229 research outputs found
Coronary revascularisation in stable patients after an acute coronary syndrome: a propensity analysis of early invasive versus conservative management in a register-based cohort study
OBJECTIVES: To compare the effectiveness of in-hospital medical therapy versus coronary revascularisation added to medical therapy in patients who stabilised after an acute coronary syndrome (ACS).
DESIGN: Propensity score-matched cohort study from the database of the Tampere ACS registry.
SETTING: A single academic hospital in Finland.
PARTICIPANTS: 1149 patients with a recent ACS, but no serious coexisting conditions: recurrent ischaemic episodes despite adequate medical therapy, haemodynamic instability, overt congestive heart failure and serious ventricular arrhythmias. PRIMARY AND SECONDARY OUTCOME MEASURES: The composite endpoint of major acute cardiovascular events (MACEs): unstable angina requiring rehospitalisation, stroke, myocardial infarction and all-cause mortality, at 6-month follow-up.
RESULTS: Compared with standard medical treatment, revascularisation was associated with a lower rate of MACEs at 6 months in patients of the first quintile (HR 0.81; 95% CI 0.66 to 0.99), but a higher rate of MACEs in the fifth quintile (HR 4.74, CI 1.36 to 16.49; p=0.014). There were no significant differences in the rates of MACEs in the remaining three quintiles. Patients of the first quintile were the oldest (79.7\ub18.3 years) and had a more significant (p<0.001) history of prior myocardial infarction (37%) and poor renal function (creatine, \ub5mol/l: 114.9\ub170.7). They also showed the highest C reactive protein (7.3\ub19.5 mg/l) levels.
CONCLUSIONS: Our findings suggest that in-hospital coronary revascularisation did not lead to any advantage with signal of possible harm in the great majority of patients who stabilised after an ACS. An early invasive management strategy may be best reserved for elderly patients having high-risk clinical features and biochemical evidence of a strong inflammatory activity
Down Regulation of a Matrix Degrading Cysteine Protease Cathepsin L, by Acetaldehyde: Role of C/EBPα
BACKGROUND: The imbalance between extra cellular matrix (ECM) synthesis and degradation is critical aspect of various hepatic pathologies including alcohol induced liver fibrosis. This study was carried out to investigate the effect of acetaldehyde on expression of an extra cellular matrix degrading protease cathepsin L (CTSL) in HepG2 cells. METHODOLOGY AND RESULTS: We measured the enzymatic activity, protein and, mRNA levels of CTSL in acetaldehyde treated and untreated cells. The binding of CAAT enhancer binding protein α (C/EBP α) to CTSL promoter and its key role in the transcription from this promoter and conferring responsiveness to acetaldehyde was established by site directed mutagenesis, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP) assays and siRNA technology. Acetaldehyde treatment significantly decreased CTSL activity and protein levels in HepG2 cells. A similar decrease in the mRNA levels and promoter activity was also observed. This decrease by acetaldehyde was attributed to the fall in the liver enriched transcription factor C/EBP α levels and it's binding to the CTSL promoter. Mutagenesis of C/EBP α binding motifs revealed the key role of this factor in CTSL transcription as well as conferring responsiveness to acetaldehyde. The siRNA mediated silencing of the C/EBP α expression mimicked the effect of acetaldehyde on CTSL levels and its promoter activity. It also abolished the responsiveness of this promoter to acetaldehyde. CONCLUSION: Acetaldehyde down regulates the C/EBP α mediated CTSL expression in hepatic cell lines. The decreased expression of CTSL may at least in part contribute to ECM deposition in liver which is a hallmark of alcoholic liver fibrosis
Interacting Supernovae: Types IIn and Ibn
Supernovae (SNe) that show evidence of strong shock interaction between their
ejecta and pre-existing, slower circumstellar material (CSM) constitute an
interesting, diverse, and still poorly understood category of explosive
transients. The chief reason that they are extremely interesting is because
they tell us that in a subset of stellar deaths, the progenitor star may become
wildly unstable in the years, decades, or centuries before explosion. This is
something that has not been included in standard stellar evolution models, but
may significantly change the end product and yield of that evolution, and
complicates our attempts to map SNe to their progenitors. Another reason they
are interesting is because CSM interaction is an efficient engine for making
bright transients, allowing super-luminous transients to arise from normal SN
explosion energies, and allowing transients of normal SN luminosities to arise
from sub-energetic explosions or low radioactivity yield. CSM interaction
shrouds the fast ejecta in bright shock emission, obscuring our normal view of
the underlying explosion, and the radiation hydrodynamics of the interaction is
challenging to model. The CSM interaction may also be highly non-spherical,
perhaps linked to binary interaction in the progenitor system. In some cases,
these complications make it difficult to definitively tell the difference
between a core-collapse or thermonuclear explosion, or to discern between a
non-terminal eruption, failed SN, or weak SN. Efforts to uncover the physical
parameters of individual events and connections to possible progenitor stars
make this a rapidly evolving topic that continues to challenge paradigms of
stellar evolution.Comment: Final draft of a chapter in the "SN Handbook". Accepted. 25 pages, 3
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Quantitative analysis of WC stars: Constraints on neon abundances from ISO/SWS spectroscopy
Neon abundances are derived in four Galactic WC stars -- gamma Vel (WR11,
WC8+O7.5III), HD156385 (WR90, WC7), HD192103 (WR135, WC8), and WR146 (WC5+O8) -
using mid-infrared fine structure lines obtained with ISO/SWS. Stellar
parameters for each star are derived using a non-LTE model atmospheric code
(Hillier & Miller 1998) together with ultraviolet (IUE), optical (INT, AAT) and
infrared (UKIRT, ISO) spectroscopy. In the case of gamma Vel, we adopt results
from De Marco et al. (2000), who followed an identical approach.
ISO/SWS datasets reveal the [NeIII] 15.5um line in each of our targets, while
[NeII] 12.8um, [SIV] 10.5um and [SIII] 18.7um are observed solely in gamma Vel.
Using a method updated from Barlow et al. (1988) to account for clumped winds,
we derive Ne/He=3-4x10^-3 by number, plus S/He=6x10^-5 for gamma Vel. Neon is
highly enriched, such that Ne/S in gamma Vel is eight times higher than cosmic
values. However, observed Ne/He ratios are a factor of two times lower than
predictions of current evolutionary models of massive stars. An imprecise
mass-loss and distance were responsible for the much greater discrepancy in
neon content identified by Barlow et al.
Our sample of WC5--8 stars span a narrow range in T* (=55--71kK), with no
trend towards higher temperature at earlier spectral type, supporting earlier
results for a larger sample by Koesterke & Hamann (1995). Stellar luminosities
range from 100,000 to 500,000 Lo, while 10^-5.1 < Mdot/(Mo/yr) < 10^-4.5,
adopting clumped winds, in which volume filling factors are 10%. In all cases,
wind performance numbers are less than 10, significantly lower than recent
estimates. Carbon abundances span 0.08 < C/He < 0.25 by number, while oxygen
abundances remain poorly constrained.Comment: 16 pages,7 figures accepted for MNRA
Gemini GMOS spectroscopy of HeII nebulae in M33
We have carried out a narrow-band survey of the Local Group galaxy, M33, in
the HeII4686 emission line, to identify HeII nebulae in this galaxy. With
spectroscopic follow-up observations, we confirm three of seven candidate
objects, including identification of two new HeII nebulae, BCLMP651, HBW673. We
also obtain spectra of associated ionizing stars for all the HII regions,
identifying two new WN stars. We demonstrate that the ionizing source for the
known HeII nebula, MA 1, is consistent with being the early-type WN star MC8
(M33-WR14), by carrying out a combined stellar and nebular analysis of MC8 and
MA1. We were unable to identify the helium ionizing sources for HBW 673 and
BCLMP 651, which do not appear to be Wolf-Rayet stars. According to the
[OIII]5007/Hbeta vs [NII]6584/Halpha diagnostic diagram, excitation mechanisms
apart from hot stellar continuum are needed to account for the nebular emission
in HBW 673, which appears to have no stellar source at all.Comment: Accepted for publication in Astronomy and Astrophysics. 22 pages, 10
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Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE) : a prospective, randomised, open-label, non-inferiority trial
Background Coronary artery bypass grafting (CABG) is the standard treatment for revascularisation in patients with left main coronary artery disease, but use of percutaneous coronary intervention (PCI) for this indication is increasing. We aimed to compare PCI and CABG for treatment of left main coronary artery disease. Methods In this prospective, randomised, open-label, non-inferiority trial, patients with left main coronary artery disease were enrolled in 36 centres in northern Europe and randomised 1: 1 to treatment with PCI or CABG. Eligible patients had stable angina pectoris, unstable angina pectoris, or non-ST-elevation myocardial infarction. Exclusion criteria were ST-elevation myocardial infarction within 24 h, being considered too high risk for CABG or PCI, or expected survival of less than 1 year. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause mortality, non-procedural myocardial infarction, any repeat coronary revascularisation, and stroke. Non-inferiority of PCI to CABG required the lower end of the 95% CI not to exceed a hazard ratio (HR) of 1 . 35 after up to 5 years of follow-up. The intention-to-treat principle was used in the analysis if not specified otherwise. This trial is registered with ClinicalTrials.gov identifier, number NCT01496651. Findings Between Dec 9, 2008, and Jan 21, 2015, 1201 patients were randomly assigned, 598 to PCI and 603 to CABG, and 592 in each group entered analysis by intention to treat. Kaplan-Meier 5 year estimates of MACCE were 29% for PCI (121 events) and 19% for CABG (81 events), HR 1 . 48 (95% CI 1 . 11-1 . 96), exceeding the limit for non-inferiority, and CABG was significantly better than PCI (p=0 . 0066). As-treated estimates were 28% versus 19% (1 . 55, 1 . 18-2 . 04, p= 0 . 0015). Comparing PCI with CABG, 5 year estimates were 12% versus 9% (1 . 07, 0 . 67-1 . 72, p= 0 . 77) for all-cause mortality, 7% versus 2% (2 . 88, 1 . 40-5 . 90, p= 0 . 0040) for non-procedural myocardial infarction, 16% versus 10% (1 . 50, 1 . 04-2 . 17, p= 0 . 032) for any revascularisation, and 5% versus 2% (2 . 25, 0 . 93-5 . 48, p= 0 . 073) for stroke. Interpretation The findings of this study suggest that CABG might be better than PCI for treatment of left main stem coronary artery disease.Peer reviewe
Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease
sharma et al. define a new primary atopic disorder caused by heterozygous gain-of-function variants in STAT6. this results in severe, early-onset allergies, and is seen in 16 patients from 10 families. Anti-IL-4R & alpha; antibody and JAK inhibitor treatment were highly effective.STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. we have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. the cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). all patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and T(H)2 skewing. Precision treatment with the anti-IL-4R & alpha; antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. this study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder
Convection in Binary Fluid Mixtures. II. Localized Traveling Waves. (Physical Review E, in press)
Nonlinear, spatially localized structures of traveling convection rolls are
investigated in quantitative detail as a function of Rayleigh number for two
different Soret coupling strengths (separation ratios) with Lewis and Prandtl
numbers characterizing ethanol-water mixtures. A finite-difference method was
used to solve the full hydrodynamic field equations numerically. Structure and
dynamics of these localized traveling waves (LTW) are dominated by the
concentration field. Like in the spatially extended convective states ( cf.
accompanying paper), the Soret-induced concentration variations strongly
influence, via density changes, the buoyancy forces that drive convection. The
spatio-temporal properties of this feed-back mechanism, involving boundary
layers and concentration plumes, show that LTW's are strongly nonlinear states.
Light intensity distributions are determined that can be observed in side-view
shadowgraphs. Detailed analyses of all fields are made using colour-coded
isoplots, among others. In the frame comoving with their drift velocity, LTW's
display a nontrivial spatio-temporal symmetry consisting of time-translation by
half an oscillation period combined with vertical reflection through the
horizontal midplane of the layer. A time-averaged concentration current is
driven by a phase difference between the waves of concentration and vertical
velocity in the bulk of the LTW state. The associated large-scale concentration
redistribution stabilizes the LTW and controls its drift velocity into the
quiescent fluid by generating a buoyancy-reducing concentration "barrier" ahead
of the leading LTW front. The selection of the width of the LTW's is
investigated and comparisons with experiments are presented.Comment: 18 pages and 6 figures as uuencoded Postscript file (using uufiles) 1
color figure as uuencoded Postscript file, a high resolution version of the
color figure (about 10MB) can be requested from [email protected] or
[email protected].: (Barten)present address: PSI, CH-5232 Villigen
PSI, Switzerlan
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