Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials

OBJECTIVE: To assess whether genetic subgroups in recent amyotrophic lateral sclerosis (ALS) trials responded to treatment with lithium carbonate, but that the treatment effect was lost in a large cohort of nonresponders. METHODS: Individual participant data were obtained from 3 randomized trials investigating the efficacy of lithium carbonate. We matched clinical data with data regarding the UNC13A and C9orf72 genotype. Our primary outcome was survival at 12 months. On an exploratory basis, we assessed whether the effect of lithium depended on the genotype. RESULTS: Clinical data were available for 518 of the 606 participants. Overall, treatment with lithium carbonate did not improve 12-month survival (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.7-1.4; p = 0.96). Both the UNC13A and C9orf72 genotype were independent predictors of survival (HR 2.4, 95% CI 1.3-4.3; p = 0.006 and HR 2.5, 95% CI 1.1-5.2; p = 0.032, respectively). The effect of lithium was different for UNC13A carriers (p = 0.027), but not for C9orf72 carriers (p = 0.22). The 12-month survival probability for UNC13A carriers treated with lithium carbonate improved from 40.1% (95% CI 23.2-69.1) to 69.7% (95% CI 50.4-96.3). CONCLUSIONS: This study incorporated genetic data into past ALS trials to determine treatment effects in a genetic post hoc analysis. Our results suggest that we should reorient our strategies toward finding treatments for ALS, start focusing on genotype-targeted treatments, and standardize genotyping in order to optimize randomization and analysis for future clinical trials

withdrawn 2017 hrs ehra ecas aphrs solaece expert consensus statement on catheter and surgical ablation of atrial fibrillation

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Clinical Features and Outcomes of Patients With Malignancy and Takotsubo Syndrome: Observations From the International Takotsubo Registry

BackgroundClinical characteristics and outcomes of takotsubo syndrome (TTS) patients with malignancy have not been fully elucidated. This study sought to explore differences in clinical characteristics and to investigate short‐ and long‐term outcomes in TTS patients with or without malignancy.Methods and ResultsTTS patients were enrolled from the International Takotsubo Registry. The TTS cohort was divided into patients with and without malignancy to investigate differences in clinical characteristics and to assess short‐ and long‐term mortality. A subanalysis was performed comparing long‐term mortality between a subset of TTS patients with or without malignancy and acute coronary syndrome (ACS) patients with or without malignancy. Malignancy was observed in 16.6% of 1604 TTS patients. Patients with malignancy were older and more likely to have physical triggers, but less likely to have emotional triggers compared with those without malignancy. Long‐term mortality was higher in patients with malignancy (PP=0.17). In a subanalysis, long‐term mortality was comparable between TTS patients with malignancies and ACS patients with malignancies (P=0.13). Malignancy emerged as an independent predictor of long‐term mortality.ConclusionsA substantial number of TTS patients show an association with malignancy. History of malignancy might increase the risk for TTS, and therefore, appropriate screening for malignancy should be considered in these patients.</p

Search for standard-model Z and Higgs bosons decaying into a bottom-antibottom quark pair in proton-antiproton collisions at 1.96 TeV

The Collider Detector at Fermilab collected a unique sample of jets originating from bottom-quark fragmentation (b-jets) by selecting online proton-antiproton (p[¯ over p]) collisions with a vertex displaced from the p[¯ over p] interaction point, consistent with the decay of a bottom-quark hadron. This data set, collected at a center-of-mass energy of 1.96 TeV, and corresponding to an integrated luminosity of 5.4  fb[superscript -1], is used to measure the Z-boson production cross section times branching ratio into b[¯ over b]. The number of Z→b[¯ over b] events is determined by fitting the dijet-mass distribution, while constraining the dominant b-jet background, originating from QCD multijet events, with data. The result, σ(p[¯ over p]→Z)×B(Z→b[¯ over b])=1.11 ± 0.08(stat) ± 0.14(syst)  nb, is the most precise measurement of this process, and is consistent with the standard-model prediction. The data set is also used to search for Higgs-boson production. No significant signal is expected in our data and the first upper limit on the cross section for the inclusive p[¯ over p]→H→b[¯ over b] process at √s=1.96  TeV is set, corresponding to 33 times the expected standard-model cross section, or σ=40.6  pb, at the 95% confidence level.National Science Foundation (U.S.)United States. Department of EnergyAlfred P. Sloan Foundatio

Search for the Exotic Meson X(5568) with the Collider Detector at Fermilab

A search for the exotic meson X(5568) decaying into the B[subscript s][superscript 0]π[superscript ±] final state is performed using data corresponding to 9.6  fb[superscript -1] from pp[over ¯] collisions at sqrt[s]=1960  GeV recorded by the Collider Detector at Fermilab. No evidence for this state is found and an upper limit of 6.7% at the 95% confidence level is set on the fraction of B[subscript s][superscript 0] produced through the X(5568)→B[subscript s][superscript 0]π[superscript ±} process

Search for standard-model Z and Higgs bosons decaying into a bottom-antibottom quark pair in proton-antiproton collisions at 1.96 TeV

The Collider Detector at Fermilab collected a unique sample of jets originating from bottom-quark fragmentation (b-jets) by selecting online proton-antiproton (pp̄) collisions with a vertex displaced from the pp̄ interaction point, consistent with the decay of a bottom-quark hadron. This data set, collected at a center-of-mass energy of 1.96 TeV, and corresponding to an integrated luminosity of 5.4 fb-1, is used to measure the Z-boson production cross section times branching ratio into bb̄. The number of Z→bb̄ events is determined by fitting the dijet-mass distribution, while constraining the dominant b-jet background, originating from QCD multijet events, with data. The result, σ(pp̄→Z)×B(Z→bb̄)=1.11±0.08(stat)±0.14(syst) nb, is the most precise measurement of this process, and is consistent with the standard-model prediction. The data set is also used to search for Higgs-boson production. No significant signal is expected in our data and the first upper limit on the cross section for the inclusive pp̄→H→bb̄ process at s=1.96 TeV is set, corresponding to 33 times the expected standard-model cross section, or σ=40.6 pb, at the 95% confidence level

Search for the Exotic Meson X(5568) with the Collider Detector at Fermilab

A search for the exotic meson X(5568) decaying into the Bs0π± final state is performed using data corresponding to 9.6 fb-1 from pp̄ collisions at s=1960 GeV recorded by the Collider Detector at Fermilab. No evidence for this state is found and an upper limit of 6.7% at the 95% confidence level is set on the fraction of Bs0 produced through the X(5568)→Bs0π± process

Tevatron Run II combination of the effective leptonic electroweak mixing angle

Drell-Yan lepton pairs produced in the process pp→â.,"+â.,"-+X through an intermediate γ∗/Z boson have an asymmetry in their angular distribution related to the spontaneous symmetry breaking of the electroweak force and the associated mixing of its neutral gauge bosons. The CDF and D0 experiments have measured the effective-leptonic electroweak mixing parameter sin2θefflept using electron and muon pairs selected from the full Tevatron proton-antiproton data sets collected in 2001-2011, corresponding to 9-10 fb-1 of integrated luminosity. The combination of these measurements yields the most precise result from hadron colliders, sin2θefflept=0.23148±0.00033. This result is consistent with, and approaches in precision, the best measurements from electron-positron colliders. The standard model inference of the on-shell electroweak mixing parameter sin2θW, or equivalently the W-boson mass MW, using the zfitter software package yields sin2θW=0.22324±0.00033 or equivalently, MW=80.367±0.017 GeV/c2

Search for B-s(0) -> mu(+) mu(-) and B-0 -> mu(+) mu(-) decays with the full CDF Run II data set (vol 87, 072003, 2013)

Erratum: Search for Bs0 →μ+μ- and B0 →μ+μ- decays with the full CDF Run II data set (Physical Review D (2013) 87 (072003