Improvement of Left Ventricular Function by Permanent Direct His-Bundle Pacing in a Case with Dilated Cardiomyopathy

The patient was a 67-year-old female diagnosed with dilated cardiomyopathy. She had chronic atrial fibrillation (AF) with bradycardia and low left ventricular function (left ventricular ejection fraction (LVEF) 40%). She was admitted for congestive heart failure. She remained New York Heart Association (NYHA) functional class III due to AF bradycardia. Pacemaker implantation was necessary for treatment of heart failure and administration of dose intensive β-blockers. As she had normal His-Purkinje activation, we examined the optimal pacing sites. Hemodynamics of His-bundle pacing and biventricular pacing were compared. Pulmonary capillary wedge pressure (PCWP) was significantly lower on Hisbundle pacing than right ventricular (RV) apical pacing and biventricular pacing (13mmHg, 19mmHg, and 19mmHg, respectively) with an almost equal cardiac index. Based on the examination we implanted a permanent pacemaker for Direct His-bundle pacing (DHBP). After the DHBP implantation, the LVEF immediately improved from 40% to 55%, and BNP level decreased from 422 pg/ml to 42 pg/ml. The number of premature ventricular complex (PVC) was decreased, and non sustained ventricular tachycardia (NSVT) disappeared. Pacing threshold for His-bundle pacing has remained at the same level. His-bundle pacing has been maintained during 27 months and her long-term DHBP can improve cardiac function and the NYHA functional class

Mathematical Identification of Critical Reactions in the Interlocked Feedback Model

Dynamic simulations are necessary for understanding the mechanism of how biochemical networks generate robust properties to environmental stresses or genetic changes. Sensitivity analysis allows the linking of robustness to network structure. However, it yields only local properties regarding a particular choice of plausible parameter values, because it is hard to know the exact parameter values in vivo. Global and firm results are needed that do not depend on particular parameter values. We propose mathematical analysis for robustness (MAR) that consists of the novel evolutionary search that explores all possible solution vectors of kinetic parameters satisfying the target dynamics and robustness analysis. New criteria, parameter spectrum width and the variability of solution vectors for parameters, are introduced to determine whether the search is exhaustive. In robustness analysis, in addition to single parameter sensitivity analysis, robustness to multiple parameter perturbation is defined. Combining the sensitivity analysis and the robustness analysis to multiple parameter perturbation enables identifying critical reactions. Use of MAR clearly identified the critical reactions responsible for determining the circadian cycle in the Drosophila interlocked circadian clock model. In highly robust models, while the parameter vectors are greatly varied, the critical reactions with a high sensitivity are uniquely determined. Interestingly, not only the per-tim loop but also the dclk-cyc loop strongly affect the period of PER, although the dclk-cyc loop hardly changes its amplitude and it is not potentially influential. In conclusion, MAR is a powerful method to explore wide parameter space without human-biases and to link a robust property to network architectures without knowing the exact parameter values. MAR identifies the reactions critically responsible for determining the period and amplitude in the interlocked feedback model and suggests that the circadian clock intensively evolves or designs the kinetic parameters so that it creates a highly robust cycle

Validation of tsunami numerical simulation models for an idealized coastal industrial site

Numerous tsunami numerical models have been proposed, but their prediction accuracies have not been directly compared. For quantifying the modeling uncertainties, the authors statistically analyzed the prediction results submitted by participants in the tsunami blind contest held at the 17th World Conference on Earthquake Engineering. The reproducibility of offshore water level generated due to the tsunami with soliton fission significantly decreased when the nonlinear shallow water equation models (NSWE) was used compared to threedimensional (3D) models. The inundation depth was reproduced well in 3D models. However, the reproducibility of wave forces acting on the structure and velocities over land was lower in 3D models than that in NSWE models. For cases where the impulsive tsunami wave pressure generated could not be calculated based on the hydrostatic assumption, the prediction accuracy of the NSWE models was higher than that of the 3D models. The prediction accuracies of both models were not improved at small grid-cell sizes. The NSWE model cannot simulate the short-wave component and vertical pressure distribution. Therefore, further developments in 3D models and smoothed particle hydrodynamics methods (SPH) are needed. The presented results contribute to the future development of tsunami numerical simulation tools

Validation of tsunami numerical simulation models for an idealized coastal industrial site

Numerous tsunami numerical models have been proposed, but their prediction accuracies have not been directly compared. For quantifying the modeling uncertainties, the authors statistically analyzed the prediction results submitted by participants in the tsunami blind contest held at the 17th World Conference on Earthquake Engineering. The reproducibility of offshore water level generated due to the tsunami with soliton fission significantly decreased when the nonlinear shallow water equation models (NSWE) was used compared to three-dimensional (3D) models. The inundation depth was reproduced well in 3D models. However, the reproducibility of wave forces acting on the structure and velocities over land was lower in 3D models than that in NSWE models. For cases where the impulsive tsunami wave pressure generated could not be calculated based on the hydrostatic assumption, the prediction accuracy of the NSWE models was higher than that of the 3D models. The prediction accuracies of both models were not improved at small grid-cell sizes. The NSWE model cannot simulate the short-wave component and vertical pressure distribution. Therefore, further developments in 3D models and smoothed particle hydrodynamics methods (SPH) are needed. The presented results contribute to the future development of tsunami numerical simulation tools.Published versio