scholarly journals T vector velocity: A new ECG biomarker for identifying drug effects on cardiac ventricular repolarization

2018 ◽  
Author(s):  
Werner Bystricky ◽  
Christoph Maier ◽  
Gary Gintant ◽  
Dennis Bergau ◽  
Kent Kamradt ◽  
...  
Keyword(s):  
Electrical Activity ◽  
Drug Effects ◽  
Ventricular Repolarization ◽  
The Body ◽  
Calcium Currents ◽  
Published Data ◽  
Ion Currents ◽  
Vector Velocity ◽  
Surface Ecg ◽  
Auc Value

AbstractWe present a new family TrX of ECG biomarkers based on the T vector velocity (TVV) for assessing drug effects on ventricular repolarization. Assuming a link between the TVV and the instantaneous change of the cellular action potentials, drugs accelerating repolarization by blocking inward (depolarizing) ion currents cause a relative increase of the TVV, while drugs delaying repolarization by blocking outward ion currents cause a relative decrease of the TVV.Evaluating the published data from two FDA funded studies, the TrX effect profiles indicate increasingly delayed electrical activity over the entire repolarization process for drugs solely reducing outward potassium current (dofetilide, moxifloxacin). For drugs eliciting block of the inward sodium or calcium currents (mexiletine, lidocaine), the TrX effect profiles were consistent with accelerated electrical activity in the initial repolarization phase. For multichannel blocking drugs (ranolazine) or drug combinations blocking multiple ion currents (dofetilide + mexiletine, dofetilide + lidocaine), the overall TrX effect profiles indicate a superposition of the individual TrX effect profiles.The parameter Tr40c allows separating pure potassium channel blocking drugs from multichannel blocking drugs with an area under the ROC curve (AUC) value of 0.90, CI = [0.88 to 0.92]. This is significantly larger than the performance of J-Tpeakc (0.81, CI = [0.78 to 0.84]) using the published data from the second FDA study. Further performance improvement was achieved by combining the ten parameters Tr10c to Tr100c in a logistic regression model, resulting in an AUC value of 0.94.The TVV based approach substantially improves assessment of drug effects on cardiac repolarization, providing a plausible and improved mechanistic link between drug effects on ionic currents and overall ventricular repolarization reflected in the body surface ECG. TVV may contribute to a better assessment of the proarrhythmic risk of drugs beyond QTc prolongation and JTpeakc.

A new method to determine the electrical transfer function of the human thorax

2007 ◽  
Vol 293 (6) ◽  
pp. H3440-H3447 ◽  
Author(s):  
Jeffrey J. Goldberger ◽  
Haris Subacius ◽  
Indranil Sen-Gupta ◽  
David Johnson ◽  
Alan H. Kadish ◽  
...  
Keyword(s):  
Electrical Activity ◽  
Transfer Functions ◽  
Phase Transfer ◽  
Electrophysiological Study ◽  
Linear Regression Analysis ◽  
The Body ◽  
Cardiac Electrical Activity ◽  
Intracardiac Electrogram ◽  
Body Tissues ◽  
Surface Ecg

Traditional analyses have assumed that cardiac electrical activity is reflected on the surface ECG without distortion as the signal passes through the body tissues. This study aims to explore the frequency dependence of thoracic attenuation of surface-recorded intracardiac electrical activity. Twenty patients (14 men, 55 ± 15 yr of age) undergoing electrophysiological study were enrolled. Rectangular unipolar stimuli were applied from a catheter positioned in the right ventricular apical area and another in the posteroseptal area without contact with the myocardium. An orthogonal Frank-lead surface ECG and a unipolar intracardiac electrogram near the pacing site were recorded. Frequency domain characteristics of the signal-averaged pacing impulses were analyzed. Linear regression analysis showed significant frequency-dependent attenuation in the magnitude transfer functions ( R2 = 0.84–0.89, P < 0.0001) and good linear fit for the phase transfer characteristics ( R2 = 0.98–1.0, P < 0.0001). Age, physical dimension, and respiratory characteristics had significant effects on the magnitude and phase characteristics of the transfer functions. Application of models of the low- and high-slope transfer functions to signal-averaged ECGs from 33 subjects showed differences in the attenuation of P and T waves relative to the QRS.

scholarly journals T vector velocity: A new ECG biomarker for identifying drug effects on cardiac ventricular repolarization

PLoS ONE ◽  
2019 ◽  
Vol 14 (7) ◽  
pp. e0204712 ◽  
Author(s):  
Werner Bystricky ◽  
Christoph Maier ◽  
Gary Gintant ◽  
Dennis Bergau ◽  
Kent Kamradt ◽  
...  
Keyword(s):  
Drug Effects ◽  
Ventricular Repolarization ◽  
Vector Velocity

The Role of Computer Modeling in Electrocardiography

1990 ◽  
Vol 29 (04) ◽  
pp. 282-288 ◽  
Author(s):  
A. van Oosterom
Keyword(s):  
Electrical Activity ◽  
Computer Modeling ◽  
Body Surface ◽  
Electrical Current ◽  
The Body ◽  
Volume Conductor ◽  
Current Generator ◽  
Cardiac Electrical Activity ◽  
Source Models

AbstractThis paper introduces some levels at which the computer has been incorporated in the research into the basis of electrocardiography. The emphasis lies on the modeling of the heart as an electrical current generator and of the properties of the body as a volume conductor, both playing a major role in the shaping of the electrocardiographic waveforms recorded at the body surface. It is claimed that the Forward-Problem of electrocardiography is no longer a problem. Several source models of cardiac electrical activity are considered, one of which can be directly interpreted in terms of the underlying electrophysiology (the depolarization sequence of the ventricles). The importance of using tailored rather than textbook geometry in inverse procedures is stressed.

scholarly journals Prevention of Advanced Cancer by Vitamin D3 Supplementation: Interaction by Body Mass Index Revisited

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1408
Author(s):  
Hermann Brenner ◽  
Sabine Kuznia ◽  
Clarissa Laetsch ◽  
Tobias Niedermaier ◽  
Ben Schöttker
Keyword(s):  
Body Mass Index ◽  
Vitamin D ◽  
Cancer Patients ◽  
Body Mass ◽  
Advanced Cancer ◽  
Vitamin D3 ◽  
Normal Weight ◽  
The Body ◽  
Published Data ◽  
Vitamin D3 Supplementation

Meta-analyses of randomized controlled trials (RCTs) have demonstrated a protective effect of vitamin D3 (cholecalciferol) supplementation against cancer mortality. In the VITAL study, a RCT including 25,871 men ≥ 50 years and women ≥ 55 years, protective effects of vitamin D3 supplementation (2000 IU/day over a median of 5.3 years) with respect to incidence of any cancer and of advanced cancer (metastatic cancer or cancer death) were seen for normal-weight participants but not for overweight or obese participants. We aimed to explore potential reasons for this apparent variation of vitamin D effects by body mass index. We conducted complementary analyses of published data from the VITAL study on the association of body weight with cancer outcomes, stratified by vitamin D3 supplementation. Significantly increased risks of any cancer and of advanced cancer were seen among normal-weight participants compared to obese participants in the control group (relative risk (RR), 1.27; 95% confidence interval (CI), 1.07–1.52, and RR, 1.44; 95% CI, 1.04–1.97, respectively). No such patterns were seen in the intervention group. Among those with incident cancer, vitamin D3 supplementation was associated with a significantly reduced risk of advanced cancer (RR, 0.86; 95% CI, 0.74–0.99). The observed patterns point to pre-diagnostic weight loss of cancer patients and preventive effects of vitamin D3 supplementation from cancer progression as plausible explanations for the body mass index (BMI)—intervention interactions. Further research, including RCTs more comprehensively exploring the potential of adjuvant vitamin D therapy for cancer patients, should be pursued with priority.

scholarly journals Classification of Shoulder X-ray Images with Deep Learning Ensemble Models

2021 ◽  
Vol 11 (6) ◽  
pp. 2723
Author(s):  
Fatih Uysal ◽  
Fırat Hardalaç ◽  
Ozan Peker ◽  
Tolga Tolunay ◽  
Nil Tokgöz
Keyword(s):  
Deep Learning ◽  
Performance Test ◽  
The Body ◽  
Test Accuracy ◽  
Cohen’S Kappa ◽  
X Ray ◽  
Cohen's Kappa ◽  
Auc Value ◽  
Magnetic Resonance Imaging Mri ◽  
Fully Connected

Fractures occur in the shoulder area, which has a wider range of motion than other joints in the body, for various reasons. To diagnose these fractures, data gathered from X-radiation (X-ray), magnetic resonance imaging (MRI), or computed tomography (CT) are used. This study aims to help physicians by classifying shoulder images taken from X-ray devices as fracture/non-fracture with artificial intelligence. For this purpose, the performances of 26 deep learning-based pre-trained models in the detection of shoulder fractures were evaluated on the musculoskeletal radiographs (MURA) dataset, and two ensemble learning models (EL1 and EL2) were developed. The pre-trained models used are ResNet, ResNeXt, DenseNet, VGG, Inception, MobileNet, and their spinal fully connected (Spinal FC) versions. In the EL1 and EL2 models developed using pre-trained models with the best performance, test accuracy was 0.8455, 0.8472, Cohen’s kappa was 0.6907, 0.6942 and the area that was related with fracture class under the receiver operating characteristic (ROC) curve (AUC) was 0.8862, 0.8695. As a result of 28 different classifications in total, the highest test accuracy and Cohen’s kappa values were obtained in the EL2 model, and the highest AUC value was obtained in the EL1 model.

Hippocampal pyramidal cells: significance of dendritic ionic conductances for neuronal function and epileptogenesis

1979 ◽  
Vol 42 (2) ◽  
pp. 476-496 ◽  
Author(s):  
R. D. Traub ◽  
R. Llinas
Keyword(s):  
Hot Spots ◽  
Potassium Conductance ◽  
Pyramidal Cells ◽  
Calcium Currents ◽  
Membrane Properties ◽  
Repetitive Firing ◽  
Published Data ◽  
Neuronal Responses ◽  
Voltage Dependent ◽  
Hippocampal Pyramidal Cells

1. Starting with published data derived mainly from hippocampal slice preparations, we have used computer-modeling techniques to study hippocampal pyramidal cells (HPCs). 2. The dendrites of the HPC apparently have a short electrotonic length. Calcium spikes are apparently generated by a voltage-dependent mechanism whose kinetics are slow in comparison with those generating sodium spikes of the soma. Inward calcium currents are assumed to trigger a long-lasting potassium conductance. This slow calcium-potassium system, which in our model is located predominantly on the dendrites, provides a heuristic model to describe the mechanism for a) the after-depolarization following an HPC soma (sodium) spike, b) the long afterhyperpolarization following repetitive firing, c) bursts of spikes that sometimes occur after orthodromic or antidromic stimulation, and d) the buildup of the "depolarizing shift" during the strong synaptic input presumed to occur during seizures. 3. Fast prepotentials or d-spikes are shown to arise most probably from dendritic "hot spots" of sodium-regenerative membrane. The limited amplitude and short duration of these prepotentials imply that the hot spots are located on small dendrites. 4. Dendritic electroresponsiveness, first postulated for the HPC by Spencer and Kandel (52), is analyzed quantitatively here and is shown to provide rich integrative possibilities for this cell. Our model suggests that, for these nerve cells, alterations in specific membrane properties, particularly calcium electroresponsiveness, can lead to bursting behavior that resembles epileptogenic neuronal responses.

scholarly journals Multiple Linear Regression Analysis of lncRNA–Disease Association Prediction Based on Clinical Prognosis Data

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Bo Wang ◽  
Jing Zhang
Keyword(s):  
Prostate Cancer ◽  
Linear Regression ◽  
Multiple Linear Regression ◽  
Cancer Survival ◽  
Disease Association ◽  
The Body ◽  
Survival Prediction ◽  
Clinical Prognosis ◽  
Disease Associations ◽  
Auc Value

Long noncoding RNAs (lncRNAs) have an important role in various life processes of the body, especially cancer. The analysis of disease prognosis is ignored in current prediction on lncRNA–disease associations. In this study, a multiple linear regression model was constructed for lncRNA–disease association prediction based on clinical prognosis data (MlrLDAcp), which integrated the cancer data of clinical prognosis and the expression quantity of lncRNA transcript. MlrLDAcp could realize not only cancer survival prediction but also lncRNA–disease association prediction. Ultimately, 60 lncRNAs most closely related to prostate cancer survival were selected from 481 alternative lncRNAs. Then, the multiple linear regression relationship between the prognosis survival of 176 patients with prostate cancer and 60 lncRNAs was also given. Compared with previous studies, MlrLDAcp had a predominant survival predictive ability and could effectively predict lncRNA–disease associations. MlrLDAcp had an area under the curve (AUC) value of 0.875 for survival prediction and an AUC value of 0.872 for lncRNA–disease association prediction. It could be an effective biological method for biomedical research.

scholarly journals Association between Cancer and Anatomical Site of Venous Thromboembolic Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-6
Author(s):  
David A Froehling ◽  
Damon E. Houghton ◽  
Waldemar E. Wysokinski ◽  
Robert D. McBane ◽  
Danielle Vlazny ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Upper Extremity ◽  
Renal Vein ◽  
The Body ◽  
Published Data ◽  
Anatomical Site ◽  
Pulmonary Emboli ◽  
Vein Thrombosis ◽  
Deep Vein ◽  
Active Cancer

Background:There is limited published data on the association between malignancy and the location of venous thromboembolism (VTE) in the body. Aims:Assess the location of VTE in the body in patients with active cancer and compare these results in patients without malignancy. Methods:Consecutive patients enrolled in the Mayo Clinic VTE Registry between March 1, 2013 and November 30, 2019 for acute VTE were followed prospectively. Anatomical site of thrombosis and malignancy status were recorded. Patient outcomes were assessed in person, by mailed questionnaire, or by a scripted phone interview. Active cancer was defined as treatment for malignancy within the last six months or not yet in remission. Results:During the study period there were 2,798 patients with acute VTE (1256 with and 1542 without active cancer). Pulmonary emboli were more common in patients with active cancer compared to patients without cancer (49.5% vs. 39.7%, p&lt;0.001). Upper extremity deep vein thrombosis (11.4 % vs. 7.7%, p&lt;0.001), renal vein thrombi (1.4% vs. 0.2%, p&lt;0.001) and splanchnic vein thrombi (9.3% vs. 6.0%, p=0.001) were all more common in patients with active cancer compared to patients without cancer. Conclusion:Compared to those without malignancy, patients with active cancer were more likely to have pulmonary emboli, upper extremity deep vein thrombosis, renal vein thrombi, and splanchnic vein thrombi. Disclosures No relevant conflicts of interest to declare.

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