Prediction of Sudden Cardiac Death With Ultra-Short-Term Heart Rate Fluctuations.

BACKGROUND: Conventional measures of heart rate variability (HRV) have shown only modest associations with sudden cardiac death (SCD). Detrended fluctuation analysis (DFA), with novel methodological developments to evaluate the short-term scaling exponent, is a potentially superior method compared to conventional HRV tools. OBJECTIVES: In this study, the authors studied the analysis of the association between DFA and SCD. METHODS: The investigators studied the predictive value of ultra-short-term heart rate fluctuations (1-minute electrocardiogram samples) with DFA at rest and during different stages of physical exertion for incident SCD among 2,794 participants undergoing clinical exercise testing in the prospective FINCAVAS (Finnish Cardiovascular Study). The novel key DFA measure, the short-scale scaling exponent computed with second-order detrending (DFA2 α1), was the main exposure variable. SCDs were defined by American Heart Association/European Society of Cardiology criteria using death certificates with written accounts of the events. RESULTS: During a median follow-up of 8.3 years (Q1-Q3: 6.4-10.5), 83 SCDs occurred. DFA2 α1 measured at rest (but not in exercise) associated highly significantly with the risk of SCD, with 1-SD lower values associating with a 2.4-fold (Q1-Q3: 2.0-3.0) risk (P < 0.001). The results persisted when adjusting for other major risk factors for SCD, including age, cardiovascular morbidities, cardiorespiratory fitness, heart rate reduction, and left ventricular ejection fraction. Associations between conventional HRV parameters (measured at any stage of exercise or at rest) and SCD were substantially weaker and statistically nonsignificant after adjusting for other risk factors. CONCLUSIONS: Ultra-short-term DFA2 α1, when measured at rest, is a powerful and independent predictor of SCD. The association between DFA2 α1 and SCD is modified by physical exertion.

Accurate QT correction method from transfer entropy.

Background: The QT interval in the electrocardiogram (ECG) is a fundamental risk measure for arrhythmic adverse cardiac events. However, the QT interval depends on the heart rate and must be corrected accordingly. The present QT correction (QTc) methods are either simple models leading to under- or overcorrection, or impractical in requiring long-term empirical data. In general, there is no consensus on the best QTc method. Objective: We introduce a model-free QTc method-AccuQT-that computes QTc by minimizing the information transfer from R-R to QT intervals. The objective is to establish and validate a QTc method that provides superior stability and reliability without models or empirical data. Methods: We tested AccuQT against the most commonly used QT correction methods by using long-term ECG recordings of more than 200 healthy subjects from PhysioNet and THEW databases. Results: AccuQT overperforms the previously reported correction methods: the proportion of false-positives is reduced from 16% (Bazett) to 3% (AccuQT) for the PhysioNet data. In particular, the QTc variance is significantly reduced and thus the RR-QT stability is increased. Conclusion: AccuQT has significant potential to become the QTc method of choice in clinical studies and drug development. The method can be implemented in any device recording R-R and QT intervals.

Estimation of physiological exercise thresholds based on dynamical correlation properties of heart rate variability.

Aerobic and anaerobic thresholds of the three-zone exercise model are often used to evaluate the exercise intensity and optimize the training load. Conventionally, these thresholds are derived from the respiratory gas exchange or blood lactate concentration measurements. Here, we introduce and validate a computational method based on the RR interval (RRI) dynamics of the heart rate (HR) measurement, which enables a simple, yet reasonably accurate estimation of both metabolic thresholds. The method utilizes a newly developed dynamical detrended fluctuation analysis (DDFA) to assess the real-time changes in the dynamical correlations of the RR intervals during exercise. The training intensity is shown to be in direct correspondence with the time- and scale-dependent changes in the DDFA scaling exponent. These changes are further used in the definition of an individual measure to estimate the aerobic and anaerobic threshold. The results for 15 volunteers who participated in a cyclo-ergometer test are compared to the benchmark lactate thresholds, as well as to the ventilatory threshods and alternative HR-based estimates based on the maximal HR and the conventional detrended fluctuation analysis (DFA). Our method provides the best overall agreement with the lactate thresholds and provides a promising, cost-effective alternative to conventional protocols, which could be easily integrated in wearable devices. However, detailed statistical analysis reveals the particular strengths and weaknessess of each method with respect to the agreement and consistency with the thresholds-thus underlining the need for further studies with more data.

Asymmetric Roughness of Elastic Interfaces at the Depinning Threshold.

Roughness of driven elastic interfaces in random media is typically understood to be characterized by a single roughness exponent ζ. We show that at the depinning threshold, due to symmetry breaking caused by the direction of the driving force, elastic interfaces with local, long-range, and mean-field elasticity exhibit asymmetric roughness. It is manifested as a skewed distribution of the local interface heights, and can be quantified by using detrended fluctuation analysis to compute a spectrum of local, segment-level scaling exponents. The asymmetry is observed as approximately linear dependence of the local scaling exponents on the difference of the segment height from the mean interface height.

Propagation of waves in high Brillouin zones: Chaotic branched flow and stable superwires.

We report unexpected classical and quantum dynamics of a wave propagating in a periodic potential in high Brillouin zones. Branched flow appears at wavelengths shorter than the typical length scale of the ordered periodic structure and for energies above the potential barrier. The strongest branches remain stable indefinitely and may create linear dynamical channels, wherein waves are not confined directly by potential walls as electrons in ordinary wires but rather, indirectly and more subtly by dynamical stability. We term these superwires since they are associated with a superlattice.

Dynamical heart beat correlations during running.

Fluctuations of the human heart beat constitute a complex system that has been studied mostly under resting conditions using conventional time series analysis methods. During physical exercise, the variability of the fluctuations is reduced, and the time series of beat-to-beat RR intervals (RRIs) become highly non-stationary. Here we develop a dynamical approach to analyze the time evolution of RRI correlations in running across various training and racing events under real-world conditions. In particular, we introduce dynamical detrended fluctuation analysis and dynamical partial autocorrelation functions, which are able to detect real-time changes in the scaling and correlations of the RRIs as functions of the scale and the lag. We relate these changes to the exercise intensity quantified by the heart rate (HR). Beyond subject-specific HR thresholds the RRIs show multiscale anticorrelations with both universal and individual scale-dependent structure that is potentially affected by the stride frequency. These preliminary results are encouraging for future applications of the dynamical statistical analysis in exercise physiology and cardiology, and the presented methodology is also applicable across various disciplines.

Scaling and correlation properties of RR and QT intervals at the cellular level.

We study complex scaling properties of RR and QT intervals of electrocardiograms (ECGs) with their equivalences at the cellular level, that is, inter-beat intervals (IBI) and field potential durations (FPD) of spontaneously beating human-induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) aggregates. Our detrended fluctuation analysis and Poincaré plots reveal remarkable similarities between the ECG and hiPSC-CM data. In particular, no statistically significant difference was found in the short- and long-term scaling exponents α1 and α2 of RR and QT intervals and their cellular equivalences. Previously unknown scaling properties of FPDs of hiPSC-CM aggregates reveal that the increasing scaling exponent of QT intervals as a function of the time scale, is an intrinsic feature at the cellular level.

Normal and Anomalous Diffusion in Soft Lorentz Gases.

Motivated by electronic transport in graphenelike structures, we study the diffusion of a classical point particle in Fermi potentials situated on a triangular lattice. We call this system a soft Lorentz gas, as the hard disks in the conventional periodic Lorentz gas are replaced by soft repulsive scatterers. A thorough computational analysis yields both normal and anomalous (super)diffusion with an extreme sensitivity on model parameters. This is due to an intricate interplay between trapped and ballistic periodic orbits, whose existence is characterized by tonguelike structures in parameter space. These results hold even for small softness, showing that diffusion in the paradigmatic hard Lorentz gas is not robust for realistic potentials, where we find an entirely different type of diffusion.

Information transfer in QT-RR dynamics: Application to QT-correction.

The relation between the electrical properties of the heart and the beating rate is essential for the heart functioning. This relation is central when calculating the "corrected QT interval" - an important measure of the risk of potentially lethal arrhythmias. We use the transfer entropy method from information theory to quantitatively study the mutual dynamics of the ventricular action potential duration (the QT interval) and the length of the beat-to-beat (RR) interval. We show that for healthy individuals there is a strong asymmetry in the information transfer: the information flow from RR to QT dominates over the opposite flow (from QT to RR), i.e. QT depends on RR to a larger extent than RR on QT. Moreover, the history of the intervals has a strong effect on the information transfer: at sufficiently long QT history length the information flow asymmetry inverts and the RR influence on QT dynamics weakens. Finally, we demonstrate that the widely used QT correction methods cannot properly capture the changes in the information flows between QT and RR. We conclude that our results obtained through a model-free informational perspective can be utilised to improve and test the QT correction schemes in clinics.

Strong quantum scarring by local impurities.

We discover and characterise strong quantum scars, or quantum eigenstates resembling classical periodic orbits, in two-dimensional quantum wells perturbed by local impurities. These scars are not explained by ordinary scar theory, which would require the existence of short, moderately unstable periodic orbits in the perturbed system. Instead, they are supported by classical resonances in the unperturbed system and the resulting quantum near-degeneracy. Even in the case of a large number of randomly scattered impurities, the scars prefer distinct orientations that extremise the overlap with the impurities. We demonstrate that these preferred orientations can be used for highly efficient transport of quantum wave packets across the perturbed potential landscape. Assisted by the scars, wave-packet recurrences are significantly stronger than in the unperturbed system. Together with the controllability of the preferred orientations, this property may be very useful for quantum transport applications.

The Effects of Pharmacological Compounds on Beat Rate Variations in Human Long QT-Syndrome Cardiomyocytes.

Healthy human heart rate fluctuates overtime showing long-range fractal correlations. In contrast, various cardiac diseases and normal aging show the breakdown of fractal complexity. Recently, it was shown that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) intrinsically exhibit fractal behavior as in humans. Here, we investigated the fractal complexity of hiPSC-derived long QT-cardiomyocytes (LQT-CMs). We recorded extracellular field potentials from hiPSC-CMs at baseline and under the effect of various compounds including ß-blocker bisoprolol, ML277, a specific and potent IKs current activator, as well as JNJ303, a specific IKs blocker. From the peak-to-peak-intervals, we determined the long-range fractal correlations by using detrended fluctuation analysis. Electrophysiologically, the baseline corrected field potential durations (cFPDs) were more prolonged in LQT-CMs than in wildtype (WT)-CMs. Bisoprolol did not have significant effects to the cFPD in any CMs. ML277 shortened cFPD in a dose-dependent fashion by 11 % and 5-11 % in WT- and LQT-CMs, respectively. JNJ303 prolonged cFPD in a dose-dependent fashion by 22 % and 7-13 % in WT- and LQT-CMs, respectively. At baseline, all CMs showed fractal correlations as determined by short-term scaling exponent α. However, in all CMs, the α was increased when pharmacological compounds were applied indicating of breakdown of fractal complexity. These findings suggest that the intrinsic mechanisms contributing to the fractal complexity are not altered in LQT-CMs. The modulation of IKs channel and ß1-adrenoreceptors by pharmacological compounds may affect the fractal complexity of the hiPSC-CMs.

Coexisting Honeycomb and Kagome Characteristics in the Electronic Band Structure of Molecular Graphene.

We uncover the electronic structure of molecular graphene produced by adsorbed CO molecules on a copper (111) surface by means of first-principles calculations. Our results show that the band structure is fundamentally different from that of conventional graphene, and the unique features of the electronic states arise from coexisting honeycomb and Kagome symmetries. Furthermore, the Dirac cone does not appear at the K-point but at the Γ-point in the reciprocal space and is accompanied by a third, almost flat band. Calculations of the surface structure with Kekulé distortion show a gap opening at the Dirac point in agreement with experiments. Simple tight-binding models are used to support the first-principles results and to explain the physical characteristics behind the electronic band structures.

Fluctuations of hi-hat timing and dynamics in a virtuoso drum track of a popular music recording.

Long-range correlated temporal fluctuations in the beats of musical rhythms are an inevitable consequence of human action. According to recent studies, such fluctuations also lead to a favored listening experience. The scaling laws of amplitude variations in rhythms, however, are widely unknown. Here we use highly sensitive onset detection and time series analysis to study the amplitude and temporal fluctuations of Jeff Porcaro's one-handed hi-hat pattern in "I Keep Forgettin'"-one of the most renowned 16th note patterns in modern drumming. We show that fluctuations of hi-hat amplitudes and interbeat intervals (times between hits) have clear long-range correlations and short-range anticorrelations separated by a characteristic time scale. In addition, we detect subtle features in Porcaro's drumming such as small drifts in the 16th note pulse and non-trivial periodic two-bar patterns in both hi-hat amplitudes and intervals. Through this investigation we introduce a step towards statistical studies of the 20th and 21st century music recordings in the framework of complex systems. Our analysis has direct applications to the development of drum machines and to drumming pedagogy.

Controlled high-fidelity navigation in the charge stability diagram of a double quantum dot.

We propose an efficient control protocol for charge transfer in a double quantum dot. We consider numerically a two-dimensional model system, where the quantum dots are subjected to time-dependent electric fields corresponding to experimental gate voltages. Our protocol enables navigation in the charge stability diagram from a state to another through controllable variation of the fields. We show that the well-known adiabatic Landau-Zener transition-when supplemented with a time-dependent field tailored with optimal control theory-can remarkably improve the transition speed. The results also lead to a simple control scheme obtained from the experimental charge stability diagram that requires only a single parameter. Eventually, we can achieve the ultrafast performance of the composite pulse protocol that allows the system to be driven at the quantum speed limit.

Scaling in the correlation energies of two-dimensional artificial atoms.

We find an unexpected scaling in the correlation energy of artificial atoms, i.e., harmonically confined two-dimensional quantum dots. The scaling relation is found through extensive numerical examinations including Hartree-Fock, variational quantum Monte Carlo, density functional, and full configuration interaction calculations. We show that the correlation energy, i.e., the true ground-state total energy minus the Hartree-Fock total energy, follows a simple function of the Coulomb energy, confinement strength and number of electrons. We find an analytic expression for this function, as well as for the correlation energy per particle and for the ratio between the correlation and total energies. Our tests for independent diffusion Monte Carlo and coupled-cluster results for quantum dots-including open-shell data-confirm the generality of the scaling obtained. As the scaling also applies well to ≳100 electrons, our results give interesting prospects for the development of correlation functionals within density functional theory.