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A stochastic nonlinear autoregressive algorithm reflects nonlinear dynamics of heart-rate fluctuations.

Current methods for detecting nonlinear determinism in a time series require long and stationary data records, as most of them assume that the observed dynamics arise only from the internal, deterministic workings of the system, and the stochastic portion of the signal (the noise component) is assumed to be negligible. To explicitly account for the stochastic portion of the data we recently developed a method based on a stochastic nonlinear autoregressive (SNAR) algorithm. The method iteratively estimates nonlinear autoregressive models for both the deterministic and stochastic portions of the signal. Subsequently, the Lyapunov exponents (LE) are calculated for the estimated models in order to examine if nonlinear determinism is present in the deterministic portion of the fitted model. To determine if nonlinear dynamic analysis of heart-rate fluctuations can be used to assess arrhythmia susceptibility by predicting the outcome of invasive cardiac electrophysiologic study (EPS), we applied the SNAR algorithm to noninvasively measured resting sinus-rhythm heart-rate signals obtained from 16 patients. Our analysis revealed that a positive LE was highly correlated to a patient with a positive outcome of EPS. We found that the statistical accuracy of the SNAR algorithm in predicting the outcome of EPS was 88% (sensitivity=100%, specificity=75%, positive predictive value=80%, negative predictive value=100%, p=0.0019). Our results suggest that the SNAR algorithm may serve as a noninvasive probe for screening high-risk populations for malignant cardiac arrhythmias.

Adult↗

Nonlinear dynamics of heart rate variability in cocaine-exposed neonates during sleep.

The aim of this study was to determine the effects of prenatal cocaine exposure (PCE) on the dynamics of heart rate variability in full-term neonates during sleep. R-R interval (RRI) time series from 9 infants with PCE and 12 controls during periods of stable quiet sleep and active sleep were analyzed using autoregressive modeling and nonlinear dynamics. There were no differences between the two groups in spectral power distribution, approximate entropy, correlation dimension, and nonlinear predictability. However, application of surrogate data analysis to these measures revealed a significant degree of nonlinear RRI dynamics in all subjects. A parametric model, consisting of a nonlinear delayed-feedback system with stochastic noise as the perturbing input, was employed to estimate the relative contributions of linear and nonlinear deterministic dynamics in the data. Both infant groups showed similar proportional contributions in linear, nonlinear, and stochastic dynamics. However, approximate entropy, correlation dimension, and nonlinear prediction error were all decreased in active versus quiet sleep; in addition, the parametric model revealed a doubling of the linear component and a halving of the nonlinear contribution to overall heart rate variability. Spectral analysis indicated a shift in relative power toward lower frequencies. We conclude that 1) RRI dynamics in infants with PCE and normal controls are similar; and 2) in both groups, sympathetic dominance during active sleep produces primarily periodic low-frequency oscillations in RRI, whereas in quiet sleep vagal modulation leads to RRI fluctuations that are broadband and dynamically more complex.

Cocaine↗

Virtual enantiomers as the solution of optical activity's deterministic offset problem.

Deterministic offsets have remained one of optical activity's most intractable problems. To the extent that the mechanisms by which they are produced do not depend on the chiroptical properties of the sample, they can be eliminated by the subtraction of measurements done on both enantiomers. We show that it is possible to create, by purely optical means, by the sole use of half-wave retarders, the optical antipode of a chiral molecule, to measure the chiroptical properties of the molecule and of its optically generated antipode, and to recover, by subtracting the measurements, the offset-free data of the enantiomer which is physically present. We moreover show that it is possible to do the measurements in a way that eliminates offsets that might occur through the influence of the differing chiroptical properties of the two antipodes. The procedure can be repeated, and by doing so, an almost arbitrarily high precision can be reached. The method is demonstrated by offset-free Raman optical activity back-scattering spectra measured in the so-called scattered circular polarization mode, one of optical activity's so far largely unsolved measurement problems. Such measurements can now be done with 2 mg of substance, in throw-away capillary cells, and on compounds sealed in cylindrical vials.

Alkanes↗

Minimizing costs while meeting safety requirements: Modeling deterministic (imperfect) staggered tests using standard Markov models for SIL calculations.

In industry, potentially hazardous (technical) structures are equipped with safety systems in order to protect people, the environment, and assets from the consequences of accidents by reducing the probability of incidents occurring. Not only companies but also society will want to know what the effect of these safety measures is: society in terms of "likelihood of undesired events" and companies in addition in terms of "value for money," the expected benefits per dollar or euro invested that these systems provide. As a compromise between demands from society (the safer the better) and industry (but against what cost), in many countries government has decided to impose standards to industry with respect to safety requirements. These standards use the average probability of failure on demand as the main performance indicator for these systems, and require, for the societal reason given before, that this probability remain below a certain value depending on a given risk. The main factor commonly used in industry to "fine-tune" the average probability of failure on demand for a given system configuration in order to comply with these standards against financial risk for the company is "optimizing" the test strategy (interval, coverage, and procedure). In industry, meeting the criterion on the average probability of failure on demand is often demonstrated by using well accepted mathematical models such as Markov models from literature and adapting them for the actual situation. This paper shows the implications and potential pitfalls when using this commonly used practical approach for a situation where the test strategy is changed. Adapting an existing Markov model can lead to unexpected results, and this paper will demonstrate that a different model has to be developed. In addition, the authors propose an approach that can be applied in industry without suffering from the problems mentioned above.

Journal Article↗

Patient and staff dose during CT guided biopsy, drainage and coagulation.

Patient and staff dose during CT guided coagulation of osteoid osteoma, tissue biopsy and abscess drainage were evaluated retrospectively on a conventional CT scanner and prospectively on a scanner equipped with fluoroscopic CT. The computed tomography dose index (CTDI) and the individual dose equivalent, i.e. the penetrating dose for workers at a depth of 10 mm tissue, were measured. Evaluation of CTDI enabled effective dose and maximum skin entrance doses for the patient to be determined. Doses were assessed for 96 CT guided interventions, including 16 drainages with average effective doses of 13.5 mSv and 9.3 mSv for the conventional CT scanner and the scanner with spiral CT fluoroscopy, respectively, 49 biopsies (effective doses of 8 mSv and 6.1 mSv, respectively), and 31 coagulations of osteoid osteoma (effective doses of 2.1 mSv and 0.8 mSv, respectively). Effective doses to patients were in the same range as those observed for regular diagnostic CT examinations. Entrance skin doses were well below the 2 Gy threshold for deterministic skin effects on the CT scanner equipped with fluoroscopic function (0.03-0.33 Gy), whilst skin doses on the conventional scanner were considerably higher (0.09-1.61 Gy). This is mainly owing to the fact that on the conventional scanner mAs was rarely reduced for scans evaluating needle position whereas low mAs per rotation was selected on the scanner with the fluoroscopy option. The maximum dose to a worker measured outside the lead apron was 28 microSv for one single procedure. The mean dose per procedure was below 10 microSv for radiologists and below 1 microSv for radiographers. Correcting for attenuation of the lead apron, the doses to workers are very low.

Biopsy↗

Induction mechanism of a single gene molecule: stochastic or deterministic?

A new field of gene expression regulation research is emerging that has previously been overlooked. This new area is concerned with distinguishing the expression of a single gene from the averaged expression of many gene copies within the cell population. This paper reviews research focused on individual genes in inducible gene expression systems. The main experimental strategy is to measure the gene expression level of a single cell containing a single reporter gene molecule. In contrast to the commonly held belief, gene induction is found to be stochastic under certain conditions. The possible mechanisms and implications are discussed.

Gene Expression Regulation↗

Inclusive fitness for traits affecting metapopulation demography.

Defining computable analytical measures of the effects of selection in populations with demographic and environmental stochasticity is a long-standing problem. We derive an analytical measure which takes in account all consequences of the discrete nature of deme size. Expressions of this measure are detailed for infinite island models of population structure. As an illustration we consider the evolution of dispersal in populations made of small demes with environmental and demographic stochasticity. We confirm some results obtained from the analysis of models based on deterministic approximations. In particular, when there is an Allee effect, we show that evolution of the dispersal rate may lead the metapopulation to extinction. Thus, selection on the dispersal rate could restrict the distribution of species subject to Allee effects. This selection-driven extinction is prevented by kin selection when the environmental extinction rate is small.

Alleles↗

Charge displacements in a single potassium ion channel macromolecule during gating.

Single ion channel currents can only provide indirect information on channel molecular events (except for timing). In contrast, the electric displacement currents associated with channel gating, termed gating currents, can provide direct information regarding the channel molecule's conformational changes. However, thus far gating currents have been measured only from ensembles of numerous stochastically activated channels and therefore the information they provide is limited. This work presents, for the first time, measurements of gating currents from a single channel molecule. Averaging close to 8000 pre-open currents, aligned to the single channel opening time, enabled the detection of single channel gating currents with a resolution of 2 electron charges. The measured charge displacements show: 1) a slow component, approximately 2 fA above baseline level, assumed to represent stochastic conformational changes, and 2) transients, the most significant of which occur 1.1 and 0.3 ms before channel opening. The transients most likely represent apparent deterministic stages in the gating process. The largest transient current peak was 5.1 +/- 1.6 fA and the total equivalent charge transported across the membrane was 4.7 +/- 2.5 electron charges. This data is unique also in that it presents monitoring of the behavior of a single, well-defined macromolecule.

Animals↗

Analyzing the dynamics of hand tremor time series.

We investigate physiological, essential and parkinsonian hand tremor measured by the acceleration of the stretched hand. Methods from the theory of dynamical systems and from stochastics are used. It turns out that the physiological tremor can be described as a linear stochastic process, and that the parkinsonian tremor is nonlinear and deterministic, even chaotic. The essential tremor adopts a middle position, it is nonlinear and stochastic.

Hand↗

Reduction of correlation dimension in human respiration by inhaling a mixture gas of 5% carbon dioxide and 95% oxygen.

In order to investigate the effect of the respiratory control system on deterministic behavior in respiration, we used nonlinear analysis in subjects breathing a mixture gas of 5% carbon dioxide (CO2) and 95% oxygen (O2) (CO2-mixed gas). The respiratory movements during breathing air or CO2-mixed gas in eight healthy volunteers were measured. We estimated the values of the correlation dimension (D2) in respiratory movement using Grassberger-Procaccia algorithm. The respiratory movements during inhaling either air or CO2-mixed gas showed a nonlinear behavior using surrogate data method. The values of D2 in respiratory movement during inhaling CO2-mixed gas (1.77 +/- 0.17) were significantly smaller than those during inhaling air (2.52 +/- 0.60) (P < 0.05). This might be related to a prompt change in the nonlinear signal from the central respiratory chemical system.

Adult↗

Individual based modeling and parameter estimation for a Lotka-Volterra system.

Stochastic component, inevitable in biological systems, makes problematic the estimation of the model parameters from a single sequence of measurements, despite the complete knowledge of the system. We studied the problem of parameter estimation using individual-based computer simulations of a 'Lotka-Volterra world'. Two kinds (species) of particles--X (preys) and Y (predators)--moved on a sphere according to deterministic rules and at the collision (interaction) of X and Y the particle X was changed to a new particle Y. Birth of preys and death of predators were simulated by addition of X and removal of Y, respectively, according to exponential probability distributions. With this arrangement of the system, the numbers of particles of each kind might be described by the Lotka-Volterra equations. The simulations of the system with low (200-400 particles on average) number of individuals showed unstable oscillations of the population size. In some simulation runs one of the species became extinct. Nevertheless, the oscillations had some generic properties (e.g. mean, in one simulation run, oscillation period, mean ratio of the amplitudes of the consecutive maxima of X and Y numbers, etc.) characteristic for the solutions of the Lotka-Volterra equations. This observation made it possible to estimate the four parameters of the Lotka-Volterra model with high accuracy and good precision. The estimation was performed using the integral form of the Lotka-Volterra equations and two parameter linear regression for each oscillation cycle separately. We conclude that in spite of the irregular time course of the number of individuals in each population due to stochastic intraspecies component, the generic features of the simulated system evolution can provide enough information for quantitative estimation of the system parameters.

Animals↗

Measurement and calculation of the fast-neutron and photon spectra from the core boundary to the biological shielding in the WWER-1000 reactor model.

The fast-neutron and photon space-energy distributions have been measured in an axially (1.25 m active height) and azimuthally (60 degree symmetry sector) shortened model of the WWER-1000 reactor assembled in the LR-0 experimental reactor. The space-energy distributions have been calculated with the stochastic code MCNP and the deterministic three-dimensional code TORT. Selected results are presented and discussed in the paper. This work has been done in the frame of the EU 5th FW project REDOS REDOS, Reactor Dosimetry: Accurate determination and benchmarking of radiation field parameters, relevant for reactor pressure vessel monitoring. EURATOM Programme, Call 2000/C 294/04). All geometry and material composition data of the model as well as the available experimental data were carefully checked and revised.

Algorithms↗

Scaling laws in adsorption on bivariate surfaces.

The adsorption of particles with nearest-neighbor attractive and repulsive interactions is studied through Monte Carlo simulation on bivariate surfaces characterized by patches of weak and strong adsorbing sites of size l. Patches are considered to have either a square or a strip geometry and they can be either arranged in a deterministic ordered structure or in a random way. Quantities are identified that scale obeying power laws as a function of the scale length l. The consequences of this finding are discussed for the determination of the energetic topography of the surface from adsorption measurements.

Journal Article↗

Occurrence, oral exposure and risk assessment of volatile organic compounds in drinking water for Izmir.

Concentrations of volatile organic compounds (VOCs) were measured in the drinking water in Province of Izmir, Turkey, and associated health risks due to ingestion of these compounds were investigated using population weighted random samples. A total of 100 houses were visited in different districts of Izmir and drinking water samples were collected from consumers' drinking water source. Questionnaires were administered to one participant in each house to determine demographics and drinking water consumption rates. Oral exposure and risks were estimated for each participant and Izmir population by deterministic and probabilistic approaches, respectively. The four trihalomethane (THM) species (i.e., chloroform, bromodichloromethane, dibromochloromethane, and bromoform), benzene, toluene, p-xylene, and naphthalene were the most frequently detected VOCs with concentrations ranging from below detection limit to 35 microg/l. The risk estimates were found to be less than the values reported in the literature with few exceptions. Noncarcinogenic risks attributable to ingestion of VOCs for Izmir population were negligible, whereas the mean carcinogenic risk estimates for bromodichloromethane and dibromochloromethane were above the de minimis level of one in a million (10(-6)). For all VOCs, the concentrations measured in metropolitan area were greater than those in other districts. All THM species were detected in higher concentrations in tap water, whereas nontap water contained more benzene, toluene, p-xylene, and naphthalene. Therefore, the concentrations of the latter four compounds and associated risks increased with increasing income and education level since bottled water was used in larger proportions within these subgroups. The results of this study showed that oral exposure to drinking water contaminants and associated risks may be higher than the acceptable levels even if the concentrations fall below the standards.

Administration, Oral↗

Abnormalities in beat to beat complexity of heart rate dynamics in patients with a previous myocardial infarction.

OBJECTIVES: The purpose of this research was to study possible abnormalities in the beat to beat complexity of heart rate dynamics in patients with a previous myocardial infarction. BACKGROUND: Analysis of approximate entropy of time series data provides information on the complexity of both deterministic and random processes. It has been proposed that regularity or loss of complexity of RR interval dynamics may be related to pathologic states, but this hypothesis has not been well tested in cardiovascular disorders. METHODS: Approximate entropy and conventional time and frequency domain measures of RR interval variability were compared between 40 healthy subjects with no evidence of heart disease and 40 patients with coronary artery disease and a previous Q wave myocardial infarction. The groups were matched with respect to age, and cardiac medication was discontinued in the patients with coronary artery disease before the 24-h electrocardiographic recordings. RESULTS: Approximate entropy was significantly higher in the postinfarction patients (1.21 +/- 0.18 [mean +/- SD]) than in the healthy subjects (1.05 +/- 0.11, p < 0.001), whereas the standard deviation of RR intervals (63 +/- 19 vs. 86 +/- 23 ms, p < 0.001) and the very low, low and high frequency spectral components were lower (p < 0.01, p < 0.001, p < 0.05, respectively). Approximate entropy was not related to the time domain or the spectral components of heart rate variability and was more commonly abnormal in postinfarction patients (62.5%) than any linear measure (from 20% to 42.5%) when the 90% percentile of the values obtained for healthy subjects was defined as the normal range for each measure. CONCLUSIONS: Despite reduced linear measures of heart rate variability, the unpredictability or randomness of beat to beat heart rate dynamics is increased in patients with a previous myocardial infarction. Complexity analysis of RR interval dynamics may provide useful information on abnormalities in heart rate behavior that are not easily detected by the commonly used moment statistics.

Adult↗

Dynamical assessment of physiological systems and states using recurrence plot strategies.

Physiological systems are best characterized as complex dynamical processes that are continuously subjected to and updated by nonlinear feedforward and feedback inputs. System outputs usually exhibit wide varieties of behaviors due to dynamical interactions between system components, external noise perturbations, and physiological state changes. Complicated interactions occur at a variety of hierarchial levels and involve a number of interacting variables, many of which are unavailable for experimental measurement. In this paper we illustrate how recurrence plots can take single physiological measurements, project them into multidimensional space by embedding procedures, and identify time correlations (recurrences) that are not apparent in the one-dimensional time series. We extend the original description of recurrence plots by computing an array of specific recurrence variables that quantify the deterministic structure and complexity of the plot. We then demonstrate how physiological states can be assessed by making repeated recurrence plot calculations within a window sliding down any physiological dynamic. Unlike other predominant time series techniques, recurrence plot analyses are not limited by data stationarity and size constraints. Pertinent physiological examples from respiratory and skeletal motor systems illustrate the utility of recurrence plots in the diagnosis of nonlinear systems. The methodology is fully applicable to any rhythmical system, whether it be mechanical, electrical, neural, hormonal, chemical, or even spacial.

Animals↗

[Can exposure to low doses have effects?].

This paper aims to discuss the scientific evidence to answer the question in the title. After a brief mention of the fundamental toxicological principles of risk assessment (hazard, exposure, susceptibility, risk), the concepts of dose-response, dose-effect and threshold-dose are presented. The difference between adverse effects with and those without a threshold is highlighted, together with the corresponding methodologies used in risk assessment for the definition of the limit values, i.e. the No Observed Adverse Effect Level (NOAEL) and Safety Factor (SF) method and the Virtually Safe Dose (VSD) method. The two methods correspond to two different types of effect, i.e. deterministic and stochastic, and to two different shapes of the dose-response curve at low doses. The various possible meanings (semantic, toxicological and practical) of the terms "low doses" are discussed: a dose (or concentration) may be low because it does not cause measurable adverse effects (as from Paracelsus' aphorism) or because it is too low to be (analytically) measurable or because it is close to or within the "normal" values of a reference population or because it is well below the exposure limit(s). These various concepts are presented also in relation with the controversial concept of "moderate risk" introduced by a recent Italian legislation (D. Lgs 25/02) on the protection of the workers against chemical risk. It would not be appropriate to set a level of risk simply based on the dose (or the level of exposure) without considering the two other components of risk, i.e. hazard and susceptibility, whose estimation also needs a careful and competent evaluation by the occupational physician. For a thorough discussion of the "moderate risk" concept see a specific paper in these Proceedings. So, clinical, epidemiological and toxicological evidence indicates that in some individuals, groups of the population or circumstances, adverse effects can be observed or expected even at low doses, at which the large majority of the population shows no effect. This is due to a number of factors including toxicological interactions, immunoallergic mechanisms, metabolic hypersusceptibility, both genetic (polymorphism) and acquired (phenotype), preexisting traits or diseases, living habits, diet and others. The Authors conclude therefore that to ensure the protection of all the workers' health and safety, the clinical, toxicological and epidemiological expertise of the occupational physician appears to be fundamental and unreplacable.

Dose-Response Relationship, Drug↗

Risks and benefits of long-term treatment with estrogens.

The goal of contemporary hormone replacement is to minimize net predictable lifetime risk; success therefore depends upon quantitative assessments of the net quality of life, of net morbidity and of net mortality. Estrogens ameliorate menopausal symptoms, maintain bone integrity, and produce endometrial cancer; these facts and their quantitative aspects can be stimulated. Other links are gradually becoming clear: estrogens increase biliary disease, but prevent heart disease, and, it now seems, stroke. Conventional wisdom to the contrary notwithstanding, a critical review suggests that breast cancer is probably increased in frequency by long-term estrogen use; the increase is modest as a risk factor but because breast cancer is a common disease, it is substantial in absolute terms. The addition of progestin seems attractive as a method of opposing undesirable estrogenic effects on the endometrium. In fact, there is reason for concern about the effect of an added progestin upon the risks from breast cancer, heart disease, and stroke; even the magnitude of the expected reduction in endometrial cancer may not be great when the hormone is administered sequentially. Using a simple deterministic model of post-menopausal life with hormone replacement, we have inserted available estimates of the regimen-specific relative risk for each outcome, and translated each net impact into common denominators of morbidity and mortality. While estrogens probably increase net morbidity, as measured by either the number of hospitalizations to be anticipated or by the more arbitrary measure of expected days of disability, these negative changes are mostly due to gallbladder disease and endometrial cancer, both largely treatable conditions. Largely because of protection against heart disease, estrogen replacement in modest dose is likely to reduce substantially the number of deaths to be expected in women treated through age 75 and even into more advanced age. Hormone replacement which includes systemic progestin supplementation has not been empirically tested; it may be beneficial, but it is at least as likely to be harmful. Either a modest increment in the number of additional breast cancers produced by estrogens, a modest reduction in the number of cardiac events prevented by estrogens, or a simultaneous minor shift in the same direction for each condition, would have the effect of shifting the net reduction in cumulative deaths into an increase in the number of deaths as a result of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗