Robust Geometry Estimation using the Generalized Voronoi Covariance Measure

The Voronoi Covariance Measure of a compact set K of R^d is a tensor-valued measure that encodes geometric information on K and which is known to be resilient to Hausdorff noise but sensitive to outliers. In this article, we generalize this notion to any distance-like function delta and define the delta-VCM. We show that the delta-VCM is resilient to Hausdorff noise and to outliers, thus providing a tool to estimate robustly normals from a point cloud approximation. We present experiments showing the robustness of our approach for normal and curvature estimation and sharp feature detection

Development of a medium-high throughput electrophysiology method to study cellular heterogeneity in the rabbit heart

Sudden cardiac death (SCD) is a prominent cause of death worldwide today, mainly occurring as a result of coronary heart disease, cardiomyopathies, and inherited or induced arrhythmia syndromes. Survival following sudden cardiac arrest (SCA) has improved in the past decades, but the majority of cases of SCD remain unwitnessed. Although advances have been made towards the investigation of the mechanisms behind SCD, it remains a poorly understood phenomenon. Environmental factors have been identified and associated with increased arrhythmic risk, and most prominently, drug-induced arrhythmias constitute a serious hurdle to both cardiac and non-cardiac drug development. The past decade has seen pro-arrhythmic screening of new compounds become routine, and develop into a major point of interest for drug development. Specifically, the onset of drug-induced polymorphic ventricular tachycardia, such as torsade de pointes (TdP), is of particular interest to cardiac research. The concept of electrophysiological heterogeneity in cardiac muscle holds exciting potential for explaining the pathophysiology of TdP, but quantifying cellular heterogeneity using conventional methods is a challenge. This work developed and refined a fluorescence-based, medium/high-throughput electrophysiological assay to process large cell populations (~50-500 cells) from single hearts. Using this novel approach, transmural electrophysiological differences were found between regions of individual hearts, replicating published work with a 3 to 4-fold reduction in hearts sampled, and additionally providing a previously unknown quantification of cellular heterogeneity in isolated cardiomyocyte populations, in both healthy and failing rabbit hearts. Further classification of electrophysiological differences within smaller regions of the ventricle yielded evidence of repolarisation gradients across the myocardium, with vast overlap in repolarisation duration, challenging the dogma of region-specific repolarisation duration. Lastly, by specifically blocking hERG channels and L-type calcium channels in cardiac subregions (sub-epicardial apex and base) strong evidence was found for heterogeneous electrophysiology response amongst isolated cell populations. Specifically, sub-epicardial action potential shortening using nifedipine was strongly APD dependent, whereby baseline AP duration determined the extent of APD shortening via drug-induced ICa-L blockade. Sub-epicardial AP prolongation mediated via IKr block using dofetilide also produced non-homogeneous cell response in the form of two distinct population responses: (i) The majority (~85%) was made up of normal responding cells, experiencing ~20-30ms AP prolongation not dependent on baseline APD (P100ms AP prolongation, beyond the pacing cycle length (>500ms) without any evidence of early-afterdepolarisations. Large experimental samples of AP parameters gathered in this study can provide real-world data parameter space ranges for mathematical model development, showing that ion channel conductance ranges used today to predict drug responses at the organ level may be too restrictive, or inaccurate. Iterative model adjustment using large experimental datasets can help constrain models and improve their predictive power, saving time by reducing computational power required

0346: Neonatal arterial switch operation: the sooner the better!

ObjectiveTo evaluate the impact of preoperative management on in-hospital post-operative outcomes after an arterial switch operation (ASO) in newborns with transposition of the great arteries (TGA)MethodsIn this retrospective monocentric study, we included all newborns with TGA±ventricular septal defect who underwent an ASO between 2008 and 2014. Collected data included demographics, clinical and anatomic characteristics, and preoperative management (Rashkind, prostaglandin infusion, mechanical ventilation, age at surgery). Univariate and multivariate analyses were performed to study the impact of preoperative characteristics on time to extubation, a surrogate marker of postoperative morbidity.ResultsAmong the 59 included newborns, 47 (79%) had an antenatal diagnosis, 31 (52%) received prostaglandins (median duration: 96 h; range 0-192h), and 38 (65%) underwent a Rashkind procedure. Mean age at surgery was 5±2 days. The mortality rate was 5% (n=3). Younger age at surgery significantly increased the probability to be extubated within 2 days after surgery, both in univariate analysis (Odd ratio 0.64; confidence interval 0.44-0.92) (p=0.01) and after adjustment for preoperative characteristics and management (OR 0.61; CI 0.39-0.95) (p=0.03). The presence of coronary anomalies tended to increase time to extubation, whereas Rashkind procedure and prostaglandin treatment had no impact.ConclusionOur study shows that younger age at surgery is associated with lower postoperative morbidity in newborns undergoing an ASO. These findings suggest that early surgery is preferable to delay with palliative management such as Rashkind and/or Prostaglandins

Electrophysiological heterogeneity in large populations of rabbit ventricular cardiomyocytes

Aims: Cardiac electrophysiological heterogeneity includes: (i) regional differences in action potential (AP) waveform, (ii) AP waveform differences in cells isolated from a single region, (iii) variability of the contribution of individual ion currents in cells with similar AP durations (APDs). The aim of this study is to assess intra-regional AP waveform differences, to quantify the contribution of specific ion channels to the APD via drug responses and to generate a population of mathematical models to investigate the mechanisms underlying heterogeneity in rabbit ventricular cells. Methods and results: APD in ∼50 isolated cells from subregions of the LV free wall of rabbit hearts were measured using a voltage-sensitive dye. When stimulated at 2 Hz, average APD90 value in cells from the basal epicardial region was 254 ± 25 ms (mean ± standard deviation) in 17 hearts with a mean interquartile range (IQR) of 53 ± 17 ms. Endo-epicardial and apical-basal APD90 differences accounted for ∼10% of the IQR value. Highly variable changes in APD occurred after IK(r) or ICa(L) block that included a sub-population of cells (HR) with an exaggerated (hyper) response to IK(r) inhibition. A set of 4471 AP models matching the experimental APD90 distribution was generated from a larger population of models created by random variation of the maximum conductances (Gmax) of 8 key ion channels/exchangers/pumps. This set reproduced the pattern of cell-specific responses to ICa(L) and IK(r) block, including the HR sub-population. The models exhibited a wide range of Gmax values with constrained relationships linking ICa(L) with IK(r), ICl, INCX, and INaK. Conclusion: Modelling the measured range of inter-cell APDs required a larger range of key Gmax values indicating that ventricular tissue has considerable inter-cell variation in channel/pump/exchanger activity. AP morphology is retained by relationships linking specific ionic conductances. These interrelationships are necessary for stable repolarization despite large inter-cell variation of individual conductances and this explains the variable sensitivity to ion channel block

Kvalita veřejných služeb

V první kapitole se zabývám definicí veřejného sektoru, popisuji metodologické přístupy a metody hodnocení kvality veřejným sektorem.V druhé části popisuji město Turnov, jak v samosprávné činnosti, tak i ve výkonu státní správy.Hodnocení jsem provedla formou dotazníku

Familial Recurrence Patterns in Congenitally Corrected Transposition of the Great Arteries: An International Study

International audienc