Critical postsynaptic density 95/disc large/zonula occludens-1 interactions by glutamate receptor 1 (GluR1) and GluR2 required at different subcellular sites

Interactions between AMPA receptor subunits and proteins containing postsynaptic density 95/disc large/zonula occludens-1 (PDZ) domains have been shown to play critical roles in the proper trafficking of receptors to excitatory synapses. Synaptic accumulation of AMPA receptors containing the glutamate receptor 1 (GluR1) subunit can be driven by calcium/calmodulin-dependent protein kinase II activity or long-term potentiation and requires an interaction between GluR1 and a type I PDZ domain-containing protein. Synaptic incorporation of AMPA receptors with only GluR2 occurs continuously, and this requires an interaction between GluR2 and a type II PDZ domain-containing protein. We used dual-channel, two-photon laser scanning microscopy to provide high-resolution visualization and quantification of green fluorescent protein-tagged AMPA receptors in different subcellular compartments. We showed that mutations on GluR1 or GluR2 AMPA subunit that perturb interactions with PDZ domain proteins lead to the accumulation of these receptors at different subcellular sites. GluR1 mutants accumulate in the dendrite, whereas GluR2 mutants accumulate in dendritic spines. This suggests that the critical PDZ domain interactions are required for entry into spines for GluR1 and for entry into synapses for GluR2

Precision tests of the Standard Model with leptonic and semileptonic kaon decays

We present a global analysis of leptonic and semileptonic kaon decays data, including all recent results by BNL-E865, KLOE, KTeV, ISTRA+, and NA48. Experimental results are critically reviewed and combined, taking into account theoretical (both analytical and numerical) constraints on the semileptonic kaon form factors. This analysis leads to a very accurate determination of Vus and allows us to perform several stringent tests of the Standard Model

Patient-Reported Satisfaction and Study Drug Discontinuation: Post-Hoc Analysis of Findings from ROCKET AF.

IntroductionPatient-reported outcomes (PROs) and satisfaction endpoints are increasingly important in clinical trials and may be associated with treatment adherence. In this post hoc substudy from ROCKET AF, we examined whether patient-reported satisfaction was associated with study drug discontinuation.MethodsROCKET AF (n = 14,264) compared rivaroxaban with warfarin for prevention of stroke and systemic embolism in patients with atrial fibrillation. We analyzed treatment satisfaction scores: the Anti-Clot Treatment Scale (ACTS) and Treatment Satisfaction Questionnaire for Medication version II (TSQM II). We compared satisfaction with study drug between the two treatment arms, and examined the association between satisfaction and patient-driven study drug discontinuation (stopping study drug due to withdrawal of consent, noncompliance, or loss to follow-up).ResultsA total of 1577 (11%) patients participated in the Patient Satisfaction substudy; 1181 (8.3%) completed both the ACTS and TSQM II 4 weeks after starting study drug. Patients receiving rivaroxaban did not experience significant differences in satisfaction compared with those receiving warfarin. During a median follow-up of 1.6 years, 448 premature study drug discontinuations occurred (213 rivaroxaban group; 235 warfarin group), of which 116 (26%) were patient-driven (52 [24%] rivaroxaban group; 64 [27%] warfarin group). No significant differences were observed between satisfaction level and rates of patient-driven study drug discontinuation.ConclusionsStudy drug satisfaction did not predict rate of study drug discontinuation. No significant difference was observed between satisfaction with warfarin and rivaroxaban, as expected given the double-blind trial design. Although these results are negative, the importance of PRO data will only increase, and these analyses may inform future studies that explore the relationship between drug-satisfaction PROs, adherence, and clinical outcomes. CLINICALTRIALS.GOV: NCT00403767.FundingThe ROCKET AF trial was funded by Johnson & Johnson and Bayer

Three-Dimensional Self-Navigated T2 Mapping for the Detection of Acute Cellular Rejection After Orthotopic Heart Transplantation.

T2 mapping is a magnetic resonance imaging technique measuring T2 relaxation time, which increases with the myocardial tissue water content. Myocardial edema is a component of acute cellular rejection (ACR) after heart transplantation. This pilot study compares in heart transplantation recipients a novel high resolution 3-dimensional (3D) T2-mapping technique with standard 2-dimensional (2D) T2-mapping for ACR detection. Consecutive asymptomatic patients (n = 26) underwent both 3D T2 mapping and reference 2D T2 mapping magnetic resonance imaging on the day of endomyocardial biopsy (EMB). 3D T2 maps were obtained at an isotropic spatial resolution of 1.72 mm (voxel volume 5.1 mm(3)). 2D and 3D maps were matched anatomically, and maximum segmental T2 values were compared blinded to EMB results. In addition, all 3D T2 maps were rendered as 3D images and inspected for foci of T2 elevation. T2 values of segments from 2D and reformatted 3D T2 maps agreed (p > 0.5). The highest 2D segmental T2 values were 49.9 ± 4.0 ms (no ACR = 0R, n = 18), 48.9 ± 0.8 ms (mild ACR = 1R, n = 3), and 65.0 ms (moderate ACR = 2R). Rendered 3D T2 maps of cases with 1R showed foci with significantly elevated T2 signal (T2 = 58.2 ± 3.6 ms); 5 cases (28%) in the 0R group showed foci with increased T2 values (>2 SD above adjacent tissue) that were not visible on the 2D T2 maps. This pilot study in a small cohort suggests equivalency of standard segmental analysis between 3D and 2D T2-mapping. 3D T2 mapping provides a spatial resolution that permits detection of foci with elevated T2 in patients with mild ACR

Measurement of the branching ratio of the decay Ξ0→Σ+μ−νˉμ\Xi^{0}\rightarrow \Sigma^{+} \mu^{-} \bar{\nu}_{\mu}

From the 2002 data taking with a neutral kaon beam extracted from the CERN-SPS, the NA48/1 experiment observed 97 $\Xi^{0}\rightarrow \Sigma^{+} \mu^{-} \bar{\nu}_{\mu}$ candidates with a background contamination of $30.8 \pm 4.2$ events. From this sample, the BR($\Xi^{0}\rightarrow \Sigma^{+} \mu^{-} \bar{\nu}_{\mu}$) is measured to be $(2.17 \pm 0.32_{\mathrm{stat}}\pm 0.17_{\mathrm{syst}})\times10^{-6}$

Prospects for K+→π+ννˉK^+ \to \pi^+ \nu \bar{ \nu } at CERN in NA62

The NA62 experiment will begin taking data in 2015. Its primary purpose is a 10% measurement of the branching ratio of the ultrarare kaon decay $K^+ \to \pi^+ \nu \bar{ \nu }$, using the decay in flight of kaons in an unseparated beam with momentum 75 GeV/c.The detector and analysis technique are described here.Comment: 8 pages for proceedings of 50 Years of CP

Recent NA48/2 and NA62 results

The NA48/2 Collaboration at CERN has accumulated and analysed unprecedented statistics of rare kaon decays in the $K_{e4}$ modes: $K_{e4}(+-)$ ($K^\pm \to \pi^+ \pi^- e^\pm \nu$) and $K_{e4}(00)$ ($K^\pm \to \pi^0 \pi^0 e^\pm \nu$) with nearly one percent background contamination. It leads to the improved measurement of branching fractions and detailed form factor studies. New final results from the analysis of 381 $K^\pm \to \pi^\pm \gamma \gamma$ rare decay candidates collected by the NA48/2 and NA62 experiments at CERN are presented. The results include a decay rate measurement and fits to Chiral Perturbation Theory (ChPT) description.Comment: Prepared for the Proceedings of "Moriond QCD and High Energy Interactions. March 22-29 2014." conferenc

Measurement of K^0_e3 form factors

The semileptonic decay of the neutral K meson, KL -> pi e nu (Ke3), was used to study the strangeness-changing weak interaction of hadrons. A sample of 5.6 million reconstructed events recorded by the NA48 experiment was used to measure the Dalitz plot density. Admitting all possible Lorentz-covariant couplings, the form factors for vector (f_+(q^2)), scalar (f_S) and tensor (f_T) interactions were measured. The linear slope of the vector form factor lambda_+ = 0.0284+-0.0007+-0.0013 and values for the ratios |f_S/f_+(0)| = 0.015^{+0.007}_{-0.010}+-0.012 and |f_T/f_+(0)| = 0.05^{+0.03}_{-0.04}+-0.03 were obtained. The values for f_S and f_T are consistent with zero. Assuming only Vector-Axial vector couplings, lambda_+ = 0.0288+-0.0004+-0.0011 and a good fit consistent with pure V-A couplings were obtained. Alternatively, a fit to a dipole form factor yields a pole mass of M = 859+-18 MeV, consistent with the K^*(892) mass.Comment: 16 pages, 7 figures. submitted to Phys. Lett.

Data Integration in Cardiac Surgery Health Care Institution: Experience at G. Pasquinucci Heart Hospital

During the last ten years the Hospital Information System (HIS) was developed at the Institute of Clinical Physiology of National Research Council (IFC-CNR), recently reorganized on clinical side into the "Gabriele Monasterio Foundation" (FGM) by joint efforts of CNR, Tuscany Region and Universities. At G.Pasquinucci Heart Hospital (GPH), currently FGM\u27s section in Massa, the HIS was adapted and extended to Cardiac Surgery and Pediatric Cardiology. Data archiving and middleware integration through HIS network, connecting GPH with head institution in Pisa, allowed to achieve full secure access to patient information from any workstation within hospital or outside. PACS was developed using Open Source DICOM utilities. Electronic Medical Record is daily used since 2005 on both inpatients and outpatients. Recently telediagnosis was set up between Balkan countries and GPH in Massa