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Background: Pediatric liver transplant recipients are at increased risk of post‐transplant infections. The purpose of this study was to quantify hepatitis A and B non‐immunity based on antibody titers in liver transplant recipients. Methods: We conducted a retrospective chart review of 107 pediatric liver transplant recipients at a single medical center from 2000 to 2017. We compared hepatitis immune patients to non‐immune patients and studied response to vaccination in patients immunized post‐transplantation. Results: Eighty‐one percent of patients had pre‐transplant immunity to hepatitis A whereas 68% had pre‐transplant immunity to hepatitis B. Post‐transplant hepatitis B immunity decreased to 33% whereas post‐transplant hepatitis A immunity remained high at 82%. Older age and time since transplantation were significantly associated with hepatitis B non‐immunity. Most patients responded to doses post‐transplantation with 78% seroconversion following hepatitis A re‐immunization and 83% seroconversion following hepatitis B re‐immunization. Conclusions: Pediatric liver transplant recipients are at risk of hepatitis A and B non‐immunity, particularly with respect to hepatitis B. Boosters post‐transplant may improve immunity to hepatitis viruses. [ABSTRACT FROM AUTHOR]

There is a critical knowledge gap about how glacier retreat in remote and rapidly warming tropical montane watersheds will impact solute export, which has implications for downstream geochemical cycling and ecological function. Because tropical glacierized watersheds are often uniquely characterized by year‐round ablation, upslope vegetation migration, and significant groundwater flow, baseline understanding is needed of how spatiotemporal variables within these watersheds control outlet hydrochemistry. We implemented a recently developed reactive transport watershed model, BioRT‐Flux‐PIHM, for a sub‐humid glacierized watershed in the Ecuadorian Andes with young volcanic soils and fractured bedrock. We found a unique simulated concentration and discharge (C‐Q) pattern that was mostly chemostatic but superimposed by dilution episodes. The chemostatic background was attributed to large simulated contributions of groundwater (subsurface lateral flow) to streamflow, of which a notable fraction (37%) comprised infiltrated ice‐melt. Relatively constant concentrations were further maintained in the model because times and locations of lower mineral surface wetting and dissolution were offset by concentrating effects of greater evapotranspiration. Ice‐melt did not all infiltrate in simulations, especially during large precipitation events, when high surface runoff contributions to discharge triggered dilution episodes. In a model scenario without ice‐melt, major ion concentrations, including Na+, Ca2+, and Mg2+, became more strongly chemostatic and higher, but weathering rates decreased, attenuating export by 23%. We expect this reduction to be exacerbated by higher evapotranspiration and drier conditions with expanded vegetation. This work brings to light the importance of subsurface meltwater flow, ecohydrological variability, and interactions between melt and precipitation for controlling hydrochemical processes in tropical watersheds with rapidly retreating glaciers. Key Points: Integrated hydrologic model with reactive transport can probe spatiotemporally variable hydrochemical processes in data‐sparse watershedUnique C‐Q pattern due to infiltrated ice‐melt, weathering with groundwater, vegetation‐driven ET, and melt + precipitation dilution eventsAs glaciers fully retreat, concentrations increase and become more chemostatic, but solute export decreases due to lower stream discharge [ABSTRACT FROM AUTHOR]

Introduction: Sudden cardiac death (SCD) risk assessment is limited, particularly in patients with nonischemic cardiomyopathies. This is the first application, in patients with cardiomyopathies, of two novel risk markers, regional restitution instability index (R2I2) and peak electrocardiogram restitution slope (PERS), which have been shown to be predictive of ventricular arrhythmias (VA) or death in ischemic heart disease patients. Methods: Blinded retrospective study of 50 patients: 33 dilated cardiomyopathy and 17 other; undergoing electrophysiological study (EPS) for SCD risk stratification, and 29 controls with structurally normal hearts undergoing EPS. R2I2 was calculated from an EPS using electrocardiogram surrogates for action potential duration and diastolic interval. Cut‐offs for high and low R2I2/PERS were predefined. Results: R2I2 was significantly higher in study than control patients (0.99 ± 0.05 vs. 0.63 ± 0.04, p <.001). PERS showed a trend to higher values in the study group (1.18[0.63] vs. 1.09[0.54], p =.07). During median follow up of 5.6 years [interquartile range 1.9 years], nine study patients reached the endpoint of VA/death. Patients who experienced VA/death showed trends to higher mean R2I2 (1.14 ± 0.07 vs.0.95 ± 0.05, p =.12) and PERS (1.46[0.49] vs. 1.13[0.62], p =.22). A Cox proportional hazards model using grouped markers: R2I2 < 1.03 + PERS < 1.21/either R2I2 ≥ 1.03 or PERS ≥ 1.21/R2I2 ≥ 1.03 + PERS ≥ 1.21; significantly predicted VA/death (p =.02) with a hazard ratio per positive component of 3.2 (95% confidence interval 1.2–8.8). Conclusion: R2I2≥ 1.03 + PERS ≥ 1.21 may predict VA/death in patients with cardiomyopathies. R2I2 ≥ 1.03 + PERS ≥ 1.21 have the potential to play an important role in SCD risk stratification in cardiomyopathies but their validity should be confirmed in a larger study. [ABSTRACT FROM AUTHOR]

Peatlands are among the largest natural sources of atmospheric methane (CH4) worldwide. Peatland emissions are projected to increase under climate change, as rising temperatures and shifting precipitation accelerate microbial metabolic pathways favorable for CH4 production. However, how these changing environmental factors will impact peatland emissions over the long term remains unknown. Here, we investigate a novel data set spanning an exceptionally long 11 years to analyze the influence of soil temperature and water table elevation on peatland CH4 emissions. We show that higher water tables dampen the springtime increases in CH4 emissions as well as their subsequent decreases during late summer to fall. These results imply that any hydroclimatological changes in northern peatlands that shift seasonal water availability from winter to summer will increase annual CH4 emissions, even if temperature remains unchanged. Therefore, advancing hydrological understanding in peatland watersheds will be crucial for improving predictions of CH4 emissions. Plain Language Summary: Methane (CH4) emissions from wetlands are the largest natural source of atmospheric CH4 worldwide and are expected to increase under global warming. Because of a scarcity of field observations, we do not yet know how wetland CH4 emissions will be affected by future climates and under what conditions. In this study, we use a newly developed long‐term data set of CH4 flux measurements at a northern peatland to demonstrate the importance of seasonal water availability in controlling the sensitivity of CH4 emission increase to soil temperature. Our results suggest that a shift in water availability from winter to summer may result in higher annual CH4 emissions, even if soil temperatures remain the same. Key Points: A newly developed long‐term data set of methane (CH4) flux measurements at a northern peatland is analyzedSeasonal water availability is shown to control the sensitivity of CH4 emissions to increase in soil temperatureShifting water availability from winter to summer may result in higher annual CH4 emissions, even if soil temperatures remain the same [ABSTRACT FROM AUTHOR]

Aims: Studies of remote monitoring (RM) in heart failure (HF) speculate that patients with atrial fibrillation (AF) derive the greatest benefit. We compared the impact of RM vs. usual care on clinical outcomes for patients with and without AF enrolled in the Remote Management of Heart Failure Using Implanted Electronic Devices (REM-HF) trial.Methods and Results: Rhythm status was available for 1561 patients (94.6%). Three categories were defined based on total AF duration during the first year of follow-up: (i) no AF (n = 1211, 77.6%), (ii) paroxysmal AF (≥6 min to ≤7 days; n = 92, 5.9%), and (iii) persistent/permanent AF (>7 days; n = 258, 16.5%). Clinical activity, mortality, and hospitalisation rates were compared between treatment strategies for each group. RM resulted in a greater volume of clinical activity in patients with any AF, vs. no AF, with the highest per-patient intervention required for patients with persistent/permanent AF. During 2.8 ± 0.8 years of follow-up, RM was not associated with a reduction in all-cause or cardiovascular mortality for patients with AF. However, in patients with persistent/permanent AF, RM conferred an increased risk of recurrent cardiovascular [hazard ratio (HR) 1.40, 95% confidence interval (CI) 1.06-1.85, P = 0.018] and HF-related (HR 2.05, 95% CI 1.14-3.69, P = 0.016) hospitalisations.Conclusion: In patients with HF and a cardiac implanted electronic device, RM generated greater clinical activity for patients with AF, with no associated reduction in mortality, and conversely, greater risk of cardiovascular hospitalisation amongst patients with persistent/permanent AF. RM strategies may vary in their capability to guide HF management; modified approaches may be needed to improve outcomes for HF patients with AF. [ABSTRACT FROM AUTHOR]

Key points: Cardiac electrophysiology and Ca2+ handling change rapidly during the fight‐or‐flight response to meet physiological demands.Despite dramatic differences in cardiac electrophysiology, the cardiac fight‐or‐flight response is highly conserved across species.In this study, we performed physiological sympathetic nerve stimulation (SNS) while optically mapping cardiac action potentials and intracellular Ca2+ transients in innervated mouse and rabbit hearts.Despite similar heart rate and Ca2+ handling responses between mouse and rabbit hearts, we found notable species differences in spatio‐temporal repolarization dynamics during SNS.Species‐specific computational models revealed that these electrophysiological differences allowed for enhanced Ca2+ handling (i.e. enhanced inotropy) in each species, suggesting that electrophysiological responses are fine‐tuned across species to produce optimal cardiac fight‐or‐flight responses. Sympathetic activation of the heart results in positive chronotropy and inotropy, which together rapidly increase cardiac output. The precise mechanisms that produce the electrophysiological and Ca2+ handling changes underlying chronotropic and inotropic responses have been studied in detail in isolated cardiac myocytes. However, few studies have examined the dynamic effects of physiological sympathetic nerve activation on cardiac action potentials (APs) and intracellular Ca2+ transients (CaTs) in the intact heart. Here, we performed bilateral sympathetic nerve stimulation (SNS) in fully innervated, Langendorff‐perfused rabbit and mouse hearts. Dual optical mapping with voltage‐ and Ca2+‐sensitive dyes allowed for analysis of spatio‐temporal AP and CaT dynamics. The rabbit heart responded to SNS with a monotonic increase in heart rate (HR), monotonic decreases in AP and CaT duration (APD, CaTD), and a monotonic increase in CaT amplitude. The mouse heart had similar HR and CaT responses; however, a pronounced biphasic APD response occurred, with initial prolongation (50.9 ± 5.1 ms at t = 0 s vs. 60.6 ± 4.1 ms at t = 15 s, P < 0.05) followed by shortening (46.5 ± 9.1 ms at t = 60 s, P = NS vs. t = 0). We determined the biphasic APD response in mouse was partly due to dynamic changes in HR during SNS and was exacerbated by β‐adrenergic activation. Simulations with species‐specific cardiac models revealed that transient APD prolongation in mouse allowed for greater and more rapid CaT responses, suggesting more rapid increases in contractility; conversely, the rabbit heart requires APD shortening to produce optimal inotropic responses. Thus, while the cardiac fight‐or‐flight response is highly conserved between species, the underlying mechanisms orchestrating these effects differ significantly. Key points: Cardiac electrophysiology and Ca2+ handling change rapidly during the fight‐or‐flight response to meet physiological demands.Despite dramatic differences in cardiac electrophysiology, the cardiac fight‐or‐flight response is highly conserved across species.In this study, we performed physiological sympathetic nerve stimulation (SNS) while optically mapping cardiac action potentials and intracellular Ca2+ transients in innervated mouse and rabbit hearts.Despite similar heart rate and Ca2+ handling responses between mouse and rabbit hearts, we found notable species differences in spatio‐temporal repolarization dynamics during SNS.Species‐specific computational models revealed that these electrophysiological differences allowed for enhanced Ca2+ handling (i.e. enhanced inotropy) in each species, suggesting that electrophysiological responses are fine‐tuned across species to produce optimal cardiac fight‐or‐flight responses. [ABSTRACT FROM AUTHOR]

Aims: Hypoglycaemia is associated with increased cardiovascular risk among individuals with diabetes mellitus. It has been hypothesized that hypoglycaemia may trigger autonomic changes leading to increased cardiac arrhythmia risk. We conducted a systematic review and meta‐analysis to explore this association. Materials and methods: Ovid Medline, Embase, Scopus, Web of Science and Cochrane were searched from inception to October 10, 2017. We included studies of adults with diabetes (Type 1 or Type 2) that compared acute electrocardiogram (ECG) changes during episodes of hypoglycaemia and euglycaemia. Results: Our search resulted in 4625 citations, among which 20 studies met the predefined inclusion criteria. Finally, 12 studies were included in the descriptive analysis and 15 in the meta‐analysis. Overall hypoglycaemia was associated with a reduction in heart rate variability and an increase in arrhythmia occurrence. QTc interval length was more significantly prolonged during hypoglycaemia compared to euglycaemia (pooled mean difference [95% confidence intervals] [0.64 (0.27‐1.01], P = ·001). Subgroup analysis based on diabetes type showed that QTc prolongation occurred in individuals with Type 1 and Type 2 diabetes; however, the change between euglycaemia reached statistical significance only among individuals with Type 1 diabetes. Conclusion: Our findings suggest that hypoglycaemia results in ECG alterations that are associated with increased risk of cardiac arrhythmia, which is associated with increased cardiovascular events and mortality. More clinical studies are needed to determine the cardiac risks of hypoglycaemia in individuals with diabetes, especially in Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Key points: Ageing results in changes to cardiac electrophysiology, Ca2+ handling, and β‐adrenergic responsiveness. Sympathetic neurodegeneration also occurs with age, yet detailed action potential and Ca2+ handling responses to physiological sympathetic nerve stimulation (SNS) in the aged heart have not been assessed. Optical mapping in mouse hearts with intact sympathetic innervation revealed reduced responsiveness to SNS in the aged atria (assessed by heart rate) and aged ventricles (assessed by action potentials and Ca2+ transients). Sympathetic nerve density and noradrenaline content were reduced in aged ventricles, but noradrenaline content was preserved in aged atria. These results demonstrate that reduced responsiveness to SNS in the atria may be primarily due to decreased β‐adrenergic receptor responsiveness, whereas reduced responsiveness to SNS in the ventricles may be primarily due to neurodegeneration. Abstract: The objective of this study was to determine how age‐related changes in sympathetic structure and function impact cardiac electrophysiology and intracellular Ca2+ handling. Innervated hearts from young (3‐4 months, YWT, n = 10) and aged (20‐24 months, AGED, n = 11) female mice (C57Bl6) were optically mapped using the voltage (Vm,)‐ and calcium (Ca2+)‐sensitive indicators Rh237 and Rhod2‐AM. Sympathetic nerve stimulation (SNS) was performed at the spinal cord (T1‐T3). β‐Adrenergic responsiveness was assessed with isoproterenol (1 μM, ISO). Sympathetic nerve density and noradrenaline content were also quantified. Stimulation thresholds necessary to produce a defined increase in heart rate (HR) with SNS were higher in AGED vs. YWT hearts (5.4 ± 0.4 vs. 3.8 ± 0.4 Hz, P < 0.05). Maximal HR with SNS was lower in AGED vs. YWT (20.5 ± 3.41% vs. 73.0 ± 7.63% increase, P < 0.05). β‐Adrenergic responsiveness of the atria (measured as percentage increase in HR with ISO) was decreased in AGED vs. YWT hearts (75.3 ± 22.5% vs. 148.5 ± 19.8%, P < 0.05). SNS significantly increased action potential duration (APD) in YWT but not AGED. Ca2+ transient durations and rise times were unchanged by SNS, yet AGED hearts had an increased susceptibility to Ca2+ alternans and ventricular arrhythmias. β‐Adrenergic responsiveness of all ventricular parameters were similar between AGED and YWT. Sympathetic nerve density and noradrenaline content were decreased in the AGED ventricle, but not atria, compared to YWT. These data suggest that decreased responsiveness to SNS in the aged atria may be primarily due to decreased β‐adrenergic responsiveness, whereas decreased responsiveness to SNS in the aged ventricles may be primarily due to nerve degeneration. [ABSTRACT FROM AUTHOR]

Background Silent cerebral lesions (SCLs) are a potential complication of left atrial radiofrequency ablation (RFA) procedures for paroxysmal atrial fibrillation (PAF). We aimed to compare the incidence of SCLs in patients treated with irrigated RFA multielectrode catheters (nMARQ® Catheter group) and irrigated focal RFA catheters (NAVISTAR® THERMOCOOL® Catheter; TC group) after PAF ablation from subpopulation neurological assessment (SNA) cohorts of the REVOLUTION and reMARQable studies. Methods Data from SNA cohorts in the prospective, nonrandomized REVOLUTION study (March 2011-September 2013) and the prospective, randomized, controlled reMARQable study (October 2013-November 2015) were included. The incidence of SCLs was assessed pre- and postablation using magnetic resonance imaging. Neurological deficits were assessed using the National Institutes of Health Stroke Scale, modified Rankin Scale, and Montreal Cognitive Assessment. Results A total of 37 patients from REVOLUTION and 76 patients from reMARQable were included in the SNA cohort of each study. In the REVOLUTION SNA cohort, the incidence of SCLs was 21.1% (4/19) in the nMARQ® Catheter group and 5.9% (1/17) in the TC group. Findings from REVOLUTION helped inform the reMARQable study protocol's stringent anticoagulation regimen. SCL incidence was subsequently reduced in both groups (nMARQ® Catheter, 7.9%; TC, 3.3%). No permanent neurological deficits were observed. Conclusion Adherence to a stringent anticoagulation regimen prior to and during ablation procedures appears to be an important factor in minimizing the risk of SCL. [ABSTRACT FROM AUTHOR]

To investigate the passive muscle tension of the quadriceps muscle heads in male athletes clinically diagnosed with patellar tendinopathy ( PT) with those of healthy controls and explore the interplay between passive muscle tension and patellar tendon stiffness. Between November 2012 and December 2013, 66 male athletes (mean age of 21.1 ± 4.4 years) were examined using supersonic shear wave imaging technology. The passive tension of the vastus lateralis ( VL) and rectus femoris ( RF) muscles and patellar tendon stiffness were assessed. The shear elastic modulus of the VL muscle was increased by 26.5% ( P < 0.001) in the subjects with PT when compared with the controls. Greater passive tension in the VL was associated with higher patellar tendon stiffness ( r = 0.38; P = 0.001). The vastus lateralis muscle of the quadriceps shows increase in passive muscle tension in jumping athletes with patellar tendinopathy. These findings suggest that increase in muscle tension is not similar in the individual muscles of the quadriceps muscle. Traditional stretching of the whole quadriceps muscle might not be targeted to the tight muscle heads. [ABSTRACT FROM AUTHOR]

Recent studies show sulfur redox processes in terrestrial settings are more important than previously considered, but much remains uncertain about how these processes respond to dynamic hydrologic conditions in natural field settings. We used field observations from a sulfate-impacted wetland and stream in the mining region of Minnesota (USA) to calibrate a reactive transport model and evaluate sulfur and coupled geochemical processes under contrasting hydrogeochemical scenarios. Simulations of different hydrological conditions showed that flux and chemistry differences between surface water and deeper groundwater strongly control hyporheic zone geochemical profiles. However, model results for the stream channel versus wetlands indicate sediment organic carbon content to be the more important driver of sulfate reduction rates. A complex nonlinear relationship between sulfate reduction rates and geochemical conditions is apparent from the model's higher sensitivity to sulfate concentrations in settings with higher organic content. Across all scenarios, simulated e− balance results unexpectedly showed that sulfate reduction dominates iron reduction, which is contrary to the traditional thermodynamic ladder but corroborates recent experimental findings by Hansel et al. (2015) that 'cryptic' sulfur cycling could drive sulfate reduction in preference over iron reduction. Following the thermodynamic ladder, our models shows that high surface water sulfate slows methanogenesis in shallow sediments, but field observations suggest that sulfate reduction may not entirely suppress methane. Overall, our results show that sulfate reduction may serve as a major component making up and influencing terrestrial redox processes, with dynamic hyporheic fluxes controlling sulfate concentrations and reaction rates, especially in high organic content settings. [ABSTRACT FROM AUTHOR]

The role of mastication is to prepare a bolus for safe swallowing. The Swallow Safe model defines deformability, slippiness, and cohesiveness as key properties that influence whether a bolus is safe to swallow. Defining these properties numerically is difficult and current instruments used for bolus analysis have limitations. The slip extrusion test (SET) was developed to objectively measure the swallowability of the bolus through determination of its resistance to deformation and slip. The test measures the force needed to extrude a bolus through a bag as it is pulled through a pair of rollers, imitating the swallowing action of a bolus. Three food model systems were used to evaluate the SET: (a) viscous solutions with varying viscosity, (b) gels with varying hardness, and (c) particulate systems of varying cohesion. The test was applied to peanut boluses produced in vivo to demonstrate its potential in characterizing boluses. The deformation and slip resistance measurements correlated well with the hardness and viscosity measurements of the gels and viscous solutions respectively (correlation coefficient r = .94 between deformation resistance and hardness; r = .85 for slip resistance and hardness in gels; r = .98 for deformation resistance and viscosity; r = .93 for slip resistance and viscosity in solutions). The advantage of the SET is it can evaluate the swallowability of a wide range of foods of different structure and composition. It could potentially be used to investigate the properties of boluses throughout oral processing and help in establishing the criteria for a safe to swallow bolus in a quantitative way. Practical applications The test could be used to measure bolus properties from the initial stages of breakdown to the point of swallow for all types of food. The ability to measure the changes in bolus properties through all stages of breakdown using the same instrument is a significant development. The resistance to deformation and slip are quantitative measurements that could potentially be used to further develop the Swallow Safe model by providing numerical limits to the identified properties. This could be of interest to the development of foods for dysphagia sufferers. [ABSTRACT FROM AUTHOR]

AlGaN/GaN high electron mobility transistors (HEMTs) on Si were fabricated and studied using sputtered TiN Schottky gate. The sputtered TiN on AlGaN/GaN HEMTs exhibit an improved Schottky barrier height (SBH) of ∼1.1 eV, which is larger than the Schottky contacts formed by the other reported TiN-based stacks and by most of Ni/Au-free materials. The improvement of SBH is due to the increase of metal work function either by the incorporation of oxygen in sputtered TiN or by using a high N2/Ar ratio during the sputtering process. Although the HEMTs with TiN gate show comparable DC output and transfer characteristics compared to devices with Ni/Au gate, they exhibit enhanced OFF-state breakdown voltages (BVgd) of ∼48-58 V. This is consistent with the observation of an order of magnitude lower reverse gate leakage current and is also well agreed by the enhanced SBH of the sputtered TiN as compared to the Ni/Au gate. With reference to the HEMTs with Ni/Au gate, a slight increase of dynamic/static on-resistances ( Rds[ON]) ratio (∼8%) was observed in the sputtered TiN gate HEMTs. [ABSTRACT FROM AUTHOR]

Background: Irregular broad complex tachycardia (BCT) may be due to atrial fibrillation (AF) occurring in the presence of ventricular pre-excitation (pre-excited AF) or bundle branch block (BBB-AF). While irregularity is a defining characteristic of AF, it is a common subjective impression that greater variability in manifestation exists for pre-excited AF than BBB-AF. This difference can potentially be exploited for distinguishing the two conditions if some means can be found to quantify it.Methods: For each of 75 ECGs showing irregular BCT (41 pre-excited AF and 34 BBB-AF), a random sample of 10 distinct QRS complexes were selected for quantitative measurement of variability in manifestation, which included the standard deviation (SD) of the width, the SD of the axis, and the coefficient of variation (CV) of the amplitude of the QRS complex.Results: Pre-excited AF showed statistically significantly greater values than BBB-AF with respect to these measures, and receiver-operating characteristic curves showed that these differences could be useful for their discrimination. For the SD of QRS width, a cut-off value of 8 ms appeared optimal (sensitivity 1.00 and specificity 0.79). For the SD of QRS axis, a cut-off value of 2.5 degrees appeared optimal (sensitivity 0.84 and specificity 0.56). For the CV of QRS amplitude, a cut-off value of 0.10 appeared optimal (sensitivity 0.82 and specificity 0.76).Conclusions: Pre-excited AF demonstrated greater variability than BBB-AF in manifestation. The measures of variability developed can potentially be useful for diagnosing irregular BCT in practice, especially in the context of automated computer-aided diagnosis. [ABSTRACT FROM AUTHOR]

Aside from antimalarials, there is currently no treatment for cerebral malaria, a fulminant neurological complication of P. falciparum infection that is a leading cause of death in African children. In the mouse model of cerebral malaria, cross-presentation of parasite antigens by brain endothelial cells is thought to be a crucial late step in pathogenesis. We have investigated three proteasome inhibitors as potential adjunct therapies: bortezomib, carfilzomib and ONX-0914. Only carfilzomib, an irreversible inhibitor of both constitutive proteasomes and immunoproteasomes, was able to inhibit cross-presentation of malaria antigen by murine brain endothelial cells in vitro. To mimic the clinical setting, carfilzomib was co-administered with artesunate only when infected mice exhibited neurological defects. However, there was no improvement in survival compared to artesunate monotherapy. The treatment failure was explained by the inability of daily or twice daily bolus doses of carfilzomib to inhibit cross-presentation by brain endothelial cells in vivo. We also report here that bortezomib, which has been associated with neurological adverse events, accelerated death in ECM-infected mice. Future investigations of proteasome inhibitors for modulating cross-presentation during malaria infection should focus on sustained and targeted delivery to brain endothelial cells. [ABSTRACT FROM AUTHOR]

nMARQ AF Ablation Background nMARQ is a multipolar catheter designed to simultaneously ablate at multiple sites around the pulmonary vein (PV) circumference with a single radiofrequency application. We sought to define the safety and efficacy of atrial fibrillation (AF) ablation with the nMARQ catheter. Methods In a multicenter study, patients with drug-refractory AF were included. Procedural outcomes were documented at 1 year. Results 374 patients underwent PV isolation using nMARQ (age 60 ± 10 years, 264 male), of whom 263 patients had paroxysmal AF (PAF), while 111 patients had persistent AF. A total of 1,468 of 1,474 veins (99.6%) were isolated with the nMARQ catheter alone. Thirty-five (13%) PAF patients and 30 (27%) persistent AF patients underwent additional ablation at non-PV sites (2.4 ± 1.4 non-PV sites). Procedure time for PV isolation only was 1.9 ± 0.7 hours (fluoroscopy 24 ± 14 minutes). Procedure time for PV isolation and non-PV ablation was 2.4 ± 1.0 hours (fluoroscopy 30 ± 23 minutes). Major adverse events occurred in two patients (0.5%); one esophago-pericardial fistula and a second, mortality due to sepsis of unknown cause. One-year follow-up data were available in 65 (25%) PAF and 20 (18%) persistent AF patients. Forty-two (65%) PAF and 13 (65%) persistent AF patients were free of arrhythmia at 1 year. In patients undergoing repeat procedures (n = 17) the most frequent points of PV reconnection were: anterior RSPV, inferior RIPV, and superior LSPV. Conclusions AF ablation with nMARQ is associated with short procedure times and high acute success rates. Further research is necessary to more clearly define long-term outcome. [ABSTRACT FROM AUTHOR]

Aims We wish to assess the clinical and cost-effectiveness of remote monitoring of heart failure patients with cardiac implanted electronic devices. Methods REM-HF is a multicentre, randomized, non-blinded, parallel trial designed to compare weekly remote monitoring-driven management with usual care for patients with cardiac implanted electronic devices ( ICD, CRT-D, or CRT-P). The trial is event driven, and the final analysis will be performed when 546 events have been observed or the study is terminated at the interim analysis. We have randomized 1650 patients to be followed up for a minimum of 2 years. Patients will remain in the trial up to study termination. The first patient was randomized in September 2011 and the study is expected to complete in early 2016. The primary combined endpoint is time to first event of all-cause death or unplanned hospitalization for cardiovascular reasons. An economic evaluation will be performed, estimating the cost per quality-adjusted lifeyear, with direct costs estimated from the National Health Service perspective and quality of life assessed by the EQ-5D, Short-Form12, and Kansas City Cardiomyopathy Questionnaires. The study design has been informed by a feasibility study. Conclusion REM-HF is a multicentre randomized study that will provide important data on the effect of remote monitoring-driven management of implanted cardiac devices on morbidity and mortality, as well as the cost-effectiveness of this approach. Trial registration: UKCRN 10383. [ABSTRACT FROM AUTHOR]

Frequency Trajectory of Atrial Fibrillation Introduction The role of substrates in the maintenance of persistent atrial fibrillation (persAF) remains poorly understood. The use of dominant frequency (DF) mapping to guide catheter ablation has been proposed as a potential strategy, but the characteristics of high DF sites have not been extensively studied. This study aimed to assess the DF spatiotemporal stability using high density noncontact mapping (NCM) in persAF. Methods and Results Eight persAF patients were studied using NCM during AF. Ventricular far-field cancellation was performed followed by the calculation of DF using Fast Fourier Transform. Analysis of DF stability and spatiotemporal behavior were investigated including characteristics of the highest DF areas (HDFAs). A total of 16,384 virtual electrograms (VEGMs) and 232 sequential high density 3-dimensional DF maps were analyzed. The percentage of DF stable points decreased rapidly over time. Repetition or reappearance of DF values were noted in some instances, occurring within 10 seconds in most cases. Tracking the HDFAs' center of gravity revealed 3 types of propagation behavior, namely (i) local, (ii) cyclical, and (iii) chaotic activity, with the former 2 patterns accounting for most of the observed events. Conclusions DF of individual VEGMs was temporally unstable, although reappearance of DF values occurred at times. Hence, targeting sites of 'peak DF' from a single time frame is unlikely to be a reliable ablation strategy. There appears to be a predominance of local and cyclical activity of HDFAs hinting a potentially nonrandom temporally periodic behavior that provides further mechanistic insights into the maintenance of persAF. [ABSTRACT FROM AUTHOR]

New findings What is the topic of this review? This article addresses the relationship between vagus nerve activity and malignant ventricular arrhythmias. It focuses on the clinical association of an impaired vagal tone in cardiac disease states with high mortality from sudden cardiac death and the potential underlying mechanisms., What advances does it highlight? The article summarizes the mounting evidence that vagal innervation in the cardiac ventricle plays a key direct role in the prevention of the initiation of ventricular fibrillation. Data are presented on the role that nitric oxide plays in mediating the effects of vagal protection against ventricular fibrillation, supporting the notion that a separate non-muscarinic, nitrergic population of vagal neurons is responsible for this protection., Sudden cardiac death remains a significant unresolved clinical problem, with many of the deaths being due to malignant ventricular arrhythmias. Markers of abnormal autonomic function have been shown to be strong prognostic predictors, highlighting the important relationship between reduced vagal tone and malignant ventricular arrhythmias, such as ventricular fibrillation, in cardiac patients. Exploring the mechanisms underlying the autonomic modulation of ventricular fibrillation, my group has shown that vagus nerve stimulation protects against ventricular fibrillation in the innervated isolated heart preparation. We have provided direct evidence that nitric oxide is released in the ventricle with cervical vagus nerve stimulation and NO mediates the antifibrillatory actions of vagus nerve stimulation in the ventricle. Classical physiology teaches that vagal postganglionic nerves modulate the heart via acetylcholine acting at muscarinic receptors and, dogmatically, that there is little vagal effect in the ventricle, as innervation was believed to be sparse. Mounting evidence from many species now supports the presence of a rich vagal innervation in the ventricle. Data from my group showing that the protective actions of vagus nerve stimulation against ventricular fibrillation and NO release are preserved in the presence of muscarinic block support the notion that a population of nitrergic neurons could be responsible. This potentially exploitable downstream pathway together with the availability of vagus nerve stimulators make it an exciting time to investigate the development of an effective strategy of vagal protection against ventricular fibrillation in the clinical setting. [ABSTRACT FROM AUTHOR]

We have studied the drain current dispersion characteristics of conventional AlGaN/GaN HEMTs and SiN/Al2O3/AlGaN/GaN metal-insulator-semiconductor high electron mobility transistors (MISHEMT) fabricated on silicon substrate. The fabricated MISHEMT exhibited an IDmaxof >1000 mA/mm and gmmax of 241 mS/mm. Compared to conventional AlGaN/GaN HEMTs, about an order of magnitude lower gate leakage current and a ∼ 60% reduction in drain current ( ID) collapse was observed in the MISHEMTs. The observation of low ID collapse is due to the occurrence of low interface state density (6.39 × 1010 eV-1 cm-2) between the bilayer dielectric (SiN/Al2O3) and GaN surface which is confirmed through the AC-conductance method. (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

The Impact of Power Output During Percutaneous Catheter Radiofrequency Ablation Introduction Percutaneous catheter radiofrequency ablation (RFA) has been widely used to treat patients with atrial fibrillation (AF). Success rates are, however, variable and optimal levels of power used and duration of power delivery have not been fully established. Different ablation centers continue to use various power protocols. We undertook a comprehensive systematic review to evaluate the impact of power output during RFA for AF on efficacy and safety. Methods and results We systematically searched MEDLINE and Cochrane Central Register of Controlled Trials databases for studies on power output during percutaneous RFA for AF. The marked heterogeneous nature of the studies prohibited a meta-analysis. The main findings were (1) power output of ≤30 watts (W) has good safety profiles but low efficacy rates; (2) power output of >30 W-<45 W is safe with good efficacy; (3) power output of ≥ 45 W has a better efficacy profile but associated with a high risk of complications; (4) delivery of higher power of ≥ 45 W at shorter duration (15-20 seconds) is safe and efficacious; and (5) energy titration with visualization of microbubbles by intracardiac echocardiography (ICE) has better efficacy and safety profiles compared to RFA without ICE. Conclusions Despite the overall reduced quality data relating power to outcomes of RFA for AF, the optimal power output showing good efficacy and safety profiles appears generically to be >30 W-<45 W, with significant variation in the literature. [ABSTRACT FROM AUTHOR]

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Despite advances in our understanding of the pathology of heart failure modern conventional pharmacological therapies have proved insufficient. The application of electrical impulses during the refractory period of the cardiac contractile cycle, so-called cardiac contractility modulation (CCM), presents a new therapeutic approach with promising results demonstrated in clinical trials to date. The mechanism by which CCM exerts its effects remains inconclusive with conflicting reports. This article provides a concise review of the experimental and clinical CCM studies conducted to date with particular focus on areas of controversy and unexplored avenues of interest with this novel electrical therapy. [ABSTRACT FROM AUTHOR]

The effects of direct autonomic nerve stimulation on the heart may be quite different to those of perfusion with pharmacological neuromodulating agents. This study was designed to investigate the effect of autonomic nerve stimulation on intracellular calcium fluorescence using fura-2 AM in the isolated Langendorff-perfused rabbit heart preparation with intact dual autonomic innervation. The effects of autonomic nerve stimulation on cardiac force and calcium transients were more obvious during intrinsic sinus rhythm. High-frequency (15 Hz, n= 5) right vagus nerve stimulation (VS) decreased heart rate from 142.7 ± 2.6 to 75.5 ± 10.2 beats min–1 and left ventricular pressure from 36.4 ± 3.2 to 25.9 ± 1.9 mmHg, whilst simultaneously decreasing the diastolic and systolic level of the calcium transient. Direct sympathetic nerve stimulation (7 Hz, n= 8) increased heart rate (from 144.7 ± 10.5 to 213.2 ± 4.9 beats min–1) and left ventricular pressure (from 37.5 ± 3.6 to 43.7 ± 2.8 mmHg), whilst simultaneously increasing the diastolic and systolic level of the calcium transient. During constant ventricular pacing, the high-frequency right vagus nerve stimulation did not have any direct effect on ventricular force or the calcium transient ( n= 8), but was effective in reducing the effect of direct sympathetic nerve stimulation. [ABSTRACT FROM AUTHOR]

Information regarding vagal innervation in the cardiac ventricle is limited and the direct effect of vagal stimulation on ventricular myocardial function is controversial. We have recently provided indirect evidence that the anti-fibrillatory effect of vagus nerve stimulation on the ventricle is mediated by nitric oxide (NO). The aim of this study was to provide direct evidence for the release of nitric oxide in the cardiac ventricle during stimulation of the efferent parasympathetic fibres of the cervical vagus nerve. The isolated innervated rabbit heart was employed with the use of the NO fluorescent indicator 4,5-diaminofluorescein diacetate (DAF-2 DA) during stimulation of the cervical vagus nerves and acetylcholine perfusion in the absence and presence of the non-specific NO synthase inhibitor NG-nito-l-arginine (l-NNA) and the neuronal NO synthase selective inhibitor 1-(2-trifluormethylphenyl)imidazole (TRIM). Using the novel fluorescence method in the beating heart, we have shown that NO-dependent fluorescence is increased by 0.92 ± 0.26, 1.20 ± 0.30 and 1.91 ± 0.27% (during low, medium and high frequency, respectively) in the ventricle in a stimulation frequency-dependent manner during vagus nerve stimulation, with comparable increases seen during separate stimulation of the left and right cervical vagus nerves. Background fluorescence is reduced during perfusion withl-NNA and the increase in fluorescence during high frequency vagal stimulation is inhibited during perfusion with bothl-NNA (1.97 ± 0.35% increase beforel-NNA, 0.00 ± 0.02% duringl-NNA) and TRIM (1.78 ± 0.18% increase before TRIM, −0.11 ± 0.08% during TRIM). Perfusion with 0.1 μm acetylcholine increased NO fluorescence by 0.76 ± 0.09% which was blocked byl-NNA (change of 0.00 ± 0.03%) but not TRIM (increase of 0.82 ± 0.21%). Activation of cardiac parasympathetic efferent nerve fibres by stimulation of the cervical vagus is associated with NO production and release in the ventricle of the rabbit, via the neuronal isoform of nitric oxide synthase. [ABSTRACT FROM AUTHOR]

We have previously shown that direct vagus nerve stimulation (VNS) reduces the slope of action potential duration (APD) restitution while simultaneously protecting the heart against induction of ventricular fibrillation (VF) in the absence of any sympathetic activity or tone. In the current study we have examined the role of nitric oxide (NO) in the effect of VNS. Monophasic action potentials were recorded from a left ventricular epicardial site on innervated, isolated rabbit hearts ( n= 7). Standard restitution, effective refractory period (ERP) and VF threshold (VFT) were measured at baseline and during VNS in the presence of the NO synthase inhibitor NG-nitro-l-arginine (l-NA, 200 μm) and during reversing NO blockade withl-arginine (l-Arg, 1 mm). Data represent the mean ±s.e.m. The restitution curve was shifted upwards and became less steep with VNS when compared to baseline.l-NA blocked the effect of VNS whereasl-Arg restored the effect of VNS. The maximum slope of restitution was reduced from 1.17 ± 0.14 to 0.60 ± 0.09 (50 ± 5%, P < 0.0001) during control, from 0.98 ± 0.14 to 0.93 ± 0.12 (2 ± 10%, P= NS) in the presence ofl-NA and from 1.16 ± 0.17 to 0.50 ± 0.10 (41 ± 9%, P= 0.003) withl-Arg plusl-NA. ERP was increased by VNS in control from 119 ± 6 ms to 130 ± 6 ms (10 ± 5%, P= 0.045) and this increase was not affected byl-NA (120 ± 4 to 133 ± 4 ms, 11 ± 3%, P= 0.0019) orl-Arg withl-NA (114 ± 4 to 123 ± 4 ms, 8 ± 2%, P= 0.006). VFT was increased from 3.0 ± 0.3 to 5.8 ± 0.5 mA (98 ± 12%, P= 0.0017) in control, 3.4 ± 0.4 to 3.8 ± 0.5 mA (13 ± 12%, P= 0.6) during perfusion withl-NA and 2.5 ± 0.4 to 6.0 ± 0.7 mA (175 ± 50%, P= 0.0017) during perfusion withl-Arg plusl-NA. Direct VNS increased VFT and flattened the slope of APD restitution curve in this isolated rabbit heart preparation with intact autonomic nerves. These effects were blocked usingl-NA and reversed by replenishing the substrate for NO production withl-Arg. This is the first study to demonstrate that NO plays an important role in the anti-fibrillatory effect of VNS on the rabbit ventricle, possibly via effects on APD restitution. [ABSTRACT FROM AUTHOR]

Gain of chromosome 5p is seen in over 50% of advanced cervical squamous cell carcinomas (SCCs), although the genes responsible for the selective advantage provided by this abnormality are poorly understood. In the W12 cervical carcinogenesis model, we observed that 5p gain was rapidly selected over ∼15 population doublings and was associated with the acquisition of a growth advantage and invasiveness. The most significantly upregulated transcript following 5p gain was the microRNA (miRNA) processor Drosha. In clinically progressed cervical SCC, Drosha copy-number gain was seen in 21/36 clinical samples and 8/10 cell lines and there was a significant association between Drosha transcript levels and copy-number gain. Other genes in the miRNA processing pathway, DGCR8, XPO5 and Dicer, showed infrequent copy-number gain and over-expression. Drosha copy-number and expression were not elevated in pre-malignant cervical squamous intraepithelial lesions. Importantly, global miRNA profiling showed that Drosha over-expression in cervical SCC appears to be of functional significance. Unsupervised principal component analysis of a mixed panel of cervical SCC cell lines and clinical specimens showed clear separation according to Drosha over-expression. miRNAs most significantly associated with Drosha over-expression are implicated in carcinogenesis in other tissues, suggesting that they regulate fundamental processes in neoplastic progression. Our evidence suggests that copy-number driven over-expression of Drosha and consequent changes in miRNAs are likely to be important contributors to the selective advantage provided by 5p gain in cervical neoplastic progression. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

For many oncogenes, increased expression resulting from copy number gain confers a selective advantage to cells that consequently make up the tumour bulk. To identify oncogenes of potential biological significance in cervical squamous cell carcinoma (SCC), 36 primary samples and ten cell lines were screened by array comparative genomic hybridization (CGH). The most commonly occurring regions of copy number gain that also showed amplification were 5p15.2-14.3 (59%), 5p13.3 (65%), and 5p13.2-13.1 (63%). Gene copy numbers were significantly associated with expression levels for three candidate oncogenes at these loci: OSMR (oncostatin M receptor) ( p = 0.03), PDZK3 (PDZ domain containing protein 3) ( p = 0.04), and TRIO (triple functional domain) ( p = 0.03). Further examination by fluorescence in situ hybridization on a tissue microarray of 110 primary cervical SCC samples revealed copy number gain frequencies of 60.9%, 57.3%, and 54.5% for OSMR, PDZK3, and TRIO, respectively, with OSMR adversely influencing overall patient survival independently of tumour stage ( p = 0.046). By array CGH, copy number gain of OSMR was not seen in any of 40 microdissected precursor cervical squamous intraepithelial lesions (SILs). Moreover, global mRNA expression analysis, using Affymetrix U133A 2.0 Arrays, showed no overexpression of OSMR in SILs, suggesting that OSMR gain and overexpression are relatively late steps in cervical carcinogenesis. In the cervical SCC cell lines CaSki and SW756, exogenous OSM activated downstream-signalling elements of OSMR including STAT3, p44/42 MAPK, and S6 ribosomal protein, and induced transcription of the angiogenic factor VEGF, effects that were reduced by OSMR depletion using RNA interference. We conclude that copy number gain of OSMR is frequently found in cervical SCC and is associated with adverse clinical outcome. As well as being a potential prognostic marker, OSMR is a candidate cell surface therapeutic target. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The interaction between the effects of vagus nerve stimulation (VS) and sympathetic stimulation (SS) on intrinsic heart rate was studied in the novel innervated isolated rabbit heart preparation. The effects of background VS, at different frequencies - 2 Hz (low), 5 Hz (medium), 7 Hz (high) -- on the chronotropic effects of different frequencíes of SS - 2 Hz (low), 5 Hz (medium), 10 Hz (high) -- were studied. The experiments were repeated in the reverse direction studying the effects of different levels of background SS on the chronotropic effects of different levels of VS. Background VS reduced the overall positive chronotropic effect of SS at steady state in a frequency dependent manner and the rate of increase in heart rate during low and medium SS (but not high SS) was slowed in the presence of background VS. These results suggest that pre- and postjunctional mechanisms may be involved in the sympatho-vagal interaction on heart rate. On the other hand, the chronotropic effect of VS was enhanced in the presence of background SS. Vagal stimulation appears to play a dominant role over sympathetic stimulation in chronotropic effects on the isolated heart. The innervated isolated heart preparation is a valuable model to study the complex mechanisms underlying the interaction between sympathetic and parasympathetic stimulation on cardiac function. [ABSTRACT FROM AUTHOR]

The reliable and accurate diagnosis of regular broad complex tachycardia (BCT) by the ECG is a goal that has eluded clinicians and electrophysiologists alike for years. This article explores the reason for this by first giving an historical account on the development of the subject. Next, the electrophysiological mechanisms of ventricular tachycardia, supraventricular tachycardia with aberrant conduction, and preexcited tachycardia, the three main differential diagnoses for regular BCT, according to the latest knowledge from cellular and clinical electrophysiology study will be reviewed, together with considerations on how such understanding may help account for the manifestations of these tachycardias on the ECC and the difficulty in distinguishing between them. Finally, the use of electrophysiological study as the criterion standard for diagnosing regular BCT, as has been the case in most studies on the subject, will be critiqued in terms of the potential for misdiagnosis by the method and the use of any ECC diagnostic algorithms developed with its aid in the acute medical care setting. [ABSTRACT FROM AUTHOR]

The authors previously proposed a Bayesian approach to the electrocardiographic diagnosis of regular broad complex tachycardia (BCT), which can be due to VT or supraventricular tachycardia with aberrant conduction (SVTAC). They also published an account comparing the theoretical merits in the design of two of the most commonly used diagnostic algorithms for the same purpose, those of Brugada et al. and Griffith et al. In this study, a direct head-to-head comparison was performed on the practical performances of the three algorithms in this study. A set of 111 ECGs showing regular BGT (77 VT, 34 SVTAG) whose diagnoses were confirmed by electrophysiological study was shown to five internists in general medicine at a district general hospital. The observers were asked to comment on whether the EGG criteria in the three algorithms tested were fulfilled or not, and a computer program then derived the corresponding diagnoses. The sensitivity and specificity for VT achieved by the Brugada algorithm were 92% and 44%, 92% and 44% by the Griffith algorithm, and 97% and 56% by the Bayesian algorithm. The Bayesian algorithm achieved a higher sensitivity and specificity than the other two algorithms, but the differences are not statistically significant (P = 0.6583 and P = 0.5334, respectively). The Brugada, Griffith, and Bayesian algorithms show comparable performances in terms of overall sensitivity and specificity when tested in practice. Of the three algorithms, the Griffith algorithm excels in simplicity and is the easiest to implement in practice. The Bayesian algorithm achieved slightly higher values for sensitivity and specificity than the Brugada and Griffith algorithms but may be more suitable for automated computer-aided diagnosis of EGG due to its complexity. [ABSTRACT FROM AUTHOR]

This article reviews the data related to psychosocial adjustment of young ICD recipients, postulates theories to explain potential adjustment difficulties to ICD therapy experienced by younger recipients, and suggests clinical management techniques for addressing the unique psychosocial concerns of young ICD recipients. Studies of young ICD recipients suggest that a wide range of psychosocial adjustment issues are prominent in the post-ICD implantation period and that the issues may be different from older ICD recipients. The disability-stress-coping model and the transactional-stress-coping model are postulated as explanations for the unique adjustment concerns of children and adolescents with ICDs. Social comparison theory is also applied to the concerns of young adults with ICDs such that they often lack same age peers to compare experiences with cardiac difficulties. Brief, clinic-based interventions by health care providers, like a screening and referral heuristic and an "ICD Buddy" system, are suggested to increase effective coping and decrease social isolation for young ICD recipients. [ABSTRACT FROM AUTHOR]

AF may appear as an irregular broad complex tachycardia (BCT) If atrioventricular conduction occurs via an accessory pathway (preexcited AF) or if bundle branch block (BBB). preexistent or rate related. exists in the His-Purkinje system (BBB-AF). While BBB-AF is relatively benign, preexcited AF may herald sudden cardiac death. Hence it is important that the two conditions can be reliably distinguished. Yet. there is no preexistent algorithms for this purpose. Griffith et ah previously proposed a simple algorithm for a similar problem, that of distinguishing the two differential diagnoses for regular BCT: VT and SVT with BBB, on the basis that unless the QBS morphologies in V1 and V6 are absolutely typical of BBB, VT will be diagnosed. The authors propose an extrapolation of this principle to irregular BCT by stating that, unless the QRS morphologies in V1 and V6 are absolutely typical of BBB. preexcited AF will be diagnosed. Seventy-five ECGs showing irregular BCT (41 preexcited AF and 34 BBB-AF) were shown to two fellows in electrophvsiology who were given no other information and were instructed to diagnose preexcited AF unless the QRS morphology pattern was typical of BBB. Observer 1 achieved a sensitivity of 100% (41⁄41) and a specificity of 79% (27⁄34), while observer 2 achieved a sensitivity of 100% and a specificity of 85% (29⁄34). By QRS morphology pattern, an average sensitivity of 100% and specificity of 82% were achieved for the diagnosis of irregular RCT. The algorithm is simple and easy to implement and recommended for clinical use. [ABSTRACT FROM AUTHOR]

Despite numerous attempts at devising algorithms for diagnosing broad complex tachycardia (BCT) on the basis of the electrocardiogram (ECG), misdiagnosis is still common. The reason for this may lie with difficulty in implementing existent algorithms in practice, due to imperfect ascertainment of ECG features within them. An attempt was made to approach the problem afresh with the Bayesian inference by the construction of a diagnostic algorithm centered around the likelihood ratio (LR). Previously studied EGG features most effective in discriminating ventricular tachycardia (VT) from supraventricular tachycardia with aberrant conduction (SVTAC), according to their LR values, were selected for inclusion into a Bayesian diagnostic algorithm. A test set of 244 BCT ECGs was assembled and shown to three independent observers who were blinded to the diagnoses made at electrophysiological study. Their diagnostic accuracy by the Bayesian algorithm was compared against that by clinical judgement with the diagnoses from EPS as the criteria! standard. Clinical judgement correctly diagnosed 35% of SVTAC, 85% of VT, and 47% of fascicular tachycardia. In comparison, by the Bayesian algorithm devised, 52% of SVTAC, 95% of VT, and 97% of fascicular tachycardia were correctly diagnosed. The Bayesian algorithm devised has proved to be superior to the clinical judgement of the observers who participated in this study, and theoretically will obviate the problem of imperfect ascertainment of ECC features. Hence, it holds the promise for being an effective tool for routine use in clinical practice. [ABSTRACT FROM AUTHOR]

Temperature-Sensitive Focal Atrial Tachycardia. Temperature sensitivity has not been reported in focal atrial tachycardia. We describe a patient with a left atrial tachycardia whose tachycardia rate was affected by hot and cold drinks. The effects were still evident after autonomic blockade. The arrhythmia focus was located at the entrance of the left upper pulmonary vein. Radiofrequency ablation was carried out, which proved to be difficult, but it was successful after several applications of energy, suggesting an epicardial location of the arrhythmia focus. Sensitivity of atrial tachycardia rate to the temperature of food or drink ingested suggests a left atrial focus with a posterior and possibly epicardial location. [ABSTRACT FROM AUTHOR]

This paper describes eight new alleles (B∗0807, B∗0809, B∗1551, B∗3529, B∗3532, B∗4025, B∗5304 and B∗5508) that have been found by routine HLA-B genotyping with sequence-specific oligonucleotides (SSOs). All of the new alleles have variations which cause changes in residues that occur within antigen binding pockets and T-cell recognition sites of the antigen. The new polymorphisms within these new alleles may affect the nature and specificity of peptide binding and cause differential T-cell activation, which may have an affect in transplantation. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 68-year-old woman who was referred for first-time ablation of symptomatic paroxysmal atrial fibrillation (AF).Topics discussed include selection of a single catheter approach to mapping and ablation, disclosure of a left-sided superior vena cava (LSVC) draining into a markedly dilated coronary sinus (CS) and deployment of nMARQ Catheter System in the LSVC for targeting markedly fractionated signals in bipolar and unipolar energy delivery configurations.

The objective of this article is to propose a highly effective computer-based teaching methods in an image-processing course. The image-processing course is heavily mathematically oriented. With the multimedia technology, it is easy to implement an innovative teaching methods using computer to attract student attention in the image-processing course. However, such technology has not lived up to the potential of effective teaching and learning. To teach the students on how to derive a mathematics expression by using a computer is not effective as using chalk and a blackboard. Students tend to forget the process of the mathematics derivations, and hence, it is not easy to remember mathematics formulas. Therefore, to make multimedia technology useful for teaching and learning, one needs to incorporate vast amounts of artificial intelligence techniques into computer software. © 1997 John Wiley & Sons, Inc. Comput Appl Eng Educ 5: 111–114, 1997 [ABSTRACT FROM AUTHOR]

With the ambient temperature well regulated (22.8 ± 0.2°C, mean ± 95 % confidence limits), the gingival sulcus temperatures of 21 human subjects were measured, and gingival plaque indices recorded. All subjects had clinically healthy gingiva. The sulcus temperatures of the mandibular teeth were found to be higher than those of the maxillary teeth by 0.7 ± 0.2°C. In both arches, the sulcus temperatures of the molars exceeded those of the incisors by 1.5 ± 0.3°C, this difference being statistically significant. The mean gingival sulcus temperature averaged over the entire dentition was found to be 33.9 ± 0.4°C. Attempts to show a correlation between gingival inflammation and sulcus temperature, although unsuccessful, suggested that such a correlation might be demonstrated through the use of more sophisticated instrumentation. The profile of normal gingival sulcus temperatures established herein shows a marked agreement with published data concerning the distribution of the blood supply to the periodontal ligaments of individual human teeth. It could serve as a reference for studies of heat transfer in dental and periodontal tissues as well as providing a clinical norm for use in the assessment of periodontal inflammation. [ABSTRACT FROM AUTHOR]

A review is presented of "Increasing T-type calcium channel activity by β-adrenergic stimulation contributes to β-adrenergic regulation of heart rates" by Y. Li et. al., which explores the role of T-type calcium channels in heart rate modulation through adrenergic activation with isoproterenol.

ABSTRACT Background Methods Results Conclusion Pulmonary vein isolation (PVI) has been established as an effective management option for symptomatic paroxysmal atrial fibrillation (PAF). We aimed to explore the role of P‐wave parameters in a 12‐lead electrocardiogram (ECG) in predicting the success of repeat PAF ablation.We enrolled consecutive patients who underwent a second AF ablation procedure for PAF in a UK tertiary center after an index ablation conducted between 2018 and 2019 and a repeat ablation up to 2021. A digital 12‐lead ECG was recorded with a 1–50‐Hz bandpass filter applied. P‐wave duration (PWD), P‐wave voltage (PWV), P‐wave dispersion (PWDisp), and P‐wave terminal force in V1 (PTFV1) were measured before and after the procedure. Changes were correlated with the 12‐month clinical outcome. Procedural success was freedom from ECG‐documented AF up to 12 months following ablation.Study criteria were satisfied by 72 patients, of which 43 (60%) had successful repeat PVI at 12 months. The mean age is 65, and 47 (65%) were males. The demographics were comparable between both study arms. PWD decreased after successful repeat ablations (136.7 to 124.6 ms, p = 0.01) and failed repeat ablations (135.4 to 125.3 ms, p = 0.009) without a significant change between both arms. PMV and PWDisp did not change significantly after both study arms. PTFV1 significantly decreased after successful repeat ablations (‐3.1 to ‐4.4 mm.s, p = 0.005) without a significant change after failed ablations (‐2.9 to ‐2.7 mm.s, p = 0.42). Changes were statistically significant between both arms (p = 0.004).PTFV1 reduction following the second AF ablation was correlated with successful repeat AF ablation at 12 months. [ABSTRACT FROM AUTHOR]

The article describes the case of a 41-year-old primigravid woman with placenta accreta in the upper uterine segment following myomectomy. Topics covered include the results of her ultrasound examination, the risk factors for invasive placentation and the retrospective review of antenatal ultrasound imaging.

Cardiac resynchronization therapy (CRT) has become an accepted treatment for selected patients with drug-resistant heart failure. Data for patients in atrial fibrillation (AF) remains limited but suggests benefit in these patients too. We report the case of an 82-year-old patient with heart failure, VVIR permanent pacemaker, and permanent AF who had an upgrade to triple-site CRT implantation with good clinical response. Triple-site ventricular pacing may enhance the chance of response and LV reverse remodeling and should be considered in AF patients undergoing CRT implantation. [ABSTRACT FROM AUTHOR]