Multivariable analysis of outcome predictors and adjustment of main outcome results to baseline data profile in randomized controlled trials: Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST)

<p><b>Background and Purpose:</b> The Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST) unadjusted results demonstrated that intravenous alteplase is well tolerated and that the effects were comparable with those seen in randomized, controlled trials (RCTs) when used in routine clinical practice within 3 hours of ischemic stroke onset. We aimed to identify outcome predictors and adjust the outcomes of the SITS-MOST to the baseline characteristics of RCTs.</p> <p><b>Methods:</b> The study population was SITS-MOST (n=6483) and pooled RCTs (n=464) patients treated with intravenous alteplase within 3 hours of stroke onset. Multivariable, backward stepwise regression analyses (until P≤0.10) were performed to identify the outcome predictors for SITS-MOST. Variables appearing either in the final multivariable model or differing (P<0.10) between SITS-MOST and RCTs were included in the prediction model for the adjustment of outcomes. Main outcome measures were symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale deterioration ≥1 within 7 days with any hemorrhage (RCT definition), mortality, and independency as defined by modified Rankin Score of 0 to 2 at 3 months.</p> <p><b>Results:</b> The adjusted proportion of symptomatic intracerebral hemorrhage for SITS-MOST was 8.5% (95% CI, 7.9 to 9.0) versus 8.6% (6.3 to 11.6) for pooled RCTs; mortality was 15.5% (14.7 to 16.2) versus 17.3% (14.1 to 21.1); and independency was 50.4% (49.6 to 51.2) versus 50.1% (44.5 to 54.7), respectively. In the multivariable analysis, older age, high blood glucose, high National Institutes of Health Stroke Scale score, and current infarction on imaging scans were related to poor outcome in all parameters. Systolic blood pressure, atrial fibrillation, and weight were additional predictors of symptomatic intracerebral hemorrhage. Current smokers had a lower rate of symptomatic intracerebral hemorrhage. Disability before current stroke (modified Rankin Score 2 to 5), diastolic blood pressure, antiplatelet other than aspirin, congestive heart failure, patients treated in new centers, and male sex were related to high mortality at 3 months.</p> <p><b>Conclusions:</b> The adjusted outcomes from SITS-MOST were almost identical to those in relevant RCTs and reinforce the conclusion drawn previously in the unadjusted analysis. We identified several important outcome predictors to better identify patients suitable for thrombolysis.</p&gt

X Her and TX Psc: Two cases of ISM interaction with stellar winds observed by Herschel

The asymptotic giant branch (AGB) stars X Her and TX Psc have been imaged at 70 and 160 microns with the PACS instrument onboard the Herschel satellite, as part of the large MESS (Mass loss of Evolved StarS) Guaranteed Time Key Program. The images reveal an axisymmetric extended structure with its axis oriented along the space motion of the stars. This extended structure is very likely to be shaped by the interaction of the wind ejected by the AGB star with the surrounding interstellar medium (ISM). As predicted by numerical simulations, the detailed structure of the wind-ISM interface depends upon the relative velocity between star+wind and the ISM, which is large for these two stars (108 and 55 km/s for X Her and TX Psc, respectively). In both cases, there is a compact blob upstream whose origin is not fully elucidated, but that could be the signature of some instability in the wind-ISM shock. Deconvolved images of X Her and TX Psc reveal several discrete structures along the outermost filaments, which could be Kelvin-Helmholtz vortices. Finally, TX Psc is surrounded by an almost circular ring (the signature of the termination shock?) that contrasts with the outer, more structured filaments. A similar inner circular structure seems to be present in X Her as well, albeit less clearly.Comment: 11 pages, Astronomy & Astrophysics, in pres

Implications of LHC Searches on SUSY Particle Spectra: The pMSSM Parameter Space with Neutralino Dark Matter

We study the implications of LHC searches on SUSY particle spectra using flat scans of the 19-parameter pMSSM phase space. We apply constraints from flavour physics, g_mu-2, dark matter and earlier LEP and Tevatron searches. The sensitivity of the LHC SUSY searches with jets, leptons and missing energy is assessed by reproducing with fast simulation the recent CMS analyses after validation on benchmark points. We present results in terms of the fraction of pMSSM points compatible with all the constraints which are excluded by the LHC searches with 1 fb^{-1} and 15 fb^{-1} as a function of the mass of strongly and weakly interacting SUSY particles. We also discuss the suppression of Higgs production cross sections for the MSSM points not excluded and contrast the region of parameter space tested by the LHC data with the constraints from dark matter direct detection experiments.Comment: 14 pages, 13 figures. v2: increased statistics, to appear in EPJ

The Kondo Resonance in Electron Spectroscopy

The Kondo resonance is the spectral manifestation of the Kondo properties of the impurity Anderson model, and also plays a central role in the dynamical mean-field theory (DMFT) for correlated electron lattice systems. This article presents an overview of electron spectroscopy studies of the resonance for the 4f electrons of cerium compounds, and for the 3d electrons of V_2O_3, including beginning efforts at using angle resolved photoemission to determine the k-dependence of the resonance. The overview includes the comparison and analysis of spectroscopy data with theoretical spectra as calculated for the impurity model and as obtained by DMFT, and the Kondo volume collapse calculation of the cerium alpha-gamma phase transition boundary, with its spectroscopic underpinnings.Comment: 32 pages, 11 figures, 151 references; paper for special issue of J. Phys. Soc. Jpn. on "Kondo Effect--40 Years after the Discovery

Supersymmetry Without Prejudice

We begin an exploration of the physics associated with the general CP-conserving MSSM with Minimal Flavor Violation, the pMSSM. The 19 soft SUSY breaking parameters in this scenario are chosen so as to satisfy all existing experimental and theoretical constraints assuming that the WIMP is a conventional thermal relic, ie, the lightest neutralino. We scan this parameter space twice using both flat and log priors for the soft SUSY breaking mass parameters and compare the results which yield similar conclusions. Detailed constraints from both LEP and the Tevatron searches play a particularly important role in obtaining our final model samples. We find that the pMSSM leads to a much broader set of predictions for the properties of the SUSY partners as well as for a number of experimental observables than those found in any of the conventional SUSY breaking scenarios such as mSUGRA. This set of models can easily lead to atypical expectations for SUSY signals at the LHC.Comment: 61 pages, 24 figs. Refs., figs, and text added, typos fixed; This version has reduced/bitmapped figs. For a version with better figs please go to http://www.slac.stanford.edu/~rizz

Dark Matter in the MSSM

We have recently examined a large number of points in the parameter space of the phenomenological MSSM, the 19-dimensional parameter space of the CP-conserving MSSM with Minimal Flavor Violation. We determined whether each of these points satisfied existing experimental and theoretical constraints. This analysis provides insight into general features of the MSSM without reference to a particular SUSY breaking scenario or any other assumptions at the GUT scale. This study opens up new possibilities for SUSY phenomenology both in colliders and in astrophysical experiments. Here we shall discuss the implications of this analysis relevant to the study of dark matter.Comment: 27 pages, 19 figs; Journal version in NJP issue "Focus on Dark Matter and Particle Physics". Previous version had 26 pages, 19 figures. Text and some figures have been update

Common genetic determinants of lung function, subclinical atherosclerosis and risk of coronary artery disease

Chronic obstructive pulmonary disease (COPD) independently associates with an increased risk of coronary artery disease (CAD), but it has not been fully investigated whether this co-morbidity involves shared pathophysiological mechanisms. To identify potential common pathways across the two diseases, we tested all recently published single nucleotide polymorphisms (SNPs) associated with human lung function (spirometry) for association with carotid intima-media thickness (cIMT) in 3,378 subjects with multiple CAD risk factors, and for association with CAD in a case-control study of 5,775 CAD cases and 7,265 controls. SNPs rs2865531, located in the CFDP1 gene, and rs9978142, located in the KCNE2 gene, were significantly associated with CAD. In addition, SNP rs9978142 and SNP rs3995090 located in the HTR4 gene, were associated with average and maximal cIMT measures. Genetic risk scores combining the most robustly spirometry-associated SNPs from the literature were modestly associated with CAD, (odds ratio (OR) (95% confidence interval (CI95) = 1.06 (1.03, 1.09); P-value = 1.5×10-4, per allele). In conclusion, our study suggests that some genetic loci implicated in determining human lung function also influence cIMT and susceptibility to CAD. The present results should help elucidate the molecular underpinnings of the co-morbidity observed across COPD and CAD