Impact of common risk factors of fibrosis progression in chronic hepatitis C.

OBJECTIVE The natural course of chronic hepatitis C varies widely. To improve the profiling of patients at risk of developing advanced liver disease, we assessed the relative contribution of factors for liver fibrosis progression in hepatitis C. DESIGN We analysed 1461 patients with chronic hepatitis C with an estimated date of infection and at least one liver biopsy. Risk factors for accelerated fibrosis progression rate (FPR), defined as ≥0.13 Metavir fibrosis units per year, were identified by logistic regression. Examined factors included age at infection, sex, route of infection, HCV genotype, body mass index (BMI), significant alcohol drinking (≥20 g/day for ≥5 years), HIV coinfection and diabetes. In a subgroup of 575 patients, we assessed the impact of single nucleotide polymorphisms previously associated with fibrosis progression in genome-wide association studies. Results were expressed as attributable fraction (AF) of risk for accelerated FPR. RESULTS Age at infection (AF 28.7%), sex (AF 8.2%), route of infection (AF 16.5%) and HCV genotype (AF 7.9%) contributed to accelerated FPR in the Swiss Hepatitis C Cohort Study, whereas significant alcohol drinking, anti-HIV, diabetes and BMI did not. In genotyped patients, variants at rs9380516 (TULP1), rs738409 (PNPLA3), rs4374383 (MERTK) (AF 19.2%) and rs910049 (major histocompatibility complex region) significantly added to the risk of accelerated FPR. Results were replicated in three additional independent cohorts, and a meta-analysis confirmed the role of age at infection, sex, route of infection, HCV genotype, rs738409, rs4374383 and rs910049 in accelerating FPR. CONCLUSIONS Most factors accelerating liver fibrosis progression in chronic hepatitis C are unmodifiable.

Grammaire de l'Hébreu biblique [nebst] Paradigmes et index

par Paul Jou͏̈on

Radiocarbon dating of modern peat profiles: Pre- and post-bomb C-14 variations in the construction of age-depth models

We present studies of 9 modern (up to 400-yr-old) peat sections from Slovenia, Switzerland, Austria, Italy, and Finland. Precise radiocarbon dating of modern samples is possible due to the large bomb peak of atmospheric 14C concentration in 1963 and the following rapid decline in the 14C level. All the analyzed 14C profiles appeared concordant with the shape of the bomb peak of atmospheric 14C concentration, integrated over some time interval with a length specific to the peat section. In the peat layers covered by the bomb peak, calendar ages of individual peat samples could be determined almost immediately, with an accuracy of 23 yr. In the pre-bomb sections, the calendar ages of individual dated samples are determined in the form of multi-modal probability distributions of about 300 yr wide (about AD 16501950). However, simultaneous use of the post-bomb and pre-bomb 14C dates, and lithological information, enabled the rejection of most modes of probability distributions in the pre-bomb section. In effect, precise age-depth models of the post-bomb sections have been extended back in time, into the wiggly part of the 14C calibration curve.

Nonperturbative results for two-index conformal windows

Via large and small N c relations we derive nonperturbative results about the conformal window of two-index theories. Using Schwinger-Dyson methods as well as four-loops results we estimate subleading corrections and show that naive large number of colors extrapolations are unreliable when N c is less than about six. Nevertheless useful nonper-turbative inequalities for the size of the conformal windows, for any number of colors, can be derived. By further observing that the adjoint conformal window is independent of the number of colors we argue, among other things, that: the large N c two-index conformal window is twice the conformal window of the adjoint representation (which can be determined at small N c) expressed in terms of Dirac fermions; lattice results for adjoint matter can be used to provide independent information on the conformal dynamics of two-index theories such as SU(N c) with two and four symmetric Dirac flavors.

High-resolution AMS (super 14) C dating of post-bomb peat archives of atmospheric pollutants.

Peat deposits in Greenland and Denmark were investigated to show that high-resolution dating of these archives of atmospheric deposition can be provided for the last 50 years by radiocarbon dating using the atmospheric bomb pulse. (super 14) C was determined in macrofossils from sequential one cm slices using accelerator mass spectrometry (AMS). Values were calibrated with a general-purpose curve derived from annually averaged atmospheric (super 14) CO (sub 2) values in the northernmost northern hemisphere (NNH, 30 degrees -90 degrees N). We present a through review of (super 14) C bomb-pulse data from the NNH including our own measurements made in tree rings and seeds from Arizona as well as other previously published data. We show that our general-purpose calibration curve is valid for the whole NNH producing accurate dates within 1-2 years. In consequence, (super 14) C AMS can precisely date individual points in recent peat deposits within the range of the bomb-pulse (from the mid-1950s on). Comparing the (super 14) C AMS results with the customary dating method for recent peat profiles by (super 210) Pb, we show that the use of (super 137) Cs to validate and correct (super 210) Pb dates proves to be more problematic than previously supposed. As a unique example of our technique, we show how this chronometer can be applied to identify temporal changes in Hg concentrations from Danish and Greenland peat cores.

Impact of body mass index on long-term clinical outcomes after second-generation drug eluting stent implantation: Insights from the international global RESOLUTE program

BACKGROUND An increased body mass index (BMI) is associated with a high risk of cardiovascular disease and reduction in life expectancy. However, several studies reported improved clinical outcomes in obese patients treated for cardiovascular diseases. The aim of the present study is to investigate the impact of BMI on long-term clinical outcomes after implantation of zotarolimus eluting stents. METHODS Individual patient data were pooled from the RESOLUTE Clinical Program comprising five trials worldwide. The study population was sorted according to BMI tertiles and clinical outcomes were evaluated at 2-year follow-up. RESULTS Data from a total of 5,127 patients receiving the R-ZES were included in the present study. BMI tertiles were as follow: I tertile (≤ 25.95 kg/m(2) -Low or normal weight) 1,727 patients; II tertile (>25.95 ≤ 29.74 kg/m(2) -overweight) 1,695 patients, and III tertile (>29.74 kg/m(2) -obese) 1,705 patients. At 2-years follow-up no difference was found for patients with high BMI (III tertile) compared with patients with normal or low BMI (I tertile) in terms of target lesion failure (I-III tertile, HR [95% CI] = 0.89 [0.69, 1.14], P = 0.341; major adverse cardiac events (I-III tertile, HR [95% CI] = 0.90 [0.72, 1.14], P = 0.389; cardiac death (I-III tertile, HR [95% CI] = 1.20 [0.73, 1.99], P = 0.476); myocardial infarction (I-III tertile, HR [95% CI] = 0.86 [0.55, 1.35], P = 0.509; clinically-driven target lesion revascularization (I-III tertile, HR [95% CI] = 0.75 [0.53, 1.08], P = 0.123; definite or probable stent thrombosis (I-III tertile, HR [95% CI] = 0.98 [0.49, 1.99], P = 0.964. CONCLUSIONS In the present study, the patients' body mass index was found to have no impact on long-term clinical outcomes after coronary artery interventions.

1D.03: Inactive Matrix Gla Protein is Assocated with Renal Resistive Index in a Population-Based Study

OBJECTIVE Renal resistive index (RRI) varies directly with renal vascular stiffness and pulse pressure. RRI correlates positively with arteriolosclerosis in damaged kidneys and predicts progressive renal dysfunction. Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular (CV) markers, CV outcomes and mortality. In this study we hypothesize that increased RRI is associated with high levels of dp-ucMGP. DESIGN AND METHOD We recruited participants via a multi-center family-based cross-sectional study in Switzerland exploring the role of genes and kidney hemodynamics in blood pressure regulation. Dp-ucMGP was quantified in plasma samples by sandwich ELISA. Renal doppler sonography was performed using a standardized protocol to measure RRIs on 3 segmental arteries in each kidney. The mean of the 6 measures was reported. Multiple regression analysis was performed to estimate associations between RRI and dp-ucMGP adjusting for sex, age, pulse pressure, mean pressure, renal function and other CV risk factors. RESULTS We included 1035 participants in our analyses. Mean values were 0.64 ± 0.06 for RRI and 0.44 ± 0.21 (nmol/L) for dp-ucMGP. RRI was positively associated with dp-ucMGP both before and after adjustment for sex, age, body mass index, pulse pressure, mean pressure, heart rate, renal function, low and high density lipoprotein, smoking status, diabetes, blood pressure and cholesterol lowering drugs, and history of CV disease (P < 0.001). CONCLUSIONS RRI is independently and positively associated with high levels of dp-ucMGP after adjustment for pulse pressure and common CV risk factors. Further studies are needed to determine if vitamin K supplementation can have a positive effect on renal vascular stiffness and kidney function.

Changes in blood lipids and their associations with changes in measures of height, weight and body mass index from age 8 to 18 years: Project Heartbeat!

A variety of studies indicate that the process of athrosclerosis begins in childhood. There was limited information on the association of the changes in anthropometric variables to blood lipids in school age children and adolescents. Previous longitudinal studies of children typically with insufficient frequency of observation could not provide sound inference on the dynamics of change in blood lipids. The aims of this analysis are (1) to document the sex- and ethnic-specific trajectory and velocity curves of blood lipids (TC, LDL-C, HDL-C and TG); (2) to evaluate the relationship of changes in anthropometric variables, such as height, weight and BMI, to blood lipids from age 8 to 18 years. ^ Project HeartBeat! is a longitudinal study designed to examine the patterns of serial change in major cardiovascular risk factors. Cohort of three different age levels, 8, 11 and 14 years at baseline, with a total of 678 participants were enrolled. Each member of these cohorts was examined three times per year for up to four years. ^ Sex- and ethnic-specific trajectory and velocity curves of blood lipids; demonstrated the complex and polyphasic changes in TC, LDL-C, HDL-C and TG longitudinally. The trajectory curves of TC, LDL-C and HDL-C with age showed curvilinear patterns of change. The velocity change in TC, HDL-C and LDL-C showed U-shaped curves for non-Blacks, and nearly linear lines in velocity of TG for both Blacks and non-Blacks. ^ The relationship of changes in anthropometric variables to blood lipids was evaulated by adding height, weight, or BMI and associated interaction terms separately to the basic age-sex models. Height or height gain had a significant negative association with changes in TC, LDL-C and HDL-C. Weight or BMI gain showed positive associations with TC, LDL-C and TC, and a negative relationship with HDL-C. ^ Dynamic changes of blood lipids in school age children and adolescents observed from this analysis suggested that using fixed screening criteria under the current NCEP guidelines for all ages 2–19 may not be appropriate for this age group. The association of increasing BMI or weight to an adverse blood lipid profile found in this analysis also indicated that weight or BMI monitoring could be a future intervention to be implemented in the pediatric population. ^

Hat Moses Maimonides dem Krypto-Mohammedanismus gehuldigt? : Nach geschichtlichen Quellen untersucht, mit wichtigen Anmerkungen, hebr. Noten, nebst einem alphabetisch-geordneten chronologischen Index der wichtigern jüdischen Gelehrten aus Spanien und der Provence

von Herman Kahan

Prevalence and determinants of hepatitis B co-infection among a United States Veterans Administration cohort with hepatitis C

Background and aim. Hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection is associated with increased risk of cirrhosis, decompensation, hepatocellular carcinoma, and death. Yet, there is sparse epidemiologic data on co-infection in the United States. Therefore, the aim of this study was to determine the prevalence and determinants of HBV co-infection in a large United States population of HCV patients. ^ Methods. The National Veterans Affairs HCV Clinical Case Registry was used to identify patients tested for HCV during 1997–2005. HCV exposure was defined as two positive HCV tests (antibody, RNA or genotype) or one positive test combined with an ICD-9 code for HCV. HCV infection was defined as only a positive HCV RNA or genotype. HBV exposure was defined as a positive test for hepatitis B core antibodies, hepatitis B surface antigen, HBV DNA, hepatitis Be antigen, or hepatitis Be antibody. HBV infection was defined as only a positive test for hepatitis B surface antigen, HBV DNA, or hepatitis Be antigen within one year before or after the HCV index date. The prevalence of exposure to HBV in patients with HCV exposure and the prevalence of HBV infection in patients with HCV infection were determined. Multivariable logistic regression was used to identify demographic and clinical determinants of co-infection. ^ Results. Among 168,239 patients with HCV exposure, 58,415 patients had HBV exposure for a prevalence of 34.7% (95% CI 34.5–35.0). Among 102,971 patients with HCV infection, 1,431 patients had HBV co-infection for a prevalence of 1.4% (95% CI 1.3–1.5). The independent determinants for an increased risk of HBV co-infection were male sex, positive HIV status, a history of hemophilia, sickle cell anemia or thalassemia, history of blood transfusion, cocaine and other drug use. Age >50 years and Hispanic ethnicity were associated with a decreased risk of HBV co-infection. ^ Conclusions. This is the largest cohort study in the United States on the prevalence of HBV co-infection. Among veterans with HCV, exposure to HBV is common (∼35%), but HBV co-infection is relatively low (1.4%). There is an increased risk of co-infection with younger age, male sex, HIV, and drug use, with decreased risk in Hispanics.^

Characterization of the interaction between local cerebral metabolic rate for glucose and acid -base index in ischemic rat brain employing a double-isotope methodology

The association between increases in cerebral glucose metabolism and the development of acidosis is largely inferential, based on reports linking hyperglycemia with poor neurological outcome, lactate accumulation, and the severity of acidosis. We measured local cerebral metabolic rate for glucose (lCMRglc) and an index of brain pH--the acid-base index (ABI)--concurrently and characterized their interaction in a model of focal cerebral ischemia in rats in a double-label autoradiographic study, using ($\sp{14}$C) 2-deoxyglucose and ($\sp{14}$C) dimethyloxazolidinedione. Computer-assisted digitization and analysis permitted the simultaneous quantification of the two variables on a pixel-by-pixel basis in the same brain slices. Hemispheres ipsilateral to tamponade-induced middle cerebral occlusion showed areas of normal, depressed and elevated glucose metabolic rate (as defined by an interhemispheric asymmetry index) after two hours of ischemia. Regions of normal glucose metabolic rate showed normal ABI (pH $\pm$ SD = 6.97 $\pm$ 0.09), regions of depressed lCMRglc showed severe acidosis (6.69 $\pm$ 0.14), and regions of elevated lCMRglc showed moderate acidosis (6.88 $\pm$ 0.10), all significantly different at the.00125 level as shown by analysis of variance. Moderate acidosis in regions of increased lCMRglc suggests that anaerobic glycolysis causes excess protons to be generated by the uncoupling of ATP synthesis and hydrolysis. ^

(Figure 2) Organic carbon content, stable isotope ratios, TEX86 index and sea surface temperature reconstruction for the early Aptian of ODP Hole 198-1207B

The Cretaceous has long been recognized as a time when greenhouse conditions were fueled by elevated atmospheric CO2 and accompanied by perturbations of the global carbon cycle described as oceanic anoxic events (OAEs). Yet, the magnitude and frequency of temperature change during this interval of warm and equable climate are poorly constrained. Here we present a high-resolution record of sea-surface temperatures (SSTs) reconstructed using the TEX86 paleothermometer for a sequence of early Aptian organic-rich sediments deposited during the first Cretaceous OAE (OAE1a) at Shatsky Rise in the tropical Pacific. SSTs range from ~30 to ~36 °C and include two prominent cooling episodes of ~4 °C. The cooler temperatures reflect significant temperature instability in the tropics likely triggered by changes in carbon cycling induced by enhanced burial of organic matter. SST instability recorded during the early Aptian in the Pacific is comparable to that reported for the late Albian-early Cenomanian in the Atlantic, suggesting that such climate perturbations may have recurred during the Cretaceous with concomitant consequences for biota and the marine environment.

Estudio comparativo del cariotipo en especies de Miltinea Ravenna, Phycella Lindl. y Rhodophiala C. Presl (Amaryllidaceae) de Chile

La familia Amaryllidaceae se encuentra distribuida en diversas regiones de Chile y Sudamérica. De los 11 géneros reconocidos por Ravenna, al menos tres de ellos presentan un reconocido potencial ornamental: Miltinea Ravenna, endémico de Chile y conformado por la especie Miltinea maulensis (Ravenna) Ravenna, Phycella Lindley, endémico de Chile, conformado por cuatro especies y distribuido desde el valle de Elqui hasta la altura de la región de Arauco y Rhodophiala C. Presl. presente en el sur de Brasil, Uruguay, Bolivia, Argentina y Chile conformado por un número aproximado de 40 especies. Actualmente, la información taxonómica tradicional para diferenciar los géneros presentes en Chile es insuficiente. Es por ello que se utilizó la citotaxonomía como una herramienta y fuente de evidencia taxonómica. El objetivo de esta investigación fue realizar un estudio comparativo de los cariotipos en representantes de tres géneros de Amaryllidaceae que crecen en Chile con el fin de ayudar a clarificar la posición taxonómica de ellos. Las especies analizadas fueron: Miltinea maulensis (Ravenna) Ravenna, Phycella australis Ravenna, Rhodophiala araucana (Phil.) Traub, Rhodophiala montana (Phil.) Traub, y Rhodophiala pratensis (Poepp.) Traub. Los resultados obtenidos indicaron que Miltinea maulensis y Phycella australis presentan características cariológicas muy similares, tanto en el número cromosómico, fórmula cariotípica e índices cromosómicos. Estas características permitirían considerar Miltinea como un sinónimo de Phycella. Por último, las tres especies de Rhodophiala analizadas comparten características citológicas muy similares, como por ejemplo, la presencia de una región NOR en el brazo largo del cromosoma 7, idéntico número cromosómico e índices de asimetría de los cariotipos casi iguales.

Caso L.C. vs Perú. Comunicación Nº 22/2009

Dictamen aprobado por el Comité en su 50º período de sesiones, celebrado del 3 al 21 de octubre de 2011