751 research outputs found

    Prevalence and clinical consequences of Hepatitis E in patients who underwent liver transplantation for chronic Hepatitis C in the United States

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    Background: Infection with hepatitis E virus (HEV) in immunocompromised patients can lead to severe liver disease. Treatment options for HEV include peginterferon or ribavirin, routinely also used for the treatment of hepatitis C virus (HCV) infection. We determined the prevalence and clinical consequences of HEV in United States (US) based patients who underwent liver transplantation (LT) for chronic HCV. Methods: Seroprevalence of HEV in 145 US LT recipients with a history of chronic HCV was determined pre-LT, 1, 3 and 5 years post-LT. All last available samples and all samples in IgM positive patients and post-LT IgG seroconverters were tested for HEV RNA. Results: Overall anti-HEV seroprevalence was 42 %. Five patients were HEV IgM positive pre-LT, one patient had IgM seroconversion post-LT and eight patients had IgG seroconversion post-LT. None of the tested samples were positive for HEV RNA. Eight out of nine of the post-LT seroconverters had been treated for HCV recurrence before or at the moment of seroconversion. Conclusions: LT recipients in the US are at risk of acquiring HEV. Post-LT HCV treatment with interferons and/or ribavirin may have protected patients against chronic HEV. With the arrival of new direct antiviral agents for the treatment of HCV and the elimination of peginterferon and ribavirin from HCV treatment regimens, the prevalence of chronic HEV in this population may rise again

    Air-Sea Interactions in a High-Resolution Ocean-Atmosphere Simulation

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    During the past few years the Goddard Earth Observing System (GEOS) and Massachusetts Institute of Technology (MIT) modeling groups have produced, respectively, global atmosphere-only and ocean-only simulations with km-scale grid spacing. These simulations have proved invaluable for process studies and for the development of satellite and in-situ sampling strategies. Nevertheless, a key limitation of these "nature" simulations is the lack of interaction between the ocean and the atmosphere, which limits their usefulness for studying air-sea interactions and for designing observing missions to study these interactions. We present here results from a coupled GEOS-MIT "nature run" simulation, wherein we have coupled a cubed-sphere-720 (~ 1/8) configuration of the GEOS atmosphere to a lat-lon-cap-1080 (~ 1/12) configuration of the MIT ocean. We compare near-surface diagnostics of this fully coupled ocean-atmosphere simulation to equivalent atmosphere-only and ocean-only simulations. A particular focus of the comparisons is the coupled versus uncoupled differences in interactions between Sea Surface Temperature (SST) and ocean surface wind. We discuss, in particular, a several-day mode of temporal variability in the SST-wind cycle and how it is represented in the different model simulations and in observationally-based products. A mechanism for the cycle, which is driven by SST-wind feedback, is proposed

    Model Calculations for the Two-Fragment Electro-Disintegration of 4^4He

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    Differential cross sections for the electro-disintegration process e+4He3H+p+ee + {^4He} \longrightarrow {^3H}+ p + e' are calculated, using a model in which the final state interaction is included by means of a nucleon-nucleus (3+1) potential constructed via Marchenko inversion. The required bound-state wave functions are calculated within the integrodifferential equation approach (IDEA). In our model the important condition that the initial bound state and the final scattering state are orthogonal is fulfilled. The sensitivity of the cross section to the input p3Hp{^3H} interaction in certain kinematical regions is investigated. The approach adopted could be useful in reactions involving few cluster systems where effective interactions are not well known and exact methods are presently unavailable. Although, our Plane-Wave Impulse Approximation results exhibit, similarly to other calculations, a dip in the five-fold differential cross-section around a missing momentum of 450MeV/c\sim 450 MeV/c, it is argued that this is an artifact of the omission of re-scattering four-nucleon processes.Comment: 16 pages, 6 figures, accepted for publication by Phys.Rev.

    Photo- and Electro-Disintegration of 3He at Threshold and pd Radiative Capture

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    The present work reports results for: pd radiative capture observables measured at center-of-mass (c.m.) energies in the range 0--100 keV and at 2 MeV by the TUNL and Wisconsin groups, respectively; contributions to the Gerasimov-Drell-Hearn (GDH) integral in 3He from the two- up to the three-body breakup thresholds, compared to experimental determinations by the TUNL group in this threshold region; longitudinal, transverse, and interference response functions measured in inclusive polarized electron scattering off polarized 3He at excitation energies below the threshold for breakup into ppn, compared to unpolarized longitudinal and transverse data from the Saskatoon group. The calculations are based on a realistic Hamiltonian with two- and three-nucleon interactions and a realistic current operator, including one- and two-body components. The theoretical predictions obtained by including only one-body currents are in violent disagreement with data. These differences between theory and experiment are, to a large extent, removed when two-body currents are taken into account, although some rather large discrepancies remain in the c.m. energy range 0--100 keV, particularly for the pd differential cross section and tensor analyzing power at small angles, and contributions to the GDH integral. A rather detailed analysis indicates that these discrepancies have, in large part, a common origin, and can be traced back to an excess strength obtained in the theoretical calculation of the E1 reduced matrix element associated with the pd channel having L,S,J=1,1/2,3/2. It is suggested that this lack of E1 strength observed experimentally might have implications for the nuclear interaction at very low energies. Finally, the validity of the long-wavelength approximation for electric dipole transitions is discussed.Comment: 47 pages RevTex file, 10 PostScript figures, submitted to Phys. Rev.

    Genome-wide association study of borderline personality disorder reveals genetic overlap with the bipolar disorder, schizophrenia and major depression

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    Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of Bipolar Disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was: (i) to detect genes and gene-sets involved in BOR; and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, Major Depression (MDD) and Schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests,and gene-set-analyses were performed in 998 BOR patients and 1,545 controls. LD score regression was used to detect genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Genebased analysis yielded two significant genes: DPYD (p=4.42x10-7) and PKP4 (p=8.67x10-7); and gene-set-analysis yielded a significant finding for exocytosis (GO:0006887, pFDR=0.019). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [p=2.99x10-3]), SCZ (rg=0.34 [p=4.37x10-5]), and MDD (rg=0.57 [p=1.04x10-3]). Our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies

    Variational methods

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    International audienceThis contribution presents derivative-based methods for local sensitivity analysis, called Variational Sensitivity Analysis (VSA). If one defines an output called the response function, its sensitivity to inputs variations around a nominal value can be studied using derivative (gradient) information. The main issue of VSA is then to provide an efficient way of computing gradients. This contribution first presents the theoretical grounds of VSA: framework and problem statement, tangent and adjoint methods. Then it covers pratical means to compute derivatives, from naive to more sophisticated approaches, discussing their various 2 merits. Finally, applications of VSA are reviewed and some examples are presented, covering various applications fields: oceanography, glaciology, meteorology

    Development of a versatile laboratory experiment to teach the metabolic transformation of hydrolysis

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    In this paper we describe an easy, reliable, versatile and inexpensive laboratory experiment to teach the metabolic transformation of hydrolysis to Pharmacy students. The experiment does not require the sacrifice of any experimental animal, or any work with organs or tissues, and so can be implemented in a typical university chemistry laboratory. We used acetylsalicylic acid (ASA), hexyl salicylate (HS) and two enzymes, a lipase and an esterase. Since both ASS and HS liberate salicylic acid (SA) upon hydrolysis, students can evaluate the different enzymatic transformations by monitoring the amount of SA liberated. The learning outcomes are an enhanced student understanding of: (1) the process of hydrolysis; (2) the application of enzymatic transformations of molecules from food to xenobiotics; (3) the differences between the general specificity of substrate of both enzymes; (4) the concepts of the lipophilic pocket; (5) the catalytic triad and its regioselectivity in relation to the ester bond. A questionnaire was administered to participating students at three points in time: at the beginning of the module, after enzymatic hydrolysis was taught in class, and after the laboratory experiment. From an analysis of the questionnaire data we conclude that this practical helped Pharmacy students to understand these concepts

    Genome-wide Association Study of Borderline Personality Disorder Reveals Genetic Overlap with Bipolar Disorder, Major Depression and Schizophrenia

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    Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case–control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10−7) and PKP4 (P=8.67 × 10−7); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, PFDR=0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [P=2.99 × 10−3]), SCZ (rg=0.34 [P=4.37 × 10−5]) and MDD (rg=0.57 [P=1.04 × 10−3]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies

    North Atlantic simulations in Coordinated Ocean-ice Reference Experiments phase II (CORE-II). Part I: Mean states

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    Simulation characteristics from eighteen global ocean–sea-ice coupled models are presented with a focus on the mean Atlantic meridional overturning circulation (AMOC) and other related fields in the North Atlantic. These experiments use inter-annually varying atmospheric forcing data sets for the 60-year period from 1948 to 2007 and are performed as contributions to the second phase of the Coordinated Ocean-ice Reference Experiments (CORE-II). The protocol for conducting such CORE-II experiments is summarized. Despite using the same atmospheric forcing, the solutions show significant differences. As most models also differ from available observations, biases in the Labrador Sea region in upper-ocean potential temperature and salinity distributions, mixed layer depths, and sea-ice cover are identified as contributors to differences in AMOC. These differences in the solutions do not suggest an obvious grouping of the models based on their ocean model lineage, their vertical coordinate representations, or surface salinity restoring strengths. Thus, the solution differences among the models are attributed primarily to use of different subgrid scale parameterizations and parameter choices as well as to differences in vertical and horizontal grid resolutions in the ocean models. Use of a wide variety of sea-ice models with diverse snow and sea-ice albedo treatments also contributes to these differences. Based on the diagnostics considered, the majority of the models appear suitable for use in studies involving the North Atlantic, but some models require dedicated development effort
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