409 research outputs found

    Reduction of myocardial infarction by postischemic administration of the calpain inhibitor A-705253 in comparison to the Na(+)/H(+) exchange inhibitor Cariporide (R) in isolated perfused rabbit hearts

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    The calpain inhibitor A-705253 and the Na(+)/H(+) exchange inhibitor Cariporide (R) were studied in isolated perfused rabbit hearts subjected to 60 min occlusion of the ramus interventricularis of the left coronary artery (below the origin of the first diagonal branch), followed by 120 min of reperfusion. The inhibitors were added to the perfusion fluid solely or in combination at the beginning of reperfusion. Hemodynamic monitoring and biochemical analysis of perfusion fluid from the coronary outflow were performed. Myocardial infarct size and area at risk (transiently not perfused myocardium) were determined from left ventricular slices after a special staining procedure with Evans blue and 2,3,5-triphenyltetrazolium chloride. The infarcted area (dead myocardium) was 72.7 +/- 4.0% of the area at risk in untreated controls, but was significantly smaller in the presence of the inhibitors. The largest effect was observed with 10(-6) M A-705253, which reduced the infarcted area to 49.2 +/- 4.1% of the area at risk, corresponding to a reduction of 33.6%. Cariporide (R) at 10(-6) M reduced the infarct size to the same extent. The combination of both inhibitors, however, did not further improve cardioprotection. No significant difference was observed between the experimental groups in coronary perfusion, left ventricular pressure, heart rate, or in the release of lactate dehydrogenase and creatine kinase from heart muscle

    The European Network for Translational Research in Atrial Fibrillation (EUTRAF): objectives and initial results.

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    Atrial fibrillation (AF) is the most common sustained arrhythmia in the general population. As an age-related arrhythmia AF is becoming a huge socio-economic burden for European healthcare systems. Despite significant progress in our understanding of the pathophysiology of AF, therapeutic strategies for AF have not changed substantially and the major challenges in the management of AF are still unmet. This lack of progress may be related to the multifactorial pathogenesis of atrial remodelling and AF that hampers the identification of causative pathophysiological alterations in individual patients. Also, again new mechanisms have been identified and the relative contribution of these mechanisms still has to be established. In November 2010, the European Union launched the large collaborative project EUTRAF (European Network of Translational Research in Atrial Fibrillation) to address these challenges. The main aims of EUTRAF are to study the main mechanisms of initiation and perpetuation of AF, to identify the molecular alterations underlying atrial remodelling, to develop markers allowing to monitor this processes, and suggest strategies to treat AF based on insights in newly defined disease mechanisms. This article reports on the objectives, the structure, and initial results of this network

    Some Relations between Twisted K-theory and E8 Gauge Theory

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    Recently, Diaconescu, Moore and Witten provided a nontrivial link between K-theory and M-theory, by deriving the partition function of the Ramond-Ramond fields of Type IIA string theory from an E8 gauge theory in eleven dimensions. We give some relations between twisted K-theory and M-theory by adapting the method of Diaconescu-Moore-Witten and Moore-Saulina. In particular, we construct the twisted K-theory torus which defines the partition function, and also discuss the problem from the E8 loop group picture, in which the Dixmier-Douady class is the Neveu-Schwarz field. In the process of doing this, we encounter some mathematics that is new to the physics literature. In particular, the eta differential form, which is the generalization of the eta invariant, arises naturally in this context. We conclude with several open problems in mathematics and string theory.Comment: 23 pages, latex2e, corrected minor errors and typos in published versio

    Cost-Effectiveness Analyses of an Absorbable Antibacterial Envelope for Use in Patients at Increased Risk of Cardiac Implantable Electronic Device Infection in Germany, Italy, and England

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    Objectives: To model the cost-effectiveness of the TYRX Absorbable Antibacterial Envelope when used in patients at increased risk of cardiac implantable electronic device (CIED) infection in the context of 3 European healthcare systems: Germany, Italy, and England. Methods: A decision tree model with a lifetime horizon was populated using data from the Worldwide Randomized Antibiotic Envelope Infection Prevention Trial, a large multicenter randomized controlled trial. Use of the antibacterial envelope adjunctive to standard of care was compared to standard of care infection prevention alone. Patients in the model were divided into subgroups based on presence of factors known to increase infection risk. Results: The antibacterial envelope had the most favorable cost-effectiveness profile when patients had previously experienced CIED infection, had a history of immunosuppressive therapy, or had a Prevention of Arrhythmia Device Infection Trial (PADIT) score indicating high risk of infection (scores ≥6) at cost-effectiveness thresholds of €50 000 in Germany (assumed in the absence of an official threshold), €40 000 in Italy, and £30 000 in England. Probabilistic sensitivity analysis indicated that the antibacterial envelope was likely to be cost-effective in patients with other risk factors (including replacement of high power CIEDs, generator replacement with lead modification, and PADIT scores indicating intermediate risk of infection) when used with some device types and in some countries. Conclusions: The absorbable antibacterial envelope was associated with cost-effectiveness ratios below European benchmarks in selected patients at increased risk of infection, suggesting the envelope provides value for European healthcare systems by reducing CIED infections

    An ERP study reveals how training with Dual N-Back task affects risky decision making in a gambling task in ADHD patients

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    Impaired decision making and Working Memory (WM) are among the characteristic symptoms of patients affected by Attention Deficit/Hyperactivity Disorder (ADHD). In order to investigate whether a WM training can affect the attitude towards risky decision making, we designed a study where participants had to perform a Probabilistic Gambling Task. Our study has demonstrated that WM training affects in a different way controls and ADHD patients, who showed an increased tendency towards a risk-taking attitude in case of the adaptive variant of the memory task. In ADHD patients, the frontal sites appeared the most affected, whereas global brain activity was likely to be affected in controls. This study shows also the benefits of cognitive training in ADHD patients, but in healthy subjects too

    Attaining sinus rhythm mediates improved outcome with early rhythm control therapy of atrial fibrillation: the EAST - AFNET 4 trial.

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    BACKGROUND: A strategy of systematic, early rhythm control (ERC) improves cardiovascular outcomes in patients with atrial fibrillation (AF). It is not known which aspects of ERC contribute to outcome reduction. METHODS: Using the EAST - AFNET 4 trial data set, potential mediators of the effect of early rhythm control were identified in the total study population at 12-month follow-up and further interrogated by use of a 4-way decomposition of the treatment effect in an exponential model predicting future primary outcome events. RESULTS: Fourteen potential mediators of ERC were identified at the 12-month visit. Of these, sinus rhythm at 12 months explained 81% of the treatment effect of ERC compared to usual care during the remainder of follow-up (4.1 years). In patients not in sinus rhythm at 12 months, ERC did not reduce future cardiovascular outcomes (hazard ratio 0.94, 95% confidence interval 0.65-1.67). Inclusion of AF recurrence in the model only explained 31% of the treatment effect, and inclusion of systolic blood pressure at 12 months only 10%, respectively. There was no difference in outcomes in patients who underwent AF ablation compared to those who did not undergo AF ablation. CONCLUSIONS: The effectiveness of early rhythm control therapy is mediated by the presence of sinus rhythm at 12 months in the EAST - AFNET 4 trial. Clinicians implementing early rhythm control should aim for rapid and sustained restoration of sinus rhythm in patients with recently diagnosed AF and cardiovascular comorbidities.Funded by AFNET, DZHK, EHRA, Deutsche Herzstiftung (DHS), Abbott Laboratories, Sanofi. EAST-AFNET 4 ISRCTN number, ISRCTN04708680; ClinicalTrials.gov number, NCT01288352; EudraCT number, 2010 -021258-20

    Spherical Universe topology and the Casimir effect

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    The mode problem on the factored 3--sphere is applied to field theory calculations for massless fields of spin 0, 1/2 and 1. The degeneracies on the factors, including lens spaces, are neatly derived in a geometric fashion. Vacuum energies are expressed in terms of the polyhedral degrees and equivalent expressions given using the cyclic decomposition of the covering group. Scalar functional determinants are calculated and the spectral asymmetry function treated by the same approach with explicit forms on one-sided lens spaces.Comment: 33 pages, 1 figure. Typos corrected and one reference adde

    Atrial fibrillation after pulmonary lobectomy for lung cancer affects long-term survival in a prospective single-center study

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    <p>Abstract</p> <p>Background</p> <p>Atrial fibrillation (AF) after thoracic surgery is a continuing source of morbidity and mortality. The effect of postoperative AF on long-term survival however has not been studied. Our aim was to evaluate the impact of AF on early outcome and on survival > 5 years after pulmonary lobectomy for lung cancer.</p> <p>Methods</p> <p>From 1996 to June 2009, 454 consecutive patients undergoing lobectomy for lung cancer were enrolled and followed-up until death or study end (October 2010). Patients with postoperative AF were identified; AF was investigated with reference to its predictors and to short- and long-term survival (> 5 years).</p> <p>Results</p> <p>Hospital mortality accounted for 7 patients (1.5%), while postoperative AF occurred in 45 (9.9%). Independent AF predictors were: preoperative paroxysmal AF (odds ratio [OR] 5.91; 95%CI 2.07 to 16.88), postoperative blood transfusion (OR 3.61; 95%CI 1.67 to 7.82) and postoperative fibro-bronchoscopy (OR 3.39; 95%CI 1.48 to 7.79). Patients with AF experienced higher hospital mortality (6.7% vs. 1.0%, p = 0.024), longer hospitalization (15.3 ± 10.1 vs. 12.2 ± 5.2 days, p = 0.001) and higher intensive care unit admission rate (13.3% vs. 3.9%, p = 0.015). The median follow-up was 36 months (maximum: 179 months). Among the 445 discharged subjects with complete follow-up, postoperative AF was not an independent predictor of mortality; however, among the 151 5-year survivors, postoperative AF independently predicted poorer long-term survival (HR 3.75; 95%CI 1.44 to 9.08).</p> <p>Conclusion</p> <p>AF after pulmonary lobectomy for lung cancer, in addition to causing higher hospital morbidity and mortality, predicts poorer long-term outcome in 5-year survivors.</p
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