Comparative Evaluation of Whole Body and Hepatic Insulin Resistance Using Indices from Oral Glucose Tolerance Test in Morbidly Obese Subjects with Nonalcoholic Fatty Liver Disease

Nonalcoholic Fatty Liver Disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is a marker of Insulin Resistance (IR). Euglycemic-hyperinsulinemic clamp is the gold standard for measuring whole body IR (hepatic + peripheral IR). However, it is an invasive and expensive procedure. Homeostasis Model Assessment Index for Insulin Sensitivity (HOMA-IS), Quantitative Insulin Sensitivity Check Index (QUICKI) for hepatic IR and Insulin Sensitivity Index (ISI0,120), and Whole Body Insulin Sensitivity Index (WBISI) for whole body IR are the indices calculated after Oral Glucose Tolerance Test (OGTT). We used these indices as noninvasive methods of IR (inverse of insulin sensitivity) estimation and compared hepatic/peripheral components of whole body IR in NAFLD. Methods. 113 morbidly obese, nondiabetic subjects who underwent gastric bypass surgery and intraoperative liver biopsy were included in the study. OGTT was performed preoperatively and the indices were calculated. Subjects were divided into closely matched groups as normal, fatty liver (FL) and Non-Alcoholic Steatohepatitis (NASH) based on histology. Results. Whole body IR was significantly higher in both FL and NASH groups (NAFLD) as compared to Normal, while hepatic IR was higher only in NASH from Normal. Conclusions. FL is a manifestation of peripheral IR but not hepatic IR

Requirements of SLP76 tyrosines in ITAM and integrin receptor signaling and in platelet function in vivo

Src homology 2 domain–containing leukocyte phosphoprotein of 76 kD (SLP76), an adaptor that plays a critical role in platelet activation in vitro, contains three N-terminal tyrosine residues that are essential for its function. We demonstrate that mice containing complementary tyrosine to phenylalanine mutations in Y145 (Y145F) and Y112 and Y128 (Y112/128F) differentially regulate integrin and collagen receptor signaling. We show that mutation of Y145 leads to severe impairment of glycoprotein VI (GPVI)–mediated responses while preserving outside-in integrin signaling. Platelets from Y112/128F mice, although having mild defects in GPVI signaling, exhibit defective actin reorganization after GPVI or αIIbβ3 engagement. The in vivo consequences of these signaling defects correlate with the mild protection from thrombosis seen in Y112/128F mice and the near complete protection observed in Y145F mice. Using genetic complementation, we further demonstrate that all three phosphorylatable tyrosines are required within the same SLP76 molecule to support platelet activation by GPVI

Linkage and related analyses of Barrett's esophagus and its associated adenocarcinomas

BACKGROUND: Familial aggregation and segregation analysis studies have provided evidence of a genetic basis for esophageal adenocarcinoma (EAC) and its premalignant precursor, Barrett's esophagus (BE). We aim to demonstrate the utility of linkage analysis to identify the genomic regions that might contain the genetic variants that predispose individuals to this complex trait (BE and EAC). METHODS: We genotyped 144 individuals in 42 multiplex pedigrees chosen from 1000 singly ascertained BE/EAC pedigrees, and performed both model‐based and model‐free linkage analyses, using S.A.G.E. and other software. Segregation models were fitted, from the data on both the 42 pedigrees and the 1000 pedigrees, to determine parameters for performing model‐based linkage analysis. Model‐based and model‐free linkage analyses were conducted in two sets of pedigrees: the 42 pedigrees and a subset of 18 pedigrees with female affected members that are expected to be more genetically homogeneous. Genome‐wide associations were also tested in these families. RESULTS: Linkage analyses on the 42 pedigrees identified several regions consistently suggestive of linkage by different linkage analysis methods on chromosomes 2q31, 12q23, and 4p14. A linkage on 15q26 is the only consistent linkage region identified in the 18 female‐affected pedigrees, in which the linkage signal is higher than in the 42 pedigrees. Other tentative linkage signals are also reported. CONCLUSION: Our linkage study of BE/EAC pedigrees identified linkage regions on chromosomes 2, 4, 12, and 15, with some reported associations located within our linkage peaks. Our linkage results can help prioritize association tests to delineate the genetic determinants underlying susceptibility to BE and EAC

Predicting Barrett's Esophagus in Families: An Esophagus Translational Research Network (BETRNet) Model Fitting Clinical Data to a Familial Paradigm

Barrett’s esophagus (BE) is often asymptomatic and only a small portion of BE patients are currently diagnosed and under surveillance. Therefore, it is important to develop risk prediction models to identify high-risk individuals with BE. Familial aggregation of BE and esophageal adenocarcinoma (EAC), and the increased risk of EAC for individuals with a family history, raise the necessity of including genetic factors in the prediction model. Methods to determine risk prediction models using both risk covariates and ascertained family data are not well-developed

Measurement of the quasi-elastic axial vector mass in neutrino-oxygen interactions

The weak nucleon axial-vector form factor for quasi-elastic interactions is determined using neutrino interaction data from the K2K Scintillating Fiber detector in the neutrino beam at KEK. More than 12,000 events are analyzed, of which half are charged-current quasi-elastic interactions nu-mu n to mu- p occurring primarily in oxygen nuclei. We use a relativistic Fermi gas model for oxygen and assume the form factor is approximately a dipole with one parameter, the axial vector mass M_A, and fit to the shape of the distribution of the square of the momentum transfer from the nucleon to the nucleus. Our best fit result for M_A = 1.20 \pm 0.12 GeV. Furthermore, this analysis includes updated vector form factors from recent electron scattering experiments and a discussion of the effects of the nucleon momentum on the shape of the fitted distributions.Comment: 14 pages, 10 figures, 6 table

Measurement of the Branching Fraction for B- --> D0 K*-

We present a measurement of the branching fraction for the decay B- --> D0 K*- using a sample of approximately 86 million BBbar pairs collected by the BaBar detector from e+e- collisions near the Y(4S) resonance. The D0 is detected through its decays to K- pi+, K- pi+ pi0 and K- pi+ pi- pi+, and the K*- through its decay to K0S pi-. We measure the branching fraction to be B.F.(B- --> D0 K*-)= (6.3 +/- 0.7(stat.) +/- 0.5(syst.)) x 10^{-4}.Comment: 7 pages, 1 postscript figure, submitted to Phys. Rev. D (Rapid Communications

Study of e+e- --> pi+ pi- pi0 process using initial state radiation with BABAR

The process e+e- --> pi+ pi- pi0 gamma has been studied at a center-of-mass energy near the Y(4S) resonance using a 89.3 fb-1 data sample collected with the BaBar detector at the PEP-II collider. From the measured 3pi mass spectrum we have obtained the products of branching fractions for the omega and phi mesons, B(omega --> e+e-)B(omega --> 3pi)=(6.70 +/- 0.06 +/- 0.27)10-5 and B(phi --> e+e-)B(phi --> 3pi)=(4.30 +/- 0.08 +/- 0.21)10-5, and evaluated the e+e- --> pi+ pi- pi0 cross section for the e+e- center-of-mass energy range 1.05 to 3.00 GeV. About 900 e+e- --> J/psi gamma --> pi+ pi- pi0 gamma events have been selected and the branching fraction B(J/psi --> pi+ pi- pi0)=(2.18 +/- 0.19)% has been measured.Comment: 21 pages, 37 postscript figues, submitted to Phys. Rev.

Measurement of Branching Fraction and Dalitz Distribution for B0->D(*)+/- K0 pi-/+ Decays

We present measurements of the branching fractions for the three-body decays B0 -> D(*)-/+ K0 pi^+/-$and their resonant submodes$B0 -> D(*)-/+ K*+/- using a sample of approximately 88 million BBbar pairs collected by the BABAR detector at the PEP-II asymmetric energy storage ring. We measure: B(B0->D-/+ K0 pi+/-)=(4.9 +/- 0.7(stat) +/- 0.5 (syst)) 10^{-4} B(B0->D*-/+ K0 pi+/-)=(3.0 +/- 0.7(stat) +/- 0.3 (syst)) 10^{-4} B(B0->D-/+ K*+/-)=(4.6 +/- 0.6(stat) +/- 0.5 (syst)) 10^{-4} B(B0->D*-/+ K*+/-)=(3.2 +/- 0.6(stat) +/- 0.3 (syst)) 10^{-4} From these measurements we determine the fractions of resonant events to be : f(B0-> D-/+ K*+/-) = 0.63 +/- 0.08(stat) +/- 0.04(syst) f(B0-> D*-/+ K*+/-) = 0.72 +/- 0.14(stat) +/- 0.05(syst)Comment: 7 pages, 3 figures submitted to Phys. Rev. Let

Forward induction and entry deterrence: an experiment

The Dixit (Econ J 90:95–106, 1980) hypothesis that incumbents use investment in capacity to deter potential entrants has found little empirical support. Bagwell and Ramey (J Econ 27:660–680, 1996) propose a model where, in the unique game-theoretic prediction based on forward induction or iterated elimination of weakly-dominated strategies, the incumbent does not have the strategic advantage. We conduct an experiment with games inspired by these models. In the Dixit-style game, the incumbent monopolizes the market most of the time even without the investment in capacity. In our Bagwell-and-Ramey-style game, the incumbent also tends to keep the market, in contrast to the predictions of an entrant advantage. Nevertheless, we fin strong evidence that forward induction affects the behavior of most participants. The results of our games suggest that players perceive that the firs mover has an advantage without having to pre-commit capacity. In our Bagwell–Ramey game, evolution and learning do not drive out this perception. We back these claims with data analysis and a theoretical framework for dynamics.Publicad