ENGINEERING CAPABILITIES OF IN-PILE IRRADIATION FACILITIES USED BY GE-ANPD

GE-ANPD had exclusive use of irradiation testing facilities in four reactors: the Materials Test Reactor (MTR), the Engineering Test Reactor (ETR), the Low lntensity Test Reactor (LlTR), and the Oak Ridge Research Reactor (ORR). A compilation of data concerning the GE-ANPD facilities in these reactors is presented. lnstrumentation capabilities, dimensions of the in-pile tubes, flow characteristics, control capabilities, and detailed design data are listed. (auth

Negative Regulation of Hepatitis C Virus Specific Immunity Is Highly Heterogeneous and Modulated by Pegylated Interferon-Alpha/Ribavirin Therapy

Specific inhibitory mechanisms suppress the T-cell response against the hepatitis C virus (HCV) in chronically infected patients. However, the relative importance of suppression by IL-10, TGF-β and regulatory T-cells and the impact of pegylated interferon-alpha and ribavirin (PegIFN-α/ribavirin) therapy on these inhibitory mechanisms are still unclear. We revealed that coregulation of the HCV-specific T-cell responses in blood of 43 chronic HCV patients showed a highly heterogeneous pattern before, during and after PegIFN-α/ribavirin. Prior to treatment, IL-10 mediated suppression of HCV-specific IFN-γ production in therapy-naive chronic HCV patients was associated with higher HCV-RNA loads, which suggests that protective antiviral immunity is controlled by IL-10. In addition, as a consequence of PegIFN-α/ribavirin therapy, negative regulation of especially HCV-specific IFN-γ production by TGF-β and IL-10 changed dramatically. Our findings emphasize the importance of negative regulation for the dysfunctional HCV-specific immunity, which should be considered in the design of future immunomodulatory therapies

Screening for type 2 diabetes in a high-risk population: Study design and feasibility of a population-based randomized controlled trial

Background: We describe the design and present the results of the first year of a population-based study of screening for type 2 diabetes in individuals at high risk of developing the disease. High risk is defined as having abdominal obesity. Methods. Between 2006 and 2007, 79,142 inhabitants of two Dutch municipalities aged 40-74 years were approached to participate in screening. Eligible participants had a self-reported waist circumference of 80 cm for women and 94 cm for men, and no known pre-existing diabetes. Of the respondents (n=20,578; response rate 26%), 16,135 were abdominally obese. In total, 10,609 individuals gave written informed consent for participation and were randomized into either the screening (n=5305) or the control arm (n=5304). Participants in the screening arm were invited to have their fasting plasma glucose (FPG) measured and were referred to their general practitioner (GP) if it was 6.1 mmol/L. In addition, blood lipids were determined in the screening arm, because abdominal obesity is often associated with cardiovascular risk factors. Participants in both arms received written healthy lifestyle information. Between-group differences were analyzed with Chi-square tests and logistic regression (categorical variables) and unpaired t-tests (continuous variables). Results: The screening attendance rate was 84.1%. Attending screening was associated with age at randomization (OR=1.03, 95% CI 1.02-1.04), being married (OR=1.57, 95% CI 1.33-1.83) and not-smoking currently (OR=0.52, 95% CI 0.44-0.62). Of the individuals screened, 5.6% had hyperglycemia, and a further 11.6% had an estimated absolute cardiovascular disease risk of 5% or higher, according to the Systematic Coronary Risk Evaluation risk model. These participants were referred to their GP. Conclusions: Self-reported home-assessed waist circumference could feasibly detect persons at high risk of hyperglycemia or cardiovascular disease. Continuation of the large-scale RCT is warranted to test the hypothesis that targeted population-based screening for type 2 diabetes leads to a significant reduction in cardiovascular morbidity and mortality

Adherence to a plant-based, high-fibre dietary pattern is related to regression of non-alcoholic fatty liver disease in an elderly population

Dietary lifestyle intervention is key in treating non-alcoholic fatty liver disease (NAFLD). We aimed to examine the longitudinal relation between well-established dietary patterns as well as population-specific dietary patterns and NAFLD. Participants from two subsequent visits of the Rotterdam Study were included. All underwent serial abdominal ultrasonography (median follow-up: 4.4 years) and filled in a food frequency questionnaire. Secondary causes of steatosis were excluded. Dietary data from 389 items were collapsed into 28 food groups and a posteriori dietary patterns were identified using factor analysis. Additionally, we scored three a priori dietary patterns (Mediterranean Diet Score, Dutch Dietary Guidelines and WHO-score). Logistic mixed regression models were used to examine the relation between dietary patterns and NAFLD. Analyses were adjusted for demographic, lifestyle and metabolic factors. We included 963 participants of whom 343 had NAFLD. Follow-up data was available in 737 participants. Incident NAFLD was 5% and regressed NAFLD was 30%. We identified five a posteriori dietary patterns (cumulative explained variation [R2] = 20%). The patterns were characterised as: vegetable and fish, red meat and alcohol, traditional, salty snacks and sauces, high fat dairy & refined grains pattern. Adherence to the traditional pattern (i.e. high intake of vegetable oils/stanols, margarines/butters, potatoes, whole grains and sweets/desserts) was associated with regression of NAFLD per SD increase in Z-score (0.40, 95% CI 0.15–1.00). Adherence to the three a priori patterns all showed regression of NAFLD, but only the WHO-score showed a distinct association (0.73, 95% CI 0.53–1.00). Hence, in this large elderly population, adherence to a plant-based, high-fibre and low-fat diet was related to regression of NAFLD

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

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

Prediction of long-term clinical outcome in a diverse chronic hepatitis B population: Role of the PAGE-B score

An abundance of noninvasive scores have been associated with fibrosis and hepatocellular carcinoma (HCC) development. We aimed to compare the prognostic ability of these scores in relation to liver histology in chronic hepatitis B (CHB) patients. Liver biopsies from treatment-naïve CHB patients at one tertiary care centre were scored by a single hepato-pathologist. Laboratory values at liver biopsy were used to calculate the PAGE-B, REACH-B, GAG-HCC, CU-HCC and FIB-4 scores. Any clinical event was defined as HCC development, liver failure, transplantation and mortality. HCC and mortality data were obtained from national database registries. Of 557 patients, 40 developed a clinical event within a median follow-up of 10.1 (IQR 5.7-15.9) years. The PAGE-B score predicted any clinical event (C-statistic.86, 95% CI: 0.80-0.92), HCC development (C-statistic.91) and reduced transplant-free survival (C-statistic.83) with good accuracy, also when stratified by ethnicity, antiviral therapy after biopsy or advanced fibrosis. The C-statistics (95% CI) of the REACH-B, GAG-HCC, CU-HCC and FIB-4 scores for any event were.70 (0.59-0.81),.82 (0.75-0.89),.73 (0.63-0.84) and.79 (0.69-0.89), respectively. The PAGE-B event risk assessment improved modestly when combined with the Ishak fibrosis stage (C-statistic.87, 95% CI: 0.82-0.93). The PAGE-B score showed the best performance in assessing the likelihood of developing a clinical event among a diverse CHB population over 15 years of follow-up. Additional liver histological characteristics did not appear to provide a clinically significant improvement

Peptides from the variable region of specific antibodies are shared among lung cancer patients

Late diagnosis of lung cancer is still the main reason for high mortality rates in lung cancer. Lung cancer is a heterogeneous disease which induces an immune response to different tumor antigens. Several methods for searching autoantibodies have been described that are based on known purified antigen panels. The aim of our study is to find evidence that parts of the antigen-binding-domain of antibodies are shared among lung cancer patients. This was investigated by a novel approach based on sequencing antigen-binding- fragments (Fab) of immunoglobulins using proteomic techniques without the need of previously known antigen panels. From serum of 93 participants of the NELSON trial IgG was isolated and subsequently digested into Fab and Fc. Fab was purified from the digested mixture by SDS-PAGE. The Fab containing gel-bands were excised, tryptic digested and measured on a nano-LC-Orbitrap-Mass- spectrometry system. Multivariate analysis of the mass spectrometry data by linear canonical discriminant analysis combined with stepwise logistic regression resulted in a 12-antibody-peptide model which was able to distinguish lung cancer patients from controls in a high risk population with a sensitivity of 84% and specificity of 90%. With our Fab-purification combined Orbitrap-mass-spectrometry approach, we found peptides from the variable-parts of antibodies which are shared among lung cancer patients

ITPA polymorphisms are associated with hematological side effects during antiviral therapy for chronic HCV infection

Background/Objective Genetic polymorphisms in the inosine triphosphatase (ITPA) gene have been associated with the protection from early ribavirin(RBV)-induced hemolytic anemia among patients with chronic hepatitis C virus (HCV) infection. The aim of the present study was to investigate the association between the functional ITPA variants and hematological side effects during antiviral therapy with pegylated interferon (PegIFN) and RBV. Patients and Methods This cohort study included all consecutive Caucasian patients treated for chronic HCV infection with PegIFN and RBV between 2000 and 2009 for whom a serum sample was available for genetic testing. The predicted inosine triphosphate pyrophosphatase (ITPase) activity was based on the genotypes of the SNPs rs1127354 and rs7270101. Decline in hemoglobin (Hb) during antiviral therapy, as well as dose reductions, blood transfusions and use of erythropoietin were assessed. Results In total, 213 patients were included. The predicted ITPase activity was normal among 152 (71%) patients; 61 (29%) patients had ITPase deficiency. By multivariable linear regression, RBV dose in mg per kilogram (Beta 0.09, 95%CI 0.04-0.13, p<0.001) and normal ITPase activity (Beta 0.89, 95%CI 0.64-1.14, p<0.001) were associated with more Hb decline at week 4 of treatment. Patients with normal ITPase activity underwent more dose adjustments of RBV than patients with ITPase deficiency (19(13%) vs 1(2%),p = 0.014) and received erythropoietin more frequently (12 (8%) vs 0 (0%),p = 0.024). Conclusion Genetic variants in the ITPA gene protected against RBV treatment-induced anemia among Caucasian patients with chronic HCV infection. Patients with normal ITPase activity underwent more dose reductions of RBV and received erythropoietin more frequently

Detector Description and Performance for the First Coincidence Observations between LIGO and GEO

For 17 days in August and September 2002, the LIGO and GEO interferometer gravitational wave detectors were operated in coincidence to produce their first data for scientific analysis. Although the detectors were still far from their design sensitivity levels, the data can be used to place better upper limits on the flux of gravitational waves incident on the earth than previous direct measurements. This paper describes the instruments and the data in some detail, as a companion to analysis papers based on the first data.Comment: 41 pages, 9 figures 17 Sept 03: author list amended, minor editorial change