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Common genetic variants of FOXP2 may contribute to schizophrenia vulnerability, but controversial results have been reported for this proposal. Here we evaluated the potential impact of the common FOXP2 rs2396753 polymorphism in schizophrenia. It was previously reported to be part of a risk haplotype for this disease and to have significant effects on gray matter concentration in the patients. We undertook the first examination into whether rs2396753 affects the brain expression of FOXP2 and a replication study of earlier neuroimaging findings of the influence of this genetic variant on brain structure. FOXP2 expression levels were measured in postmortem prefrontal cortex samples of 84 male subjects (48 patients and 36 controls) from the CIBERSAM Brain and the Stanley Foundation Array Collections. High-resolution anatomical magnetic resonance imaging was performed on 79 male subjects (61 patients, 18 controls) using optimized voxel-based morphometry. We found differences in FOXP2 expression and brain morphometry depending on the rs2396753, relating low FOXP2 mRNA levels with reduction of gray matter density. We detected an interaction between rs2396753 and the clinical groups, showing that heterozygous patients for this polymorphism have gray matter density decrease and low FOXP2 expression comparing with the heterozygous controls. This study shows the importance of independent replication of neuroimaging genetic studies of FOXP2 as a candidate gene in schizophrenia. Furthermore, our results suggest that the FOXP2 rs2396753 affects mRNA levels, thus providing new knowledge about its significance as a potential susceptibility polymorphism in schizophrenia.

Background The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is a prospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) in patients with newly diagnosed mycosis fungoides (MF). Objectives To identify (i) differences in first-line approaches according to tumour-nodes-metastasis-blood (TNMB) staging; (ii) parameters related to a first-line systemic approach and (iii) response rates and QoL measures. Methods In total, 395 newly diagnosed patients with early-stage MF (stage IA-IIA) were recruited from 41 centres in 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review. Results The most common first-line therapy was skin-directed therapy (SDT) (322 cases, 81 center dot 5%), while a smaller percentage (44 cases, 11 center dot 1%) received systemic therapy. Expectant observation was used in 7 center dot 3%. In univariate analysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA, 20%; IA-IB vs. IIA, P < 0 center dot 001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0 center dot 001), higher modified Severity Weighted Assessment Tool (> 10, 15%

This work summarizes the recent developments of a numerical framework to predict the mechanical behaviour of thermoplastic composites. It supports the design of a next generation thermoplastic multi-functional fuselage which uses advanced joining techniques such as thermoplastic welding to reduce both weight and cost by limiting the amount of mechanical fasteners required. At the lower end of the testing pyramid the framework is able to accurately predict typical preliminary design allowables such as laminate, open-hole and welded joints strength through a high-fidelity modelling approach. This information is then passed on to the structural level in a validated building-block approach to efficiently virtual test the compression strength of fuselage panels during post-buckling while also taking into account the influence of damages at the skin-stiffener interface.

In this paper, the interlaminar stresses in open-hole laminates subjected to compressive loads are analysed using a numerical model. This model implements the Serial/Parallel Mixing Theory (S/PMT) and a Continuum Damage Mechanics (CDM) approach. The S/PMT estimates the global stiffness in the laminate from fibre and matrix properties. The CDM approach models the damage initiation due to fibre microbuckling. The global response estimated by the model was verified with experimental data from the literature. The model predicts that the damage initiates in the laminate middle-plane where the thickest block of plies oriented in the load direction is located, and progressively propagates to the nearest block of layers with the same orientation. Two laminate stacking sequences were analysed. The interlaminar stresses around the hole presented symmetry with respect to the load direction and the perpendicular axis, being located the maximum and minimum values in different angular positions for each stress component and laminate.

Background The contacts of people with pulmonary tuberculosis (PTB) have a high risk of becoming infected and developing tuberculosis (TB). Our aim was to determine the incidence of TB and its risk factors in a cohort of contacts with latent TB infection (LTBI) detected through contact tracing of smear-positive PTB cases. Methods and findings We performed a population-based retrospective cohort study including contacts that had LTBI, and were contacts of people with PTB who started treatment between 2008 and 2014. We followed up contacts until they developed TB or until the end date for follow-up (31st December 2016). We used Kaplan-Meier curves to compute incidence at 2 and 5 years, and Cox regression to compute hazard ratios (HR) and their 95% confidence intervals (CI). We analyzed 3097 close contacts of 565 PTB cases. After exclusion of 81 coprevalent TB cases, 953 contacts had LTBI, of which 14 developed TB. Their risk of developing TB after two and five years was 0.7% (CI: 0.3-1.6) and 1.8% (CI: 1.1-3.1) respectively. Contacts who had not been referred for LTBI treatment had a 1.0% (CI: 0.24.0) risk at 5 years. Risk of developing TB at 5 years was 1.2% (CI: 0.5-3.0) among people who completed treatment, and 11.1% (CI: 5.1-23.3) for those who did not. Risk factors for TB were not completing LTBI treatment (HR 9.4, CI: 2.9-30.8) and being female (HR 3.5, CI: 1.1-11-3). Conclusions LTBI treatment plays a fundamental role in decreasing the risk of developing TB. It is necessary to achieve a maximum contact tracing coverage and the highest possible compliance with LTBI treatment.