Levosimendan for the prevention of acute organ dysfunction in sepsis

BACKGROUND Levosimendan is a calcium-sensitizing drug with inotropic and other properties that may improve outcomes in patients with sepsis. METHODS We conducted a double-blind, randomized clinical trial to investigate whether levosimendan reduces the severity of organ dysfunction in adults with sepsis. Patients were randomly assigned to receive a blinded infusion of levosimendan (at a dose of 0.05 to 0.2 μg per kilogram of body weight per minute) for 24 hours or placebo in addition to standard care. The primary outcome was the mean daily Sequential Organ Failure Assessment (SOFA) score in the intensive care unit up to day 28 (scores for each of five systems range from 0 to 4, with higher scores indicating more severe dysfunction; maximum score, 20). Secondary outcomes included 28-day mortality, time to weaning from mechanical ventilation, and adverse events. RESULTS The trial recruited 516 patients; 259 were assigned to receive levosimendan and 257 to receive placebo. There was no significant difference in the mean (±SD) SOFA score between the levosimendan group and the placebo group (6.68±3.96 vs. 6.06±3.89; mean difference, 0.61; 95% confidence interval [CI], −0.07 to 1.29; P=0.053). Mortality at 28 days was 34.5% in the levosimendan group and 30.9% in the placebo group (absolute difference, 3.6 percentage points; 95% CI, −4.5 to 11.7; P=0.43). Among patients requiring ventilation at baseline, those in the levosimendan group were less likely than those in the placebo group to be successfully weaned from mechanical ventilation over the period of 28 days (hazard ratio, 0.77; 95% CI, 0.60 to 0.97; P=0.03). More patients in the levosimendan group than in the placebo group had supraventricular tachyarrhythmia (3.1% vs. 0.4%; absolute difference, 2.7 percentage points; 95% CI, 0.1 to 5.3; P=0.04). CONCLUSIONS The addition of levosimendan to standard treatment in adults with sepsis was not associated with less severe organ dysfunction or lower mortality. Levosimendan was associated with a lower likelihood of successful weaning from mechanical ventilation and a higher risk of supraventricular tachyarrhythmia. (Funded by the NIHR Efficacy and Mechanism Evaluation Programme and others; LeoPARDS Current Controlled Trials number, ISRCTN12776039.

Distinguishing among Technicolor/Warped Scenarios in Dileptons

Models of dynamical electroweak symmetry breaking usually include new spin-1 resonances, whose couplings and masses have to satisfy electroweak precision tests. We propose to use dilepton searches to probe the underlying structure responsible for satisfying these. Using the invariant mass spectrum and charge asymmetry, we can determine the number, parity, and isospin of these resonances. We pick three models of strong/warped symmetry breaking, and show that each model produces specific features that reflect this underlying structure of electroweak symmetry breaking and cancellations.Comment: Added missing referenc

Searches for phenomena beyond the Standard Model at the LHC with the ATLAS and CMS detectors

The LHC has delivered several fb-1 of data in spring and summer 2011, opening new windows of opportunity for discovering phenomena beyond the Standard Model. A summary of the searches conducted by the ATLAS and CMS experiments based on about 1 fb-1 of data is presented.Comment: Presented at Lepton-Photon 2011, Mumbai, India; 10 pages, 11 figure

PGB pair production at LHC and ILC as a probe of the topcolor-assisted technicolor models

The topcolor-assisted technicolor (TC2) model predicts some light pseudo goldstone bosons (PGBs), which may be accessible at the LHC or ILC. In this work we study the pair productions of the charged or neutral PGBs at the LHC and ILC. For the productions at the LHC we consider the processes proceeding through gluon-gluon fusion and quark-antiquark annihilation, while for the productions at the ILC we consider both the electron-positron collision and the photon-photon collision. We find that in a large part of parameter space the production cross sections at both colliders can be quite large compared with the low standard model backgrounds. Therefore, in future experiments these productions may be detectable and allow for probing TC2 model.Comment: 26 pages, 16 figures. slight changes in the text; notations for curves changed; references adde

Top and Bottom Seesaw from Supersymmetric Strong Dynamics

We propose a top and bottom seesaw model with partial composite top and bottom quarks. Such composite quarks and topcolor gauge bosons are bound states from supersymmetric strong dynamics by Seiberg duality. Supersymmetry breaking also induces the breaking of topcolor into the QCD gauge coupling. The low energy description of our model reduces to a complete non-minimal extension of the top seesaw model with bottom seesaw. The non-minimal nature is crucial for Higgs mixings and the appearance of light Higgs fields. The Higgs fields are bound states of partial composite particles with the lightest one compatible with a 125 GeV Higgs field which was discovered at the LHC.Comment: Minor changes, Published Versio

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH

LHC Predictions from a Tevatron Anomaly in the Top Quark Forward-Backward Asymmetry

We examine the implications of the recent CDF measurement of the top-quark forward-backward asymmetry, focusing on a scenario with a new color octet vector boson at 1-3 TeV. We study several models, as well as a general effective field theory, and determine the parameter space which provides the best simultaneous fit to the CDF asymmetry, the Tevatron top pair production cross section, and the exclusion regions from LHC dijet resonance and contact interaction searches. Flavor constraints on these models are more subtle and less severe than the literature indicates. We find a large region of allowed parameter space at high axigluon mass and a smaller region at low mass; we match the latter to an SU(3)xSU(3)/SU(3) coset model with a heavy vector-like fermion. Our scenario produces discoverable effects at the LHC with only 1-2 inverse femtobarns of luminosity at 7-8 TeV. Lastly, we point out that a Tevatron measurement of the b-quark forward-backward asymmetry would be very helpful in characterizing the physics underlying the top-quark asymmetry.Comment: 35 pages, 10 figures, 4 table

Current quark mass dependence of nucleon magnetic moments and radii

A calculation of the current-quark-mass-dependence of nucleon static electromagnetic properties is necessary in order to use observational data as a means to place constraints on the variation of Nature's fundamental parameters. A Poincare' covariant Faddeev equation, which describes baryons as composites of confined-quarks and -nonpointlike-diquarks, is used to calculate this dependence The results indicate that, like observables dependent on the nucleons' magnetic moments, quantities sensitive to their magnetic and charge radii, such as the energy levels and transition frequencies in Hydrogen and Deuterium, might also provide a tool with which to place limits on the allowed variation in Nature's constants.Comment: 23 pages, 2 figures, 4 tables, 4 appendice

UK adults' implicit and explicit attitudes towards obesity: a cross-sectional study.

Background: Anti-fat attitudes may lead to stigmatisation of and lowered self-esteem in obese people. Examining anti-fat attitudes is warranted given that there is an association with anti-fat behaviours. Previous studies, mainly outside the UK, have demonstrated that anti-fat attitudes are increasing over time. Methods: The study was cross-sectional with a sample of 2380 participants (74.2 % female; aged 18–65 years). In an online survey participants reported demographic characteristics and completed a range of implicit and explicit measures of obesity related attitudes. Results: Perceptions of obesity were more negative than reported in previously. Main effects indicated more negative perceptions in males, younger respondents and more frequent exercisers. Attitudes about obesity differed in relation to weight category, and in general were more positive in obese than non-obese respondents. Conclusions: This is the first study to demonstrate anti-fat attitudes across different sections of the UK population. As such, this study provides the first indication of the prevalence of anti-fat attitudes in UK adults. Interventions to modify these attitudes could target specific groups of individuals with more negative perceptions as identified here. Future work would be useful that increases understanding of both implicit and explicit attitudes towards obesity

Linear confinement without dilaton in bottom-up holography for walking technicolour

In PRD78(2008)055005 [arXiv:0805.1503 [hep-ph]] and PRD79(2009)075004 [arXiv:0809.1324 [hep-ph]], we constructed a holographic description of walking technicolour theories using both a hard- and a soft-wall model. Here, we show that the dilaton field becomes phenomenologically irrelevant for the spectrum of spin-one resonances once a term is included in the Lagrangian that mixes the Goldstone bosons and the longitudinal components of the axial vector mesons. We show how this mixing affects our previous results and we make predictions about how this description of technicolour can be tested.Comment: 7 pages, no figure