Genetic variants associated with increased risk of malignant pleural mesothelioma: a genome-wide association study

Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, only 5–17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors. To identify the genetic risk factors that may contribute to the development of MPM, we conducted a genome-wide association study (GWAS; 370,000 genotyped SNPs, 5 million imputed SNPs) in Italy, among 407 MPM cases and 389 controls with a complete history of asbestos exposure. A replication study was also undertaken and included 428 MPM cases and 1269 controls from Australia. Although no single marker reached the genome-wide significance threshold, several associations were supported by haplotype-, chromosomal region-, gene- and gene-ontology process-based analyses. Most of these SNPs were located in regions reported to harbor aberrant alterations in mesothelioma (SLC7A14, THRB, CEBP350, ADAMTS2, ETV1, PVT1 and MMP14 genes), causing at most a 2–3-fold increase in MPM risk. The Australian replication study showed significant associations in five of these chromosomal regions (3q26.2, 4q32.1, 7p22.2, 14q11.2, 15q14). Multivariate analysis suggested an independent contribution of 10 genetic variants, with an Area Under the ROC Curve (AUC) of 0.76 when only exposure and covariates were included in the model, and of 0.86 when the genetic component was also included, with a substantial increase of asbestos exposure risk estimation (odds ratio, OR: 45.28, 95% confidence interval, CI: 21.52–95.28). These results showed that genetic risk factors may play an additional role in the development of MPM, and that these should be taken into account to better estimate individual MPM risk in individuals who have been exposed to asbestos.Giuseppe Matullo ... Lyle J. Palmer ... et al

Prototype ATLAS IBL Modules using the FE-I4A Front-End Readout Chip

The ATLAS Collaboration will upgrade its semiconductor pixel tracking detector with a new Insertable B-layer (IBL) between the existing pixel detector and the vacuum pipe of the Large Hadron Collider. The extreme operating conditions at this location have necessitated the development of new radiation hard pixel sensor technologies and a new front-end readout chip, called the FE-I4. Planar pixel sensors and 3D pixel sensors have been investigated to equip this new pixel layer, and prototype modules using the FE-I4A have been fabricated and characterized using 120 GeV pions at the CERN SPS and 4 GeV positrons at DESY, before and after module irradiation. Beam test results are presented, including charge collection efficiency, tracking efficiency and charge sharing.Comment: 45 pages, 30 figures, submitted to JINS

Encoding order and developmental dyslexia:a family of skills predicting different orthographic components

We investigated order encoding in developmental dyslexia using a task that presented nonalphanumeric visual characters either simultaneously or sequentially—to tap spatial and temporal order encoding, respectively—and asked participants to reproduce their order. Dyslexic participants performed poorly in the sequential condition, but normally in the simultaneous condition, except for positions most susceptible to interference. These results are novel in demonstrating a selective difficulty with temporal order encoding in a dyslexic group. We also tested the associations between our order reconstruction tasks and: (a) lexical learning and phonological tasks; and (b) different reading and spelling tasks. Correlations were extensive when the whole group of participants was considered together. When dyslexics and controls were considered separately, different patterns of association emerged between orthographic tasks on the one side and tasks tapping order encoding, phonological processing, and written learning on the other. These results indicate that different skills support different aspects of orthographic processing and are impaired to different degrees in individuals with dyslexia. Therefore, developmental dyslexia is not caused by a single impairment, but by a family of deficits loosely related to difficulties with order. Understanding the contribution of these different deficits will be crucial to deepen our understanding of this disorder

The changing impact of age on colorectal cancer surgery. A trend analysis.

OBJECTIVE: The aim of the study was to evaluate the changing influence of age on the outcomes of colorectal cancer surgery in a retrospective trend analysis. METHODS: Data on 985 patients undergoing colorectal cancer surgery were collected during 1975-1984 and 1995-2004. Variables and outcomes of patients aged < 65, 65-74, 75-84 and 85+ years were compared with intra- and interdecade analyses. Endpoints of the study were postoperative mortality, 5-year overall and cancer-related survivals. RESULTS: The rate of elderly patients undergoing colorectal cancer surgery increased significantly from 1975-1984 to 1995-2004. Distribution of American Society of Anesthesiology score and cancer stage remained unchanged over time. The rate of palliative procedures decreased over time, most significantly in the older age groups. In 1995-2004 the palliation rate was similar across all age groups. The rate of emergency surgery also decreased, but it remained higher in older age groups. Operative mortality rate decreased over time across all age groups, but age-related differences were still observed in the 1995-2004 series. Cancer-related survival after curative surgery increased from 58% in 1975-1984 to 64% in 1995-2004 in 75+ years patients, while it increased from 56% to 78% in patients aged 74 years or younger. CONCLUSIONS: Elderly patients with colorectal cancer benefited substantially from healthcare progress during the last 30 years. The reduction of palliative procedures and the decline in operative mortality document the efficacy of not restricting the access to radical surgery for these patient