SCREENING FOR HEPATITIS C Response from Hepatitis C Trust, BASL, BIA, BVHG, BSG, and BHIVA to article asking whether widespread screening for hepatitis C is justified

This is the peer reviewed published version of the following article: Response from Hepatitis C Trust, BASL, BIA, BVHG, BSG, and BHIVA to article asking whether widespread screening for hepatitis C is justified, which has been published in final form at 10.1136/bmj.h998. This article may be used for non-commercial purposes in accordance with BMJ's Terms and Conditions for Self-Archiving.This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/ by/4.0

Transcriptome-Wide Association Supplements Genome-Wide Association in Zea mays.

Modern improvement of complex traits in agricultural species relies on successful associations of heritable molecular variation with observable phenotypes. Historically, this pursuit has primarily been based on easily measurable genetic markers. The recent advent of new technologies allows assaying and quantifying biological intermediates (hereafter endophenotypes) which are now readily measurable at a large scale across diverse individuals. The usefulness of endophenotypes for delineating the regulatory landscape of the genome and genetic dissection of complex trait variation remains underexplored in plants. The work presented here illustrated the utility of a large-scale (299-genotype and seven-tissue) gene expression resource to dissect traits across multiple levels of biological organization. Using single-tissue- and multi-tissue-based transcriptome-wide association studies (TWAS), we revealed that about half of the functional variation acts through altered transcript abundance for maize kernel traits, including 30 grain carotenoid abundance traits, 20 grain tocochromanol abundance traits, and 22 field-measured agronomic traits. Comparing the efficacy of TWAS with genome-wide association studies (GWAS) and an ensemble approach that combines both GWAS and TWAS, we demonstrated that results of TWAS in combination with GWAS increase the power to detect known genes and aid in prioritizing likely causal genes. Using a variance partitioning approach in the largely independent maize Nested Association Mapping (NAM) population, we also showed that the most strongly associated genes identified by combining GWAS and TWAS explain more heritable variance for a majority of traits than the heritability captured by the random genes and the genes identified by GWAS or TWAS alone. This not only improves the ability to link genes to phenotypes, but also highlights the phenotypic consequences of regulatory variation in plants

HypTrails: A Bayesian Approach for Comparing Hypotheses About Human Trails on the Web

When users interact with the Web today, they leave sequential digital trails on a massive scale. Examples of such human trails include Web navigation, sequences of online restaurant reviews, or online music play lists. Understanding the factors that drive the production of these trails can be useful for e.g., improving underlying network structures, predicting user clicks or enhancing recommendations. In this work, we present a general approach called HypTrails for comparing a set of hypotheses about human trails on the Web, where hypotheses represent beliefs about transitions between states. Our approach utilizes Markov chain models with Bayesian inference. The main idea is to incorporate hypotheses as informative Dirichlet priors and to leverage the sensitivity of Bayes factors on the prior for comparing hypotheses with each other. For eliciting Dirichlet priors from hypotheses, we present an adaption of the so-called (trial) roulette method. We demonstrate the general mechanics and applicability of HypTrails by performing experiments with (i) synthetic trails for which we control the mechanisms that have produced them and (ii) empirical trails stemming from different domains including website navigation, business reviews and online music played. Our work expands the repertoire of methods available for studying human trails on the Web.Comment: Published in the proceedings of WWW'1

Reconstructing 3D x-ray CT images of polymer gel dosimeters using the zero-scan method

In this study x-ray CT has been used to produce a 3D image of an irradiated PAGAT gel sample, with noise-reduction achieved using the ‘zero-scan’ method. The gel was repeatedly CT scanned and a linear fit to the varying Hounsfield unit of each pixel in the 3D volume was evaluated across the repeated scans, allowing a zero-scan extrapolation of the image to be obtained. To minimise heating of the CT scanner’s x-ray tube, this study used a large slice thickness (1 cm), to provide image slices across the irradiated region of the gel, and a relatively small number of CT scans (63), to extrapolate the zero-scan image. The resulting set of transverse images shows reduced noise compared to images from the initial CT scan of the gel, without being degraded by the additional radiation dose delivered to the gel during the repeated scanning. The full, 3D image of the gel has a low spatial resolution in the longitudinal direction, due to the selected scan parameters. Nonetheless, important features of the dose distribution are apparent in the 3D x-ray CT scan of the gel. The results of this study demonstrate that the zero-scan extrapolation method can be applied to the reconstruction of multiple x-ray CT slices, to provide useful 2D and 3D images of irradiated dosimetry gels

Agent-based modeling and simulation for the design of the future european Air Traffic Management system: the experience of CASSIOPEIA

The SESAR (Single European Sky ATM Research) program is an ambitious re-search and development initiative to design the future European air traffic man-agement (ATM) system. The study of the behavior of ATM systems using agent-based modeling and simulation tools can help the development of new methods to improve their performance. This paper presents an overview of existing agent-based approaches in air transportation (paying special attention to the challenges that exist for the design of future ATM systems) and, subsequently, describes a new agent-based approach that we proposed in the CASSIOPEIA project, which was developed according to the goals of the SESAR program. In our approach, we use agent models for different ATM stakeholders, and, in contrast to previous work, our solution models new collaborative decision processes for flow traffic management, it uses an intermediate level of abstraction (useful for simulations at larger scales), and was designed to be a practical tool (open and reusable) for the development of different ATM studies. It was successfully applied in three stud-ies related to the design of future ATM systems in Europe

microRNA-10b enhances pancreatic cancer cell invasion by suppressing TIP30 expression and promoting EGF and TGF-β actions

Increased microRNA-10b (miR-10b) expression in the cancer cells in pancreatic ductal adenocarcinoma (PDAC) is a marker of disease aggressiveness. In the present study, we determined that plasma miR-10b levels are significantly increased in PDAC patients by comparison with normal controls. By gene profiling, we identified potential targets downregulated by miR-10b, including Tat-interacting protein 30 (TIP30). Immunoblotting and luciferase reporter assays confirmed that TIP30 was a direct miR-10b target. Downregulation of TIP30 by miR-10b or siRNA-mediated silencing of TIP30 enhanced epidermal growth factor (EGF)-dependent invasion. The actions of miR-10b were abrogated by expressing a modified TIP30 cDNA resistant to miR-10b. EGF-induced EGF receptor (EGFR) tyrosine phosphorylation and extracellular signal–regulated kinase phosphorylation were enhanced by miR-10b, and these effects were mimicked by TIP30 silencing. The actions of EGF in the presence of miR-10b were blocked by EGFR kinase inhibition with erlotinib and by dual inhibition of PI3K (phosphatidylinositol 3′-kinase) and MEK. Moreover, miR-10b, EGF and transforming growth factor-beta (TGF-β) combined to markedly increase cell invasion, and this effect was blocked by the combination of erlotinib and SB505124, a type I TGF-β receptor inhibitor. miR-10b also enhanced the stimulatory effects of EGF and TGF-β on cell migration and epithelial–mesenchymal transition (EMT) and decreased the expression of RAP2A, EPHB2, KLF4 and NF1. Moreover, miR-10b overexpression accelerated pancreatic cancer cell (PCC) proliferation and tumor growth in an orthotopic model. Thus, plasma miR-10b levels may serve as a diagnostic marker in PDAC, whereas intra-tumoral miR-10b promotes PCC proliferation and invasion by suppressing TIP30, which enhances EGFR signaling, facilitates EGF–TGF-β cross-talk and enhances the expression of EMT-promoting genes, whereas decreasing the expression of several metastasis-suppressing genes. Therefore, therapeutic targeting of miR-10b in PDAC may interrupt growth-promoting deleterious EGF–TGF-β interactions and antagonize the metastatic process at various levels