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Twin-family studies of perceptual speed ability. II. Parameter estimation.

Offspring of monozygotic (MZ) twins form half-ships that permit a direct test of maternal effects and differentiate several sources of between-family environmental variance. Combined with conventional twin data, these genetic half-sibships provide a unique data set for estimating sources of variation in quantitative traits. To illustrate, genetic and environmental parameters were estimated for Identical Pictures Test data obtained from children of MZ twin parents and an (approximate) age-matched cohort of like-sex twins. Analyses of variance of the data, standardized for age and sex, yield 12 mean squares to which gene-environment models were fit. Maximum-likelihood estimation revealed a complete absence of maternal influences and shared environmental effects; a simple two-parameter model, assuming random mating and attributing variation in test scores to additive genes and within-family environment, adequately accounts for the familial data.

Adolescent

Parameter estimation for a prosthetic ankle.

The mechanical parameters of a model of an energy storage and return ankle prosthesis are estimated for normal level walking by means of an optimization procedure. The walking cycle is divided into six fields, such that the power does not change sign within each field; the transition between successive fields occurs at zero power. The optimal spring stiffness as a function of time, is found by optimizing a quadratic cost function to minimize the difference between the estimated ankle moments and the moments in normal walking. The optimization is subjected to four continuous constraints within each field and to two continuity constraints for the transitions between successive fields. The time-varying spring stiffness and the implications of additional external energy are discussed and are presented as recommendations for the designer.

Ankle Joint

Identifiability: the first step in parameter estimation.

The observations in an experiment define a set of observational parameters that are functions of the basic kinetic parameters of the model of the system. The problem of identifiability is concerned with whether the observational parameters uniquely specify the basic kinetic parameters. As such, it depends only on the functional relation between the two levels of parameters and not on errors of observation and the estimation procedure. It should be checked before doing the experiment. Given initial estimates of the basic kinetic parameters, identifiability can be checked, in a local sense, from data generated by simulating the experiment on the model.

Computer Simulation

CO2 control of breathing: parameter estimation and stability evaluation.

A method is developed to evaluate system stability for the CO2 control of breathing in individuals by using data from the dynamics of CO2 rebreathing and elimination. The theoretical basis of the method is a physiological model of the CO2 respiratory control system and an explicit stability index (SI). The SI is algebraically related to the model parameters: system volume (Vs), cardiac output (Q), circulatory transit time (ts), and controller gain (G). A sequential optimization scheme is shown to yield estimates of the model parameters by comparing the alveolar ventilation and PCO2 of the model output with corresponding experimental data. Model simulation of CO2 rebreathing and elimination with different parameter values demonstrate that all parameters except ts have significant effect on the outputs. Least-squares estimation of the parameters using model-generated data with added noise showed good precision for all parameters (except ts). This analysis is performed with parameter values chosen to produce overdamped and underdamped responses that would occur in normal and abnormal respiratory control systems, respectively. It is anticipated that SI values of the (overdamped) normal and (underdamped) abnormal systems differ by much more than the variation produced by imprecision of the parameter estimates. For this circumstance, the method is expected to be sensitive enough to distinguish normal from abnormal CO2 respiratory control of individual subjects.

Carbon Dioxide

Relationships among growth hormone and prolactin secretory parameter estimates in Holstein bulls and their predicted differences for lactational traits.

Selection of dairy sires is based on the production records of their female ancestors, half-sibs and daughters. No trait expressed by the sire is used. Concentrations of growth hormone (GH) and prolactin (PRL), hormones produced in both males and females that are fundamental in lactation, may be correlated with production. A study was conducted to determine whether measures of these hormones in the sire would be useful predictors of lactational ability of daughters. Blood samples were collected at 15-min intervals for 8 h from 26 Holstein bulls (5.5 yr of age) that had one progeny summary available. Plasma concentrations of GH and PRL were quantified and the mean and baseline concentrations and the frequency and mean amplitude of the secretory peaks were determined for each bull. Concentrations among these values and bulls' predicted differences (PD) were determined. Significant negative correlations were detected for frequency of GH peaks and PD for yield of milk, fat and protein; correlations were positive for PRL baseline concentrations and PD for fat and protein (P less than .10), and correlations were negative for frequency of PRL peaks and PD for milk, fat and protein (P less than .10). Addition of estimates of bull hormone secretory parameters to breeding values based on performance of relatives considerably improved the accuracy (R2) for predicting progeny performance from sire information. Certain characteristics of the patterns of GH and PRL secretion may be heritable and aid in identification of superior dairy animals.

Animals

Transducer characterization from pressure amplitude distribution measurements using a Kalman filter as parameter estimation algorithm.

The amplitude and frequency contents of a received ultrasound pulse depends on the spatial pressure amplitude distribution of the sound field, as produced by the transducer in the medium, and on the position and orientation of the reflecting surface in this field. Often, the geometry of the reflecting surface and the acoustical properties of the medium are known or can be estimated. Then it is practical to determine the transducer parameters in order to calculate the distortion of a reflected ultrasound pulse. Apart from geometrical parameters such as size and mechanical focusing, the surface velocity amplitude distribution (SVAD) of a transducer is of major importance. For some transducer configurations this SVAD may be described with a limited number of parameters. This paper presents a method, based on a Kalman filter algorithm, to assess the transducer parameters by measurement of the spatial sound field pressure amplitude distribution in various planes for different emission frequencies. Comparison of the measured pressure amplitudes with those calculated using the estimated values of the parameters shows that this method yields reliable results.

Acoustics

Identifiability and parameter estimation.

In experiments on biological systems one often cannot measure all state variables (compartments). Given a particular experiment of that type, a basic kinetic parameter may have no effect on the observations; such a parameter is an insensible parameter for that experiment. A parameter may influence the observations and not be uniquely determinable; such a parameter is nonidentifiable for that experiment. Only identifiable parameters can be estimated uniquely, by that experiment. I review the basic theory to check identifiability for a nominal value of a parameter (local identifiability), and present some examples of problems that may arise in estimation.

Kinetics

Simulation of calcium homeostasis: modeling and parameter estimation.

The system that regulates plasma calcium in the bird has been formalized into a model based on a series of differential equations and solved by computer simulation. Bone, kidney, and intestine have been considered as the control subsystems, with parathyroid hormone and 1,25-dihydroxycholecalciferol as the regulating hormones. The parameters used in the simulation model have been computed either from published results or by specifically designed experiments described here. For the estimation of parameters, an iterative procedure has been developed that was designed to minimize the sum of square errors between observed and system-simulated values. Parameters of 1,25-dihydroxycholecalciferol metabolism were experimentally obtained from the kinetic behavior of the 3H-labeled hormone in rachitic birds after a single dose. Model parameters have been adjusted using the results of in vivo calcium loading and validated by an EDTA infusion experiment. The simulation model has been used to study the hierarchy of the activities of the three control subsystems and of the regulating hormones, at different calcium intakes. Positive or negative errors in plasma calcium resulted in an asymmetry in the activities of the controlling systems, bone and kidney, whereas the intestine is characterized by its relatively long response time.

Animals

A model of intestinal iron absorption and plasma iron kinetics: optimal parameter estimates for normal dogs.

A multicompartment model describing the physiological processes of intestinal iron absorption has been developed. The model accounts for uptake by the intestinal mucosa of iron in the lumen, followed by either iron incorporation into a mucosal storage pool (presumably ferritin) or direct iron transfer to the plasma. To enable analysis of iron absorption from noninvasive measurements, plasma iron kinetics were also analyzed. The model was validated in studies of three beagle dogs given oral 59Fe-citrate and intravenous 55Fe-transferrin simultaneously. Model parameters were estimated from the best (least-squares) fit of the model outputs to the tracer iron activity in venous blood samples and in the whole body. The parameter values show that both incorporation of iron into the mucosal storage pool and transfer of iron from the mucosa to the plasma occur at rates approximately 100 times greater than mucosal uptake of iron from the gut lumen. Further, release of iron from mucosal storage, while measurable, occurs at a slow rate. The study demonstrates the practicality of this noninvasive approach for the simultaneous study of iron absorption and plasma iron kinetics.

Animals

Hemodynamic parameter estimation from ocular fluorescein angiograms.

BACKGROUND: A method is proposed for parameterizing choroidal blood flow from fluorescein angiograms. METHODS: After digitizing and aligning the angiographic sequence, the intensity build-up curves of fluorescence are analysed per pixel (approx. 10 microns in fundo). Two models are compared. A one-compartment model predicts an exponential build-up curve, from which the following parameters are estimated: maximum fluorescence, dye appearance time and local perfusion rate (reciprocal of the time constant of the exponential). To account for the contribution of the systemic circulation to the shape of the build-up curve, a two-compartment model is used which predicts a bi-exponential curve. RESULTS: Introduction of the second (systemic) compartment resulted in a significant improvement of fit in 37 of 48 patients studied. The rate constants of the systemic compartment found were mainly in the range of 0.30-1.00 s-1. CONCLUSION: For the individual patient, the local perfusion rates may vary strongly, with lower perfusion rates possibly being of prognostic value for ocular diseases such as glaucoma or diabetic retinopathy.

Blood Flow Velocity

HPLC-analysis and preliminary pharmacokinetic parameter estimations of chloroquine.

An HPLC method for the separate determination of chloroquine and its major metabolites has been developed. Separation was on an octadecyl RP column. Fluorimetric detection followed after on-line post-column buffering of the mobile phase to pH = 9.25. The method is highly selective for the compounds of interest with a detection limit down to 1 ng/ml. Preliminary data on the pharmacokinetics of chloroquine are reported, as obtained with this method. Kinetic parameters were estimated with the aid of the non-linear regression computer programme NON-LIN.

Chloroquine

Logistic curve fitting and parameter estimation using nonlinear noniterative least-squares regression analysis.

A microcomputer program has been developed for the fitting of the logistic curve to biological, medical, and other experimental data. In addition to supplying estimates for all of the logistic curve parameters, the program provides the fitted result for each input datum thus allowing for the immediate assessment of the logistic curve and detection of possible outliers.

Biometry

Parameter estimation in a three-compartment model for blood alcohol curves.

Models of alcohol input and absorption are crucial to the description and understanding of the effects of alcohol in the human body. In this paper, the pharmacokinetics of alcohol after oral administration are described by a three-compartment model with a supposed concentration-dependent absorption and elimination. The absorption of alcohol from the small intestine into the blood is represented by a first-order rate constant ka. To describe the delay in peak concentration of alcohol the gastric emptying rate is represented as a first-order parameter with a feedback control depending on the amount of alcohol remaining in the stomach. The alcohol ingestion can then be represented as a bolus input. The elimination process is described by a model similar to the Michaelis-Menten model for enzyme kinetics. Parameters are estimated by means of an iterative algorithm minimizing a non-linear function. A good fit of the model was obtained for blood alcohol curves from six men and six women who each had received an alcohol dose of 28.5 g on three consecutive days. It is concluded that the model can be recommended to describe adequately the absorption and elimination of alcohol.

Adult

Kinetic model of glucose-6-phosphate dehydrogenase from red blood cells. Parameter estimation from progress curves and simulation of regulatory properties.

A kinetic model of human and mouse glucose-6-phosphate dehydrogenase is presented which takes into account the substrates and all inhibitors of significant importance in the red cell. The parameter values were estimated by analysis of progress curves. The applicability of a new method based on non-linear regression to complex enzyme kinetics was proved. The in vivo-regulation of glucose-6-phosphate dehydrogenase is examined by determining elasticity coefficients and by using simple simulation experiments. The model is convenient to describe the behaviour of enzyme activity under physiological conditions.

Adenosine Triphosphate

Pharmacokinetic calculator program for generation of initial parameter estimates from a three-compartment infusion model.

A polyexponential curve-stripping program, KIN, is described for use on the HP-41CV programmable calculator. The program may be used in the analysis of plasma-concentration-time curves for a three-compartment intravenous bolus or infusion model with linear elimination processes. The coefficients and hybrid rate constants of the exponential function are then used to compute pharmacokinetic parameters (volume of the central compartment, intercompartmental rate transfer constants), which may be used as initial estimates of model parameters in non-linear regression curve-fitting procedures.

Computers

A new method of parameter estimation from progress curves.

A mathematical procedure is presented which permits kinetic parameters to be determined from progress curve data. The method is applicable to any kind of enzymatic reaction which can be described by a single rate equation. A general criterion is derived to check the accuracy of the method. An application to a simulated 2-substrate reaction is given.

Half-Life

Simulation studies of influenza epidemics: assessment of parameter estimation and sensitivity.

The influenza simulation model of Elveback et al is used to evaluate the accuracy of the maximum likelihood procedure of Longini et al for estimating the secondary attack rate in households. The sample population from the Tecumseh Respiratory Illness Study is mapped into the simulation model and simulations are carried out over a range of parameter values and conditions, some of which were derived from influenza seasons in Tecumseh and from the Seattle Flu Study for the years 1975-1980. The estimation procedure is found to be quite robust for parameter values preset within appropriate limits for influenza. However, a significant difference is found between the preset and estimated household contact parameter for epidemics of medium and high intensity when the preset value is zero. Incremental increases in the household contact parameter are shown to produce marked increases in the overall infection attack rate demonstrating that household spread is an important link in maintaining infection in other mixing groups such as schools, preschool groups and neighbourhood clusters of households.

Adolescent