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A capacitively coupled noise circulating voltage-controlled oscillator (VCO) is proposed. Through capacitive coupling from the LC tank to the gates of the active devices, a simple inductor-based resonator can realize the same noise circulating effect as the conventional transformer-based topology, leading to a more compact chip area, as well as larger tuning range. The proposed VCO is fabricated with a 28-nm CMOS process using only thick-oxide devices. The core chip area is 0.09 mm2. The measured oscillation frequency ranges from 6.17 to 10.45 GHz, and the phase noise at 1-MHz offset is from −121.6 to −115 dBc/Hz, with a power dissipation from 32 to 41 mW under a 1.8-V supply voltage across the frequency tuning range. The achieved figure-of-merit with tuning range (FoM $_{T}$ ) is from 193.1 to 196.4 dBc/Hz.

This paper reports a new readout integrated circuit designed for hybridization with P-on-N detector such as InSb, HgCdTe and InGaAs, and it can support a wide range of system through flexibility and versatile functions. This ROIC is fabricated using CSMC 0.18um double poly, six metal process that utilized high-speed CMOS transistors. The device can work at temperatures of 80K with 5.5V supply voltage. It still has a build-in temperature sensor to detect the temperature of the chip. The pixel cell occupies an area of 25×25µm2 with an input charge-handling of 18Me- carriers. After testing at 80K, the output swing was larger than 3V; the power consumption of chip was about 180mW; the output noise was about 400uV and its dynamic range was about 78dB.

Background Risk stratification in non‐ischemic myocardial disease poses a challenge. While cardiovascular magnetic resonance (CMR) is a comprehensive tool, the electrocardiogram (ECG) provides quick impactful clinical information. Studying the relationships between CMR and ECG can provide much‐needed risk stratification. We evaluated the electrocardiographic signature of myocardial fibrosis defined as presence of late gadolinium enhancement (LGE) or extracellular volume fraction (ECV) ≥29%. Methods We evaluated 240 consecutive patients (51% female, 47.1 ± 16.6 years) referred for a clinical CMR who underwent 12‐lead ECGs within 90 days. ECG parameters studied to determine association with myocardial fibrosis included heart rate, QRS amplitude/duration, T‐wave amplitude, corrected QT and QT peak, and Tpeak‐Tend. Abnormal T‐wave was defined as low T‐wave amplitude ≤200 µV or a negative T wave, both in leads II and V5. Results Of the 147 (61.3%) patients with myocardial fibrosis, 67 (28.2%) had ECV ≥ 29%, and 132 (54.6%) had non‐ischemic LGE. An abnormal T‐wave was more prevalent in patients with versus without myocardial fibrosis (66% versus 42%, p

Objective Long QT-Syndrome (LQTS) patients are at risk of arrhythmias and seizures. We investigated whether autonomic and cardiac repolarization measures differed based on LQTS genotypes, and in LQTS patients with vs. without arrhythmias and seizures. Methods We used 24-h ECGs from LQTS1 (n = 87), LQTS2 (n = 50), and LQTS genotype negative patients (LQTS(−), n = 16). Patients were stratified by LQTS genotype, and arrhythmias/seizures. Heart rate variability (HRV) and QT variability index (QTVI) measures were compared between groups during specific physiological states (minimum, middle, & maximum sympathovagal balance, LF/HF). Results were further tested using logistic regression for each ECG measure, and all HRV measures in a single multivariate model. Results Across multiple physiological states, total autonomic (SDNN) and vagal (RMSSD, pNN50) function were lower and repolarization dynamics (QTVI) were elevated in LQTS(+), LQTS1, and LQTS2, compared to LQTS(−). Many measures remained significant in the regression models. Multivariate modeling demonstrated that SDNN, RMSSD, and pNN50 were independent markers of LQTS(+) vs. LQTS(−), and SDNN and pNN50 were markers for LQTS1 vs. LQTS(−). During sympathovagal balance (middle LF/HF), RMSSD and pNN50 distinguished LQTS1 vs. LQTS2. LQTS1 patients with arrhythmias had lower total (SDNN) and vagal (RMSSD and pNN50) autonomic function, and SDNN remained significant in the models. In contrast, ECG measures did not differ in LQTS2 patients with vs. without arrhythmias, and LQTS1 and LQTS2 with vs. without seizures. Conclusion Autonomic (HRV) and cardiac repolarization (QTVI) ECG measures differ based on LQTS genotype and history of arrhythmias in LQTS1. SDNN, RMSSD, and pNN50 were each independent markers for LQTS genotype.

Background Cardiac Resynchronization Therapy (CRT) is widely used for treating selected heart failure patients, but patients with myocardial scar respond worse to treatment. The Selvester QRS scoring system estimates myocardial scar burden using 12-lead ECG. This study's objective was to investigate the scores correlation to mortality in a CRT population. Methods and results Data on consecutive CRT patients was collected. 401 patients with LBBB and available ECG data were included in the study. QuAReSS software was used to perform Selvester scoring. Mean Selvester score was 6.4, corresponding to 19% scar burden. The endpoint was death or heart transplant; outcome was analyzed using Cox proportional hazards models. A Selvester score > 8 was significantly associated with higher risk of the combined endpoint (HR 1.59, p = .014, CI 1.09–2.3). Conclusion Higher Selvester scores correlate to mortality in CRT patients with strict LBBB and might be of value in prognosticating survival.

Introduction Sleep disordered breathing (SDB) is associated with increased mortality. Obstructive apneas/hypopneas have been associated with an increase in both QTc duration and QT variability. These markers of ventricular repolarization are associated with arrhythmias and death. It is unknown whether SDB-related QTc changes are responsible for the relationship between QTc/QT variability and cardiovascular death (CVD). Methods From the Sleep Heart Health Study, we randomly selected 200 subjects in each of four groups based on overall apnea/hypopnea index: those with no SDB and those in either, mild, moderate or severe SDB at baseline, matched for gender, age and BMI. Respiratory-related channels and electrocardiograms (ECG) from each polysomnography were analyzed. QTc was calculated using Bazett’s heart rate correction. The following measures of QT variability were obtained: i) standard deviation of QT intervals (SDQT) at 1- and 5-minute intervals and ii) short-term interval QT variability (STVQT) at 5-minute intervals. Cox proportional hazards regression models were used to evaluate potential predictors of CVD. Results Twenty-nine subjects were excluded either due to missing data or low quality ECG. The 771 subjects included were 68±10 years of age, half were female. During follow-up, 220 subjects (28.5%) died of CVD among whom, 67 (30.5%) had comorbid severe SDB, 45 (20.5%) had no SDB, and the remaining CVD deaths had mild (47, 21.4%) and moderate 61 (27.7%) SDB. The CVD patients were more likely to be older(p Conclusion SDB was not a factor in the relationship between QTc prolongation/QT variability and CVD. Support (if any) American Academy of Sleep Medicine Foundation (203-JF-18), National Institutes of Health (HL126140), University of Arizona Health Sciences Career and Development Award (5299903)

Item does not contain fulltext INTRODUCTION: We evaluated the association between a novel electrocardiographic (ECG) marker of late, rightward electrocardiographic forces (termed the lead one ratio [LOR]), and left ventricular ejection fraction (LVEF), myocardial scar, and clinical outcomes in patients with left bundle branch block (LBBB). METHODS AND RESULTS: LOR was calculated in patients with LBBB from a derivation cohort (n = 240) and receiver operator characteristic curves identified optimal threshold values for predicting myocardial scar and LVEF less than 35%. An independent validation cohort of patients with LBBB (n = 196) was used to test the association of LOR with the myocardial scar, LVEF, and the likelihood of death, heart transplant or left ventricular assist device (LVAD) implantation. The optimal thresholds in the derivation cohort were LOR less than 13.7 for identification of scar (sensitivity 55%, specificity 80%), and LOR less than 12.1 for LVEF less than 35% (sensitivity 49%, specificity 80%). In the validation cohort, LOR less than 13.7 was not associated with scar size or presence (P > 0.05 for both). LOR less than 12.1 was associated with lower LVEF (30 [20-40] versus 40 [25-55]%; P = 0.002) and predicted LVEF less than 35% in univariable (odds ratio [OR], 2.2 [1.2-4.1]; P = 0.01) and multivariable analysis (OR, 2.2 [1.2-4.3]; P = 0.02). LOR less than 12.1 was associated with scar presence when patients with nonischemic cardiomyopathy were excluded (OR = 7.2 [1.5-33.2]; P = 0.002). LOR less than 12.1 had an adjusted hazard ratio of 1.53 ([1.05-2.21]; P = 0.03) for death, transplant or LVAD implantation. CONCLUSIONS: In conclusion, ECG LOR less than 12.1 predicts reduced-LV systolic function and poorer prognosis in patients with LBBB.

Introduction The apneas and hypopneas that characterize sleep-disordered breathing (SDB) are associated with QTc prolongation and increased QT variability. There have been mixed results as to whether QTc and QT variability increase with increasing SDB severity. This study assesses whether QTc prolongation and QT variability are likely to increase with increasing severity of SDB in a large multi-center cohort. Methods 200 subjects with no SDB and approximately 600 with three levels of SDB (mild, moderate, severe) were randomly selected from the Sleep Heart Health study and matched by age, gender and BMI. SDB was defined as an apnea/hypopnea index ≥5. Respiratory and electrocardiograms (ECG) signals from polysomnography studies were analyzed. Bazett’s heart rate correction was used to calculate QTc. QT variability was measured as standard deviation of QT intervals (SDQT) and short-term interval QT variability (STVQT), at 5-minute intervals. Subjects were excluded if there were missing data or low-quality ECG. Results Seven hundred and seventy-one subjects (age 68±10 years, 51% female, 92% Caucasian) were included. One hundred and sixty-five subjects had no SDB, 235 mild, 195 moderate and 176 had severe SDB. The mean (SD) QTc was 422(29), 411(26), 419 (34) and 418 (36) ms for the no SDB, mild, moderate, and severe SDB groups, respectively (p=0.017). The mean (SD) STVQT was 7 (9), 11 (16), 8 (9) and 9 (11) for the no SDB, mild, moderate severe SDB groups, respectively (p= Conclusion QTc duration and QT variability were not increased with SDB severity. Support (if any) American Academy of Sleep Medicine Foundation (203-JF-18), National Institutes of Health (HL126140), University of Arizona Health Sciences Career Development Award (5299903), and University of Arizona Faculty Seed Grant (5833261)

Microthlaspi is a predominantly Eurasian genus which also occurs in the northernmost parts of Africa (Maghreb). The most widespread species of the genus is M. perfoliatum , which can be found from Sweden to Algeria and from Portugal to China. The other species are thought to have much more confined distribution ranges, often covering only a few hundred kilometres. This is also believed for the diploid M. erraticum , which was recently re-appraised as a taxon independent from the tetra- to hexaploid M. perfoliatum . Previously, M. erraticum was believed to be present only in Central Europe, from the East of France to Slovenia. In order to gain a deeper understanding of the ecology, evolution and migration history of Microthlaspi it was the focus of the current study to investigate, if M. erraticum is present in habitats outside Central Europe, but with microclimates similar to Central Europe. It is demonstrated that M. erraticum is much more widespread than previously thought, while other lineages apart from M. perfoliatum s.str. and M. erraticum seem to have restricted distribution ranges. The latter species was observed from the Alps and their foreland, the Balkans, the mountainous areas around the Black Sea, Southern Siberia, as well as the Altai and Tien Shan mountains. This demonstrates a widespread occurrence of this easily-overlooked species.

A novel gradual charge appointment concept is proposed to provide a clear physical insight of RESURF effects in bulk silicon lateral power devices. Due to the expandable substrate depletion region in silicon power device, the Linearly Graded Approximation is unable to fully describe the 2-D coupling effects between vertical and lateral junction. In this paper, by defining a charge appointment line, the lateral abrupt junction behaves as an effective gradual junction, thus resulting in the wider depletion layer, lower field peak and higher breakdown voltage. Based on the hypothesis, a simple 1-D model is proposed to quantify the breakdown voltage of the bulk silicon RESURF device and formulize the surface electric field. To our knowledge, the proposed model is the first 1-D model for bulk silicon RESURF device which can accurately describe the surface field profiles under various applied voltages and structure parameters. Furthermore, we provide a new RESURF criterion to explore the sensitivity of the breakdown voltage to structure parameters. Fair agreements among the analytical, numerical and experimental results verify the availability of the proposed concept and model.

Introduction Patients with untreated obstructive sleep apnea (OSA) have a 2-3—fold increased risk of cardiovascular mortality (CVD) compared with individuals without OSA. QTc prolongation and increased QT variability among OSA patients may contribute to this association. Methods Patients with OSA from the Sleep Heart Health study were identified based on polysomnography criteria and their continuous electrocardiograms (ECG) analyzed for QTc duration and QT variability. Both Fridericia’s and Bazett’s heart rate corrections were used to calculate QTc. QT variability was measured as standard deviation of QT intervals (SDQT) and normalized QT interval variance (QTVN) at 1- and 5-minute intervals and short-term interval beat-to-beat QT variability (STVQT) was measured at 5-minute intervals. Lasso with elastic-net regularization was used as the variable/covariate selection method. Cox proportional hazards regression models were used to determine predictors of CVD. Results Data from 365 patients with OSA were screened. Ninety-seven patients were excluded from analysis due to low quality ECG data (n=50) or extremely high (> ln (10)) variability in QT/QTc and/or QT variability (n=12). Fifty two percent of the sample was male with mean age 65 years (±10). Fifty-six of these patients died of CVD. The mean (SD) QTc in the group that died was 411 (30) ms and 416 (34) ms compared to 406 (24) ms and 411 (25) ms using Fridericia (Cox LR p-value 0.055) and Bazett (p=0.090), respectively. Gender, age, race, diabetes, SDQT and STVQT were significant predictors for CVD. We fit models with the covariates and SDQT (at both 1 and 5 min) and STVQT as three models and demonstrate that both SDQT and STVQT are significantly associated with CVD death (p-values of 0.0048, 0.0089, and 0.0113, respectively) and all models had high area under the curve (0.8095, 0.8085, and 0.8125, respectively). Conclusion In patients with OSA, QT variability was associated with CVD. Support American Academy of Sleep Medicine Foundation

This paper presents a digitally controlled ring oscillator (DCRO) which has a high frequency resolution. The proposed oscillator includes three tuning stages and regulates its frequency by using MOS capacitors in the output of each delay cell. The DCRO implemented in a 130 nm CMOS process operates at the center frequency of 2.4 GHz under a supply of 1.2 V. The phase noise of the presented DCRO at 1 MHz offset frequency is −106.3 dBc/Hz and the power consumption is 0.58 mW. The figure of merit obtained for the DCRO is −176.3 dBc/Hz.

INTRODUCTION Adverse electrical remodeling (AER), represented here as the sum absolute QRST integral (SAI QRST), has previously been shown to be directly associated with the risk for ventricular arrhythmia (VA). Cardiac resynchronization therapy (CRT) is known to reduce the risk for VA through various mechanisms, including reverse remodeling, and we aimed to evaluate the association between baseline AER and the risk for VA in CRT recipients. METHODS AND RESULTS The study population comprised 961 CRT-D implanted patients from the MADIT CRT study. The relationship between SAI QRST, VA risk, and VA risk/death was evaluated as a continuous and as a categorical variable-tertiles (T1 ≤ 0.527, T2 0.528-0.766, T3 > 0.766). In a multivariable model, AER was inversely associated with the risk of VA. Each unit increase in SAI QRST was associated with 64% (P = 0.007) and 54% (P = 0.003) decrease in the risk of VA and VA/death, respectively. Patients with high SAI QRST (T3) and medium SAI QRST (T2) had 52% (P

Item does not contain fulltext AIMS: We aimed to improve the electrocardiographic 2009 left bundle branch block (LBBB) Selvester QRS score (2009 LBSS) for scar assessment. METHODS: We retrospectively identified 325 LBBB patients with available ECG and cardiovascular magnetic resonance imaging (CMR) with late gadolinium enhancement from four centers (142 [44%] with CMR scar). Forty-four semi-automatically measured ECG variables pre-selected based on the 2009 LBSS yielded one multivariable model for scar detection and another for scar quantification. RESULTS: The 2009 LBSS achieved an area under the curve (AUC) of 0.60 (95% confidence interval 0.54-0.66) for scar detection, and R(2)=0.04, p

A novel silicon-on-insulator (SOI) lateral power device with step width drift region (SW) is proposed in this paper. The drift region of the new device is divided into several regions with different width increasing from source to drain. New additional electric field peaks are formed at the steps, which modulate the electric field and enhance the breakdown voltage. Meanwhile, the drift doping concentration is increased and thus reduces the specific on-resistance. Compared with the conventional device, a 35% increase in the breakdown voltage and a 21% decrease in the specific on-resistance are obtained in the proposed device.

Background Estimation of the infarct size from body-surface ECGs in post-myocardial infarction patients has become possible using the Selvester scoring method. Automation of this scoring has been proposed in order to speed-up the measurement of the score and improving the inter-observer variability in computing a score that requires strong expertise in electrocardiography. In this work, we evaluated the quality of the QuAReSS software for delivering correct Selvester scoring in a set of standard 12-lead ECGs. Method Standard 12-lead ECGs were recorded in 105 post-MI patients prescribed implantation of an implantable cardiodefibrillator (ICD). Amongst the 105 patients with standard clinical left bundle branch block (LBBB) patterns, 67 had a LBBB pattern meeting the strict criteria. The QuAReSS software was applied to these 67 tracings by two independent groups of cardiologists (from a clinical group and an ECG core laboratory) to measure the Selvester score semi-automatically. Using various level of agreement metrics, we compared the scores between groups and when automatically measured by the software. Results The average of the absolute difference in Selvester scores measured by the two independent groups was 1.4 ± 1.5 score points, whereas the difference between automatic method and the two manual adjudications were 1.2 ± 1.2 and 1.3 ± 1.2 points. Eighty-two percent score agreement was observed between the two independent measurements when the difference of score was within two point ranges, while 90% and 84% score agreements were reached using the automatic method compared to the two manual adjudications. Conclusion The study confirms that the QuAReSS software provides valid measurements of the Selvester score in patients with strict LBBB with minimal correction from cardiologists.

Stacked bonding is one of the most promising approaches to realize three-dimensional integration. In this paper, an analytical model is proposed for the low frequency and high frequency capacitance-voltage characteristics of the symmetric stacked bonding structure. The model is verified by the agreements between the analytical results and numerical simulation results using MEDICI, a two-dimensional semiconductor device simulator. Then, the influence of the doping concentration, oxide thickness and flat-band voltage on the capacitance-voltage characteristics under various bias conditions is researched. This work carries on an approach for the non-destructive characterization of the symmetric stacked bonding structure in three-dimensional integration.

Background The 2009 electrocardiographic Selvester QRS score for LBBB (2009 LBSS) is prognostic in CRT-patients. Previous studies show limited diagnostic performance in detecting and quantifying left ventricular (LV) scar determined by cardiovascular magnetic resonance imaging (CMR). We aimed to develop an improved method for ECG detection of scar using a large and broadly selected dataset of patients with LBBB. Methods and results We retrospectively identified LBBB patients (n = 325) with available ECG and late gadolinium enhancement (LGE) CMR exams from four centers (142 [44%] with > 0% CMR scar). ECG metrics were measured digitally and semi-automatically, and were compared to CMR-determined scar presence and extent. The 2009 LBSS did not accurately detect or quantify CMR scar (R 2 = 0.04, Area under the Receiver operating characteristic curve [AUC]: 0.60, [95% confidence interval: 0.54–0.66]). Multivariable stepwise logistic regression applied in 44 pre-determined ECG variables resulted in an improved 6-variable ECG model to detect CMR-scar (AUC 0.72 [0.66–0.77]). Furthermore, a single ECG variable (Lead I R/S amplitude ratio) was predictive of both scar presence (AUC 0.71 [0.65–0.77]) and of LV ejection fraction 2 = 0.21) Conclusions The 2009 LBSS does not accurately detect or quantify CMR scar. Extensive comparison of ECG and CMR identified a single ECG measure (lead I R/S amplitude ratio

A new on-chip current sensing circuit suitable for step-down switch-mode power converters (SMPC) is presented in this paper. It can be used in a high speed SMPC. The sense voltage is quite accurate and temperature independent. The structure is very simple. Only eight transistors and a sensing resistor are used. This current sensing technique has been fabricated with a standard 0.5µm DPDM CMOS process. Experimental results show that the proposed circuit can work well in DC-DC converters such that the loading current can be managed through control theories.

In this paper, a novel Lateral Diffused Metal Oxide Semiconductor (LDMOS) with linear graded drift region width is proposed. The device features a specific drift region with the lateral width increasing from source to drain, which modulates the electric field distribution and increases the doping concentration. The breakdown voltage exceeds 600V on the proposed LDMOS with 1μm SOI layer, 3μm buried oxide and 60μm drift region length. The characteristics are investigated by a three dimensional simulator. The simulation results show that a 135% increase in breakdown voltage and 5 times increase in figure of merits are achieved for the proposed device when compared with those of the conventional device.

Aims The Selvester QRS scoring system uses quantitative criteria from the standard 12-lead electrocardiogram (ECG) to estimate the myocardial scar size of patients, including those with left bundle branch block (LBBB). Automation of the scoring system could facilitate the clinical use of this technique which requires a set of multiple QRS patterns to be identified and measured. Methods and results We developed a series of algorithms to automatically detect and measure the QRS parameters required for Selvester scoring. The ‘QUantitative and Automatic REport of Selvester Score’ was designed specifically for the analysis of ECGs from patients meeting new strict criteria for complete LBBB. The algorithms were designed using a training ( n = 36) and a validation ( n = 180) set of ECGs, consisting of signal-averaged 12-lead ECGs (1000 Hz sampling) recorded from 216 LBBB patients from the MADIT-CRT. We assessed the performance of the methods using expert manually adjudicated ECGs. The average of absolute differences between automatic and adjudicated Selvester scoring was 1.2 ± 1.5 points. The range of average differences for continuous measurements of wave locations and interval durations varied between 0 and 6 ms. Erroneous detection of Q, R, S, R′, and S′ waves (oversensed or missed) were 3, 1, 1, 16, and 6%, respectively. Seven percent of notches detected in the first 40 ms were misdetected. Conclusion We propose an efficient computerized method for the automatic measurement of the Selvester score in patients with the strict LBBB.

Aims Strict left bundle branch block (LBBB) criteria were recently proposed to identify LBBB patients to benefit most from cardiac resynchronization therapy (CRT). The aim of our study was to automate identification of strict LBBB in order to facilitate its broader application. Methods We developed a series of algorithms to automatically detect and measure parameters required for strict LBBB criteria and proposed a definition of QRS notch detection. The algorithms were developed using training (n = 20) and validation (n = 592) sets consisting of signal-averaged 12-lead ECGs (1,000 Hz sampling) recorded from 612 LBBB patients from Multicenter Automatic Defibrillator Implantation Trial-CRT. Four trained clinicians independently performed adjudication on 148 different ECGs for comparing automatic and manually adjudicated results, in addition to 13 ECGs for evaluation of intraobserver variability and 32 ECGs for interobserver variability. We assessed the performance of the automated algorithms using manually adjudicated ECGs as references. Results Overall sensitivity and specificity for detecting strict LBBB were 95% and 86%, respectively. The mean absolute deviation (MAD) of QRS duration and notch/slur locations for the automated method versus the manual method was below 1 ms, and MAD values were lower than 2 ms for interobserver and intraobserver variability. Sensitivity and specificity for detecting notch and slur locations were 87% and 96% for notches and 78% and 90% for slurs using the automatic method. In addition 95% and 93% agreements for notches and 90% and 88% agreements for slurs were reached for intra- and interobserver. Conclusion The proposed algorithms automatically measure QRS features for the diagnosis of strict LBBB. Our study shows good performance in reference to manual results.

Varied Lateral Thickness (VLT) technology is a novel voltage-sustaining technology which has been developed recently. This paper focuses on the static and dynamic operation performance of SOI LDMOS using the VLT technology. Firstly, the VLT LDMOS is optimized by using the TCAD tool to maximize the off-state breakdown voltage. The results show that the drift doping concentration and the breakdown voltage of the VLT device increase by 59.2% and 11.8% compared with the conventional REduce SURface Field (RESURF) LDMOS, respectively. Secondly, the static I–V characteristic and the dynamic I–V characteristic of the both devices are investigated in detail. The carrier mobility and the impact ionization are analyzed to explore the physical mechanism of the electro-thermal couple effects under the continual and pulse biased voltages. The results show that the VLT LDMOS has higher breakdown voltage, larger operating current and improved static/dynamic Safe Operating Area (SOA).

Background Genotype‐phenotype investigations have revealed significantly larger risk for cardiac events in patients with type 1 long‐QT syndrome (LQT‐1), particularly in adult females, with missense mutation in the cytoplasmic loop (C‐loop) regions of the α subunit of the KCNQ1 gene associated with an impaired ion channel activation by adrenergic stimulus. We hypothesize that the impaired response to increases in heart rate leads to abnormal QT‐RR dynamic profiles and is responsible for the increased cardiac risk for these patients. Methods and Results We measured the QT‐RR slope in 24‐hour Holter ECGs from LQT‐1 patients with the mutations associated with impaired adrenergic stimulus (C‐loop, n=18) and compared to LQT‐1 patients with other mutations (non–C‐loop, n=48), and to a healthy control group (n=195). The diurnal QT‐RR slope was less steep in C‐loop mutation patients (0.10±0.05) than in the ECGs from non–C‐loop mutation patients (0.17±0.09, P =0.002). For female patients, slower heart rates were associated with prolonged QT and increased QT‐RR slope. Male patients with C‐loop mutations showed an impaired repolarization for shorter range of heart rates than in females, which is consistent with gender differences in triggers for events in this syndrome. Conclusions Our observations suggest that the C‐loop LQT‐1 patients have specific impaired adrenergic regulation of the ventricular repolarization. This response to heart rate increases may be useful in identification of high‐risk patients with inherited prolonged QT and may help select an optimal antiarrhythmic therapeutic strategy. ( J Am Heart Assoc . 2012;1:e000570 doi: 10.1161/JAHA.112.000570.)

A novel pixel readout circuit using a switched-capacitor integrator mode background suppression technique is proposed for long wavelength infrared (LWIR) focal plane arrays. It has ultra-low background suppression non-uniformity (BSNU) and no additional shot noise when suppressing the background current for improving signal-to-noise ratio and dynamic range. The BSNU can be as low as 529ppm for a current mismatch of 40% and a background current of 100nA.

This paper presents a new simple curvature-compensated CMOS voltage reference, which utilizes different temperature-dependent resistors, peaking current mirror circuit and subthreshold technology. Designed in a standard 0.5-µm CMOS technology, the proposed circuit achieves the reference voltage variation of 2.97mV for supply voltage ranging from 1.6 to 5V and 0.6mV for temperature varying from −20 to 80°C. It generates a reference voltage of 416mV and consumes a supply current of 0.86µA at 27°C and less than 1µA at 80°C. The occupied area is 0.037 mm2.

A low voltage MOSFET-only voltage reference using body effect and subthreshold operation is proposed in this paper1. A temperature coefficient of 5 ppm/°C from −55°C to 90 °C is achieved as the combined effects of: 1) a suppression of the temperature dependence of mobility; 2) a piecewise compensation of the temperature dependence of subthreshold slope parameter during the second half of temperature range. The voltage reference is designed in SMIC 0.13µm CMOS process. It is able to operate at power supply voltage down to 760mV and consumes a supply current of less than 1µA at 90°C.

The authors investigated whether computerized parameters quantifying ventricular repolarization delay, heterogeneity, and instability characterize individuals who developed drug-induced Torsades de Pointes. Assessing an individual's propensity to Torsades de Pointes when exposed to a QT-prolonging drug is challenging because baseline QT prolongation has limited predictive value. Five-minute digital 12-lead electrocardiograms were acquired at baseline and after a sotalol challenge in 16 patients who had a history of Torsades de Pointes in the context of a QT-prolonging drug and 17 patients who did not have such history. Computerized measurements of QTc, T peak to T end intervals (TpTe), TpTe/QTc, and QT variability were implemented, and novel quantifiers of ventricular repolarization heterogeneity from the early (ERD) and late (LRD) part of the T wave were investigated. Compared with electrocardiograms of patients without a history of Torsades de Pointes, the baseline electrocardiograms of patients with a history of Torsades de Pointes had a longer QTc and an increased repolarization heterogeneity of the early part of the T wave (ERD30%: 44 +/- 13 vs 35 +/- 8 ms, P = .02). On sotalol, the electrocardiograms from individuals with Torsades de Pointes revealed a delay of the terminal part of the T wave that was not present in patients without Torsades de Pointes (TpTe: 27 +/- 40 vs -2 +/- 21 ms, P = .02; LRD70%: 20 +/- 29 vs 2 +/- 4 ms, P = .04). Results suggest that the electrocardiogram abnormalities characterizing patients with a history of Torsades de Pointes are (1) an increased repolarization heterogeneity at baseline and (2) a sotalol-induced prolongation of the terminal part of the T wave.

In this study, we investigated the ability of a QT algorithm to detect small drug-induced QT interval prolongation by adopting a ldquohighly-automatizedrdquo approach. In a set of 8,911 digital ECGs, we analyzed the drug-concentration profile of computerized QTc to the measurements submitted to the Food and Drug Administration (FDA) by pharmaceutical companies. The RR and QT intervals were measured using lead II based on a QT algorithm included in the COMPAS software package developed at University of Rochester Medical Center, NY. When comparing the time-dependent effect of the drug on the QTc interval the automatic technique produced results similar to the measurements reported by contract research organizations to the Agency (FDA).

This paper reports the design and test of an improved direct-injection readout circuit for infrared focal plane arrays (IRFPA). In this circuit, two selectable capacitors are added in the pixel to accommodate the wide range of illumination conditions. The circuit also supports image transposition (invert/revert). A 128×128 pixels readout circuit chip which uses this improved readout circuit structure has been fabricated. A simple test bench is established to verify the availability of the readout chip. The testing method and results are also presented in this paper. The testing results show the good performance of the readout chip.

A high performance, 128×128 pixel, snapshot Readout Integrated Circuit (ROIC) for IRFPA has been fabricated with 0.5µm Double Poly Double Metal (DPDM) n-well CMOS process. The pixel cell circuit uses an improved direct injection structure with only four transistors to maintain large enough integration capacitror. One pixel cell occupies an area of 50×50µm 2 . Each row’s pixel signals are readout to the column amplifiers row by row in parallel, while the column amplifiers are reset after each row’s pixel signals are readout. The whole pixel cells are reset wholly after a frame signals are all readout. The ROIC structure also provides dynamic image transpositionxinyuanjing xinyuanjing xi (Invert, Revert) function to support a wide range of system requirements. It still has a build-in temperature sensor to detect the temperature of the chip. The measurement results show that the readout chip works well at both room temperature and 77K with 5V supply voltage. The fabricated chip has a maximum charge storage capacity of 6.48×10

several important non-cardiac drugs have been removed from the market after revealing harmful effect that was not identified during prior safety-assessment studies. We developed a new technique for the measurements of repolarization abnormalities from surface ECGs; this method improves sensitivity and specificity of the current technique used to identify the presence of abnormal ion current kinetics in the myocardial cells namely a prolongation of the QT interval on the surface ECG signal. We described in this paper the method and preliminary results, revealing the superiority of our technique that may play a role in the future of drug-safety assessment. I. INTRODUCTION Prolongation of the QT interval from the surface electrocardiogram (ECG) is currently used as a surrogate marker of drug cardiotoxicity because it is associated with an increased risk of "torsade de pointes" (TdP), a rare and dangerous type of polymorphic ventricular tachycardia (1). The US Food and Drug Agency (FDA) currently recommends to pharmaceutical companies to test the safety of all new compounds for their potential QT prolonging effect. This safety assessment is based on a clinical trial specifically designed for identifying drug- induced QT prolongation: such studies are called "thorough QT studies" (tQTS). Because there is no standard for the technique used in measuring the QT interval from the surface ECG (2), the Agency requires that the QT- measurement technique be validated on a positive control group consisting of groups of healthy individuals on an antibiotic drug called moxifloxacin that is known to prolong

Assessing the propensity of an individual to drug-induced arrhythmias when exposed to a QT-prolonging drug is challenging because baseline QT prolongation has limited predictive value. In this study, we investigated the role of computerized ECG parameters quantifying T-wave morphology for the identification of individuals who developed drug-induced torsades de pointes (TdPs). In 34 patients, 5-minute digital ECGs have been acquired at baseline and during sotalol challenge. Seventeen of these patients had a history of drug-induced TdPs. We identified specific baseline features of the T-waves common to patients with history of TdPs. The sotalol-induced changes of T-wave morphologies were also different between the two groups suggesting that ECGs may provide relevant information for the identification of patients with an increased propensity to TdPs.

BACKGROUND The clinical course and the precipitating risk factors in the congenital long QT syndrome (LQTS) are genotype specific. OBJECTIVES The goal of this study was to develop a computer algorithm allowing for electrocardiogram (ECG)-based identification and differentiation of LQT1 and LQT2 carriers. METHODS Twelve-lead ECG Holter monitor recordings were acquired in 49 LQT1 carriers, 25 LQT2 carriers, and 38 healthy subjects as controls. The cardiac beats were clustered based on heart-rate bin method. Scalar and vectorial repolarization parameters were compared for similar heart rates among study groups. The Q to Tpeak (QTpeak), the Tpeak to Tend interval, T-wave magnitude and T-loop morphology were automatically quantified using custom-made algorithms. RESULTS QTpeak from lead II and the right slope of the T-wave were the most discriminant parameters for differentiating the 3 groups using prespecified heart rate bin (75.0 to 77.5 beats/min). The predictive model utilizing these scalar parameters was validated using the entire spectrum of heart rates. Both scalar and vectorcardiographic models provided very effective identification of tested subjects in heart rates between 60 and 100 beats/min, whereas they had limited performance during tachycardia and slightly better discrimination in bradycardia. In the 60 to 100 beats/min heart rate range, the best 2-variable model identified correctly 89% of healthy subjects, 84% of LQT1 carriers, and 92% of LQT2 carriers. A model including 3 parameters based purely on scalar ECG parameters could correctly identify 90% of the population (89% of healthy subjects, 90% of LQT1 carriers, and 92% of LQT2 carriers). CONCLUSION Automatic algorithm quantifying T-wave morphology discriminates LQT1 and LQT2 carriers and healthy subjects with high accuracy. Such computerized ECG methodology could assist physicians evaluating subjects suspected for LQTS.

Over the past five years, regulatory authorities have been increasingly concerned with QT prolongations induced by non-cardiac drug and have recommended pharmaceutical companies to include a careful assessment of the QT interval in their drug development programs. There are controversies around the predictive value of QT prolongation in safety-drug assessment studies. The prolongation of the QT interval is an imperfect, but accepted, surrogate marker of drug cardiac toxicity. In this study, we hypothesize that the inhomogeneous effect of QT-prolonging drug in the different layers of the myocardium would not only delay cardiac repolarization, but also perturb the repolarization wavefront on surface ECGs. Principal component analysis (PCA) was applied to the 12-lead ECG Holier recordings. The first two eigenvectors (ev1, ev2) were computed. From PCA, several parameters were calculated based on the first eigenvector and on the T-loop. We demonstrated slower repolarization and perturbed T-wave front; 30 min after sotalol administration, turbulence of repolarization velocity increased by 9.02%, p

Atypical T wave morphology on scalar ECG may reflect abnormalities of the ventricular repolarization process but the link between these abnormalities and the occurrence of arrhythmic events is unclear. In this study, we investigated whether the occurrence of ventricular tachycardia (VT) in patients with dilated cardiomyopathy (DCM) have specific T wave morphology that may characterize their increased risk for cardiac death (CD). From 24-hour Holter ECG recordings, T-wave morphology and symmetry were quantified in the three orthogonal leads using T-wave area based measurements in addition to conventional QT interval measurements. We compared the T wave characteristics (duration and morphology) between patients according to their cardiac history (VT or CD). Our results did not evidence significant differences in QT durations between patients with and without a history of VT at any heart rate but revealed a prolongation of the terminal portion of the T-wave at high heart rate in patients with VT (91 /spl plusmn/ 21 vs. 102 /spl plusmn/ 20 ms, p = 0.03 for RR between 600-700 ms). Analysis of T wave morphology may play a role in the identification of patients with dilated cardiomyopathy at higher risk for arrhythmic events.

Results: A comparison of EMG-EDR breath locations to the reference using a 1.6-s match window (representing 20% of average breath-to-breath interval) yielded a sensitivity of 94% and a positive predictive value of 95%. Discussion: EMG-EDR performed well with minimal errors in representation of respiration activity. However, most errors were caused by one subject's occasional atrial premature beats (APBs) which inhibited MRI triggering, and thus resulted in an apparent drop in the baseline EMG levels; this caused a subsequent but temporary distortion of the EMG-EDR waveform. Data from more subjects are currently being obtained. Conclusion: On this limited data set, the ECG/EMG-derived respiration technique performs well even in the electrically noisy MRI environment. Additional algorithm logic is needed to reduce the effects of APBs. Use of this technique may allow elimination of the additional hardware of the respiratorygating belt, since ECG signals are already acquired during cardiacMRI imaging.

By solving 2-D Poisson’s equation, a new analytical model to calculate the electric field distribution of a SOI RESURF device with Dual Conduction Layers (Dual-CL) is firstly proposed. The proposed model is also available for the single RESURF and triple RESURF SOI devices without any modification. A matrix equation is developed for the determination of the lateral and vertical breakdown voltages, in which the influences of the N-top layer, P-top layer, and the N-drift region are all considered. A unified RESURF criterion of single RESURF, triple RESURF, and Dual-CL SOI devices is further derived for optimizing the structure parameters. A good agreement between the analytical results and the numerical results shows that the N-top layer and P-top layer have opposite impacts on the breakdown performance of Dual-CL SOI devices. In addition, an optimal trade-off between the breakdown voltage and the specific on-resistance for the triple RESURF and Dual-CL SOI devices is obtained due to the incorporati...

www.elsevier.com/locate/jelectrocard Heart rate bin method for identifying repolarization changes in LQT1 and LQT2 patients Martino Vaglio, Jean-Philippe Couderc, Scott McNitt, Xiaojuan Xia, Wojciech Zareba, Arthur J. Moss (Heart Research Follow-up Program, Cardiology, Department, University of Rochester Medical Center, Rochester, NY 14642, USA) The clinical course and the precipitating risk factors in the congenital long QT syndrome are genotype-specific. Among long QT syndrome mutations, KvLQT1 (LQT1) and HERG (LQT2) mutations have an increased risk of recurrent cardiac events and their early diagnosis and treatment is crucial to reduce the risk of mortality. Twelvelead electrocardiogram Holters were recorded in 49 LQT1 and 25 LQT2 carriers. The cardiac beats were clustered based on heart rate (HR) and scalar and vectorial repolarization parameters were compared for similar HR. 0022-0736/$ – see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.jelectrocard.2006.05.019 The QT, QTpeak and the Tpeak to Tend intervals, T-wave magnitude as well as T-loop morphology were automatically quantified using custom-made algorithms. T-wave magnitude and Tpeak to Tend interval from lead V5 were the most discriminant parameters. The predictive model using these scalar parameters provided 87% sensitivity and 96% specificity for discriminating LQT1 and LQT2 carriers. A model including 3 parameters based on the vectorial T-loop reached 96% of sensitivity and 96% of specificity. T-wave morphology (mainly T-wave magnitude) was found as HR-independent in LQT2 carriers, whereas it was HR-dependent in LQT1 carriers. In conclusion, automatic algorithm quantifying T-wave morphology discriminates LQT1 and LQT2 carriers with high accuracy. T-wave morphology presents distinct heart-rate dynamics by genotype.

Background: The morphology of the T-wave reflects abnormalit ies of the ventricular repolatiation process but only very few studies have shown the link between these abnormalit ies and arhythmic events. In this study, we investigated the changes in T-wave morphology in patients with dilated cardiomyopathy (DCM) and compared the morphologies between patients with or without prior documented ventricular tachycardia. Methods: An index of repolarization asymmetry (IRAc) based on the area under the T wave was computed from the T apex to quantify the morphology of the T wave, 24.hour Halter recordings with three orthogonal leads. T wave morphology was assessed in 43 patients including 10 patients with prior documented VT and 33 patients free of documented ventricular arrhythmias. W e used OUT custom-made software for repolarization analysis and analyzed the heart rate, QT apex, QT offset and two area-based parameters (QTA25% and QTa50%). Results: Patients with history of VT had significantly higher value of IRAc than patients without VT (96&28 vs. 77&17 ms, respectively; p=O.O26). None of the other repolarization parameters showed significant differences between groups. The values for the other repolarization parameters were the following: QTc apex was 332&38 for VT(-), 331&40 for VT(+);QTc25% was 255&3 for VT(-) and 235&30 for VT(+); QTc was 436&40 for VT(-) and 441&28 for VT(+). The RR intervals were 879&185 and 958&187 for VT(-) and VT (+), respectively. Conclusion: Dilated cardiomyopathy patients with history of ventricular tachycardia had more asymmetric T wave than those without arhythmic events in the past. T wave morphology analysis could lead to identifying high-risk patients with dilated cardiomyopathy.