637 research outputs found

    Imaging fibrotic responses to injury - new methods from development to pathology

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    Jost Functions and Jost Solutions for Jacobi Matrices, I. A Necessary and Sufficient Condition for Szego Asymptotics

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    We provide necessary and sufficient conditions for a Jacobi matrix to produce orthogonal polynomials with Szeg\H{o} asymptotics off the real axis. A key idea is to prove the equivalence of Szeg\H{o} asymptotics and of Jost asymptotics for the Jost solution. We also prove L2L^2 convergence of Szeg\H{o} asymptotics on the spectrum.Comment: 49 page

    Hemodynamic behavior of stentless aortic valves in long term follow-up

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    Objectives Stentless aortic valve replacements show improved hemodynamics due to larger orifice area and lower transvalvular gradients in short and mid-term follow-up. Hemodynamic long-term behavior and the adaptation of the left ventricle as well as valve-durability in patients aged ≀60 years remains unclear. Methods 7 to 16 years after aortic valve replacement, 54 patients (mean age at operation 53.1 ± years) received echocardiography and clinical examination. Mean follow-up time was 10.8 ± 2.2 years. Evaluated were NYHA class, transvalvular gradients, estimated aortic valve orifice area, degree of aortic valve insufficiency, left ventricular mass and function. Results At follow-up only one patient presented with NYHA class III. All other patients were in NYHA class I or II. Maximum and mean pressure gradients of the prostheses were 16.3 ± 7.4 mmHg and 9.1 ± 4.2 mmHg, respectively. Compared to echocardiography at discharge the mean pressure gradients dropped 18.0% (2.0 ± 0.9 mmHg) and stayed stable until 14 years after the operation. Only 5 patients showed relevant regurgitation (at 13–16 years after valve replacement), 49 showed no or trivial regurgitation. Left ventricular mass had decreased 26.5% (107.9 ± 18.5 g). Left ventricular ejection fraction (LVEF) had increased in most patients and decreased in only one. For patients with preoperatively impaired left ventricular function an increase of LVEF of 13.1 ± 3.1% was seen. Conclusion Porcine stentless aortic valves provide excellent hemodynamic long-term results without significant rise of transvalvular pressure gradients or relevant insufficiencies until 14 years after implantation, leading to sustained decrease of left ventricular mass and improvement of left ventricular function

    Resting membrane potential is less negative in trabeculae from right atrial appendages of women, but action potential duration does not shorten with age

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    Aims: The incidence of atrial fibrillation (AF) increases with age. Women have a lower risk. Little is known on the impact of age, sex and clinical variables on action potentials (AP) recorded in right atrial tissue obtained during open heart surgery from patients in sinus rhythm (SR) and in longstanding AF. We here investigated whether age or sex have an impact on the shape of AP recorded in vitro from right atrial tissue. Methods: We performed multivariable analysis of individual AP data from trabeculae obtained during heart surgery of patients in SR (n = 320) or in longstanding AF (n = 201). AP were recorded by sharp microelectrodes at 37 °C at 1 Hz. Impact of clinical variables were modeled using a multivariable mixed model regression. Results: In SR, AP duration at 90% repolarization (APD90) increased with age. Lower ejection fraction and higher body mass index were associated with smaller action potential amplitude (APA) and maximum upstroke velocity (Vmax). The use of beta-blockers was associated with larger APD90. In tissues from women, resting membrane potential was less negative and APA as well as Vmax were smaller. Besides shorter APD20 in elderly patients, effects of age and sex on atrial AP were lost in AF. Conclusion: The higher probability to develop AF at advanced age cannot be explained by a shortening in APD90. Less negative RMP and lower upstroke velocity might contribute to lower incidence of AF in women, which may be of clinical relevance.</p

    Procalcitonin guided antibiotic therapy and hospitalization in patients with lower respiratory tract infections: a prospective, multicenter, randomized controlled trial

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    <p>Abstract</p> <p>Background:</p> <p>Lower respiratory tract infections like acute bronchitis, exacerbated chronic obstructive pulmonary disease and community-acquired pneumonia are often unnecessarily treated with antibiotics, mainly because of physicians' difficulties to distinguish viral from bacterial cause and to estimate disease-severity. The goal of this trial is to compare medical outcomes, use of antibiotics and hospital resources in a strategy based on enforced evidence-based guidelines versus procalcitonin guided antibiotic therapy in patients with lower respiratory tract infections.</p> <p>Methods and design:</p> <p>We describe a prospective randomized controlled non-inferiority trial with an open intervention. We aim to randomize over a fixed recruitment period of 18 months a minimal number of 1002 patients from 6 hospitals in Switzerland. Patients must be >18 years of age with a lower respiratory tract infections <28 days of duration. Patients with no informed consent, not fluent in German, a previous hospital stay within 14 days, severe immunosuppression or chronic infection, intravenous drug use or a terminal condition are excluded. Randomization to either guidelines-enforced management or procalcitonin-guided antibiotic therapy is stratified by centre and type of lower respiratory tract infections. During hospitalization, all patients are reassessed at days 3, 5, 7 and at the day of discharge. After 30 and 180 days, structured phone interviews by blinded medical students are conducted. Depending on the randomization allocation, initiation and discontinuation of antibiotics is encouraged or discouraged based on evidence-based guidelines or procalcitonin cut off ranges, respectively. The primary endpoint is the risk of combined disease-specific failure after 30 days. Secondary outcomes are antibiotic exposure, side effects from antibiotics, rate and duration of hospitalization, time to clinical stability, disease activity scores and cost effectiveness. The study hypothesis is that procalcitonin-guidance is non-inferior (i.e., at worst a 7.5% higher combined failure rate) to the management with enforced guidelines, but is associated with a reduced total antibiotic use and length of hospital stay.</p> <p>Discussion:</p> <p>Use of and prolonged exposure to antibiotics in lower respiratory tract infections is high. The proposed trial investigates whether procalcitonin-guidance may safely reduce antibiotic consumption along with reductions in hospitalization costs and antibiotic resistance. It will additionally generate insights for improved prognostic assessment of patients with lower respiratory tract infections.</p> <p>Trial registration:</p> <p>ISRCTN95122877</p

    Valvular cardiomyopathy in aortic valve regurgitation correlates with myocardial fibrosis

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    Objective: At the tissue level, disruption of the extracellular matrix network leads to irreversible cardiac fibrosis, which contributes to myocardial dysfunction. At the myocyte level, downregulation of beta-adrenoceptors (beta-AR) reduces adaptation to increased workload. The aim of our study was to analyse the correlation between myocardial fibrosis and beta-AR sensitivity in patients with aortic valve (AV) disease. Methods: A total of 92 consecutive patients who underwent elective AV surgery between 2017–2019 were included in our study (51 with aortic regurgitation (AR-group); 41 with aortic stenosis (AS-group) and left ventricular (LV) biopsies were obtained intraoperatively. In vitro force contractility testing was performed by measuring beta-AR sensitivity (−log EC50[ISO]). In parallel, a quantitative analysis of myocardial fibrosis burden was performed. Results: Mean age at the time of AV surgery was not statistically different in both groups (AR: 53.3 ± 15.3 years vs. AS: 58.7 ± 17.0 years; p = 0.116). The LV end-diastolic diameter was significantly enlarged in the AR-group when compared to the AS-group (59.4 ± 15.6 vs. 39.7 ± 21.2; p < 0.001). Analysis of beta-AR sensitivity (AR: −6.769 vs. AS: −6.659; p = 0.316) and myocardial fibrosis (AR: 8.9% vs. AS: 11.3%; p = 0.284) showed no significant differences between patients with AS and AR. There was no correlation between myocardial fibrosis and beta-AR sensitivity in the whole study cohort (R = 0.1987; p = 0.100) or in the AS-subgroup (R = 0.009; p = 0.960). However, significant correlation of fibrosis and beta-AR sensitivity was seen in AR-patients (R = 0.363; p = 0.023). Conclusion: More severe myocardial fibrosis was associated with reduced beta-AR sensitivity in patients presenting with AR but not with AS. Therefore, our results suggest that in patients with AR, cellular myocardial dysfunction is present and correlates with the extent of myocardial fibrosis in the myocardium

    Universal scaling functions for bond percolation on planar random and square lattices with multiple percolating clusters

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    Percolation models with multiple percolating clusters have attracted much attention in recent years. Here we use Monte Carlo simulations to study bond percolation on L1×L2L_{1}\times L_{2} planar random lattices, duals of random lattices, and square lattices with free and periodic boundary conditions, in vertical and horizontal directions, respectively, and with various aspect ratio L1/L2L_{1}/L_{2}. We calculate the probability for the appearance of nn percolating clusters, Wn,W_{n}, the percolating probabilities, PP, the average fraction of lattice bonds (sites) in the percolating clusters, n_{n} (n_{n}), and the probability distribution function for the fraction cc of lattice bonds (sites), in percolating clusters of subgraphs with nn percolating clusters, fn(cb)f_{n}(c^{b}) (fn(cs)f_{n}(c^{s})). Using a small number of nonuniversal metric factors, we find that WnW_{n}, PP, n_{n} (n_{n}), and fn(cb)f_{n}(c^{b}) (fn(cs)f_{n}(c^{s})) for random lattices, duals of random lattices, and square lattices have the same universal finite-size scaling functions. We also find that nonuniversal metric factors are independent of boundary conditions and aspect ratios.Comment: 15 pages, 11 figure

    Engineering high charge transfer n-doping of graphene electrodes and its application to organic electronics.

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    Using thermally evaporated cesium carbonate (Cs2CO3) in an organic matrix, we present a novel strategy for efficient n-doping of monolayer graphene and a ∌90% reduction in its sheet resistance to ∌250 Ohm sq(-1). Photoemission spectroscopy confirms the presence of a large interface dipole of ∌0.9 eV between graphene and the Cs2CO3/organic matrix. This leads to a strong charge transfer based doping of graphene with a Fermi level shift of ∌1.0 eV. Using this approach we demonstrate efficient, standard industrial manufacturing process compatible graphene-based inverted organic light emitting diodes on glass and flexible substrates with efficiencies comparable to those of state-of-the-art ITO based devices.Funding via EU FP7 programme Grafol (Grant No. 285275) and EPSRC programme GRAPHTED (Grant No. EP/K016636/1) is acknowledged. P.R.K. acknowledges the Lindemann Trust Fellowship. J.A.A.-W. acknowledges a Research Fellowship from Churchill College, Cambridge. A.C.V. acknowledges the Conacyt Cambridge Scholarship and Roberto Rocca Fellowship.This is the author accepted manuscript. The final version is available from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C5NR03246

    External Validation of Three Prognostic Scores for Brain Metastasis Velocity in Patients Treated with Intracranial Stereotactic Radiotherapy

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    BACKGROUND AND INTRODUCTION Brain metastasis velocity (BMV) has been proposed as a prognostic factor for overall survival (OS) in patients with brain metastases (BMs). In this study, we conducted an external validation and comparative assessment of the performance of all three BMV scores. MATERIALS AND METHODS Patients treated with intracranial stereotactic radiotherapy (SRT) for BM at a single center between 2014 and 2018 were identified. Where possible, all three BMV scores were calculated. Log-rank tests and linear, logistic and Cox regression analysis were used for validation and predictor identification of OS. RESULTS For 333 of 384 brain metastasis patients, at least one BMV score could be calculated. In a sub-group of 187 patients, "classic" BMV was validated as categorical (p<0.0001) and continuous variable (HR 1.02; 95% CI 1.02-1.03; p<0.0001). In a sub-group of 284 patients, "initial" BMV was validated as categorical variable (high-risk vs. low-risk; p<0.01), but not as continuous variable (HR 1.02; 95% CI 0.99-1.04; p=0.224). "Volume-based" BMV could not be validated in a sub-group of 104 patients. On multivariable Cox regression analysis, iBMV (HR 1.85; 95% CI 1.01-3.38; p<0.05) and cBMV (HR 2.32; 95% CI 1.15 4.68; p<0.05) were predictors for OS for intermediate-risk patients after first SRT and first DBFs, respectively. cBMV proved to be the dominant predictor for OS for high-risk patients (HR 2.99; 95% CI 1.30-6.91; p<0.05). CONCLUSION This study externally validated cBMV and iBMV as prognostic scores for OS in patients treated with SRT for BMs whereas validation of vBMV was not achieved
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