A framework for dynamical generation of flavor mixing

We present a dynamical mechanism \`a la Nambu--Jona-Lasinio for the generation of masses and mixing for two interacting fermion fields. The analysis is carried out in the framework introduced long ago by Umezawa et al., in which mass generation is achieved via inequivalent representations, and that we generalize to the case of two generations. The method allows a clear identification of the vacuum structure for each physical phase, confirming previous results about the distinct physical nature of the vacuum for fields with definite mass and fields with definite flavor. Implications for the leptonic sector of the Standard Model are briefly discussed.Comment: 13 pages. Presented at "Symmetries in Science XVI, Bregenz 2013

Dynamic escape game

We introduce Dynamic Escape Game (DEC), a tool that provides emergency evacuation plans in situations where some of the escape paths may become unavailable at runtime. We formalize the setting as a reachability two-player turn-based game where the universal player has the power of inhibiting at runtime some moves to the existential player. Thus, the universal player can change the structure of the game arena along a play. DEC uses a graphical interface to depict the game and displays a winning play whenever it exists

Cardiac Response to Live Music Performance: Computing Techniques for Feature Extraction and Analysis

Strong emotions and mental stress have been linked to potentially deadly arrhythmias. Music evokes strong emotion through the regulation of tension and release and the modulation of changes and transitions. We exploit this in a novel study involving patients with implanted cardiac defibrillators to study the impact of live music performance on cardiac electrophysiology. The patients’ heart rates are artificially fixed with pacing at the higher of 80 beats per minute or 10 above the heart’s intrinsic rate. We make continuous recordings directly from the heart muscle whilst the patients are listening to a short classical music concert, which is concurrently recorded in a separate stream. The participants provide annotations of perceived boundaries/transitions and felt tension. The recorded cardiac and music information is further processed to extract relevant features. Here, we describe the experiment design, and the mathematical and computing techniques used to represent and abstract the features from the recorded data. Cardiac reaction is measured by the action potential duration (APD), approximated using the action recovery interval (ARI). The expressive parameters extracted from the music include the time varying loudness, tempo, and harmonic tension. The synchronized information layers allow for detailed analysis of immediate cardiac response to dynamically varying expressive nuances in performed music

Gaining approval for clinical research

Set-up and delivery of a clinical research project can be complicated and difficult. This article introduces the regulatory processes involved in gaining approval for clinical research and discusses the obstacles that may be encountered

Prognostic significance of exercise-induced premature ventricular complexes: a systematic review and meta-analysis of observational studies

BACKGROUND: Exercise-induced premature ventricular complexes (EI-PVCs) are common during exercise stress tests. Their optimal management and prognostic significance remain uncertain. AIM: To perform meta-analysis of observational studies on the prognostic significance of EI-PVCs. METHODS: A search was conducted on Medline and Embase. Inclusion criteria were observational studies comparing the prognosis of patients with and without EI-PVCs whilst exclusion criteria were studies without confounder adjustment and studies with zero endpoints. Composite endpoints included all-cause mortality, cardiac mortality and cardiovascular events. Relative risk of endpoints were analysed with random effects model. Meta-regression and sensitivity analysis were performed. RESULTS: Ten studies were included. In asymptomatic patients who had no clinical evidence of heart disease, EI-PVCs were associated with a pooled risk ratio of 1.82 (95% CI 1.44 to 2.30) of developing adverse cardiovascular events over 16 years. The corresponding pooled RR for patients with symptomatic heart disease was 1.36 (95% CI 1.18 to 1.57) over 5.4 years. Sensitivity analysis: only EI-PVCs on the recovery phase of an exercise test, not during exercise, had adverse prognostic significance. CONCLUSIONS: EI-PVCs are correlated with a higher risk of all cause death or cardiovascular events in the long term. This risk is elevated in asymptomatic patients without clinical heart disease and in patients with symptomatic heart disease. The fact that only EI-PVCs during recovery, and not during exercise, have poor prognostic value suggests that autonomic dysfunction may play a role in this association. Further studies are needed to see if autonomic manipulation by drugs or catheter-based methods can improve the poor prognosis associated with EI-PVCs

A multivariate time-frequency approach for tracking QT variability changes unrelated to heart rate variability

The beat-to-beat variability of the QT interval (QTV) is a marker of ventricular repolarization (VR) dynamics and it has been suggested as an index of sympathetic ventricular outflow and cardiac instability. However, QTV is also affected by RR (or heart rate) variability (RRV), and QTV due to RRV may reduce QTV specificity as a VR marker. Therefore, it would be desirable to separate QTV due to VR dynamics from QTV due to RRV. To do that, previous work has mainly focused on heart rate corrections or time-invariant autoregressive models. This paper describes a novel framework that extends classical multiple inputs/single output theory to the time-frequency (TF) domain to quantify QTV and RRV interactions. Quadratic TF distributions and TF coherence function are utilized to separate QTV into two partial (conditioned) spectra representing QTV related and unrelated to RRV, and to provide an estimates of intrinsic VR dynamics. In a simulation study, a time-varying ARMA model was used to generate signals representing realistic RRV and VR dynamics with controlled instantaneous frequencies and powers. The results demonstrated that the proposed methodology is able to accurately track changes in VR dynamics, with a correlation between theoretical and estimated patterns higher than 0.88. Data from healthy volunteers undergoing a tilt table test were analyzed and representative examples are discussed. Results show that the QTV unrelated to RRV dynamics quickly increased during orthostatic challenge

Putting (One's) Heart into Music

International audienc

Population of human ventricular cell models calibrated with in vivo measurements unravels ionic mechanisms of cardiac alternans

Cardiac alternansis an important risk factor in cardiac physiology, and is related to the initiation of many pathophysiological conditions. However, the mechanisms underlying the generation of alternans remain unclear. In this study, we used a population of computational human ventricle models based onthe O’Hara model [1] to explore the effect of 11 key factors experimentally reported to be related to alternans. In vivo experimental datasets coming from patients undergoing cardiac surgery were used in the calibration of our in silico population of models. The calibrated models in the population were divided into two groups (Normal and Alternans) depending on alternans occurrence. Our results showed that there were significant differences in the following 5 ionic currents between the two groups: fast sodium current, sodium calcium exchanger current, sodium potassium pump current, sarcoplasmic reticulum (SR) calcium release flux and SR calcium reuptake flux. Further analysis indicated that fast sodium current and SR calcium uptake were the two most significant currents that contributed to voltage and calcium alternans generation, respectively

Optimization of the global re-entry vulnerability index to minimise cycle length dependency and prediction of ventricular arrhythmias during human epicardial sock mapping

The re-entry vulnerability index (RVI) is an activation-repolarization marker recently proposed to predict sites of ventricular tachycardia (VT) initiation. RVI is inversely related to the probability of establishing a re-entry. The aim of this study was to characterize the CL dependency of RVI, assess different methods for CL-dependency corrections and test the capability of RVI to predict ventricular arrhythmias. Twenty-four subjects underwent whole heart epicardial mapping using a multi-electrode sock enabling the recording of 240 unipolar electrograms. Ventricular pacing was delivered at CLs decreasing from 600 to 350 ms in steps of 50 ms. In a separate study, 1 patient went into VT during steady state pacing. Predisposition to VT was assessed by using the 10th percentile RVI, termed global RVI. The results show that own to CL dependency of local repolarization, there was a strong positive association between RVI and CL. Local repolarization detrending and correction with the Bazett's formula eliminated the CL dependency, while a weak association was found after correction with the Fredericia's formula. In the patient who developed VT, global RVI was significantly lower than in the patients who did not develop VT. Corrections for CL dependency enhanced these differences. In conclusion, de-trending and Bazett's corrections effectively compensated for the CL dependency of RVI and global RVI may reveal predisposition to ventricular arrhythmias. Further analysis is necessary to establish the role of RVI for risk stratification