. Under the temperature conditions used, race 4 was more aggressive than race 1, as reflected in larger amounts of DNA of race 4 detected in the roots. These newly developed assays are a promising tool for epidemiological research as well as for the evaluation of control measures

Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.

We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10-7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition

The Seventh Data Release of the Sloan Digital Sky Survey

This paper describes the Seventh Data Release of the Sloan Digital Sky Survey (SDSS), marking the completion of the original goals of the SDSS and the end of the phase known as SDSS-II. It includes 11663 deg^2 of imaging data, with most of the roughly 2000 deg^2 increment over the previous data release lying in regions of low Galactic latitude. The catalog contains five-band photometry for 357 million distinct objects. The survey also includes repeat photometry over 250 deg^2 along the Celestial Equator in the Southern Galactic Cap. A coaddition of these data goes roughly two magnitudes fainter than the main survey. The spectroscopy is now complete over a contiguous area of 7500 deg^2 in the Northern Galactic Cap, closing the gap that was present in previous data releases. There are over 1.6 million spectra in total, including 930,000 galaxies, 120,000 quasars, and 460,000 stars. The data release includes improved stellar photometry at low Galactic latitude. The astrometry has all been recalibrated with the second version of the USNO CCD Astrograph Catalog (UCAC-2), reducing the rms statistical errors at the bright end to 45 milli-arcseconds per coordinate. A systematic error in bright galaxy photometr is less severe than previously reported for the majority of galaxies. Finally, we describe a series of improvements to the spectroscopic reductions, including better flat-fielding and improved wavelength calibration at the blue end, better processing of objects with extremely strong narrow emission lines, and an improved determination of stellar metallicities. (Abridged)Comment: 20 pages, 10 embedded figures. Accepted to ApJS after minor correction