Unifying automated fractionated atrial electrogram classification using electroanatomical mapping systems in persistent atrial fibrillation studies

Ablation targeting complex fractionated atrial electrograms (CFAE) for treating persistent atrial fibrillation (persAF) has shown conflicting results. Differences in automated algorithms embedded in NavX (St Jude Medical) and CARTO (Biosense Webster) could influence CF AE target identification for ablation, potentially affecting ablation outcomes. To evaluate this effect, automated CFAE classification performed by NavX and CARTO on the same bipolar electrograms from 18 persAF patients undergoing ablation was compared. Using the default thresholds, NavX classified 69±5% of the electrograms as CFAEs, while CARTO detected 35±5%% (Cohen's kappa κ≈0.3, P<0.0001). Both primary and complementary metrics for each system were optimized to balance CF AE detection for both systems. Using revised thresholds found from receiver operating characteristic curves, NavX classified 45±4%, while CARTO detected 42±5% (κ≈0.5, P<0.0001). Our work takes a first step towards the optimization of CFAE detection between NavX and CARTO by providing revised thresholds to reduce differences in CF AE classification. This would facilitate direct comparisons of persAF CFAE-guided ablation outcome guided by NavX or CARTO

Impact of Vitamin D Supplementation on Arterial Vasomotion, Stiffness and Endothelial Biomarkers in Chronic Kidney Disease Patients

Background: Cardiovascular events are frequent and vascular endothelial function is abnormal in patients with chronic kidney disease (CKD). We demonstrated endothelial dysfunction with vitamin D deficiency in CKD patients; however the impact of cholecalciferol supplementation on vascular stiffness and vasomotor function, endothelial and bone biomarkers in CKD patients with low 25-hydroxy vitamin D [25(OH)D] is unknown, which this study investigated. Methods: We assessed non-diabetic patients with CKD stage 3/4, age 17–80 years and serum 25(OH)D ,75 nmol/L. Brachial artery Flow Mediated Dilation (FMD), Pulse Wave Velocity (PWV), Augmentation Index (AI) and circulating blood biomarkers were evaluated at baseline and at 16 weeks. Oral 300,000 units cholecalciferol was administered at baseline and 8-weeks. Results: Clinical characteristics of 26 patients were: age 50614 (mean61SD) years, eGFR 41611 ml/min/1.73 m2, males 73%, dyslipidaemia 36%, smokers 23% and hypertensives 87%. At 16-week serum 25(OH)D and calcium increased (43616 to 84629 nmol/L, p,0.001 and 2.3760.09 to 2.4260.09 mmol/L; p = 0.004, respectively) and parathyroid hormone decreased (10.868.6 to 7.464.4; p = 0.001). FMD improved from 3.163.3% to 6.163.7%, p = 0.001. Endothelial biomarker concentrations decreased: E-Selectin from 566662123 to 525662058 pg/mL; p = 0.032, ICAM-1, 3.4560.01 to 3.1061.04 ng/mL; p = 0.038 and VCAM-1, 54633 to 42633 ng/mL; p = 0.006. eGFR, BP, PWV, AI, hsCRP, von Willebrand factor and Fibroblast Growth Factor-23, remained unchanged. Conclusion: This study demonstrates for the first time improvement of endothelial vasomotor and secretory functions with vitamin D in CKD patients without significant adverse effects on arterial stiffness, serum calcium or FGF-23. Trial Registration: ClinicalTrials.gov NCT0200571

Oxidation behavior of graphene-coated copper at intrinsic graphene defects of different origins

The development of ultrathin barrier films is vital to the advanced semiconductor industry. Graphene appears to hold promise as a protective coating; however, the polycrystalline and defective nature of engineered graphene hinders its practical applications. Here, we investigate the oxidation behavior of graphene-coated Cu foils at intrinsic graphene defects of different origins. Macro-scale information regarding the spatial distribution and oxidation resistance of various graphene defects is readily obtained using optical and electron microscopies after the hot-plate annealing. The controlled oxidation experiments reveal that the degree of structural deficiency is strongly dependent on the origins of the structural defects, the crystallographic orientations of the underlying Cu grains, the growth conditions of graphene, and the kinetics of the graphene growth. The obtained experimental and theoretical results show that oxygen radicals, decomposed from water molecules in ambient air, are effectively inverted at Stone-Wales defects into the graphene/Cu interface with the assistance of facilitators

A Dual Receptor Crosstalk Model of G-Protein-Coupled Signal Transduction

Macrophage cells that are stimulated by two different ligands that bind to G-protein-coupled receptors (GPCRs) usually respond as if the stimulus effects are additive, but for a minority of ligand combinations the response is synergistic. The G-protein-coupled receptor system integrates signaling cues from the environment to actuate cell morphology, gene expression, ion homeostasis, and other physiological states. We analyze the effects of the two signaling molecules complement factors 5a (C5a) and uridine diphosphate (UDP) on the intracellular second messenger calcium to elucidate the principles that govern the processing of multiple signals by GPCRs. We have developed a formal hypothesis, in the form of a kinetic model, for the mechanism of action of this GPCR signal transduction system using data obtained from RAW264.7 macrophage cells. Bayesian statistical methods are employed to represent uncertainty in both data and model parameters and formally tie the model to experimental data. When the model is also used as a tool in the design of experiments, it predicts a synergistic region in the calcium peak height dose response that results when cells are simultaneously stimulated by C5a and UDP. An analysis of the model reveals a potential mechanism for crosstalk between the Gαi-coupled C5a receptor and the Gαq-coupled UDP receptor signaling systems that results in synergistic calcium release

Serum S100B in primary progressive multiple sclerosis patients treated with interferon-beta-1a

S100B belongs to a family of calcium-binding proteins implicated in intracellular and extracellular regulatory activities. This study of serum S100B in primary progressive multiple sclerosis (PPMS) is based on data obtained from a randomized, controlled trial of Interferon β-1a in subjects with PPMS. The key questions were whether S100B levels were associated with either disability or MRI findings in primary progressive MS and whether Interferon β-1a has an effect on their S100B levels. Serial serum S100B levels were measured using an ELISA method. The results demonstrated that serum S100B is not related to either disease progression or MRI findings in subjects with primary progressive MS given Interferon β-1a. Furthermore there is no correlation between S100B levels and the primary and secondary outcome measures

EMT-Induced Stemness and Tumorigenicity Are Fueled by the EGFR/Ras Pathway

10.1371/journal.pone.0070427PLoS ONE88-POLN

The Role of Imported Cases and Favorable Meteorological Conditions in the Onset of Dengue Epidemics

Dengue/dengue hemorrhagic fever is the world's most widely spread mosquito-borne arboviral disease and threatens more than two-thirds of the world's population. Cases are mainly distributed in tropical and subtropical areas in accordance with vector habitats for Aedes aegypti and Ae. albopictus. However, the role of imported cases and favorable meteorological conditions has not yet been quantitatively assessed. This study verified the correlation between the occurrence of indigenous dengue and imported cases in the context of weather variables (temperature, rainfall, relative humidity, etc.) for different time lags in southern Taiwan. Our findings imply that imported cases have a role in igniting indigenous outbreaks, in non-endemics areas, when favorable weather conditions are present. This relationship becomes insignificant in the late phase of local dengue epidemics. Therefore, early detection and case management of imported cases through timely surveillance and rapid laboratory-diagnosis may avert large scale epidemics of dengue/dengue hemorrhagic fever. An early-warning surveillance system integrating meteorological data will be an invaluable tool for successful prevention and control of dengue, particularly in non-endemic countries

Effects of the neurogranin variant rs12807809 on thalamocortical morphology in schizophrenia

10.1371/journal.pone.0085603PLoS ONE812-POLN

Networks or structures? : organizing cultural routes around heritage values : case studies from Poland

The most common way of managing cultural heritage recently takes form of cultural routes as they seem to offer a new model of participation in culture to their recipients; they are often a peculiar anchor point for inhabitants to let them understand their identity and form the future; they offer actual tours to enter into interaction with culture and history, to build together that creation of the heritage, which so is becoming not only a touristic product, but, first of all, the space for cultural, social and civic activity. Yet, so far, according to what we know, the research problem concerning the method of cultural route organization (points on the route) into solid structures or more of the networked nature, has not been deliberated. A question arises, what values are brought by routes and how to organize routes to be the carriers of the values important for communities, where routes are functioning. And, as a consequence, if, from the point of view of the values of local communities, organizing solid route structures or organizing more widely-spaced, network-based routes would bring effects and what those effects would be. Thus, the posed question is of course scientifically imprecise because a network is a type of structure but presents a given direction for the development of cultural route structures. Our objective here is to present a certain solidity and rigidity of structure with dynamic and smooth understanding of the network. The research presented in the article is based on 3 case studies. We have selected for this purpose the three largest cultural routes in Poland, organized to various degrees. The outcome of the research was referred also to other cultural route organization research