Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group

Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 × 10−8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis

Lack of diagnostic pluripotentiality in patients at clinical high risk for psychosis: Specificity of comorbidity persistence and search for pluripotential subgroups

More than 20 years after the clinical high risk syndrome for psychosis (CHR) was first articulated, it remains controversial whether the CHR syndrome predicts onset of psychosis with diagnostic specificity or predicts pluripotential diagnostic outcomes. Recently, analyses of observational studies, however, have suggested that the CHR syndrome is not pluripotential for emergent diagnostic outcomes. The present report conducted additional analyses in previously reported samples to determine (1) whether comorbid disorders were more likely to persist in CHR patients compared to a comparison group of patients who responded to CHR recruitment efforts but did not meet criteria, termed help-seeking comparison subjects (HSC); and (2) whether clinically defined pluripotential CHR subgroups could be identified. All data were derived from 2 multisite studies in which DSM-IV structured diagnostic interviews were conducted at baseline and at 6-month intervals. Across samples we observed persistence of any nonpsychotic disorder in 80/147 CHR cases (54.4%) and in 48/84 HSC cases (57.1%, n.s.). Findings with persistence of anxiety, depressive, and bipolar disorders considered separately were similar. Efforts to discover pluripotential CHR subgroups were unsuccessful. These findings add additional support to the view that the CHR syndrome is not pluripotential for predicting various diagnostic outcomes but rather is specific for predicting emergent psychosis

Measurement of the Charged Multiplicities in b, c and Light Quark Events from Z0 Decays

Average charged multiplicities have been measured separately in $b$, $c$ and light quark ($u,d,s$) events from $Z^0$ decays measured in the SLD experiment. Impact parameters of charged tracks were used to select enriched samples of $b$ and light quark events, and reconstructed charmed mesons were used to select $c$ quark events. We measured the charged multiplicities: $\bar{n}_{uds} = 20.21 \pm 0.10 (\rm{stat.})\pm 0.22(\rm{syst.})$, $\bar{n}_{c} = 21.28 \pm 0.46(\rm{stat.}) ^{+0.41}_{-0.36}(\rm{syst.})$ $\bar{n}_{b} = 23.14 \pm 0.10(\rm{stat.}) ^{+0.38}_{-0.37}(\rm{syst.})$, from which we derived the differences between the total average charged multiplicities of $c$ or $b$ quark events and light quark events: $\Delta \bar{n}_c = 1.07 \pm 0.47(\rm{stat.})^{+0.36}_{-0.30}(\rm{syst.})$ and $\Delta \bar{n}_b = 2.93 \pm 0.14(\rm{stat.})^{+0.30}_{-0.29}(\rm{syst.})$. We compared these measurements with those at lower center-of-mass energies and with perturbative QCD predictions. These combined results are in agreement with the QCD expectations and disfavor the hypothesis of flavor-independent fragmentation.Comment: 19 pages LaTex, 4 EPS figures, to appear in Physics Letters

Measurement of W Polarisation at LEP

The three different helicity states of W bosons produced in the reaction e+ e- -> W+ W- -> l nu q q~ at LEP are studied using leptonic and hadronic W decays. Data at centre-of-mass energies \sqrt s = 183-209 GeV are used to measure the polarisation of W bosons, and its dependence on the W boson production angle. The fraction of longitudinally polarised W bosons is measured to be 0.218 \pm 0.027 \pm 0.016 where the first uncertainty is statistical and the second systematic, in agreement with the Standard Model expectation

Measurement of W Polarisation at LEP

The three different helicity states of W bosons produced in the reaction e+ e- -> W+ W- -> l nu q q~ at LEP are studied using leptonic and hadronic W decays. Data at centre-of-mass energies \sqrt s = 183-209 GeV are used to measure the polarisation of W bosons, and its dependence on the W boson production angle. The fraction of longitudinally polarised W bosons is measured to be 0.218 \pm 0.027 \pm 0.016 where the first uncertainty is statistical and the second systematic, in agreement with the Standard Model expectation

Bose-Einstein Correlations of Neutral and Charged Pions in Hadronic Z Decays

Bose-Einstein correlations of both neutral and like-sign charged pion pairs are measured in a sample of 2 million hadronic Z decays collected with the L3 detector at LEP. The analysis is performed in the four-momentum difference range 300 MeV < Q < 2 GeV. The radius of the neutral pion source is found to be smaller than that of charged pions. This result is in qualitative agreement with the string fragmentation model

Measurement of the W+W-gamma Cross Section and Direct Limits on Anomalous Quartic Gauge Boson Couplings at LEP

The process e+e- -> W+W-gamma is analysed using the data collected with the L3 detector at LEP at a centre-of-mass energy of 188.6GeV, corresponding to an integrated luminosity of 176.8pb^-1. Based on a sample of 42 selected W+W- candidates containing an isolated hard photon, the W+W-gamma cross section, defined within phase-space cuts, is measured to be: sigma_WWgamma = 290 +/- 80 +/- 16 fb, consistent with the Standard Model expectation. Including the process e+e- -> nu nu gamma gamma, limits are derived on anomalous contributions to the Standard Model quartic vertices W+W- gamma gamma and W+W-Z gamma at 95% CL: -0.043 GeV^-2 < a_0/Lambda^2 < 0.043 GeV^-2 0.08 GeV^-2 < a_c/Lambda^2 < 0.13 GeV^-2 0.41 GeV^-2 < a_n/Lambda^2 < 0.37 GeV^-2

Production of Single W Bosons at \sqrt{s}=189 GeV and Measurement of WWgamma Gauge Couplings

Single W boson production in electron-positron collisions is studied with the L3 detector at LEP. The data sample collected at a centre-of-mass energy of \sqrt{s} = 188.7GeV corresponds to an integrated luminosity of 176.4pb^-1. Events with a single energetic lepton or two acoplanar hadronic jets are selected. Within phase-space cuts, the total cross-section is measured to be 0.53 +/- 0.12 +/- 0.03 pb, consistent with the Standard Model expectation. Including our single W boson results obtained at lower \sqrt{s}, the WWgamma gauge couplings kappa_gamma and lambda_gamma are determined to be kappa_gamma = 0.93 +/- 0.16 +/- 0.09 and lambda_gamma = -0.31 +0.68 -0.19 +/- 0.13

Study of the e+e- -> Ze+e- process at LEP

The cross section of the process e+e- -> Ze+e is measured with 0.7fb^-1 of data collected with the L3 detector at LEP. Decays of the Z boson into quarks and muons are considered at centre-of-mass energies ranging from 183GeV up to 209GeV. The measurements are found to agree with Standard Model predictions, achieving a precision of about 10% for the hadronic channel

Lambda and Sigma0 Pair Production in Two-Photon Collisions at LEP

Strange baryon pair production in two-photon collisions is studied with the L3 detector at LEP. The analysis is based on data collected at e+e- centre-of-mass energies from 91 GeV to 208 GeV, corresponding to an integrated luminosity of 844 pb-1. The processes gamma gamma -> Lambda Anti-lambda and gamma gamma -> Sigma0 Anti-sigma0 are identified. Their cross sections as a function of the gamma gamma centre-of-mass energy are measured and results are compared to predictions of the quark-diquark model