Evaluation of polygenic determinants of non-alcoholic fatty liver disease (NAFLD) by a candidate genes resequencing strategy

NAFLD is a polygenic condition but the individual and cumulative contribution of identified genes remains to be established. To get additional insight into the genetic architecture of NAFLD, GWAS-identified GCKR, PPP1R3B, NCAN, LYPLAL1 and TM6SF2 genes were resequenced by next generation sequencing in a cohort of 218 NAFLD subjects and 227 controls, where PNPLA3 rs738409 and MBOAT7 rs641738 genotypes were also obtained. A total of 168 sequence variants were detected and 47 were annotated as functional. When all functional variants within each gene were considered, only those in TM6SF2 accumulate in NAFLD subjects compared to controls (P = 0.04). Among individual variants, rs1260326 in GCKR and rs641738 in MBOAT7 (recessive), rs58542926 in TM6SF2 and rs738409 in PNPLA3 (dominant) emerged as associated to NAFLD, with PNPLA3 rs738409 being the strongest predictor (OR 3.12, 95% CI, 1.8-5.5, P 0.28 was associated with a 3-fold increased risk of NAFLD. Interestingly, rs61756425 in PPP1R3B and rs641738 in MBOAT7 genes were predictors of NAFLD severity. Overall, TM6SF2, GCKR, PNPLA3 and MBOAT7 were confirmed to be associated with NAFLD and a score based on these genes was highly predictive of this condition. In addition, PPP1R3B and MBOAT7 might influence NAFLD severity

The ATLAS Simulation: an LHC Challenge

The simulation program for the ATLAS experiment at CERN is currently in a full operational mode and integrated into the ATLAS common analysis framework, Athena. The OO approach, based on GEANT4, and in use during the DC2 data challenge has been interfaced within Athena and to GEANT4 using the LCG dictionaries and Python scripting. The robustness of the application was proved during the DC2 data challenge. The Python interface has added the flexibility, modularity and interactivity that the simulation tool requires in order to be able to provide a common implementation of different full ATLAS simulation setups, test beams and cosmic ray applications. Generation, simulation and digitization steps were exercised for performance and robustness tests. The comparison with real data has been possible in the context of the ATLAS Combined Test Beam (2004) and ongoing cosmic ray studies

Hodgkin's disease presenting below the diaphragm. The experience of the Gruppo Italiano Studio Linfomi (GISL)

Background and Objective. Infradiaphragmatic Hodgkin\ub4s disease is rare, making up 5-12% of cases in clinical stages I and II; consequently, several questions concerning prognosis and treatment strategy remain to be answered. The aim of this study was to analyze the clinical and prognostic characteristics and outcome of his condition. Methods. A series of 282 patients with CS I-II Hodgkin\ub4s disease (HD) was investigated. In 31 patients the disease was confined below the diaphragm (BDHD), and in the remaining above the diaphragm (ADHD). The presenting features and outcomes were compared in the two groups. Results. The BDHD group was older (p < 0.0002), had a higher frequency of males (p < 0.08) and a different histological subtype group distribution (p < 0.0001). Stage II BDHD patients had a worse overall survival rate (OS) than stage II ADHD patients (68.8% vs 86.6% at 8 years, p < 0.01) if age is not considered; patients with more than 40 years of age, in fact, had the same survival rates as those with ADHD. BDHD patients with intra-abdominal disease alone had worse prognostic factors and OS (p = 0.12) than patients with inguinal-femoral nodes. Interpretation and Conclusions. Although BDHD patients present distinct features, they have the same OS and relapse-free survival rate as age-adjusted ADHD patients. According to our experience patients with stage I peripheral BDHD respond well to radiotherapy-based regimens. Those with stage II and or intra-abdominal disease are more challenging; chemotherapy or a combined therapy seem to be more suitable approaches for these patients

Targeted metabolomic profiling in rat tissues reveals sex differences

Sex differences affect several diseases and are organ-and parameter-specific. In humans and animals, sex differences also influence the metabolism and homeostasis of amino acids and fatty acids, which are linked to the onset of diseases. Thus, the use of targeted metabolite profiles in tissues represents a powerful approach to examine the intermediary metabolism and evidence for any sex differences. To clarify the sex-specific activities of liver, heart and kidney tissues, we used targeted metabolomics, linear discriminant analysis (LDA), principal component analysis (PCA), cluster analysis and linear correlation models to evaluate sex and organ-specific differences in amino acids, free carnitine and acylcarnitine levels in male and female Sprague-Dawley rats. Several intra-sex differences affect tissues, indicating that metabolite profiles in rat hearts, livers and kidneys are organ-dependent. Amino acids and carnitine levels in rat hearts, livers and kidneys are affected by sex: male and female hearts show the greatest sexual dimorphism, both qualitatively and quantitatively. Finally, multivariate analysis confirmed the influence of sex on the metabolomics profiling. Our data demonstrate that the metabolomics approach together with a multivariate approach can capture the dynamics of physiological and pathological states, which are essential for explaining the basis of the sex differences observed in physiological and pathological conditions

A bayesian meta-analysis of multiple treatment comparisons of systemic regimens for advanced pancreatic cancer

© 2014 Chan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: For advanced pancreatic cancer, many regimens have been compared with gemcitabine (G) as the standard arm in randomized controlled trials. Few regimens have been directly compared with each other in randomized controlled trials and the relative efficacy and safety among them remains unclear

The ATLAS Detector Digitization Project for 2009 data taking

The ATLAS digitization project is steered by a top-level PYTHON digitization package which ensures uniform and consistent configuration across the subdetectors. The properties of the digitization algorithms were tuned to reproduce the detector response seen in lab tests, test beam data and cosmic ray running. Dead channels and noise rates are read from database tables to reproduce conditions seen in a particular run. The digits are then persistified as Raw Data Objects (RDO) with or without intermediate bytestream simulation depending on the detector type. Emphasis is put on the description of the digitization project configuration, its flexibility in events handling for processing and in the global detector configuration, as well as its variety of options including detector noise simulation, random number service, metadata and details of pile-up background events to be overlaid. The LHC beam bunch spacing is also configurable, as well as the number of bunch crossings to overlay and the default detector conditions (including noisy channels, dead electronics associated with each detector layout). Cavern background calculation, beam halo and beam gas treatment, pile-up with real data is also part of this report

Polynomial Approach for Filtering and Identification of a Class of Uncertain Systems

Abstract this paper considers the filtering and identification problems for a class of discrete-time uncertain stochastic systems that admit a finite number of linear working modes. It is shown here that this class of uncertain systems can be modeled by using a suitably defined extended system, whose state evolves according to a bilinear model. A polynomial filtering algorithm is derived for such extended system, which readily provides the polynomial estimates of both the original state and the working mode. Simulations show the effectiveness of the proposed approach and the improvements with respect to standard linear filtering algorithms

The Videofluorographic Swallowing Study in Rheumatologic Diseases: A Comprehensive Review

Autoimmune connective tissue diseases are a heterogeneous group of pathologies that affect about 10% of world population with chronic evolution in 20%-80%. Inflammation in autoimmune diseases may lead to serious damage to other organs including the gastrointestinal tract. Gastrointestinal tract involvement in these patients may also due to both a direct action of antibodies against organs and pharmacological therapies. Dysphagia is one of the most important symptom, and it is caused by failure of the swallowing function and may lead to aspiration pneumonia, malnutrition, dehydration, weight loss, and airway obstruction. The videofluorographic swallowing study is a key diagnostic tool in the detection of swallowing disorders, allowing to make an early diagnosis and to reduce the risk of gastrointestinal and pulmonary complications. This technique helps to identify both functional and structural anomalies of the anatomic chain involved in swallowing function. The aim of this review is to systematically analyze the basis of the pathological involvement of the swallowing function for each rheumatological disease and to show the main features of the videofluorographic study that may be encountered in these patients

Radar array diagnosis from undersampled data using a compressed sensing/sparse recovery technique

A Compressed Sensing/Sparse Recovery approach is adopted in this paper for the accurate diagnosis of fault array elements from undersampled data. Experimental validations on a slotted waveguide test array are discussed to demonstrate the effectiveness of the proposed procedure in the failures retrieval from a small set of measurements with respect to the number of radiating elements. Due to the sparsity feature of the proposed formulation, the method is particularly appealing for the diagnostics of large arrays, typically adopted for radar applications