Approach to Cochlear Implantation in Patients With Ventriculoperitoneal Shunts.

OBJECTIVE: To evaluate the safety and outcomes of cochlear implantation (CI) in patients with ventriculoperitoneal (VP) shunts to inform clinical practice. STUDY DESIGN: Historical cohort study. SETTING: Tertiary referral centers. METHODS: A multi-institutional historical cohort of patients with VP shunts and CI was identified and analyzed. RESULTS: A total of 46 patients (median age 8 years [interquratile range, IQR: 2-46]) with VP shunts and CI were identified. Of these, 41 (89%) patients had a VP shunt prior to CI. Based on institutional preference and individual patient factors, CI was performed contralateral to a pre-existing VP shunt in 24 of these 41 cases (59%) and ipsilateral in 17 (41%). Furthermore, pre-CI relocation of the VP shunt was performed in 3 cases (7%), and 2 patients (5%) underwent planned revision of their VP shunt concurrent with CI. In total, 2 of 27 pediatric patients (7%) required unanticipated revision shunt surgery, both contralateral to CI device placement, given VP shunt malfunction. One of 19 adult patients (5%) required shunt revision during CI due to shunt damage noted intraoperatively. Among 43 patients with available follow-up, 38 (88%) are regular CI users, with a median consonant-nucleus vowel-consonant word: score of 58% (IQR: 28-72). CONCLUSION: CI can be performed at low risk, either contralateral or ipsilateral, to a VP shunt, and does not mandate shunt revision in most cases. Additional considerations regarding CI receiver-stimulator placement are necessary with programmable shunts to mitigate device interaction. Preoperative planning, including coordination of care with neurosurgery, is important to achieving optimal outcomes.

Microbial Response to Increased Temperatures Within a Lava-Induced Hydrothermal System in Iceland: An Analogue for the Habitability of Volcanic Terrains on Mars.

Fossil hydrothermal systems on Mars are important exploration targets because they may have once been habitable and could still preserve evidence of microbial life. We investigated microbial communities within an active lava-induced hydrothermal system associated with the 2014-2015 eruption of Holuhraun in Iceland as a Mars analogue. In 2016, the microbial composition in the lava-heated water differed substantially from that of the glacial river and spring water sources that fed into the system. Several taxonomic and metabolic groups were confined to the water emerging from the lava and some showed the highest sequence similarities to subsurface ecosystems, including to the predicted thermophilic and deeply branching Candidatus Acetothermum autotrophicum. Measurements show that the communities were affected by temperature and other environmental factors. In particular, comparing glacial river water incubated in situ (5.7°C, control) with glacial water incubated within a lava-heated stream (17.5°C, warm) showed that microbial abundance, richness, and diversity increased in the warm treatment compared with the control, with the predicted major metabolism shifting from lithotrophy toward organotrophy and possibly phototrophy. In addition, thermophilic bacteria isolated from the lava-heated water and a nearby acidic hydrothermal system included the known endospore-formers Geobacillus stearothermophilus and Paenibacillus cisolokensis as well as a potentially novel taxon within the order Hyphomicrobiales. Similar lava-water interactions on Mars could therefore have generated habitable environments for microbial communities.

Adaptive Cardiac Resynchronization Therapy Effect on Electrical Dyssynchrony (aCRT-ELSYNC): A randomized controlled trial.

BACKGROUND: Adaptive cardiac resynchronization therapy (aCRT) is known to have clinical benefits over conventional CRT, but the mechanisms are unclear. OBJECTIVE: Compare effects of aCRT and conventional CRT on electrical dyssynchrony. METHODS: A prospective, double-blind, 1:1 parallel-group assignment randomized controlled trial in patients receiving CRT for routine clinical indications. Participants underwent cardiac computed tomography and 128-electrode body surface mapping. The primary outcome was change in electrical dyssynchrony measured on the epicardial surface using noninvasive electrocardiographic imaging before and 6 months post-CRT. Ventricular electrical uncoupling (VEU) was calculated as the difference between the mean left ventricular (LV) and right ventricular (RV) activation times. An electrical dyssynchrony index (EDI) was computed as the standard deviation of local epicardial activation times. RESULTS: We randomized 27 participants (aged 64 ± 12 years; 34% female; 53% ischemic cardiomyopathy; LV ejection fraction 28% ± 8%; QRS duration 155 ± 21 ms; typical left bundle branch block [LBBB] in 13%) to conventional CRT (n = 15) vs aCRT (n = 12). In atypical LBBB (n = 11; 41%) with S waves in V5-V6, conduction block occurred in the anterior RV, as opposed to the interventricular groove in strict LBBB. As compared to baseline, VEU reduced post-CRT in the aCRT (median reduction 18.9 [interquartile range 4.3-29.2 ms; P = .034]), but not in the conventional CRT (21.4 [-30.0 to 49.9 ms; P = .525]) group. There were no differences in the degree of change in VEU and EDI indices between treatment groups. CONCLUSION: The effect of aCRT and conventional CRT on electrical dyssynchrony is largely similar, but only aCRT harmoniously reduced interventricular dyssynchrony by reducing RV uncoupling.

Renal Protective Effect of Everolimus in Liver Transplantation: A Prospective Randomized Open-Label Trial.

Renal dysfunction is associated with poor long-term outcomes after liver transplantation. We examined the renal sparing effect of everolimus (EVR) compared to standard calcineurin inhibitor (CNI) immunosuppression with direct measurements of renal function over 24 months. METHODS: This was a prospective, randomized, open-label trial comparing EVR and mycophenolic acid (MPA) with CNI and MPA immunosuppression. An Investigational New Drug Application (IND # 113882) was obtained with the Food and Drug Administration as EVR is only approved for use with low-dose tacrolimus. Serum creatinine, 24-hour urine creatinine clearance, iothalamate clearance, Cockcroft-Gault creatinine clearance (CrCl), and Modification of Diet in Renal Disease estimated glomerular filtration rate were prospectively measured at 4 study visits. Nonparametric statistical tests were used for analyses, including the Mann-Whitney U test for continuous outcomes and Pearson's chi-square test for binary outcomes. Effect size was measured using Cohen's d. Patients also completed quality of life surveys using the FACT-Hep instrument at each study visit. Comparison between the 2 groups was performed using the Student t test. RESULTS: Each arm had 12 subjects; 4 patients dropped out in the EVR arm and 1 in the CNI arm by 24 months. Serum creatinine (P = 0.015), Modification of Diet in Renal Disease estimated glomerular filtration rate (P = 0.013), and 24-hour urine CrCL (P = 0.032) were significantly better at 24 months with EVR. Iothalamate clearance showed significant improvement at 12 months (P = 0.049) and a trend toward better renal function (P = 0.099) at 24 months. There was no statistical significance with Cockcroft-Gault CrCl. Adverse events were not significantly different between the 2 arms. The EVR group also showed significantly better physical, functional, and overall self-reported quality of life (P = 0.01) at 24 months. CONCLUSIONS: EVR with MPA resulted in significant long-term improvement in renal function and quality of life at 24 months after liver transplantation compared with standard CNI with MPA immunosuppression.

Analytical and Clinical Analysis of Two Automated Anti-SARS-CoV-2 Immunoassays in Pre-Pandemic and Pandemic Patient Populations.

BACKGROUND: In the absence of a safe, effective vaccine, the worldwide spread of COVID-19 (SARS-CoV-2) infection will continue. Laboratory tests with ideal precision, sensitivity, and specificity should be used in public health and clinical settings to gauge the extent of virus exposure. Toward this end, we evaluated the analytical and clinical performance of the Abbott SARS-CoV-2 IgG and the Roche Anti-SARS-CoV-2 immunoassays. METHODS: Quality control, pooled COVID-19, and non-COVID-19 patient specimens were used for the imprecision study. Two hundred and forty-six specimens from 70 patients with COVID-19 diagnosis were tested to study the sensitivity. Seventy-three non-COVID-19 control specimens were measured to study the specificity. All specimens were analyzed by both assays. RESULTS: Total analytic variability (CV) of the negative and positive controls were 5.5% and 3.6% for the Abbott assay and 4.5% and 1.9% for the Roche assay. Both assays demonstrated 100% qualitative reproducibility of negative and positive controls. The clinical specificities of the Abbott and the Roche assays were 100% (95% CI: 94%-100%) and 97% (95% CI: 90%-100%), respectively. The clinical sensitivities of the Abbott assay were 49% (95% CI: 41%-56%), 86% (95% CI: 74%-93%), and 100% (95% CI: 76%-100%) for samples collected at 0-6 days, 7-13 days, and ≥14 days after the first RT-PCR, while the sensitivities of the Roche assay were 55% (95% CI: 47%-62%), 86% (95% CI: 74%-93%), and 100% (95% CI: 76%-100%). CONCLUSIONS: This study demonstrates similar analytical and clinical performance of the Abbott and the Roche SARS-CoV-2 antibody assays, but the Roche assay may be slightly more sensitive for patients tested within 0-6 days after first positive RT-PCR of SARS-CoV-2.COVID-19 is a respiratory infectious disease caused by SARS-CoV-2. Laboratory tests with ideal precision, sensitivity, and specificity should be used in public health and clinical settings. We analyzed analytical and clinical performance of the Roche and Abbott SARS-CoV-2 antibody assays in pre-pandemic and pandemic patient populations. Additionally, we analyzed the sensitivity of both assays in patients at different stages of the disease. The 2 assays showed similar analytical and clinical performance, but the Roche assay may be slightly more sensitive for patients tested within 0-6 days after first positive RT-PCR of SARS-CoV-2. Our findings help other clinical labs select appropriate assays for SARS-CoV-2 antibody testing.

Mechanisms of Arrhythmogenicity in Hypertrophic Cardiomyopathy: Insight From Non-invasive Electrocardiographic Imaging.

BACKGROUND: Mechanisms of arrhythmogenicity in hypertrophic cardiomyopathy (HCM) are not well understood. OBJECTIVE: To characterize an electrophysiological substrate of HCM in comparison to ischemic cardiomyopathy (ICM), or healthy individuals. METHODS: We conducted a prospective case-control study. The study enrolled HCM patients at high risk for ventricular tachyarrhythmia (VT) [n = 10; age 61 ± 9 years; left ventricular ejection fraction (LVEF) 60 ± 9%], and three comparison groups: healthy individuals (n = 10; age 28 ± 6 years; LVEF > 70%), ICM patients with LV hypertrophy (LVH) and known VT (n = 10; age 64 ± 9 years; LVEF 31 ± 15%), and ICM patients with LVH and no known VT (n = 10; age 70 ± 7 years; LVEF 46 ± 16%). All participants underwent 12-lead ECG, cardiac CT or MRI, and 128-electrode body surface mapping (BioSemi ActiveTwo, Netherlands). Non-invasive voltage and activation maps were reconstructed using the open-source SCIRun (University of Utah) inverse problem-solving environment. RESULTS: In the epicardial basal anterior segment, HCM patients had the greatest ventricular activation dispersion [16.4 ± 5.5 vs. 13.1 ± 2.7 (ICM with VT) vs. 13.8 ± 4.3 (ICM no VT) vs. 8.1 ± 2.4 ms (Healthy); P = 0.0007], the largest unipolar voltage [1094 ± 211 vs. 934 ± 189 (ICM with VT) vs. 898 ± 358 (ICM no VT) vs. 842 ± 90 µV (Healthy); P = 0.023], and the greatest voltage dispersion [median (interquartile range) 215 (161-281) vs. 189 (143-208) (ICM with VT) vs. 158 (109-236) (ICM no VT) vs. 110 (106-168) µV (Healthy); P = 0.041]. Differences were also observed in other endo-and epicardial basal and apical segments. CONCLUSION: HCM is characterized by a greater activation dispersion in basal segments, a larger voltage, and a larger voltage dispersion through LV. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov Unique identifier: NCT02806479.

The Extrapulmonary Effects of Cystic Fibrosis Transmembrane Conductance Regulator Modulators in Cystic Fibrosis.

The effects of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators on lung function, pulmonary exacerbations, and quality of life have been well documented. However, CF is a multiorgan disease, and therefore an evidence base is emerging on the systemic effects of CFTR modulators beyond the pulmonary system. This is of great clinical importance, as many of these studies provide proof of concept that CFTR modulators might be used one day to prevent or treat extrapulmonary manifestations stemming from CFTR dysfunction. In this concise review of the literature, we summarize the results of key publications that have evaluated the effects of CFTR modulators on weight and growth, pancreatic function, the gastrointestinal and hepatobiliary systems, sinus disease, bone disease, exercise tolerance, fertility, mental health, and immunity. Although many of these studies have reported beneficial extrapulmonary effects related to the use of ivacaftor (IVA) in patients with CF with at least one gating mutation, most of the evidence is low or very low quality, given the limited number of patients evaluated and the lack of control groups. Based on an even smaller number of studies evaluating the extrapulmonary effects of lumacaftor-IVA, the benefits are less clear. Although limited, these studies may provide the basis for future clinical trials to evaluate CFTR modulators on the extrapulmonary manifestations of CF.

Dynamic predictive accuracy of electrocardiographic biomarkers of sudden cardiac death within a survival framework: the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: The risk of sudden cardiac death (SCD) is known to be dynamic. However, the accuracy of a dynamic SCD prediction is unknown. We aimed to measure the dynamic predictive accuracy of ECG biomarkers of SCD and competing non-sudden cardiac death (non-SCD). METHODS: Atherosclerosis Risk In Community study participants with analyzable ECGs in sinus rhythm were included (n = 15,716; 55% female, 73% white, age 54.2 ± 5.8 y). ECGs of 5 follow-up visits were analyzed. Global electrical heterogeneity and traditional ECG metrics (heart rate, QRS, QTc) were measured. Adjudicated SCD was the primary outcome; non-SCD was the competing outcome. Time-dependent area under the receiver operating characteristic curve (ROC(t) AUC) analysis was performed to assess the prediction accuracy of a continuous biomarker in a period of 3,6,9 months, and 1,2,3,5,10, and 15 years using a survival analysis framework. Reclassification improvement as compared to clinical risk factors (age, sex, race, diabetes, hypertension, coronary heart disease, stroke) was measured. RESULTS: Over a median 24.4 y follow-up, there were 577 SCDs (incidence 1.76 (95%CI 1.63-1.91)/1000 person-years), and 829 non-SCDs [2.55 (95%CI 2.37-2.71)]. No ECG biomarkers predicted SCD within 3 months after ECG recording. Within 6 months, spatial ventricular gradient (SVG) elevation predicted SCD (AUC 0.706; 95%CI 0.526-0.886), but not a non-SCD (AUC 0.527; 95%CI 0.303-0.75). SVG elevation more accurately predicted SCD if the ECG was recorded 6 months before SCD (AUC 0.706; 95%CI 0.526-0.886) than 2 years before SCD (AUC 0.608; 95%CI 0.515-0.701). Within the first 3 months after ECG recording, only SVG azimuth improved reclassification of the risk beyond clinical risk factors: 18% of SCD events were reclassified from low or intermediate risk to a high-risk category. QRS-T angle was the strongest long-term predictor of SCD (AUC 0.710; 95%CI 0.668-0.753 for ECG recorded within 10 years before SCD). CONCLUSION: Short-term and long-term predictive accuracy of ECG biomarkers of SCD differed, reflecting differences in transient vs. persistent SCD substrates. The dynamic predictive accuracy of ECG biomarkers should be considered for competing SCD risk scores. The distinction between markers predicting short-term and long-term events may represent the difference between markers heralding SCD (triggers or transient substrates) versus markers identifying persistent substrate.

Hemodialysis Procedure-Associated Autonomic Imbalance and Cardiac Arrhythmias: Insights From Continuous 14-Day ECG Monitoring.

Background In patients with end-stage kidney disease, sudden cardiac death is more frequent after a long interdialytic interval, within 6 hours after the end of a hemodialysis session. We hypothesized that the occurrence of paroxysmal arrhythmias is associated with changes in heart rate and heart rate variability in different phases of hemodialysis. Methods and Results We conducted a prospective ancillary study of the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease cohort. Continuous ECG monitoring was performed using an ECG patch, and short-term heart rate variability was measured for 3 minutes every hour (by root mean square of the successive normal-to-normal intervals, spectral analysis, Poincaré plot, and entropy), up to 300 hours. Out of enrolled participants (n=28; age 54±13 years; 57% men; 96% black; 33% with a history of cardiovascular disease; left ventricular ejection fraction 70±9%), arrhythmias were detected in 13 (46%). Nonsustained ventricular tachycardia occurred more frequently during/posthemodialysis than pre-/between hemodialysis (63% versus 37%, P=0.015). In adjusted for cardiovascular disease time-series analysis, nonsustained ventricular tachycardia was preceded by a sudden heart rate increase (by 11.2 [95% CI 10.1-12.3] beats per minute; P<0.0001). During every-other-day dialysis, root mean square of the successive normal-to-normal intervals had a significant circadian pattern (Mesor 10.6 [ 95% CI 0.9-11.2] ms; amplitude 1.5 [95% CI 1.0-3.1] ms; peak at 02:01 [95% CI 20:22-03:16] am; P<0.0001), which was replaced by a steady worsening on the second day without dialysis (root mean square of the successive normal-to-normal intervals -1.41 [95% CI -1.67 to -1.15] ms/24 h; P<0.0001). Conclusions Sudden increase in heart rate during/posthemodialysis is associated with nonsustained ventricular tachycardia. Every-other-day hemodialysis preserves circadian rhythm, but a second day without dialysis is characterized by parasympathetic withdrawal.

Cytomine: Toward an Open and Collaborative Software Platform for Digital Pathology Bridged to Molecular Investigations.

PURPOSE: Digital histology is being increasingly used in research and clinical applications. In parallel, new tissue imaging methods (e.g., imaging mass spectrometry) are currently regarded as very promising approaches for better molecular diagnosis in pathology. However, these new data sources are still often underexploited because of the lack of collaborative software to share and correlate information for multimodal analysis. EXPERIMENTAL DESIGN: The open science paradigm is followed to develop new features in the web-based Cytomine software to support next-generation digital pathology bridged to molecular investigations. RESULTS: New open-source developments allow to explore whole-slide classical histology with Matrix Assisted Laser Desorption Ionisation (MALDI) imaging and to support preprocessing for biomarker discovery using laser microdissection-based microproteomics. CONCLUSIONS AND CLINICAL RELEVANCE: The updated version of Cytomine is the first open and web-based tool to enable sharing data from classical histology, molecular imaging, and cell counting for proteomics preprocessing. It holds good promise to fulfill imminent needs in molecular histopathology.

Importance of the heart vector origin point definition for an ECG analysis: The Atherosclerosis Risk in Communities (ARIC) study.

AIM: Our goal was to investigate the effect of a global XYZ median beat construction and the heart vector origin point definition on predictive accuracy of ECG biomarkers of sudden cardiac death (SCD). METHODS: Atherosclerosis Risk In Community study participants with analyzable digital ECGs were included (n = 15,768; 55% female, 73% white, mean age 54.2 ±â€¯5.8 y). We developed an algorithm to automatically detect the heart vector origin point on a median beat. Three different approaches to construct a global XYZ beat and two methods to locate origin point were compared. Global electrical heterogeneity was measured by sum absolute QRST integral (SAI QRST), spatial QRS-T angle, and spatial ventricular gradient (SVG) magnitude, azimuth, and elevation. Adjudicated SCD served as the primary outcome. RESULTS: There was high intra-observer (kappa 0.972) and inter-observer (kappa 0.984) agreement in a heart vector origin definition between an automated algorithm and a human. QRS was wider in a median beat that was constructed using R-peak alignment than in time-coherent beat (88.1 ±â€¯16.7 vs. 83.7 ±â€¯15.9 ms; P < 0.0001), and on a median beat constructed using QRS-onset as a zeroed baseline, vs. isoelectric origin point (86.7 ±â€¯15.9 vs. 83.7 ±â€¯15.9 ms; P < 0.0001). ROC AUC was significantly larger for QRS, QT, peak QRS-T angle, SVG elevation, and SAI QRST if measured on a time-coherent median beat, and for SAI QRST and SVG magnitude if measured on a median beat using isoelectric origin point. CONCLUSION: Time-coherent global XYZ median beat with physiologically meaningful definition of the heart vector's origin point improved predictive accuracy of SCD biomarkers.

Vectorcardiogram in athletes: The Sun Valley Ski Study.

BACKGROUND: Global electrical heterogeneity (GEH) is associated with sudden cardiac death (SCD) in adults of 45 years and above. However, GEH has not been previously measured in young athletes. The goal of this study was to establish a reference for vectorcardiograpic (VCG) metrics in male and female athletes. METHODS: Skiers (n = 140; mean age 19.2 ± 3.5 years; 66% male, 94% white; 53% professional athletes) were enrolled in a prospective cohort. Resting 12-lead ECGs were interpreted per the International ECG criteria. Associations of age, sex, and athletic performance with GEH were studied. RESULTS: In age and training level-adjusted analyses, male sex was associated with a larger T vector [T peak magnitude +186 (95% CI 106-266) µV] and a wider spatial QRS-T angle [+28.2 (17.3-39.2)°] as compared to women. Spatial QRS-T angle in the ECG left ventricular hypertrophy (LVH) voltage group (n = 21; 15%) and normal ECG group did not differ (67.7 ± 25.0 vs. 66.8 ± 28.2; p = 0.914), suggesting that ECG LVH voltage in athletes reflects physiological remodeling. In contrast, skiers with right ventricular hypertrophy (RVH) voltage (n = 26, 18.6%) had wider QRS-T angle (92.7 ± 29.6 vs. 66.8 ± 28.2°; p = 0.001), larger SAI QRST (194.9 ± 30.2 vs. 157.8 ± 42.6 mV × ms; p < 0.0001), but similar peak SVG vector magnitude (1976 ± 548 vs. 1939 ± 395 µV; p = 0.775) as compared to the normal ECG group. Better athletic performance was associated with the narrower QRS-T angle. Each 10% worsening in an athlete's Federation Internationale de' Ski downhill ranking percentile was associated with an increase in spatial QRS-T angle by 2.1 (95% CI 0.3-3.9) degrees (p = 0.013). CONCLUSION: Vectorcardiograpic adds nuances to ECG phenomena in athletes.

The utility of routine clinical 12-lead ECG in assessing eligibility for subcutaneous implantable cardioverter defibrillator.

INTRODUCTION: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is a life-saving device. Recording of a specialized 3-lead electrocardiogram (ECG) is required for S-ICD eligibility assessment. The goals of this study were: (1) evaluate the effect of ECG filtering on S-ICD eligibility, and (2) simplify S-ICD eligibility assessment by development of an S-ICD ineligibility prediction tool, which utilizes the widely available routine 12-lead ECG. METHODS AND RESULTS: Prospective cross-sectional study participants [n = 68; 54% male; 94% white, with wide ranges of age (18-81 y), body mass index (19-53), QRS duration (66-150 ms), and left ventricular ejection fraction (37-77%)] underwent 12-lead supine, 3-lead supine and standing ECG recording. All 3-lead ECG recordings were assessed using the standard S-ICD pre-implantation ECG morphology screening. Backward, stepwise, logistic regression was used to build a model for 12-lead prediction of S-ICD eligibility. Select electrocardiogram waves and complexes: QRS, R-, S, and T-amplitudes on all 12 leads, averaged QT interval, QRS duration, and R/T ratio in the lead with the largest T wave (R/Tmax) were included as predictors. The effect of ECG filtering on ECG morphology was evaluated. A total of 9 participants (13%) failed S-ICD screening prior to filtering. Filtering at 3-40 Hz, similar to the S-ICD default, reduced S-ICD ineligibility to 4%. A regression model that included RII, SII-aVL, TI, II, aVL, aVF, V3-V6, and R/Tmax perfectly predicted S-ICD eligibility, with an Area Under the Receiver Operating Characteristic Curve of 1.0. CONCLUSION: Routine clinical 12-lead ECG can be used to predict S-ICD eligibility. ECG filtering may improve S-ICD eligibility.

Improving sudden cardiac death risk stratification by evaluating electrocardiographic measures of global electrical heterogeneity and clinical outcomes among patients with implantable cardioverter-defibrillators: rationale and design for a retrospective, multicenter, cohort study.

PURPOSE: Implantable cardioverter-defibrillators (ICDs) improve survival of systolic heart failure (HF) patients who are at risk of sudden cardiac death (SCD). We recently showed that electrocardiographic (ECG) global electrical heterogeneity (GEH) is independently associated with SCD in the community-dwelling cohort and developed GEH SCD risk score. The Global Electrical Heterogeneity and Clinical Outcomes (GEHCO) study is a retrospective multicenter cohort designed with two goals: (1) validate an independent association of ECG GEH with sustained ventricular tachyarrhythmias and appropriate ICD therapies and (2) validate GEH ECG risk score for prediction of sustained ventricular tachyarrhythmias and appropriate ICD therapies in systolic HF patients with primary prevention ICD. METHODS: All records of primary prevention ICD recipients with available data for analysis are eligible for inclusion. Records of ICD implantation in patients with inherited channelopathies and cardiomyopathies are excluded. Raw digital 12-lead pre-implant ECGs will be used to measure GEH (spatial QRST angle, spatial ventricular gradient magnitude, azimuth, and elevation, and sum absolute QRST integral). The primary endpoint is defined as a sustained ventricular tachyarrhythmia event with appropriate ICD therapy. All-cause death without preceding sustained ventricular tachyarrhythmia with appropriate ICD therapy will serve as a primary competing outcome. The study will draw data from the academic medical centers. RESULTS: We describe the study protocol of the first multicenter retrospective cohort of primary prevention ICD patients with recorded at baseline digital 12-lead ECG. CONCLUSION: Findings from this study will inform future trials to identify patients who are most likely to benefit from primary prevention ICD. TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT03210883.

A Multi-Scale Investigation of Global Electrical Heterogeneity: Effects of Body Habitus, Respiration, and Tissue Conductivity.

Extracardiac factors such as respiration, fluid overload and body habitus have important effects on the ECG voltage. Vectorcardiographic (VCG) Global Electrical Heterogeneity (GEH) is associated with sudden cardiac death (SCD). Risk of SCD is especially high in end-stage renal disease patients (ESRD) on dialysis. However, extracardiac factors challenge ECG interpretation in ESRD patients. The effects of extracardiac factors on GEH have not been fully studied. To1 assess effects of extracardiac factors on ECG, we conducted a multi-scale study. An experimental data of ESRD patients and a previously developed biophysically detailed heart-torso model were used to investigate the effects of respiration, fluid overload and body habitus on the VCG and GEH.

The Reproducibility of Global Electrical Heterogeneity ECG Measurements.

BACKGROUND: Global electrical heterogeneity (GEH) is a useful predictor of adverse clinical outcomes. However, reproducibility of GEH measurements on 10-second routine clinical ECG is unknown. METHODS: Data of the prospective cohort study of incident hemodialysis patients (n=253; mean age 54.6±13.5y; 56% male; 79% African American) were analysed. Two random 10-second segments of 5-minute ECG recording in sinus rhythm were compared. GEH was measured as spatial QRS-T angle, spatial ventricular gradient (SVG) magnitude and direction (azimuth and elevation), and a scalar value of SVG measured by (1) sum absolute QRST integral (SAI QRST), and (2) QT integral on vector magnitude signal (iVMQT). Bland-Altman analysis was used to calculate agreement. RESULTS: For all studied vectorcardiographic metrics, agreement was substantial (Lin's concordance coefficient >0.98), and precision was perfect (>99.99%). 95% limits of agreement were ±14° for spatial QRS-T angle, ±13° for SVG azimuth, ±4° for SVG elevation, ±14 mV*ms for SVG magnitude, and ±17 mV*ms for SAI QRST. SAI QRST and iVMQT were in substantial agreement with each other. CONCLUSION: Reproducibility of a 10-second automated GEH ECG measurements was substantial, and precision was perfect.

First demonstration of an all-solid-state optical cryocooler.

Solid-state optical refrigeration uses anti-Stokes fluorescence to cool macroscopic objects to cryogenic temperatures without vibrations. Crystals such as Yb3+-doped YLiF4 (YLF:Yb) have previously been laser-cooled to 91 K. In this study, we show for the first time laser cooling of a payload connected to a cooling crystal. A YLF:Yb crystal was placed inside a Herriott cell and pumped with a 1020-nm laser (47 W) to cool a HgCdTe sensor that is part of a working Fourier Transform Infrared (FTIR) spectrometer to 135 K. This first demonstration of an all-solid-state optical cryocooler was enabled by careful control of the various desired and undesired heat flows. Fluorescence heating of the payload was minimized by using a single-kink YLF thermal link between the YLF:Yb cooling crystal and the copper coldfinger that held the HgCdTe sensor. The adhesive-free bond between YLF and YLF:Yb showed excellent thermal reliability. This laser-cooled assembly was then supported by silica aerogel cylinders inside a vacuum clamshell to minimize undesired conductive and radiative heat loads from the warm surroundings. Our structure can serve as a baseline for future optical cryocooler devices.

Automated detection of geological landforms on Mars using Convolutional Neural Networks.

The large volume of high-resolution images acquired by the Mars Reconnaissance Orbiter has opened a new frontier for developing automated approaches to detecting landforms on the surface of Mars. However, most landform classifiers focus on crater detection, which represents only one of many geological landforms of scientific interest. In this work, we use Convolutional Neural Networks (ConvNets) to detect both volcanic rootless cones and transverse aeolian ridges. Our system, named MarsNet, consists of five networks, each of which is trained to detect landforms of different sizes. We compare our detection algorithm with a widely used method for image recognition, Support Vector Machines (SVMs) using Histogram of Oriented Gradients (HOG) features. We show that ConvNets can detect a wide range of landforms and has better accuracy and recall in testing data than traditional classifiers based on SVMs.