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Biomedical subjects

C K Peng

Publications and source records attributed to C K Peng.

At least 37 records · Page 2Linked to original sources

Scaling and universality in heart rate variability distributions.

We find that a universal homogeneous scaling form describes the distribution of cardiac variations for a group of healthy subjects, which is stable over a wide range of time scales. However, a similar scaling function does not exist for a group with a common cardiopulmonary instability associated with sleep apnea. Subtle differences in the distributions for the day- and night-phase dynamics for healthy subjects are detected.

Adult↗

Self-reported coping behavior in health and disease: assessment with a card sort game.

The authors tested the hypothesis that individuals with a variety of severe chronic illnesses and the healthy elderly exhibit a loss of flexibility in their response to a variety of stressors, compared with healthy adults. A card sort game designed to assess self-reported coping behavior under different stressful life situations was used to compare healthy adults with individuals with multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and the elderly. The healthy adults were found to exhibit more variability than any of the illness groups or the elderly. Healthy function is marked by a complex type of variability.

Adaptation, Psychological↗

Dynamic analysis of heart rate may predict subsequent ventricular tachycardia after myocardial infarction.

Dynamics analysis of RR interval behavior and traditional measures of heart rate variability were compared between postinfarction patients with and without vulnerability to ventricular tachyarrhythmias in a case-control study. Short-term fractal correlation of heart rate dynamics was better than traditional measures of heart rate variability in differentiating patients with and without life-threatening arrhythmias.

Aged↗

Predicting survival in heart failure case and control subjects by use of fully automated methods for deriving nonlinear and conventional indices of heart rate dynamics.

BACKGROUND: Despite much recent interest in quantification of heart rate variability (HRV), the prognostic value of conventional measures of HRV and of newer indices based on nonlinear dynamics is not universally accepted. METHODS AND RESULTS: We have designed algorithms for analyzing ambulatory ECG recordings and measuring HRV without human intervention, using robust methods for obtaining time-domain measures (mean and SD of heart rate), frequency-domain measures (power in the bands of 0.001 to 0.01 Hz [VLF], 0.01 to 0.15 Hz [LF], and 0.15 to 0.5 Hz [HF] and total spectral power [TP] over all three of these bands), and measures based on nonlinear dynamics (approximate entropy [ApEn], a measure of complexity, and detrended fluctuation analysis [DFA], a measure of long-term correlations). The study population consisted of chronic congestive heart failure (CHF) case patients and sex- and age-matched control subjects in the Framingham Heart Study. After exclusion of technically inadequate studies and those with atrial fibrillation, we used these algorithms to study HRV in 2-hour ambulatory ECG recordings of 69 participants (mean age, 71.7+/-8.1 years). By use of separate Cox proportional-hazards models, the conventional measures SD (P<.01), LF (P<.01), VLF (P<.05), and TP (P<.01) and the nonlinear measure DFA (P<.05) were predictors of survival over a mean follow-up period of 1.9 years; other measures, including ApEn (P>.3), were not. In multivariable models, DFA was of borderline predictive significance (P=.06) after adjustment for the diagnosis of CHF and SD. CONCLUSIONS: These results demonstrate that HRV analysis of ambulatory ECG recordings based on fully automated methods can have prognostic value in a population-based study and that nonlinear HRV indices may contribute prognostic value to complement traditional HRV measures.

Aged↗

Deviations from uniform power law scaling in nonstationary time series.

A classic problem in physics is the analysis of highly nonstationary time series that typically exhibit long-range correlations. Here we test the hypothesis that the scaling properties of the dynamics of healthy physiological systems are more stable than those of pathological systems by studying beat-to-beat fluctuations in the human heart rate. We develop techniques based on the Fano factor and Allan factor functions, as well as on detrended fluctuation analysis, for quantifying deviations from uniform power-law scaling in nonstationary time series. By analyzing extremely long data sets of up to N = 10(5) beats for 11 healthy subjects, we find that the fluctuations in the heart rate scale approximately uniformly over several temporal orders of magnitude. By contrast, we find that in data sets of comparable length for 14 subjects with heart disease, the fluctuations grow erratically, indicating a loss of scaling stability.

Adult↗

Altered fractal dynamics of gait: reduced stride-interval correlations with aging and Huntington's disease.

Fluctuations in the duration of the gait cycle (the stride interval) display fractal dynamics and long-range correlations in healthy young adults. We hypothesized that these stride-interval correlations would be altered by changes in neurological function associated with aging and certain disease states. To test this hypothesis, we compared the stride-interval time series of 1) healthy elderly subjects and young controls and of 2) subjects with Huntington's disease and healthy controls. Using detrended fluctuation analysis we computed alpha, a measure of the degree to which one stride interval is correlated with previous and subsequent intervals over different time scales. The scaling exponent alpha was significantly lower in elderly subjects compared with young subjects (elderly: 0.68 +/- 0.14; young: 0.87 +/- 0.15; P < 0.003). The scaling exponent alpha was also smaller in the subjects with Huntington's disease compared with disease-free controls (Huntington's disease: 0.60 +/- 0.24; controls: 0.88 +/-0.17; P < 0.005). Moreover, alpha was linearly related to degree of functional impairment in subjects with Huntington's disease (r = 0.78, P < 0.0005). These findings demonstrate that strike-interval fluctuations are more random (i.e., less correlated) in elderly subjects and in subjects with Huntington's disease. Abnormal alterations in the fractal properties of gait dynamics are apparently associated with changes in central nervous system control.

Adult↗

Scaling behaviour of heartbeat intervals obtained by wavelet-based time-series analysis.

Biological time-series analysis is used to identify hidden dynamical patterns which could yield important insights into underlying physiological mechanisms. Such analysis is complicated by the fact that biological signals are typically both highly irregular and non-stationary, that is, their statistical character changes slowly or intermittently as a result of variations in background influences. Previous statistical analyses of heartbeat dynamics have identified long-range correlations and power-law scaling in the normal heartbeat, but not the phase interactions between the different frequency components of the signal. Here we introduce a new approach, based on the wavelet transform and an analytic signal approach, which can characterize non-stationary behaviour and elucidate such phase interactions. We find that, when suitably rescaled, the distributions of the variations in the beat-to-beat intervals for all healthy subjects are described by a single function stable over a wide range of timescales. However, a similar scaling function does not exist for a group with cardiopulmonary instability caused by sleep apnoea. We attribute the functional form of the scaling observed in the healthy subjects to underlying nonlinear dynamics, which seem to be essential to normal heart function. The approach introduced here should be useful in the analysis of other nonstationary biological signals.

Adult↗

Age-related alterations in the fractal scaling of cardiac interbeat interval dynamics.

We postulated that aging is associated with disruption in the fractallike long-range correlations that characterize healthy sinus rhythm cardiac interval dynamics. Ten young (21-34 yr) and 10 elderly (68-81 yr) rigorously screened healthy subjects underwent 120 min of continuous supine resting electrocardiographic recording. We analyzed the interbeat interval time series using standard time and frequency domain statistics and using a fractal measure, detrended fluctuation analysis, to quantify long-range correlation properties. In healthy young subjects, interbeat intervals demonstrated fractal scaling, with scaling exponents (alpha) from the fluctuation analysis close to a value of 1.0. In the group of healthy elderly subjects, the interbeat interval time series had two scaling regions. Over the short range, interbeat interval fluctuations resembled a random walk process (Brownian noise, alpha = 1.5), whereas over the longer range they resembled white noise (alpha = 0.5). Short (alpha s)- and long-range (alpha 1) scaling exponents were significantly different in the elderly subjects compared with young (alpha s = 1.12 +/- 0.19 vs. 0.90 +/- 0.14, respectively, P = 0.009; alpha 1 = 0.75 +/- 0.17 vs. 0.99 +/- 0.10, respectively, P = 0.002). The crossover behavior from one scaling region to another could be modeled as a first-order autoregressive process, which closely fit the data from four elderly subjects. This implies that a single characteristic time scale may be dominating heartbeat control in these subjects. The age-related loss of fractal organization in heartbeat dynamics may reflect the degradation of integrated physiological regulatory systems and may impair an individual's ability to adapt to stress.

Adult↗

Fractal dynamics of human gait: stability of long-range correlations in stride interval fluctuations.

Fractal dynamics were recently detected in the apparently "noisy" variations in the stride interval of human walking. Dynamical analysis of these step-to-step fluctuations revealed a self-similar pattern: fluctuations at one time scale are statistically similar to those at multiple other time scales, at least over hundreds of steps, while healthy subjects walk at their normal rate. To study the stability of this fractal property, we analyzed data obtained from healthy subjects who walked for 1 h at their usual, slow, and fast paces. The stride interval fluctuations exhibited long-range correlations with power-law decay for up to 1,000 strides at all 3 walking rates. In contrast, during metronomically paced walking, these long-range correlations disappeared; variations in the stride interval were random (uncorrelated) and nonfractal. The long-range correlations observed during spontaneous walking were not affected by removal of drifts in the time series. Thus the fractal dynamics of spontaneous stride interval are normally quite robust and intrinsic to the locomotor system. Furthermore, this fractal property of neural output may be related to the higher nervous centers responsible for the control of walking rhythm.

Adult↗

Statistical properties of DNA sequences.

We review evidence supporting the idea that the DNA sequence in genes containing non-coding regions is correlated, and that the correlation is remarkably long range--indeed, nucleotides thousands of base pairs distant are correlated. We do not find such a long-range correlation in the coding regions of the gene. We resolve the problem of the "non-stationarity" feature of the sequence of base pairs by applying a new algorithm called detrended fluctuation analysis (DFA). We address the claim of Voss that there is no difference in the statistical properties of coding and non-coding regions of DNA by systematically applying the DFA algorithm, as well as standard FFT analysis, to every DNA sequence (33301 coding and 29453 non-coding) in the entire GenBank database. Finally, we describe briefly some recent work showing that the non-coding sequences have certain statistical features in common with natural and artificial languages. Specifically, we adapt to DNA the Zipf approach to analyzing linguistic texts. These statistical properties of non-coding sequences support the possibility that non-coding regions of DNA may carry biological information.

Algorithms↗

Fractals in biology and medicine.

Our purpose is to describe some recent progress in applying fractal concepts to systems of relevance to biology and medicine. We review several biological systems characterized by fractal geometry, with a particular focus on the long-range power-law correlations found recently in DNA sequences containing noncoding material. Furthermore, we discuss the finding that the exponent alpha quantifying these long-range correlations ("fractal complexity") is smaller for coding than for noncoding sequences. We also discuss the application of fractal scaling analysis to the dynamics of heartbeat regulation, and report the recent finding that the normal heart is characterized by long-range "anticorrelations" which are absent in the diseased heart.

Biological Evolution↗

Fractal mechanisms and heart rate dynamics. Long-range correlations and their breakdown with disease.

Under healthy conditions, the normal cardiac (sinus) interbeat interval fluctuates in a complex manner. Quantitative analysis using techniques adapted from statistical physics reveals the presence of long-range power-law correlations extending over thousands of heartbeats. This scale-invariant (fractal) behavior suggests that the regulatory system generating these fluctuations is operating far from equilibrium. In contrast, it is found that for subjects at high risk of sudden death (e.g., congestive heart failure patients), these long-range correlations break down. Application of fractal scaling analysis and related techniques provides new approaches to assessing cardiac risk and forecasting sudden cardiac death, as well as motivating development of novel physiologic models of systems that appear to be heterodynamic rather than homeostatic.

Adult↗

Quantification of scaling exponents and crossover phenomena in nonstationary heartbeat time series.

The healthy heartbeat is traditionally thought to be regulated according to the classical principle of homeostasis whereby physiologic systems operate to reduce variability and achieve an equilibrium-like state [Physiol. Rev. 9, 399-431 (1929)]. However, recent studies [Phys. Rev. Lett. 70, 1343-1346 (1993); Fractals in Biology and Medicine (Birkhauser-Verlag, Basel, 1994), pp. 55-65] reveal that under normal conditions, beat-to-beat fluctuations in heart rate display the kind of long-range correlations typically exhibited by dynamical systems far from equilibrium [Phys. Rev. Lett. 59, 381-384 (1987)]. In contrast, heart rate time series from patients with severe congestive heart failure show a breakdown of this long-range correlation behavior. We describe a new method--detrended fluctuation analysis (DFA)--for quantifying this correlation property in non-stationary physiological time series. Application of this technique shows evidence for a crossover phenomenon associated with a change in short and long-range scaling exponents. This method may be of use in distinguishing healthy from pathologic data sets based on differences in these scaling properties.

Heart Diseases↗

Long-range correlation properties of coding and noncoding DNA sequences: GenBank analysis.

An open question in computational molecular biology is whether long-range correlations are present in both coding and noncoding DNA or only in the latter. To answer this question, we consider all 33301 coding and all 29453 noncoding eukaryotic sequences--each of length larger than 512 base pairs (bp)--in the present release of the GenBank to dtermine whether there is any statistically significant distinction in their long-range correlation properties. Standard fast Fourier transform (FFT) analysis indicates that coding sequences have practically no correlations in the range from 10 bp to 100 bp (spectral exponent beta=0.00 +/- 0.04, where the uncertainty is two standard deviations). In contrast, for noncoding sequences, the average value of the spectral exponent beta is positive (0.16 +/- 0.05) which unambiguously shows the presence of long-range correlations. We also separately analyze the 874 coding and the 1157 noncoding sequences that have more than 4096 bp and find a larger region of power-law behavior. We calculate the probability that these two data sets (coding and noncoding) were drawn from the same distribution and we find that it is less than 10(-10). We obtain independent confirmation of these findings using the method of detrended fluctuation analysis (DFA), which is designed to treat sequences with statistical heterogeneity, such as DNA's known mosaic structure ("patchiness") arising from the nonstationarity of nucleotide concentration. The near-perfect agreement between the two independent analysis methods, FFT and DFA, increases the confidence in the reliability of our conclusion.

Animals↗

Systematic analysis of coding and noncoding DNA sequences using methods of statistical linguistics.

We compare the statistical properties of coding and noncoding regions in eukaryotic and viral DNA sequences by adapting two tests developed for the analysis of natural languages and symbolic sequences. The data set comprises all 30 sequences of length above 50 000 base pairs in GenBank Release No. 81.0, as well as the recently published sequences of C. elegans chromosome III (2.2 Mbp) and yeast chromosome XI (661 Kbp). We find that for the three chromosomes we studied the statistical properties of noncoding regions appear to be closer to those observed in natural languages than those of coding regions. In particular, (i) a n-tuple Zipf analysis of noncoding regions reveals a regime close to power-law behavior while the coding regions show logarithmic behavior over a wide interval, while (ii) an n-gram entropy measurement shows that the noncoding regions have a lower n-gram entropy (and hence a larger "n-gram redundancy") than the coding regions. In contrast to the three chromosomes, we find that for vertebrates such as primates and rodents and for viral DNA, the difference between the statistical properties of coding and noncoding regions is not pronounced and therefore the results of the analyses of the investigated sequences are less conclusive. After noting the intrinsic limitations of the n-gram redundancy analysis, we also briefly discuss the failure of the zeroth- and first-order Markovian models or simple nucleotide repeats to account fully for these "linguistic" features of DNA. Finally, we emphasize that our results by no means prove the existence of a "language" in noncoding DNA.

Animals↗

Statistical and linguistic features of DNA sequences.

We present evidence supporting the idea that the DNA sequence in genes containing noncoding regions is correlated, and that the correlation is remarkably long range--indeed, base pairs thousands of base pairs distant are correlated. We do not find such a long-range correlation in the coding regions of the gene. We resolve the problem of the "non-stationary" feature of the sequence of base pairs by applying a new algorithm called Detrended Fluctuation Analysis (DFA). We address the claim of Voss that there is no difference in the statistical properties of coding and noncoding regions of DNA by systematically applying the DFA algorithm, as well as standard FFT analysis, to all eukaryotic DNA sequences (33 301 coding and 29 453 noncoding) in the entire GenBank database. We describe a simple model to account for the presence of long-range power-law correlations which is based upon a generalization of the classic Levy walk. Finally, we describe briefly some recent work showing that the noncoding sequences have certain statistical features in common with natural languages. Specifically, we adapt to DNA the Zipf approach to analyzing linguistic texts, and the Shannon approach to quantifying the "redundancy" of a linguistic text in terms of a measurable entropy function. We suggest that noncoding regions in plants and invertebrates may display a smaller entropy and larger redundancy than coding regions, further supporting the possibility that noncoding regions of DNA may carry biological information.

Algorithms↗

Is walking a random walk? Evidence for long-range correlations in stride interval of human gait.

Complex fluctuations of unknown origin appear in the normal gait pattern. These fluctuations might be described as being 1) uncorrelated white noise, 2) short-range correlations, or 3) long-range correlations with power-law scaling. To test these possibilities, the stride interval of 10 healthy young men was measured as they walked for 9 min at their usual rate. From these time series, we calculated scaling indexes by using a modified random walk analysis and power spectral analysis. Both indexes indicated the presence of long-range self-similar correlations extending over hundreds of steps; the stride interval at any time depended on the stride interval at remote previous times, and this dependence decayed in a scale-free (fractallike) power-law fashion. These scaling indexes were significantly different from those obtained after random shuffling of the original time series, indicating the importance of the sequential ordering of the stride interval. We demonstrate that conventional models of gait generation fail to reproduce the observed scaling behavior and introduce a new type of central pattern generator model that successfully accounts for the experimentally observed long-range correlations.

Adult↗

Linguistic features of noncoding DNA sequences.

We extend the Zipf approach to analyzing linguistic texts to the statistical study of DNA base pair sequences and find that the noncoding regions are more similar to natural languages than the coding regions. We also adapt the Shannon approach to quantifying the "redundancy" of a linguistic text in terms of a measurable entropy function, and demonstrate that noncoding regions in eukaryotes display a smaller entropy and larger redundancy than coding regions, supporting the possibility that noncoding regions of DNA may carry biological information.

Algorithms↗