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Results for “Deterministic Measurement”

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PubMed2026

Foundation model reveals the shared organization of transcription and topologically associating domains.

The three-dimensional organization of chromatin into topologically associating domains (TADs) may impact gene regulation by bringing distant genes into contact. However, studies of TADs' function and their influence on transcription have been constrained by ambiguities in TAD boundary definitions and challenges in directly measuring their regulatory effects. We overcome these limitations by developing species-level consensus TAD maps for human and mouse by using a bag-of-genes approach that exposes an emergent regulatory structure. To quantify TAD-mediated relationships, we use a foundation model trained on 33 million transcriptomes to define a contextual similarity metric that captures higher-order relationships missed by co-expression. We find that TADs are regions of elevated co-regulation, with our framework yielding testable hypotheses about chromatin organization across cellular states. This TAD-linked enhancement is strongest during early development and declines with aging, while cancer cells show distinct TAD usage that shifts with chemotherapy. Together, these findings suggest that chromatin organization acts through probabilistic rather than deterministic mechanisms.

Humans↗

PubMed1997

Enhanced dimensional complexity of the EEG during memory for personal pain in chronic pain patients.

Associative connections between cortical cell assemblies representing pain-related memories should be stronger and more extensive in subjects with chronic pain. To test this hypothesis, the dimensional complexity of the electroencephalograph (EEG) was examined during the actual experience as well as during memory for pain. Nine chronic pain patients and nine matched healthy controls participated in the study. During acute pain induction, acute pain recall, personal stress and pain recall, the EEG was recorded from 15 scalp sites. Non-linear analysis, based on the theory of deterministic chaos, revealed higher and more widespread EEG complexity in the patients compared to the healthy controls only during the recall of the personal pain scene. The personal stress scene was rated equally aversive but did not induce more EEG complexity. These more extensive and more readily accessible pain memories may be instrumental for the persistence of chronic pain.

Adult↗

PubMed2004

Investigating ethnic inequalities in the incidence of sexually transmitted infections: mathematical modelling study.

OBJECTIVES: To investigate ethnic differences in rates of gonorrhoea using empirical sexual behaviour data in a simple mathematical model. To explore the impact of different intervention strategies in this simulated population. METHODS: The findings from cross sectional studies of gonorrhoea rates and sexual behaviour in three ethnic groups in south east London were used to determine the parameters for a deterministic, mathematical model of gonorrhoea transmission dynamics, in a population stratified by sex, sexual activity (rate of partner change), and ethnic group (white, black African, and black Caribbean). We compared predicted and observed rates of infection and simulated the effects of targeted and population-wide intervention strategies. RESULTS: In model simulations the reported sexual behaviours and mixing patterns generated major differences in the rates of gonorrhoea experienced by each subpopulation. The fit of the model to observed data was sensitive to assumptions about the degree of mixing by level of sexual activity, the numbers of sexual partnerships reported by men and women, and the degree to which observed data underestimate female infection rates. Interventions to reduce duration of infection were most effective when targeted at black Caribbeans. CONCLUSIONS: Average measures of sexual behaviour in large populations are inadequate descriptors for the epidemiology of gonorrhoea. The consistency between the model results and empirical data shows that profound differences in gonorrhoea rates between ethnic groups can be explained by modest differences in a limited number of sexual behaviours and mixing patterns. Targeting effective services to particular ethnic groups can have a disproportionate influence on disease reduction in the whole community.

Adolescent↗

PubMed2002

Estimating auditory neuronal dynamic range using a fitted function.

To obtain the dynamic range of an auditory afferent, the neuron's firing rate is plotted versus stimulus level, and the dynamic range is taken as the difference between the threshold for evoked firing, and the level at which firing rate saturates. Those dynamic range endpoints are typically defined in terms of the neuron's spontaneous firing rate and its maximum firing rate, according to a plurality of schemes, each of which depends on user-chosen sets of numerical criteria. The dynamic ranges predicted by some of these schemes are compared for the first time, and the resulting estimates can differ by a factor of 2. A step can be taken towards standardizing the measurement of neuronal dynamic range, if dynamic range is incorporated into a rate-level function as a parameter. To build this function, it is first assumed that the neuron's rate-level response reaches half its maximum at a level half-way between the threshold and the level at saturation, i.e. at threshold plus half the dynamic range. Then the firing rates at threshold and at threshold plus dynamic range are defined according to the most popular of the endpoint schemes. The resulting equation produces credible estimates of neuronal properties when fitted, and correctly predicts the behavior of the slope of the empirical rate-level plot [McGee, 1983. M.S. thesis, Creighton University; Ohlemiller et al., 1991. J. Acoust. Soc. Am. 90, 274-287]. Thus, despite not being deterministic, the new equation has remarkable predictive power. When two of the rate-level functions are added and weighted, the resulting equation fits sloping-saturating data better than any functions presently employed.

Animals↗

PubMed1993

Reassessment of human peripheral T-lymphocyte lifespan deduced from cytogenetic and cytotoxic effects of radiation.

Estimates of the mean lifetime of human peripheral blood T-lymphocytes (PBTL) have ranged from 1.5 to 10 year. To derive an improved estimate, kinetic and dose parameters of four deterministic, two-compartment models of loss and replacement of human peripheral blood lymphocytes (PBL) were fitted to a previously published extensive data set on loss of dicentrics plus rings (DR) in PBL sampled from X-ray-treated ankylosing spondylitis patients for > 20-year-post-treatment, involving a fixed external-dose regimen (with dose to PBL unknown). The four models investigated all incorporated fixed dose-response submodels for radiation-induced cytogenetic damage and cell killing that were based entirely on in vitro data for X-ray-exposed human PBTL. Two of the models are shown to provide a reasonably good prediction not only of the data on DR loss to which the models were fit, but also of corresponding data on recovery of the mean of measured total PBL. The modelling results indicate that it is unlikely that long-lived human recirculating 'memory' PBTL are homogeneous with respect to lifespan, but rather that two major subpopulations, T1 and T2, are involved having mean lifespans (and approximately 95% confidence limits) estimated to be approximately 1.1 (0.76-1.9) and approximately 6.3 (5.8-6.9) year, respectively. One of the two models consistent with the data posits that T1 (possibly 'short-term antigen-memory') cells are approximately 60% of recirculating T-lymphocytes that convert at a rate of approximately 9% year-1 into T2 (possibly 'long-term antigen-memory') cells, and that the T1 cells are virtually all derived from a central-body source such as thymus and/or central lymphatic tissues.

Cell Survival↗

PubMed1993

A method of screening for genes of major effect.

This paper describes a method for screening animal populations on an index of calculated probabilities of genotype status at an unknown single locus. Animals selected by such a method might then be candidates in test matings and genetic marker analyses for major gene detection. The method relies on phenotypic measures for a continuous trait plus identification of sire and dam. Some missing phenotypes and missing pedigree information are permitted. The method is an iterative two-step procedure, the first step estimates genotype probabilities and the second step estimates genotypic effects by regressing phenotypes on genotype probabilities, modeled as true genotype status plus error. Prior knowledge or choice of major locus-free heritability for the trait of interest is required, plus initial starting estimates of the effect on phenotype of carrying one and two copies of the unknown gene. Gene frequency can be estimated by this method, but it is demonstrated that the consequences of using an incorrect fixed prior for gene frequency are not particularly adverse where true frequency of the allele with major effect is low. Simulations involving deterministic sampling from the normal distribution lead to convergence for estimates of genotype effects at the true values, for a reasonable range of starting values, illustrating that estimation of major gene effects has a rational basis. In the absence of polygenic effects, stochastic simulations of 600 animals in five generations resulted in estimates of genotypic effects close to the true values. However, stochastic simulations involving generation and fitting of both major genotype and animal polygenic effects showed upward bias in estimates of major genotype effects. This can be partially overcome by not using information from relatives when calculating genotype probabilities-a result which suggests a route to a modified method which is unbiased and yet does use this information.

Alleles↗

PubMed1993

Evaluation of mating systems involving five breeds for integrated beef production systems: IV. Accounting for variability and genetic trends.

Computer models were used to simulate integrated cow-calf-feedlot production systems. Angus (A), Charolais (C), Hereford (H), Limousin (L), and Simmental (S) purebreds and two- and three-breed rotational crossbreds were included. Models were deterministic and based on data reported primarily from the 1970s. Variation in carcass weights were determined to predict distributions of carcass weights and values for 272- to 318-kg carcasses. Data were updated to a 1984 base by increasing birth, weaning, yearling, and mature weights to account for genetic trends within breeds. Two slaughter end points were considered: 288-kg carcass weight and low Choice grade. At low Choice grade, accounting for variation in carcass weights around the 272- to 318-kg target weight increased the estimated efficiency of A and AH crosses (input costs/carcass value), whereas at the 288-kg end point, efficiency rankings among other breed combinations were relatively unchanged. Including genetic trends resulted in increased estimated efficiencies among breed combinations with previously underweight carcasses at low Choice (A and AH), measured either as input costs/carcass weight or lean weight values. Within breeds, accounting for genetic trends and variation for weights caused breeds to be ranked differently when evaluated at low Choice.

Animals↗

PubMed1997

Spatiotemporal complexity of ventricular fibrillation revealed by tissue mass reduction in isolated swine right ventricle. Further evidence for the quasiperiodic route to chaos hypothesis.

We have presented evidence that ventricular fibrillation is deterministic chaos arising from quasiperiodicity. The purpose of this study was to determine whether the transition from chaos (ventricular fibrillation, VF) to periodicity (ventricular tachycardia) through quasiperiodicity could be produced by the progressive reduction of tissue mass. In isolated and perfused swine right ventricular free wall, recording of single cell transmembrane potentials and simultaneous mapping (477 bipolar electrodes, 1.6 mm resolution) were performed. The tissue mass was then progressively reduced by sequential cutting. All isolated tissues fibrillated spontaneously. The critical mass to sustain VF was 19.9 +/- 4.2 g. As tissue mass was decreased, the number of wave fronts decreased, the life-span of reentrant wave fronts increased, and the cycle length, the diastolic interval, and the duration of action potential lengthened. There was a parallel decrease in the dynamical complexity of VF as measured by Kolmogorov entropy and Poincaré plots. A period of quasiperiodicity became more evident before the conversion from VF (chaos) to a more regular arrhythmia (periodicity). In conclusion, a decrease in the number of wave fronts in ventricular fibrillation by tissue mass reduction causes a transition from chaotic to periodic dynamics via the quasiperiodic route.

Action Potentials↗

PubMed1992

A nonstatistical approach to estimating confidence intervals about model parameters: application to respiratory mechanics.

Estimates of parameters obtained by fitting models to physiologic data are of little use unless accompanied by confidence intervals. The standard methods for estimating confidence intervals are statistical, and make the assumption that the fitted model accounts for all the deterministic variation in the data while the residuals between the fitted model and the data reflect only stochastic noise. In practice, this is frequently not the case, as one often finds the residuals to be systematically distributed about zero. In this paper, we develop an approach for assessing confidence in a parameter estimate when the order of the model is clearly less than that of the system being modeled. Our approach does not require a parameter to have a single value located within a region of confidence. Instead, we let the parameter value vary over the data set in such a way as to provide a good fit to the entire data set. We apply our approach to the estimation of the resistance of the respiratory system in which a simple model is fitted to measurements of tracheal pressure and flow by recursive multiple linear regression. The values of resistance required to achieve a good fit are represented as a modified histogram in which the contribution of a particular resistance value to the histogram is weighted by the amount of information used in its determination. Our approach provides parameter frequency distribution functions that convey the degree of confidence one may have in the parameter, while not being based on erroneous statistical assumptions.

Airway Resistance↗

PubMed2005

Normal tissue radiosensitivity: prediction on deterministic or stochastic basis?

For the same standardized physical radiation dose there is considerable variation, among different patients, of the magnitude of early and late normal tissue reactions. Technical and clinical factors account for about one third only of these variations. Genetic or epigenetic differences between patients account for the greater proportion of interpatient radiosensitivity differences. Attempts have been made to correlate differences in the tissue radiosensitivity with the in vitro radiosensitivity of fibroblasts or lymphocytes as well as with other biological cellular processes related to cell death (mainly DNA repair and chromosomal aberrations). Apart from some genetic diseases such as ataxia telangiectasia, there were positive results in some studies that could not be reproduced in others. It is now realized that for normal tissue radiation-induced morbidity (a) cell kill is not the only factor, (b) interaction with a large number of gene products, such as IL-2, IL-6, TGF-beta, is involved, and (c) radiosensitivity differences can reflect genetic differences. Polymorphism in a wide range of genes can now be demonstrated and analyzed as a source of variations in the radiation response. cDNA microarray procedures can also allow simultaneous measurement, in the same sample, of thousands of genes and thus avoiding basing the investigation on a restricted number of genes. Preliminary results could show retrospectively a correlation between late normal tissue reactions and expression of certain genes. Using cDNA microarray before radiotherapy to predict the occurrence of serious late reactions is still under consideration. Theoretically, an efficient predictor procedure may serve in (a) detection of hypersensitive patients before submitting them to highly toxic radiotherapy regimes such as whole body irradiation, (b) detection of hypersensitive patients in clinical situations where radiotherapy can be effectively replaced by other modalities, and (c) selection of patients for elaborate radiotherapy techniques involving dose escalation to high levels.

Dose Fractionation, Radiation↗

PubMedDate not supplied

An example of variation and pattern in saltation and stasis growth dynamics.

The serial data from two siblings, aged 6.6 and 7.5 years of age at the initiation of the study, measured each evening for total standing height during 365 days, are analysed by two methods to investigate the nature of the underlying growth pattern. The saltation and stasis model, designed to identify the presence of statistically significant pulses in sequential data, is compared for goodness-of-fit to first to sixth degree polynomial functions, used to investigate the presence of a slowly varying smooth continuous function in the data, and high order polynomials of the same degree of flexibility as the individual's saltation and stasis results. The saltation and stasis model is found to better-fit the experimental data than the slowly varying smooth continuous functions (p < 0.01 to 0.001). The timing characteristics of the saltation and stasis patterns are investigated and the temporal patterns are suggestive of a non-random, aperiodical deterministic system.

Algorithms↗

PubMed2006

Fluoroscopically assisted surgical treatments of spinal disorders: conceptus radiation doses and risks.

STUDY DESIGN: A series of anterior-posterior and lateral fluoroscopic exposures at 5 spinal levels were performed on anthropomorphic phantoms simulating the 3 trimesters of gestation. OBJECTIVES: To provide normalized data for the determination of conceptus dose specific to gestational stage and treated spinal level. To estimate the conceptus radiation dose and risk associated with typical fluoroscopically guided spinal treatments performed on the pregnant patient. SUMMARY OF BACKGROUND DATA: To our knowledge, there are no available data on conceptus doses and radiogenic risks resulting from fluoroscopically guided spinal surgery of the expectant mother. METHODS: Direct measurement of conceptus doses from simulated fluoroscopic projections involved in orthopedic surgery at different spinal levels for the 3 trimesters of gestation with use of anthropomorphic phantoms and thermoluminescent dosimetry. Estimation of conceptus radiation risks from a typical pedicle screw fixation and kyphoplasty procedure using the experimentally derived data. RESULTS: Conceptus doses from fluoroscopically guided spinal treatments are smaller than 4 mGy during all gestational stages, provided that the conceptus lies outside the primarily irradiated region. The associated risks of fatal cancer during childhood and congenital malformation on its progeny are at least 2 and 1500 times, respectively, lower than the spontaneous incidence rates. When the embryo is primarily irradiated, mean conceptus dose can be as high as 105 mGy from a nonoptimized exposure. At least 35 minutes of fluoroscopy are required for the induction of deterministic effects. CONCLUSIONS: Individual dose assessment is paramount in every pregnancy. Variations in fluoroscopy practices and gestational stage significantly affect fetal doses.

Computer Simulation↗

PubMed1998

The temporal dynamics of tics in Gilles de la Tourette syndrome.

BACKGROUND: Statistical characterization of tic behavior in Gilles de la Tourette syndrome (GTS) may provide insight into the dynamic functioning of the human central nervous system, as well as improve the quantitative assessment of tic symptom severity. METHODS: Twenty-two medication-free GTS subjects underwent videotaping of their tics. The intervals between temporally adjacent tics were measured, and the statistical properties of these intervals were assessed through graphical representation of frequency distributions, autoregressive integrated moving average (ARIMA) modeling, spectral analysis, and construction of first return maps. RESULTS: The frequency distribution of tic interval durations followed an inverse power law of temporal scaling. Spectral analyses similarly demonstrated that the spectral power density of tic interval duration scales inversely with frequency. ARIMA modeling suggested that the time series for tics are nonstationary as well as moving average processes. The first return maps demonstrated "burstlike" behavior and short-term periodicity in tics, and proved that successive tic intervals are not statistically independent. Graphic display of the time series confirmed shortterm periodicity, and in addition suggested the presence of period doubling. CONCLUSIONS: These findings are suggestive though not conclusive evidence for the presence of a fractal, deterministic, and possibly chaotic process in the tic time series. These analytic methods provide insight into the temporal features of tics that commonly are described clinically (such as short-term bouts or bursting, and longer term waxing and waning), and they reveal certain important temporal features of tics that have not been clinically described. The methods may also prove useful in the improved characterization of tic symptom severity.

Adolescent↗

PubMed1995

Pattern of prolactin diurnal secretion in normal humans: evidence for nonlinear dynamics.

Prolactin (PRL) circadian profiles were analyzed using methods of nonlinear dynamics, directly from the experimental data, by combining in a single time-series (432 measurements), six individual 24-hour PRL profiles (72 measurements per profile, sampling interval = 20 min), obtained from young healthy human volunteers (4 males, 2 females), under basal conditions. Significant autocorrelation exists between any given point of the time series and a limited number of its successors. Fourier analysis showed a dominant frequency of 1 cycle/24 h, without sub-24-hour harmonics. Poincaré section indicated the presence of a fractal attractor and a sketch of the attractor revealed a highly convoluted geometric structure with a conical contour. The box-counting dimension (D0), information dimension (D1) and correlation dimension (D2) of the attractor had low, fractal values, did not differ significantly from each other, and exhibited saturation at an embedding dimension of 2. The evidence taken together suggests that, under basal conditions, the daily changes in the peripheral blood levels of PRL are governed by nonlinear deterministic dynamics, with a dominant rhythm of 1 cycle/day mixed with a higher-frequency, low-amplitude signal.

Adult↗

PubMed1990

Population biology of pseudorabies in swine.

A deterministic mathematical model of the population biology of pseudorabies in swine was used to clarify some of the basic features of the host-virus relationship and to inquire into the circumstances that promote or impede virus persistence in a single herd. When the basic reproductive rate of the infection (ie, the number of secondary infections resulting from the introduction of a single infective animal into a wholly susceptible herd) is greater than unity, the model suggests that the number of infective individuals in the herd will undergo highly damped oscillations to a final equilibrium level. The most important determinants of virus persistence are herd size and the density at which sows are maintained. There is a threshold density of susceptible individuals below which the virus will eventually be eliminated from the herd, even when specific control measures are lacking. Test and removal strategies hasten virus elimination when herd density is already below threshold, but are otherwise likely to succeed only when the removal of latent infections reduces the basic reproductive rate of the infection below unity. Vaccination strategies may also result in virus elimination, but only in relatively small herds.

Animals↗

PubMedDate not supplied

Geostatistics and Bayesian updating for transmissivity estimation in a multiaquifer system in Manitoba, Canada.

In ground water flow and transport modeling, the heterogeneous nature of porous media has a considerable effect on the resulting flow and solute transport. Some method of generating the heterogeneous field from a limited dataset of uncertain measurements is required. Bayesian updating is one method that interpolates from an uncertain dataset using the statistics of the underlying probability distribution function. In this paper, Bayesian updating was used to determine the heterogeneous natural log transmissivity field for a carbonate and a sandstone aquifer in southern Manitoba. It was determined that the transmissivity in m2/sec followed a natural log normal distribution for both aquifers with a mean of -7.2 and - 8.0 for the carbonate and sandstone aquifers, respectively. The variograms were calculated using an estimator developed by Li and Lake (1994). Fractal nature was not evident in the variogram from either aquifer. The Bayesian updating heterogeneous field provided good results even in cases where little data was available. A large transmissivity zone in the sandstone aquifer was created by the Bayesian procedure, which is not a reflection of any deterministic consideration, but is a natural outcome of updating a prior probability distribution function with observations. The statistical model returns a result that is very reasonable; that is homogeneous in regions where little or no information is available to alter an initial state. No long range correlation trends or fractal behavior of the log-transmissivity field was observed in either aquifer over a distance of about 300 km.

Bayes Theorem↗

PubMed1999

The effects of stochastic neural activity in a model predicting intensity perception with cochlear implants: low-rate stimulation.

Most models of auditory nerve response to electrical stimulation are deterministic, despite significant physiological evidence for stochastic activity. Furthermore, psychophysical models and analyses of physiological data using deterministic descriptions do not accurately predict many psychophysical phenomena. In this paper we investigate whether inclusion of stochastic activity in neural models improves such predictions. To avoid the complication of interpulse interactions and to enable the use of a simpler and faster auditory nerve model we restrict our investigation to single pulses and low-rate (< 200 pulses/s) pulse trains. We apply signal detection theory to produce direct predictions of behavioral threshold, dynamic range and intensity difference limen. Specifically, we investigate threshold versus pulse duration (the strength-duration characteristics), threshold and uncomfortable loudness (and the corresponding dynamic range) versus phase duration, the effects of electrode configuration on dynamic range and on strength-duration, threshold versus number of pulses (the temporal-integration characteristics), intensity difference limen as a function of loudness, and the effects of neural survival on these measures. For all psychophysical measures investigated, the inclusion of stochastic activity in the auditory nerve model was found to produce more accurate predictions.

Cochlear Implants↗

PubMedDate not supplied

[New standards for radiation safety and effective dose].

The scientific bases and the peculiarities of the new radiation safety standards (RSS) implemented in Russia in april 1996 are considered. A comparison is made of the merits and shortcomings of both conceptions of standardization--by means of setting dose limits for the critical organs or by means of limiting the effective dose as a measure of the total radiation risk of late effects. The application of the effective dose to practice gives unquestionable advantages for assessing the sufficiency of arrangements providing radiation safety of personnel or public protection against radiation. However the use of the effective dose for individual dose monitoring is often not good (especially in the case of internal irradiation) due to wide variation caused by oversimplifications in the applied models. Essential shortcomings of the RSS-96 are also the absence of the permissible body burden of radionuclides among the derived standards and the regulation of the mean annual (unmeasurable) values of their concentration in air. It is proposed in addition to the effective dose which limits the risk of stochastic effects to reserve in the RSS the limits of equivalent doses for the main body organs (lungs, liver). This would eliminate the deterministic effects and give the possibility of differential evaluation of the irradiation pattern. It is also proposed to replace the reglamentation of mean annual concentrations of radionuclides in air by the reglamentation of their permissible concentration in the working zone.

Humans↗