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In many applications, the highest and lowest detectable flux are both important for single photon avalanche photodiodes (APDs). The photocurrent and single-photon-counting performance of 4H-SiC APDs are investigated under a wide-range incident flux. Experimental results show that the photocurrent is sub-linearly with the incident photon rate at high-level incident flux. In addition, the ratio of photon count rate to dark count rate is non-monotonic when the incident flux increases. The highest detectable flux of the 4H-SiC APD can be extended from 3 × 103 photons/s·μm2 to more than 4 × 104 photons/s·μm2 by reducing the threshold voltage and increasing the reverse voltage.

Cracks and mechanical damages are unavoidable during the real-world application of protective epoxy coatings, resulting in localized failure, corrosion attack, and potential safety hazards. Herein, 2-aminophenyl disulfide (APD) was used as a hardener for the design and construction of a novel self-healing epoxy coating (EAPD coating) to recover the micro-scale mechanical scratches. The optical spectroscopy, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectra (FTIR) and electrochemical impedance spectroscopy (EIS) were employed to investigate the macro-micro surface morphologies, chemical compositions, self-healing behaviors, and corrosion resisting properties of the scratch-damaged and scratch-healed EAPD coatings. Due to disulfide-mediated radical exchanges and S–S bonds rearrangement, the developed EAPD coating exhibits superior thermally-triggered self-healing performance with mechanical scratches completely self-repaired after 20 min at 80 °C and sustainable recovered corrosion resistance. The created self-healing EAPD coating is thought to provide a new design strategy for the development of smart and multi-functional protective coating materials with intriguing properties.

Typical atrio-ventricular nodal re-entrant tachycardia (AVNRT) can occasionally remain easily inducible after slow pathway (SP) modification in lower Triangle of Koch (TOK). Analysis of resetting response by delivering atrial premature depolarizations (APD) from various sites (TOK, right atrium, coronary sinus and left atrium) can pin-point the culprit SP serving as the antegrade limb of the tachycardia circuit. However, the maneuver is under-utilized by most centers. We describe a case where anatomical SP modification in TOK failed to cure the arrhythmia. The resetting maneuver performed subsequently, helped us to rule out leftward inferior extension of SP and suggested right inferior SP as essential part of AVNRT circuit. Further ablation was performed at M1-M2 region (on the right side) to achieve success.

Background: Continuous ambulatory peritoneal dialysis (CAPD) is the first option for patients with end-stage renal disease under the benefit package of Thailand. Nevertheless, automated peritoneal dialysis (APD) may benefit these patients in terms of both medical and quality-of-life aspects, but it is more expensive. The economic evidence for the comparison between CAPD and APD is not inconclusive. Thus, this study aims to evaluate the cost-effectiveness of CAPD compared with APD in PD patients., Objectives: To assess the health-related quality of life and costs between patients treated with CAPD and APD., Methods: A Markov model was developed to evaluate the cost-effectiveness of CAPD and APD from the societal perspective. Costs and outcomes were calculated over a lifetime horizon and discounted at an annual rate of 3%. The outcomes were presented as quality-adjusted life-years (QALYs) of CAPD and APD. Utility scores were calculated from the utility values of the 5-level EuroQol questionnaire. A probabilistic sensitivity analysis using 5000 Monte Carlo simulations was performed to evaluate the stability of the results., Results: The costs of APD and CAPD were 12 868 080 and 11 144 786 Thai baht, respectively, whereas the QALYs were 24.28 and 24.72 QALYs, respectively. APD was more costly but less effective than CAPD. The most sensitive parameter was direct medical cost of outpatient visits. When the willingness-to-pay threshold was 160 000 Thai baht per QALY, the probability of APD providing a cost-effective alternative to CAPD was 19%., Conclusion: APD was not a cost-effective strategy as compared with CAPD at the current Thai threshold. These findings should encourage clinicians and policy makers to encompass the use of CAPD as a good value for money for PD treatment., (Copyright © 2019 ISPOR--The professional society for health economics and outcomes research. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to compare the EuroQol 5-dimension 5-level questionnaire (EQ-5D-5L), the visual analogue scale (VAS), and the Kidney Disease Quality of Life 36-Item Short-Form Survey (KDQOL-36) scores of Thai continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) patients and to compare the utility scores with the EQ-5D-5L and VAS scores of caregivers., Methods: This was a cross-sectional study completed between April 2016 and May 2017. In total, 34 CAPD patients, 30 APD patients, and their caregivers were recruited from a large university hospital in Thailand. A trained interviewer conducted face-to-face interviews. We collected demographic data and used the KDQOL-36 and EuroQol questionnaires (EQ-5D-5L and VAS) to assess the health-related quality of life. Caregivers were asked to assess their own health status using the EQ-5D-5L and VAS., Results: The EQ-5D-5L and VAS responses of the CAPD and APD patients and their caregivers were not significantly different (P > .05). More than 50% of both patient groups had mobility problems, whereas most patients had no problems with self-care, doing usual activities, pain or discomfort, and anxiety or depression. As for the KDQOL-36, the physical and mental component summaries were not significantly different, and neither were the scores for all of the kidney disease-specific dimensions, including symptoms or problems, effects of kidney disease, and burden of kidney disease (all were P > .05)., Conclusions: The results indicated that the quality of life of CAPD and APD patients and their caregivers were mostly equivalent. A further longitudinal study of utility score assessments of the differences in modality would be advantageous., (Copyright © 2020 ISPOR--The professional society for health economics and outcomes research. Published by Elsevier Inc. All rights reserved.)

The signal-to-noise ratio (SNR) of avalanche photodiode (APD) in optical detection system is greatly influenced by background radiation and operating temperature, so an APD optimal bias voltage compensation method based on machine learning is designed to accurately judge the current laser emission state and APD working state so that dichotomy compensation can be carried out to make APD work in optimal state. By means of cross-verification, the accuracy of judging laser emission state and APD working state is as high as 100% and 99.3% separately, then the number of input variables in the model is reduced appropriately by experiment and the prediction speed of the algorithm is further improved. Finally, road detection application is taken as the experimental background and comparison between the proposed method and the most widely used signal amplitude feedback compensation method is carried out. The results of this study suggest that the proposed APD optimal bias voltage compensation method based on machine learning offers a new and promising approach., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 ISA. Published by Elsevier Ltd. All rights reserved.)

Introduction: The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative proposes a three-step approach to evaluate proarrhythmogenic liability of drug candidates: effects on individual ion channels in heterologous expression systems, integrating these data into in-silico models of the electrical activity of human cardiomyocytes, and comparison with experiments on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Here we introduce patch-clamp electrophysiology techniques on hiPSC-CM to combine two of the CiPA steps in one assay., Methods: We performed automated patch-clamp experiments on hiPSC-CM (Cor.4U ® , Ncardia) using the CytoPatch™2 platform in ruptured whole-cell and β-escin-perforated-patch configurations. A combination of three voltage-clamp protocols allowed recording of five distinct ion current components (voltage-gated Na + current, L-type Ca 2+ current, transient outward K + current, delayed rectifier K + current, and "funny" hyperpolarization-activated current) from the same cell. We proved their molecular identity by either Na + replacement with choline or by applying specific blockers: nifedipine, cisapride, chromanol 293B, phrixotoxin-1, ZD7288. We developed a C++ script for automated analysis of voltage-clamp recordings and computation of ion current/conductance surface density for these five cardiac ion currents., Results: The distributions from n = 54 hiPSC-CM in "ruptured" patch-clamp vs. n = 35 hiPSC-CM in β-escin-perforated patch-clamp were similar for membrane capacitance, access resistance, and ion current/conductance surface densities. The β-escin-perforated configuration resulted in improved stability of action potential (AP) shape and duration over a 10-min interval, with APD90 decay rate 0.7 ± 1.6%/min (mean ± SD, n = 4) vs. 4.6 ± 1.1%/min. (n = 3) for "ruptured" approach (p = 0.0286, one-tailed Mann-Whitney test)., Discussion: The improved stability obtained here will allow development of CiPA-compliant automated patch-clamp assays on hiPSC-CM. Future applications include the study of multi ion-channel blocking properties of drugs using dynamic-clamp protocols, adding a valuable new tool to the arsenal of safety-pharmacology., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Human-induced pluripotent stem cell (h-iPSC)-derived cardiac myocytes are a unique model in which human myocyte function and dysfunction are studied, especially those from patients with genetic disorders. They are also considered a major advance for drug safety testing. However, these cells have considerable unexplored potential limitations when applied to quantitative action potential (AP) analysis. One major factor is spontaneous activity and resulting variability and potentially anomalous behavior of AP parameters., Objective: To demonstrate the effect of using an in silico interface on electronically expressed I(K1), a major component lacking in h-iPSC-derived cardiac myocytes., Methods: An in silico interface was developed to express synthetic I(K1) in cells under whole-cell voltage clamp., Results: Electronic I(K1) expression established a physiological resting potential, eliminated spontaneous activity, reduced spontaneous early and delayed afterdepolarizations, and decreased AP variability. The initiated APs had the classic rapid upstroke and spike and dome morphology consistent with data obtained with freshly isolated human myocytes as well as the readily recognizable repolarization attributes of ventricular and atrial cells. The application of 1 µM of BayK-8644 resulted in anomalous AP shortening in h-iPSC-derived cardiac myocytes. When I(K1) was electronically expressed, BayK-8644 prolonged the AP, which is consistent with the existing results on native cardiac myocytes., Conclusions: The electronic expression of I(K1) is a simple and robust method to significantly improve the physiological behavior of the AP and electrical profile of h-iPSC-derived cardiac myocytes. Increased stability enables the use of this preparation for a controlled quantitative analysis of AP parameters, for example, drug responsiveness, genetic disorders, and dynamic behavior restitution profiles., (© 2013 Heart Rhythm Society Published by Heart Rhythm Society All rights reserved.)

Background: Activation rate (AR) gradients develop during ventricular fibrillation (VF), with the highest AR on the surface near Purkinje system (PS) terminals (endocardium in humans and rabbits and epicardium in pigs). The application of glibenclamide to block adenosine triphosphate (ATP)-sensitive potassium current (IK(ATP)) before VF induction eliminates transmural AR gradients and prevents the induction of sustained arrhythmia. It remains unclear whether the PS, which is resistant to ischemia, is also a factor in AR heterogeneity., Objective: To dissect IK(ATP) and PS contributions to AR gradients during VF by using detailed computer simulations., Methods: We constructed rabbit ventricular models with either subendocardial or subepicardial PS terminals. Physiologically relevant IK(ATP) gradients were implemented, and early VF was induced and observed., Results: Prominent AR gradients were observed only in models with large IK(ATP) gradients. The critical underlying factor of AR gradient maintenance was refractoriness in low-IK(ATP) regions, which blocked the propagation of action potentials from high-IK(ATP) regions. The PS played no role in transmural AR gradient maintenance, but did cause local spatial heterogeneity of AR on the surface adjacent to terminals. Simulated glibenclamide application during VF led to spontaneous arrhythmia termination within a few seconds in most cases, which builds on previous experimental findings of anti-VF properties of glibenclamide pretreatment., Conclusion: Differential IK(ATP) across the ventricular wall is an important factor underlying AR gradients during VF; thus, higher epicardial AR in pigs is most likely due to an abundance of epicardial IK(ATP). For terminating early VF, our results suggest that IK(ATP) modulation is a stronger target than Purkinje ablation., (© 2013 Heart Rhythm Society. All rights reserved.)

Background: A secondary rise of intracellular Ca(2+) (Cai) and an upregulation of apamin-sensitive K(+) current (I(KAS)) are characteristic findings of failing ventricular myocytes. We hypothesize that apamin, a specific I(KAS) blocker, may induce torsades de pointes (TdP) ventricular arrhythmia from failing ventricles exhibiting secondary rises of Cai., Objective: To test the hypothesis that small conductance Ca(2+) activated IKAS maintains repolarization reserve and prevents ventricular arrhythmia in a rabbit model of heart failure (HF)., Methods: We performed Langendorff perfusion and optical mapping studies in 7 hearts with pacing-induced HF and in 5 normal control rabbit hearts. Atrioventricular block was created by cryoablation to allow pacing at slow rates., Results: The left ventricular ejection fraction reduced from 69.1% [95% confidence interval 62.3%-76.0%] before pacing to 30.4% [26.8%-34.0%] (N = 7; P < .001) after pacing. The corrected QT interval in failing ventricles was 337 [313-360] ms at baseline and 410 [381-439] ms after applying 100 nmol/L of apamin (P = .01). Apamin induced early afterdepolarizations (EADs) in 6 ventricles, premature ventricular beats (PVBs) in 7 ventricles, and polymorphic ventricular tachycardia consistent with TdP in 4 ventricles. The earliest activation site of EADs and PVBs always occurred at the site with long action potential duration and large amplitude of the secondary rises of Ca(i). Apamin induced secondary rises of Ca(i) in 1 nonfailing ventricle, but no EAD or TdP were observed., Conclusions: In HF ventricles, apamin induces EADs, PVBs, and TdP from areas with secondary rises of Ca(i). I(KAS) is important in maintaining repolarization reserve and preventing TdP in HF ventricles., (© 2013 Heart Rhythm Society. All rights reserved.)

Background: Enhanced dispersion of action potential duration (APD) is a major contributor to long QT syndrome (LQTS)-related arrhythmias., Objective: To investigate spatial correlations of regional heterogeneities in cardiac repolarization and mechanical function in LQTS., Methods: Female transgenic LQTS type 2 (LQT2; n = 11) and wild-type littermate control (LMC) rabbits (n = 9 without E4031 and n = 10 with E4031) were subjected to phase contrast magnetic resonance imaging to assess regional myocardial velocities. In the same rabbits' hearts, monophasic APDs were assessed in corresponding segments., Results: In LQT2 and E4031-treated rabbits, APD was longer in all left ventricular segments (P < .01) and APD dispersion was greater than that in LMC rabbits (P < .01). In diastole, peak radial velocities (Vr) were reduced in LQT2 and E4031-treated compared to LMC rabbits in LV base and mid (LQT2: -3.36 ± 0.4 cm/s, P < .01; E4031-treated: -3.24 ± 0.6 cm/s, P < .0001; LMC: -4.42 ± 0.5 cm/s), indicating an impaired diastolic function. Regionally heterogeneous diastolic Vr correlated with APD (LQT2: correlation coefficient [CC] 0.38, P = .01; E4031-treated: CC 0.42, P < .05). Time-to-diastolic peak Vr were prolonged in LQT2 rabbits (LQT2: 196.8 ± 2.9 ms, P < .001; E4031-treated: 199.5 ± 2.2 ms, P < .0001, LMC 183.1 ± 1.5), indicating a prolonged contraction duration. Moreover, in transgenic LQT2 rabbits, diastolic time-to-diastolic peak Vr correlated with APD (CC 0.47, P = .001). In systole, peak Vr were reduced in LQT2 and E4031-treated rabbits (P < .01) but longitudinal velocities or ejection fraction did not differ. Finally, random forest machine learning algorithms enabled a differentiation between LQT2, E4031-treated, and LMC rabbits solely based on "mechanical" magnetic resonance imaging data., Conclusions: The prolongation of APD led to impaired diastolic and systolic function in transgenic and drug-induced LQT2 rabbits. APD correlated with regional diastolic dysfunction, indicating that LQTS is not purely an electrical but an electromechanical disorder., (© 2013 Heart Rhythm Society. All rights reserved.)

Background: The concept that pore-forming Kir6.2 and regulatory SUR2A subunits form cardiac ATP-sensitive potassium (K(ATP)) channels is challenged by recent reports that SUR1 is predominant in mouse atrial K(ATP) channels., Objective: To assess SUR subunit composition of K(ATP) channels and consequence of K(ATP) activation for action potential duration (APD) in dog hearts., Methods: Patch-clamp techniques were used on isolated dog cardiomyocytes to investigate K(ATP) channel properties. Dynamic current clamp, by injection of a linear K(+) conductance to simulate activation of the native current, was used to study the consequences of K(ATP) activation on APD., Results: Metabolic inhibitor (MI)-activated current was not significantly different from pinacidil (SUR2A-specific)-activated current, and both currents were larger than diazoxide (SUR1-specific)-activated current in both the atrium and the ventricle. Mean K(ATP) conductance (activated by MI) did not differ significantly between chambers, although, within the ventricle, both MI-induced and pinacidil-induced currents tended to decrease from the epicardium to the endocardium. Dynamic current-clamp results indicate that myocytes with longer baseline APDs are more susceptible to injected K(ATP) current, a result reproduced in silico by using a canine action potential model (Hund-Rudy) to simulate epicardial and endocardial myocytes., Conclusions: Even a small fraction of K(ATP) activation significantly shortens APD in a manner that depends on existing heterogeneity in K(ATP) current and APD., (© 2013 Heart Rhythm Society. All rights reserved.)

Background: Long QT syndrome type 13 (LQT13) is caused by loss-of-function mutation in the KCNJ5-encoded cardiac G-protein-coupled inward rectifier potassium channel subtype 4 protein. The electrocardiographic (ECG) features of LQT13 are not described yet., Objective: To describe for the first time in detail the phenotype-genotype relationship of the ECG and clinical features in patients with LQT13., Methods: The 12-lead ECGs, 24-hour Holter recordings, and clinical information from KCNJ5-G387R mutation carriers of a fourth-generation Han Chinese family with LQT13 and a group of healthy Chinese individuals were analyzed., Results: Compared with the analysis of the healthy group (n = 8), age- and sex-matched pair analysis revealed that the mutation carriers (n = 8) had ventricular repolarization abnormality results in the prolongation of corrected QT and QTpeak intervals (P < .01); greater combined measure of repolarization morphology (T-wave morphology combination score) based on asymmetry, flatness, and notch (P < .01); and reduced low frequency/high frequency ratio of heart rate variability (P < .01) as a reflection of cardiac autonomic imbalance. Mean heart rate, time domain parameters of heart rate variability, time interval from T-wave peak to T-wave end, and T-wave amplitude were similar., Conclusions: This study demonstrates for the first time the ECG features of patients with LQT13. Our data suggest that QTpeak intervals and T-wave morphology combination score may be the better parameters than the corrected QT interval to predict the phenotype-genotype relationship in patients with LQT13., (© 2013 Heart Rhythm Society. All rights reserved.)

Background: Ganglionated plexi (GP) ablation has been shown to play an important role in atrial fibrillation (AF) initiation and maintenance. Also, GP ablation increases chances for prevention of AF recurrence. This study investigated the effects of GP ablation on ventricular electrophysiological properties in normal dog hearts and after acute myocardial ischemia (AMI)., Methods: Fifty anesthetized dogs were assigned into normal heart group (n=16) and AMI heart group (n=34). Ventricular dynamic restitution, effective refractory period (ERP), electrical alternans and ventricular fibrillation threshold (VFT) were measured before and after GP ablation in the normal heart group. In the AMI heart group, the incidence of ventricular arrhythmias and VFT were determined., Results: In the normal heart group, GP ablation significantly prolonged ERP, facilitated electrical alternans but did not increase ERP dispersion, the slope of restitution curves and its spatial dispersion. Also, GP ablation did not cause significant change of VFT. In the AMI heart group, the incidence of ventricular arrhythmias after GP ablation was significantly higher than that in the control group or the GP plus stellate ganglion (SG) ablation group (P<0.05). Spontaneous VF occurred in 8/12, 1/10 and 2/12 dogs in the GP ablation group, the GP plus SG ablation group and the control group, respectively (P<0.05). VFT in the GP ablation group showed a decreased trend though a significant difference was not achieved compared with the control or the GP plus SG ablation group., Conclusions: GP ablation increases the risk of ventricular arrhythmias in the AMI heart compared to the normal heart., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Slow delayed-rectifier potassium current (IKs) channels, made of the pore-forming KCNQ1 and auxiliary KCNE1 subunits, play a key role in determining action potential duration (APD) in cardiac myocytes. The consequences of drug-induced KCNQ1 splice alteration remain unknown., Objective: To study the modulation of KCNQ1 alternative splicing by amiloride and the consequent changes in IKs and action potentials (APs) in ventricular myocytes., Methods: Canine endocardial, midmyocardial, and epicardial ventricular myocytes were isolated. Levels of KCNQ1a and KCNQ1b as well as a series of splicing factors were quantified by using the reverse transcriptase-polymerase chain reaction and Western blot. The effect of amiloride-induced changes in the KCNQ1b/total KCNQ1 ratio on AP was measured by using whole-cell patch clamp with and without isoproterenol., Results: With 50 μmol/L of amiloride for 6 hours, KCNQ1a at transcriptional and translational levels increased in midmyocardial myocytes but decreased in endo- and epicardial myocytes. Likewise, changes in splicing factors in midmyocardial were opposite to that in endo- and epicardial myocytes. In midmyocardial myocytes amiloride shortened APD and decreased isoproterenol-induced early afterdepolarizations significantly. The same amiloride-induced effects were demonstrated by using human ventricular myocyte model for AP simulations under beta-adrenergic stimulation. Moreover, amiloride reduced the transmural dispersion of repolarization in pseudo-electrocardiogram., Conclusions: Amiloride regulates IKs and APs with transmural differences and reduces arrhythmogenicity through the modulation of KCNQ1 splicing. We suggested that the modulation of KCNQ1 splicing may help prevent arrhythmia., (Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Early prediction of drug-induced functional cardiotoxicity requires robust in-vitro systems suitable for medium/high throughput and easily accessible cardiomyocytes with defined reproducible properties. The xCELLigence Cardio system uses 96-well plates with interdigitated electrodes that detect the impedance changes of rhythmic contractions of stem cell-derived cardiomyocyte (SC-CM) layers. Here, we report on our initial screening experience in comparison to established (multi)cellular and in-vivo models., Methods: Impedance signals from human iPSC-CM (iCells™) and mouse eSC-CM (Cor.At™) were analyzed for contraction amplitude (CA) and duration, rise/fall time, beating rate (BR) and irregularity., Results: Following solution exchange, impedance signals re-approximated steady-state conditions after about 2 (Cor.At™) and 3h (iCells™); these time points were used to analyze drug effects. The solvent DMSO (≤1%) hardly influenced contraction parameters in Cor.At™, whereas in iCells™ DMSO (>0.1%) reduced CA and enhanced BR. The selective hERG K⁺ channel blockers E-4031 and dofetilide reduced CA and accelerated BR (≥30 nM) according to the analysis software. The latter, however, was due to burst-like contractions (300 nM) that could be detected only by visual inspection of recordings, and were more pronounced in Cor.At™ as in iCells™. In cardiac myocytes and tissue preparations, however, E4031 and dofetilide have been reported to increase cell shortening and contractile force and to reduce BR. Compounds (pentamidine, HMR1556, ATX2, TTX, and verapamil) with other mechanisms of action were also investigated; their effects differed partially between cell lines (e.g. TTX) and compared to established (multi)cellular models (e.g. HMR1556, ouabain)., Conclusion: Mouse and human stem cell-derived cardiomyocytes respond differently to drugs and these responses occasionally also differ from those originating from established in-vitro and in-vivo models. Hence, drug-induced cardiotoxic effects may be detected with this system, however, the predictive or even translational value of results is considered limited and not yet firmly established., (Copyright © 2013 Elsevier Inc. All rights reserved.)