Measurements are inevitably bound to experimental errors, whose probability distributions are generally unknown. Aim of this work is to investigate whether and to what extent unreliable assumptions concerning the nois...
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Measurements are inevitably bound to experimental errors, whose probability distributions are generally unknown. Aim of this work is to investigate whether and to what extent unreliable assumptions concerning the noise distribution influence the estimation process and to compare the efficiency of two estimation methods in the case of 'ad hoc' simulated data. Although these are generated from two-compartment systems which can model some aspects of a β-blocking agent kinetics, both linear and nonlinear, it is believed that the findings of this study are of more general interest. The results show that the minimizing algorithms do not significantly differ as for their capability of fitting a bi-exponential curve to the simulated data. Evidence is given of the ambiguities encountered when hypotheses concerning the system structure are tested against the algorithms results. Most of the findings of this work can be expected from estimation theory;however they allow a better insight into the limits of applying estimation methods to biomedical problems, because the systems structure has been drawn from drug kinetics and a large variety of additive noise characteristics has been considered.
In this paper we apply spectral analysis methods to the heart rate variability signal to assess the autonomic nervous regulation system in both normal subjects and patients affected by autonomic neuropathy. Traditiona...
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In this paper we apply spectral analysis methods to the heart rate variability signal to assess the autonomic nervous regulation system in both normal subjects and patients affected by autonomic neuropathy. Traditional methods for investigating the degree of impairment of the autonomic heart rate regulation system make use of external or self-evoked inputs, which perturb the biological system producing changes in heart rhythm and arterial pressure. Different clinical tests allow to quantify separately sympathetic and parasympathetic activity. The use of power spectral analysis of the heart rate variability signal is an appealing methodology for quantifying the activity of the autonomic nervous system since it can be performed at rest due to the natural 'spectral' separation of the sympathetic and parasympathetic controlsystems. Results show in normal patients a significant reduction of parasympathetic activity in standing position with respect to supine, and in patients affected by severe autonomic neuropathy an overall reduction of power at all frequencies. For autonomic patients there are no significant differences following postural changes.
This paper describes the development of an adaptive controller in which the controller algorithm is adjusted based on the estimated patient gain. Parallel least-squares gain estimation routines which assume different ...
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This paper describes the development of an adaptive controller in which the controller algorithm is adjusted based on the estimated patient gain. Parallel least-squares gain estimation routines which assume different drug transport delay times were employed to make the controller insensitive to unknown values of the delay. Exponential data weighting was applied to the gain estimation routine to halt estimation during periods of insufficient signal excitation. The adaptive controller was tested in simulations. The controller performance was shown to be robust over a very large range of patient characteristics. Operation of the adaptive controller was satisfactory in the presence of changing characteristics of the patient, reflex activity, long term use of the controller, and perturbations of the blood pressure signal which would be encountered in the clinical environment.
control theory, in the context of pharmacokinetic models, can be employed in the individualization of dosing regimens. We implement four approaches to this problem and examine their behavior with respect to a one comp...
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control theory, in the context of pharmacokinetic models, can be employed in the individualization of dosing regimens. We implement four approaches to this problem and examine their behavior with respect to a one compartment model of theophylline kinetics. Two of the methods treat the model parameter vector as a random variable and employ the optimization of an objective function that involves the density of the parameters. Target interval stochastic control seeks to maximize the probability that the output will fall within a specified region while quadratic stochastic control minimizes an expected sum of weighted squared deviations from specified target levels of the output. The other two strategies use separation principle control, one based on weighted least squares estimates of the model parameters and the other based on maximum a posteriori probability estimation. Extensive Monte Carlo simulations are reported and analysed.
Insulin is secreted into the portal vein by the pancreas at varying rates. The insulin secretion rate is calculated by deconvolution from C-peptide concentrations, a peptide that is co-secreted with insulin on an equi...
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Insulin is secreted into the portal vein by the pancreas at varying rates. The insulin secretion rate is calculated by deconvolution from C-peptide concentrations, a peptide that is co-secreted with insulin on an equimolar basis. This calculation has been experimentally validated. It is concluded that, in dogs, as portal insulin levels increase to 600uU/ml, the hepatic extraction of insulin falls by approximately 50% and the fractional disappearance rate of insulin by two thirds. This suggests that insulin removal by the liver is the principal component of the metabolic clearance of insulin and that it may vary under physiological circumstances. This paper provides approaches, both experimental and quantitative for determining the major parameters involved in insulin kinetics - its rate of secretion and removal by the liver, when these are varying.
The human vestibulo-ocular reflex was studied using sweep-frequencies of active head-eye movements, and autoregressive-moving average (ARMA) parameter estimation. Ten 18-second test epochs from one subject were used o...
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The human vestibulo-ocular reflex was studied using sweep-frequencies of active head-eye movements, and autoregressive-moving average (ARMA) parameter estimation. Ten 18-second test epochs from one subject were used over a frequency range from 2 to 6 Hz. An ARMA model of the (3,3) order, i.e., with three output lags and three input lags, was found to best fit the subject's data for all ten runs. Mean parameters from the ten runs showed relatively small variance. This method provides accurate predictions of eye-velocity response during active head movement conditions.
Examples are presented of the interaction between empirical testing and the development of models designed to help in the investigation of glucose, lactate, and pyruvate kinetics in vivo. Experimental evidence is pres...
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Examples are presented of the interaction between empirical testing and the development of models designed to help in the investigation of glucose, lactate, and pyruvate kinetics in vivo. Experimental evidence is presented which demonstrates that a model of glucose kinetics should account for the two physical pools in which glucose is distributed - plasma and interstitial fluid. When such a model is used to determine rapid changes in the rate of appearance of unlabeled glucose with measurements made from both compartments, accuracy is improved markedly in certain non-steady state situations over the traditional Steele equation. In the case of lactate kinetics, it is demonstrated that when the proper isotope infusion/sampling mode is used, impossible values for lactate production are obtained using the traditional approach for calculation.
This paper focuses upon the use of simple mathematical models in estimating total pulmonary compliance for clinical investigation and attempts to quantify the estimation errors that may be expected in presence of sign...
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This paper focuses upon the use of simple mathematical models in estimating total pulmonary compliance for clinical investigation and attempts to quantify the estimation errors that may be expected in presence of significant and sustained gas leakage from lungs. To this end, simulation experiments were made and mechanically ventilated patients were analyzed. The results obtained in both cases demonstrate that, in spite of good reproducibility, systematic overestimation of the compliance (ranging from 6% to 50% for normal and stiff subjects, respectively) occurs when the presence of gas leakage is neglected. Consequently, a monocompartmental extended model of respiratory mechanics is proposed and tested. This model provides reproducible and unbiased estimation of compliance and can be seen as an appropriate representation of respiratory mechanics also in presence of gas leakage.
By models of the circulation, we analyzed the responses to a rise in contractility in one chamber of the heart. The study was initiated because one-sided inotropic stimulation revealed different responses in the two v...
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By models of the circulation, we analyzed the responses to a rise in contractility in one chamber of the heart. The study was initiated because one-sided inotropic stimulation revealed different responses in the two ventricles of the in situ pig heart. In a simple two-compartment model of the circulation, both numerical data analysis and an analytical mathematical approach revealed that decrements in both maximal and minimal heart chamber volumes were to be expected when contractility was increased. This response also appeared in the right ventricle of the in situ pig heart when the effect of increased contractility in the right atrium was abolished by simultaneous atrial- and ventricular contraction. A computer-based seven compartment model of the circulation predicted these responses and offered two alternative explanations for the different-directed changes in left- and right ventricular end-diastolic volumes when the respective sides were inotropically stimulated.
A closed-loop lumped-parameter model of the cardio-vascular system (CVS) requiring little computational power has been developed. The model has the following features: (1) nonlinear elastic characteristics of arteries...
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A closed-loop lumped-parameter model of the cardio-vascular system (CVS) requiring little computational power has been developed. The model has the following features: (1) nonlinear elastic characteristics of arteries and veins;(2) detailed ventricle model, with autonomic regulation, for proper testing of the vascular system (VS);(3) simplified neural and local regulation system;(4) easy simulation of respiratory and muscular pump, gravity and hemorrhaging effects. Some simulation results, which show good agreement with experimental measurements, are presented. This CVS simulation model is an efficient tool both for the determination of the influence of artificial devices and for computer-aided teaching in medical education. It can also be used to develop regulation algorithms for the TAH. An example is presented.
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