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Results for “Deterministic Measurement”

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PubMed1985

Commitment to differentiation of human promyelocytic leukemia cells (HL60): an all-or-none event preceded by reversible losses of self-renewal potential.

A method for clonal analysis has been developed which allows the characterization of the number and type of progeny cells produced by each single cell arising during clonal evolution. The method is based on a symmetry of self-renewal exhibited by sister cells of the human promyelocytic leukemia cell line -HL60-. This permits the use of one of the sister cells to measure the potential for self renewal of the other. Using a system of sequential daughter cell transfers in semisolid medium, we have analysed self-renewal and differentiation in individual clones exposed to all-trans retinoic acid or dimethylsulfoxide (DMSO). We find that in clones exposed to chemical inducers of differentiation commitment occurs as an all-or-none event which is preceded by coordinated but reversible losses of self-renewal potential. It is concluded that the differentiation pathway of HL60 cells has two distinct portions. These are, first, a predeterministic portion, reflected by coordinated but reversible losses of self-renewal potential, and second, a deterministic portion, reflected by irreversible phenotypic differentiation.

Cell Division↗

PubMed2003

Fractal properties of sympathetic nerve discharge.

Fano factor analysis and dispersional analysis were used to characterize time series of single and multifiber spikes recorded from the preganglionic cervical sympathetic nerve and cardiac-related slow-wave activity of the whole postganglionic sympathetic vertebral nerve (VN) in anesthetized cats. Fluctuations in spike counts and interspike intervals for single preganglionic fibers proved to be fractal (i.e., time-scale invariant), as reflected by a power law relationship between indices of the variance of these properties and the window size used to make the measurements. Importantly, random shuffling of the data eliminated the power law relationships. Fluctuations in spike counts in preganglionic multifiber activity also were fractal, as were fluctuations in the height and of the area of cardiac-related slow waves recorded from the whole postganglionic VN. These fractal fluctuations were persistent (i.e., positively correlated), as reflected by a Hurst exponent significantly >0.5. Although fluctuations in the interval between cardiac-related VN slow waves were random, those in the interval between heart beats were fractal and persistent. These results demonstrate for the first time that apparently random fluctuations in sympathetic nerve discharge are, in fact, dictated by a complex deterministic process that imparts "long-term" memory to the system. Whether such time-scale invariant behavior plays a role in generating the fractal component of heart rate variability remains to be determined.

Action Potentials↗

PubMed1978

Genetic and evolutionary fitness.

The advantages and disadvantages of evolutionary fitness (probability that a single mutant line will not become extinct) and genetic fitness (mean fecundity) are compared. For deterministic processes the two are equivalent, but for stochastic branching processes they may be totally unrelated except that an absolute genetic fitness of unity or less implies an evolutionary fitness of zero. To know the variance as well as the mean family size does not in general uniquely determine the evolutionary fitness. Except where genetic fitness is close to unity, the impact of selection is shown to be rapid for the binomial, Poisson, negative binomial, and truncated negative binomial distributions. Evolutionary fitness, though somewhat cumbersome, has greater relevance to evolution, genetic counseling, and voluntary population control; but genetic fitness which is much easier to handle is the more appropriate measure where a large number of mutants is involved. Some empirical data on the transmission of various types of characters from parent to child are analyzed to allow comparison of genetic fitness, Crow's index, and a Malthusian parameter, with evolutionary fitness. There is a fair, but far from perfect, agreement among them. Multiple correlation of evolutionary fitness with mean and variance of family size taken jointly suggests a much more satisfactory approximation. It thus appears that, at the least, the population geneticist cannot afford to ignore the variance (which is not adequately represented in Crow's index). These relationships, based on two sets of data only may be accidental and should be invoked with caution. It seems more than likely that other aspects of the distribution of family size (eg, even higher moments) may contain relevant information in certain cases.

Biological Evolution↗

PubMed1995

Temporal patterns of gene expression in the antenna of the adult Drosophila melanogaster.

The time course of gene expression in the adult fruit fly has been partially characterized by using enhancer trap and reporter gene constructs that mark 49 different genes. The relative intensity of the reporter protein in individual cells of the antennae was measured as a function of adult age. Most genes showed a graduated expression, and the intensity of expression had a reproducible and characteristic time course. Different genes displayed different temporal patterns of expression and more often than not the pattern of expression was complex. We found a number of genes having patterns that scaled with life span. In these cases the intensity of gene expression was found to be invariant with respect to biological time, when expressed as a fraction of the life span of the line. The scaling was observed even when life span was varied as much as threefold. Such scaling serves to (1) further demonstrate that deterministic mechanisms such as gene regulation act to generate the temporal patterns of expression seen during adult life, (2) indicate that control of these regulatory mechanisms is linked to life span, and (3) suggest mechanisms by which this control is accomplished. We have concluded that gene expression in the adult fly is often regulated in a fashion that allows for graduated expression over time, and that the regulation itself is changing throughout adult life according to some prescribed program or algorithm.

Animals↗

PubMed2003

Direct observation of homoclinic orbits in human heart rate variability.

Homoclinic trajectories of the interbeat intervals between contractions of ventricles of the human heart are identified. The interbeat intervals are extracted from 24-h Holter ECG recordings. Three such recordings are discussed in detail. Mappings of the measured consecutive interbeat intervals are constructed. In the second and in some cases in the fourth iterate of the map of interbeat intervals homoclinic trajectories associated with a hyperbolic saddle are found. The homoclinic trajectories are often persistent for many interbeat intervals, sometimes spanning many thousands of heartbeats. Several features typical for homoclinic trajectories found in other systems were identified, including a signature of the gluing bifurcation. The homoclinic trajectories are present both in recordings of heart rate variability obtained from patients with an increased number of arrhythmias and in cases in which the sinus rhythm is dominant. The results presented are a strong indication of the importance of deterministic nonlinear instabilities in human heart rate variability.

Journal Article↗

PubMed2006

A probabilistic model of glenohumeral external rotation strength for healthy normals and rotator cuff tear cases.

The reigning paradigm of musculoskeletal modeling is to construct deterministic models from parameters of an "average" subject and make predictions for muscle forces and joint torques with this model. This approach is limited because it does not perform well for outliers, and it does not model the effects of population parameter variability. The purpose of this study was to simulate variability in musculoskeletal parameters on glenohumeral external rotation strength in healthy normals, and in rotator cuff tear case using a Monte Carlo model. The goal was to determine if variability in musculoskeletal parameters could quantifiably explain variability in glenohumeral external rotation strength. Multivariate Gamma distributions for musculoskeletal architecture and moment arm were constructed from empirical data. Gamma distributions of measured joint strength were constructed. Parameters were sampled from the distributions and input to the model to predict muscle forces and joint torques. The model predicted measured joint torques for healthy normals, subjects with supraspinatus tears, and subjects with infraspinatus-supraspinatus tears with small error. Muscle forces for the three conditions were predicted and compared. Variability in measured torques can be explained by differences in parameter variability.

Computer Simulation↗

PubMed2002

Information in the behavior stream.

The dynamic of a series of responses for four pigeons is analyzed using a discrete fast Fourier transform (FFT) and a measure of behavior's predictability. FFTs of moment-to-moment response rates reliably exhibited a continuous distribution for three of the four birds, with most of the power falling in the low frequencies-red noise. An information analysis of the predictability of a series of inter-response times (IRTs) reveals that there is some gain in prediction by knowing past behavior; moreover, predictability increases the more past behaviors are taken into account. However, the further into the future these predictions are extended, the less reliable they become-entropy. These findings suggest that the dynamic controlling behavior at the level of the individual response is, to some extent, deterministic and probably chaotic.

Journal Article↗

PubMed1994

Lack of evidence for low-dimensional chaos in heart rate variability.

INTRODUCTION: The term chaos is used to describe erratic or apparently random time-dependent behavior in deterministic systems. It has been suggested that the variability observed in the normal heart rate may be due to chaos, but this question has not been settled. METHODS AND RESULTS: Heart rate variability was assessed by recordings of consecutive RR intervals in ten healthy subjects using ambulatory ECG. All recordings were performed with the subjects at rest in the supine position. To test for the presence of nonlinearities and/or chaotic dynamics, ten surrogate time series were constructed from each experimental dataset. The surrogate data were tailored to have the same linear dynamics and the same amplitude distribution as the original data. Experimental and surrogate data were then compared using various nonlinear measures. Power spectral analysis of the RR intervals showed a 1/f pattern. The correlation dimension differed only slightly between the experimental and the surrogate data, indicating that linear correlations, and not a "strange" attractor, are the major determinants of the calculated correlation dimension. A test for nonlinear predictability showed coherent nonlinear dynamic structure in the experimental data, but the prediction error as a function of the prediction length increased at a slower rate than characteristic of a low-dimensional chaotic system. CONCLUSION: There is no evidence for low-dimensional chaos in the time series of RR intervals from healthy human subjects. However, nonlinear determinism is present in the data, and various mechanisms that could generate such determinism are discussed.

Adolescent↗

PubMed2006

Theoretical assessment of public health impact of imperfect prophylactic HIV-1 vaccines with therapeutic benefits.

This paper presents a number of deterministic models for theoretically assessing the potential impact of an imperfect prophylactic HIV-1 vaccine that has five biological modes of action, namely "take," "degree," "duration," "infectiousness," and "progression," and can lead to increased risky behavior. The models, which are of the form of systems of nonlinear differential equations, are constructed via a progressive refinement of a basic model to incorporate more realistic features of HIV pathogenesis and epidemiology such as staged progression, differential infectivity, and HIV transmission by AIDS patients. The models are analyzed to gain insights into the qualitative features of the associated equilibria. This allows the determination of important epidemiological thresholds such as the basic reproduction numbers and a measure for vaccine impact or efficacy. The key findings of the study include the following (i) if the vaccinated reproduction number is greater than unity, each of the models considered has a locally unstable disease-free equilibrium and a unique endemic equilibrium; (ii) owing to the vaccine-induced backward bifurcation in these models, the classical epidemiological requirement of vaccinated reproduction number being less than unity does not guarantee disease elimination in these models; (iii) an imperfect vaccine will reduce HIV prevalence and mortality if the reproduction number for a wholly vaccinated population is less than the corresponding reproduction number in the absence of vaccination; (iv) the expressions for the vaccine characteristics of the refined models take the same general structure as those of the basic model.

AIDS Vaccines↗

PubMed1985

[Function scintigraphy: a uniform method for quantifying organ metabolism and function].

Functional scintigraphy is a quantitative method with which metabolic parameters of an organ can be determined by measuring the time activity course of a radioactive tracer in tissue. Their quantitative value is, however, limited by inherent sources of error, e.g. the absorption of radiation in the organ or overlapping of fore- and background activities. Hitherto, existing procedures for calculation of metabolic parameters are based more on given technical possibilities than on common theoretical foundations. They are notable for their variety in methodical approach, frequently being of empirical character. Quantitative results from different institutes and hospitals can therefore rarely be compared. The present work describes a methodical approach to obtain comparable methods in nuclear medicine, by including the pharmacokinetics of a tracer in blood. This leads to the compartment analysis (deterministic) or to a stochastic (non-deterministic) description of the kinetics in an organ. The stochastic description requires the calculation of the linear response function from a convolution integral. By means of functional analytical methods a mathematical procedure has been developed which for the first time permits the calculation of the linear response function in each pixel and at any time of the study. Easily readable functional images show how relevant parameters can be calculated from the linear response function. Due to its independence on any model, the linear response function enables furthermore a regional investigation of existing or new compartment models of tracer kinetics in the organ concerned.

Bone and Bones↗

PubMed2006

Questionnaire- and measurement-based individual thyroid doses in Ukraine resulting from the Chornobyl nuclear reactor accident.

The U.S. National Cancer Institute (NCI), in cooperation with the Ministries of Health of Belarus and of Ukraine, is involved in epidemiological studies of thyroid diseases presumably related to the Chornobyl accident, which occurred in Ukraine on 26 April 1986. Within the framework of these studies, individual thyroid absorbed doses, as well as uncertainties, have been estimated for all members of the cohorts (13,215 Ukrainians and 11,918 Belarusians), who were selected from the large group of children aged 0 to 18 whose thyroids were monitored for gamma radiation within a few weeks after the accident. Information on the residence history and dietary habits of each cohort member was obtained during personal interviews. The methodology used to estimate the thyroid absorbed doses resulting from intakes of (131)I by the Ukrainian cohort subjects is described. The model of thyroid dose estimation is run in two modes: deterministic and stochastic. In the stochastic mode, the model is run 1,000 times for each subject using a Monte Carlo procedure. The geometric means of the individual thyroid absorbed doses obtained in the stochastic mode range from 0.0006 to 42 Gy. The arithmetic and geometric means of these individual thyroid absorbed doses over the entire cohort are 0.68 and 0.23 Gy, respectively. On average, the individual thyroid dose estimates obtained in the deterministic mode are about the same as the geometric mean doses obtained in the stochastic mode, while the arithmetic mean thyroid absorbed doses obtained in the stochastic mode are about 20% higher than those obtained in the deterministic mode. The distributions of the 1000 values of the individual thyroid absorbed dose estimates are found to be approximately lognormal, with geometric standard deviations ranging from 1.6 to 5.0 for most cohort subjects. For the time being, only the thyroid doses resulting from intakes of (131)I have been estimated for all subjects. Future work will include the estimation of the contributions to the thyroid doses resulting from external irradiation and from intakes of short-lived ((133)I and (132)Te) and long-lived ((134)Cs and (137)Cs) radionuclides, as well as efforts to reduce the uncertainties.

Body Burden↗

PubMed2005

Cost-effectiveness of exogenous surfactant therapy in pediatric patients with acute hypoxemic respiratory failure.

OBJECTIVE: To determine whether the use of exogenous surfactant (Infasurf) in pediatric acute hypoxemic respiratory failure is cost-effective. DESIGN: Deterministic cost-effectiveness analysis based on a Markov model. The model was calibrated using outcomes and resource utilization observed in a multiple-centered, prospective, randomized, controlled unblinded trial of Infasurf in pediatric acute hypoxemic respiratory failure. Costs were short-run direct costs estimated from the perspective of the hospital as provider. Primary outcomes were expected costs, expected survival rates, and incremental cost per life saved. SETTING: Patients in the trial were treated in one of eight pediatric intensive care units of tertiary medical centers. PATIENTS: Forty-two children with acute hypoxemic respiratory failure who were randomized to receive either standard therapy or exogenous surfactant in addition to standard therapy. MEASUREMENTS AND MAIN RESULTS: Our baseline analysis suggests that for a 10-kg child, the Infasurf strategy is both less costly (62,922 US dollars vs. 74,006 US dollars) and more effective (survival: 90.3% vs. 85.1%) and therefore dominates standard treatment. Cost savings were realized in the model because patients in the surfactant group were more likely to leave the pediatric intensive care unit sooner. The Infasurf strategy continues to dominate for children up to 60 kg. At 70 kg, the cost to save an additional life using the Infasurf strategy is 79,805 US dollars, which is still cost-effective if the provider is willing to make this tradeoff. CONCLUSIONS: For the majority of pediatric patients with acute hypoxemic respiratory failure, exogenous surfactant is cost-effective. If the use of this medication becomes standard care, a greater variety of packaging sizes could lead to decreased acquisition costs and increase the number of patients for whom this treatment is cost-effective.

Acute Disease↗

PubMed2005

A stochastic model of elbow flexion strength for subjects with and without long head biceps tear.

The classical approach of musculoskeletal modeling is to predict muscle forces and joint torques with a deterministic model constructed from parameters of an average subject. However, this type of model does not perform well for outliers, and does not model the effects of parameter variability. In this study, a Monte-Carlo model was used to stochastically simulate the effects of variability in musculoskeletal parameters on elbow flexion strength in healthy normals, and in subjects with long head biceps (LHB) rupture. The goal was to determine if variability in elbow flexion strength could be quantifiably explained with variability in musculoskeletal parameters. Parameter distributions were constructed from data in the literature. Parameters were sampled from these distributions and used to predict muscle forces and joint torques. The median and distribution of measured joint torque was predicted with small errors (< 5%). Muscle forces for both cases were predicted and compared. In order to predict measured torques for the case of LHB rupture, the median force and mean cross-sectional area in the remaining elbow flexor muscles is greater than in healthy normals. The probabilities that muscle forces for the Tear case exceed median muscle forces for the No-Tear case are 0.98, 0.99 and 0.79 for SH Biceps, brachialis and brachioradialis, respectively. Differences in variability of measured torques for the two cases are explained by differences in parameter variability.

Computer Simulation↗

PubMed2005

User-friendly models of the costs and efficacy of tsetse control: application to sterilizing and insecticidal techniques.

An interactive programme, incorporating a deterministic model of tsetse (Diptera: Glossinidae) populations, was developed to predict the cost and effect of different control techniques applied singly or together. Its value was exemplified by using it to compare: (i) the sterile insect technique (SIT), involving weekly releases optimized at three sterile males for each wild male, and (ii) insecticide-treated cattle (ITC) at 3.5/km(2). The isolated pre-treatment population of adults was 2500 males and 5000 females/km(2); if the population was reduced by 90%, its growth potential was 8.4 times per year. However, the population expired naturally when it was reduced to 0.1 wild males/km(2), due to difficulties in finding mates, so that control measures then stopped. This took 187 days with ITC and 609 days with SIT. If ITC was used for 87 days to suppress the population by 99%, subsequent control by SIT alone took 406 days; the female population increased by 48% following the withdrawal of ITC and remained above the immediate post-suppression level for 155 days; the vectorial capacity initially increased seven times and remained above the immediate post-suppression level for 300 days. Combining SIT and ITC after suppression was a little faster than ITC alone, provided the population had not been suppressed by more than 99.7%. Even when SIT was applied under favourable conditions, the most optimistic cost estimate was 20-40 times greater than for ITC. Modelling non-isolated unsuppressed populations showed that tsetse invaded approximately 8 km into the ITC area compared to approximately 18 km for SIT. There was no material improvement by using a 3-km barrier of ITC to protect the SIT area. In general, tsetse control by increasing deaths is more appropriate than reducing births, and SIT is particularly inappropriate. User-friendly models can assist the understanding and planning of tsetse control. The model, freely available via http://www.tsetse.org, allows further exploration of control strategies with user-specified assumptions.

Animals↗

PubMed1995

Dose, effect severity, and imparted energy in assessing biological effects.

Because of the widespread efforts in cancer radioepidemiological studies to attach a value of absorbed dose to each exposed individual, the notion seems to have become prevalent that dose plays an essential role in the medical determination of the diagnosis and prognosis of the individual. This view is enhanced by the fact that, while the present quantities and units for radiological physics were developed in the context of the acute effects of large exposures to radiation, e.g., in radiotherapy where they still apply well, these same quantities and units have been used, without modification, to apply to cancer radioepidemiology in the context of low level irradiation. A principle purpose of the present communication is to show that, in medicine, dose plays a limited role even in the deterministic application of therapeutic agents, and that diagnosis and estimates of prognosis in medicine are based, not on dose, but on the severity of effect on, or damage to the organ or organs involved in a particular medical condition. Thus it is "going backward" to view estimates of the severity of effect, e.g., the fraction of cells with abnormalities, or killed, as a "biological dosimeter," rather than as a quantitative estimate of the severity of effect. The use of biological indicators is of maximum value in noncancerous disease or injury in which the severity of an effect causative for organ failure and a consequent quantal, e.g., a lethal response in the individual, can be measured with increasing accuracy by modern medical techniques.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1999

Phenotypic diversity and stability of ecosystem processes.

The resistance of an ecosystem to perturbations and the speed at which it recovers after the perturbations, which is called resilience, are two important components of ecosystem stability. It has been suggested that biodiversity increases the resilience and resistance of aggregated ecosystem processes. We test this hypothesis using a theoretical model of a nutrient-limited ecosystem in a heterogeneous environment. We investigate the stability properties of the model for its simplest possible configuration, i.e. , a system consisting of two plant species and their associated detritus and local resource depletion zones. Phenotypic diversity within the plant community is described by differences in the nutrient uptake and mortality rates of the two species. The usual measure of resilience characterizes the system as a whole and thus also applies to aggregated ecosystem processes. As a rule this decreases with increased diversity, though under certain conditions it is maximum for an intermediate value of diversity. Resistance is a property that characterizes each system component and process separately. The resistance of the inorganic nutrient pools, hence of nutrient retention in the ecosystem, decreases with increased diversity. The resistance of both total plant biomass and productivity either monotonically decreases or increases over part of the parameter range with increased diversity. Furthermore, it is very sensitive to parameter values. These results support the view that there is no simple relationship between diversity and stability in equilibrium deterministic systems, whether at the level of populations or aggregated ecosystem processes. We discuss these results in relation to recent experiments.

Ecosystem↗

PubMed1982

Reduction of EEG activity caused by a light flash.

Intertrial EP variance measured in response to a brief binocularly presented flash of light decreases with a time-course that overlaps the average EP. This decrease in variance is not exclusive to the alpha frequency band (8-12 c/sec) but it is selective for it. Subjects with large initial variance tend to show a large decrease in variance. There is no relationship between the magnitude of the decrease in variance and the consistency of the EP. The phenomenon reflected by the decrease in variance is probably identical with 'event-related desynchronization.' The results support the hypothesis that an EP may consist of two processes that overlap in time: a reduction in background EEG activity and an almost deterministic transient potential change.

Brain↗

PubMed2000

Estimation of the entropy of the solar wind flow

We analyze a time series of velocities of the low-speed stream measured by the Helios spacecraft in the inner heliosphere, which is the region of space dominated by the solar wind flow. We use a nonlinear filter to give a faithful representation of the solar wind nonlinear behavior. We have demonstrated that the influence of noise in the data can be much more efficiently reduced by a nonlinear filter than with the conventional (linear) filters, and this allows a more realistic calculation of the solar wind entropy. The resulting Kolmogorov entropy is positive, and possibly the largest Lyapunov exponent is also positive locally, which would exhibit exponential sensitivity to initial conditions. Thus, these results show that the solar wind in the inner heliosphere is most likely a deterministic chaotic system.

Journal Article↗