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The amino acid requirements of growing turkeys. 1. Model construction and parameter estimation.

A model has been formulated to calculate the protein and amino acid requirements for growing turkeys. A requirement was taken as the sum of the needs for maintenance, for gain in carcass weight without feathers, and for the feathers. Parameters used in the model were obtained from a study of carcass composition along the growth period and from two balance trials with adult turkeys. The maintenance requirement was considered to be the sum of the needs for replacing skin and intestinal protein losses and for the obligatory creatinine excretion in the urine. Nitrogen retention was determined at 2.3 g/day in protein-fed adult (17 kg) male turkeys as an estimate for the replacement needs for skin protein loss. Creatinine excretion in these birds was 123 mg/day. When fed an N-free diet, 16.5 kg adult turkeys excreted a total of 3.5 g/day amino acids as a result of intestinal losses. The protein requirement for maintenance was estimated at 32 mg/day/g2/3 of body weight by summing up the different needs and dividing by .85, the coefficient of protein absorption. Protein and amino acid analyses of nude carcass and feathers and the growth curve were used to calculate the requirements for growth. These were then related to energy intake predicted by equations, which included previously determined coefficients for maintenance and growth (Hurwitz et al., 1980a), and the results of carcass lipid analysis. The calculated amino acid requirements were similar to those of the National Research Council (1977).

Amino Acids

Mechanical impedance of the canine diaphragm. Part 2. Theoretical model and parameter estimation.

In the paper the equation of motion of the small amplitude transverse forced vibration of a radially prestressed and circularly clamped thin membrane has been developed. The material of the membrane is considered to be homogeneous, isotropic, incompressible and viscoelastic. From the analytical solution of this equation the incremental mechanical impedance of the membrane was derived as a function of frequency, geometrical parameters and incremental viscoelastic coefficients of the material. The parameters of the model were fitted to experimental impedance data using a global optimisation procedure to obtain the incremental viscoelastic moduli of the canine diaphragm. The estimated quasi-static behaviour of the model is shown to be consistent with the results of experimental quasi-static measurements. It is concluded that the incremental viscoelastic moduli of a soft tissue and the stress dependence of these material coefficients can be determined by fitting the parameters of the model to the impedance data of that particular tissue.

Animals

Influence of method of model fitting and gender on estimated parameters for the relationship between starvation heat production and body size in the domestic fowl.

The relationship between starvation heat production (SHP) in kJ/d and body weight (W) in kg for domestic fowl was examined with compiled calorimetric data for 294 fowls (Johnson and Farrell, 1985). Linear regression analyses using ordinary least squares methods were performed before and after transformation of the data to a logarithmic scale (base = 10). Coefficients of determination (R2) were similar for untransformed and log-transformed data (R2's = .56 and .53, respectively). The slopes for untransformed data of males and females were different (P less than 0.033). When the model parameters for: SHP = b0 Wb1 were derived from log-transformed data, there were no significant differences in exponents for males vs. females (P greater than .95). However, when the coefficients were estimated using non-linear regression techniques, a difference was detected at the level of P = 0.072. It was determined that there is no advantage in describing the relationship of SHP as a non-linear function of W, nor is it appropriate to express physiological variables as a ratio of weight raised to some mass exponent without statistical justification. Using W or W2 as a covariable for the statistical analysis of physiological data would produce equally acceptable determinations of significance.

Animals

A simple steady state kinetic model for alcohol dehydrogenase. Use of reaction progress curves for parameters estimation at pH 7.4.

A simple rate equation for alcohol dehydrogenase was obtained by assuming independent binding sites for ethanol and NAD+ and fully competitive inhibition by the products of the reaction, acetaldehyde and NADH. A random binding order was also assumed. The rate equation is described by six parameters: four association constants (two for the substrates and two for the products of the reaction), Vf for the forward direction, and the equilibrium constant of the reaction. The six parameters were determined at pH 7.4 by numerical analysis of progress curves of reactions started with different concentrations of ethanol and NAD+. The parameters for alcohol dehydrogenase partially purified from rat liver were: Km for ethanol = 0.746 mM, Km for NAD+ = 0.0563 mM, Km for acetaldehyde = 7.07 microM, Km for NADH = 4.77 microM and Keq = 2.36 X 10(-4). The computed values allowed a very good simulation of the experimental progress curves and little variation was observed in the kinetic parameters when the reactions were started in the presence of either NADH or acetaldehyde.

Alcohol Dehydrogenase

Confidence limits for the parameter estimation in the dipole localization method on the basis of spatial correlation of background EEG.

A new residual function in the inverse problem of equivalent dipole localization methods is proposed which is based on the spatial correlation of the background EEG. This residual has the advantage that it allows the calculation of confidence limits for dipole model parameters. The method was applied to VEP data, and it was studied how the localization precision depends on the recording time of the EEG. It was found that the tangential position of an equivalent dipole can be located at 99% confidence in a region of the order 7 x 7mm for a head radius of 10cm, while the 99% confidence interval of the depth estimate is approximately 1cm, with a recording time of 20 minutes. It was also observed that an EEG recording time of more than 10-15 minutes is needed to obtain stable localization precision estimates.

Brain

Analytical approximations of sensitivities of steady state predictions to errors in parameter estimation: II. Michaelis-Menten kinetics.

Linear sensitivity theory is used to estimate the reliability of predictions of the minimum and maximum concentrations at steady state in the Michaelis-Menten model with i.v. bolus. The dependence of the relative errors in the predictions on the errors in the pharmacokinetic parameters is derived in an analytical form. It is shown that the quality of the predictions is not equally sensitive to all errors in parameters, and that the sensitivity factors vary with the degree of saturation of the system. An example of application for a drug, such as phenytoin, is discussed. It is suggested that sensitivity analysis may be useful in design of pharmacokinetic experiments aimed at the control of steady state levels for drugs with Michaelis-Menten kinetics.

Kinetics

Determination of a constitutive relation for passive myocardium: II. Parameter estimation.

In the first paper of this series, we proposed a new transversely isotropic pseudostrain-energy function W for describing the biomechanical behavior of excised noncontracting myocardium. The specific functional form of W was inferred directly from biaxial data to be a polynomial function of two coordinate invariant measures of the finite deformation and five material parameters. In this paper, best-fit values of the material parameters are determined from biaxial data using a nonlinear least-squares regression. These values of the parameters are shown to be well-determined, and the final constitutive relation is shown to have good predictive capabilities. Since the proposed constitutive relation describes much broader classes of in-vitro biaxial data than previously proposed relations, it may be better applicable to analyses of stress in the passive heart.

Animals

Discrimination of the isozymes of human placental hexosaminidase by kinetic parameter estimation.

Human placental beta-N-acetylhexosaminidase (EC 3.2.1.52) (HEX) is a lysosomal glycosyl hydrolase with an acidic pH optimum. Four isozymes (HEX B, HEX I1, HEX I2, and HEX A) have been isolated from human placenta. HEX BA derived from the subunit rearrangement of HEX A was also prepared. To determine if the isozymes of hexosaminidase differ in their kinetic parameters, the conditions for 4-methylumbelliferyl-beta-D-N-acetylglucosaminide hydrolysis were optimized for each isozyme. The Km values were essentially similar and varied from 0.64 +/- 0.06 for HEX BA to 0.85 +/- 0.13 for HEX I1. The Vmax values were similar only for HEX I1 (3.90 +/- 0.28 kat kg-1) and HEX I2 (4.40 +/- 0.17). Vmax values varied significantly between HEX A (9.68 +/- 0.52), HEX B (8.00 +/- 0.75), HEX BA (4.81 +/- 0.17), and the HEX I values.

Electrophoresis, Polyacrylamide Gel

Dynamic evaluation of human vestibulo-ocular function using white noise rotation stimulus and linear system parameter estimation techniques.

White noise acceleration inputs were used to determine the human VOR transfer function both for normal subjects and for patients falling into two pilot categories: unilateral labyrinthectomy and reduced bilateral responses. The systematic patterns shown in the transfer function of the pilot abnormal categories as compared to the normal data suggests one method of classifying test results (table I). Frequency domain linear systems parameter fits were also made using the same data. The changes in these fit parameters, when pilot abnormal data is compared to normal data, suggests the use of the parameter fits themselves as a second classification scheme (fig. 1). The second scheme is not appropriate in cases where the response is unrelated to the stimulus.

Eye Movements

Two methods for parameter estimation using multiple-trait models and beef cattle field data.

Two methods are presented for estimating variances and covariances from beef cattle field data using multiple-trait sire models. Both methods require that the first trait have no missing records and that the contemporary groups for the second trait be subsets of the contemporary groups for the first trait; however, the second trait may have missing records. One method uses pseudo expectations involving quadratics composed of the solutions and the right-hand sides of the mixed model equations. The other method is an extension of Henderson's Simple Method to the multiple trait case. Neither of these methods requires any inversions of large matrices in the computation of the parameters; therefore, both methods can handle very large sets of data. Four simulated data sets were generated to evaluate the methods. In general, both methods estimated genetic correlations and heritabilities that were close to the Restricted Maximum Likelihood estimates and the true data set values, even when selection within contemporary groups was practiced. The estimates of residual correlations by both methods, however, were biased by selection. These two methods can be useful in estimating variances and covariances from multiple-trait models in large populations that have undergone a minimal amount of selection within contemporary groups.

Analysis of Variance

Preventive distinction of patients with primary or secondary hypertension by discriminant analysis of chronobiologic parameters estimated on 24-hour blood pressure patterns.

This investigation deals with a statistical probatory that patients with primary (PH) or secondary (SH) hypertension may be correctly diagnosed by a discriminant analysis of the chronobiologic characteristics computed on the 24-hour blood pressure (BP) patterns. The methodology concerning non-invasive 24-h BP monitoring, chronobiologic analysis and the discrimination process is detailed. Substantial dissimilarities were found in the statistical distribution for systolic and diastolic BP rhythmometric parameters (mesor, amplitude and acrophase) by a retrospective assessment of two groups, consisting of 54 patients with PH and 16 patients with SH. The group-related distribution for rhythmometric parameters was found to be significantly different to generate a statistically significant intergroup discriminatory boundary. The discriminant analysis correctly diagnosed patients with PH and SH in a percentage of about 91% and 63%, respectively. The high incidence of success is convincing that the combination of 24-h BP monitoring/chronobiologic analysis/discrimination process cna be a practical tool for confidently selecting patients with a presumable PH or SH.

Adolescent

Lung structure parameters estimated from modeling aerosol deposition in isolated dog lungs.

A three-compartment model predicting the recovery of aerosol boli (i.e., the ratio of the number of particles expired to the number inspired) as a function of breath-holding time and bolus penetration was fitted to experimental data measured in nine isolated dog lungs. For each lung, the diameters of alveoli and alveolar ducts, as well as the volume fractions of alveoli, alveolar ducts, and airways, were determined as parameters providing the best fit. Parameter values were alveolar diameter = 0.116 +/- 0.007 (SE) mm, alveolar duct diameter = 0.284 +/- 0.015 mm, total alveolar volume/total lung capacity (TLC) = 0.68 +/- 0.02, total alveolar duct volume/TLC = 0.24 +/- 0.02, and total airway volume/TLC = 0.09 +/- 0.01. These values agreed with published values for linear dimensions and volumetric fractions in the canine lung. The mean alveolar diameter determined by the model in the nine lungs agreed closely with a mean value of 0.115 +/- 0.002 mm determined by morphometric analysis of photographs of the subpleural alveoli in the same lungs. The procedure of fitting the model to experimental data appears to have promise as a noninvasive probe of the lung periphery. However, aerosol-derived dimensions were more variable than morphometric ones, possibly because of interlung differences in aerosol distribution not accounted for in the model.

Aerosols

Parameter estimation of respiratory impedance measured by forced complex-wave oscillations.

Respiratory impedance data measured using the forced oscillation method were analyzed using an equivalent circuit model and the following conclusions were obtained: 1) Use of the complex wave oscillation method provided a measurement range of over 9 cmH2O/1/s with a resolution of 0.13 cmH2O/1/s. 2) The respiratory system was expressed as a two-compartment model. By expressing the circuit characteristics as phasor loci, a method was shown whereby individual impedance parameter values could be derived from the measured impedance phasor loci. 3) Under enflurane anesthesia, the model parameter values were derived as R1 = 1.2, R2 = 1.6 cmH2O/1/s, C1 = 0.02, C2 = 0.041/cmH2O and L = 0.065 cmH2O/1/s2.

Adult

Parameter estimation of cardiac geometry by ECG-gated PET imaging: validation using magnetic resonance imaging and echocardiography.

UNLABELLED: The purpose of this study was to apply and validate a previously developed model-based image analysis technique which derives estimates of regional myocardial wall thickness and the left ventricular radius directly from gated cardiac PET images. METHODS: In 11 normal volunteers, gated myocardial 18F-deoxyglucose (FDG) images with 16 equal gates spanning the entire cardiac cycle were acquired for 20 min. To improve count statistics and thus image quality, 3 and 5 of 16 gates were summed to obtain systolic and diastolic images. Based on a five-parameter model, radial profiles from systolic and diastolic PET images were fit by nonlinear regression for myocardial wall thickness, left ventricular radius and tracer activities in the blood pool, the myocardial tissue and the extracardiac background. Echocardiography and gated magnetic resonance imaging (MRI) were performed in 11 and 7 volunteers, respectively. RESULTS: We observed a significant (p < 0.001) correlation between measurements obtained by gated PET imaging and the correlative imaging modalities for myocardial wall thickness and left ventricular radius. While good agreement was observed between measurements of average radial shortening, estimates of average wall thickening differed significantly. CONCLUSION: This model-based analysis offers accurate estimates of regional recovery coefficients directly from gated cardiac PET images and may also prove useful for the assessment of myocardial contractile function. These recovery coefficients are essential for the correction of partial volume effects when quantitative PET studies are performed.

Deoxyglucose

Minimisation of parameter estimation errors in dynamic PET: choice of scanning schedules.

We addressed the general problem of finding an optimal scan schedule in positron emission tomography (PET) dynamic studies which minimises the errors in estimating the transfer constants between a set of compartments. As an example, the influence of scan intervals in PET on the accuracy of estimation of the rate constants and vascular component in the deoxyglucose method was examined using an empirical noise model. The simulated noisy curves used in the analysis were compared with patient data to validate the noise model. A series of scan schedules were compared for accuracy of fit by evaluating the determinant of the variance-covariance matrix of the fitted parameters as an index of parameter accuracy. For realistic noise levels there is a monotonic improvement in the index of parameter accuracy with increasing sampling frequency, particularly over the initial minutes after the tracer injection. However, since faster schedules are more susceptible to errors introduced by time mismatches between plasma and tissue curves and impose greater computational and memory overhead, an initial scan duration of 30 s provide a practical trade-off for dynamic PET 18F-fluoro-deoxyglucose studies.

Models, Biological

Progress curve analysis in enzyme kinetics: model discrimination and parameter estimation.

The method of progress curve analysis for enzyme-catalyzed reactions (Duggleby, R.G. and Morrison, J.F. (1977) Biochim. Biophys. acta 481, 297--312) has been extended to a two substrate, reversible reaction through the use of enzyme-catalyzed recycling of one of the products. The reaction investigated was that catalyzed by aspartate aminotransferase (L-aspartate:2-oxoglutarate aminotransferase, EC 2.6.1.1) and the product, alpha-ketoglutarate was recycled to glutamate using NADH and NH4Cl in the presence of glutamate dehydrogenase. The values determined for the kinetic parameters of the aminotransferase were found to agree well with those obtained from steady-state velocity measurements. The standard errors of the parameters, as calculated by the procedure originally described, were found to underestimate the observed variation between different experiments. Therefore, a procedure of data compression was devised which leads to more realistic values for standard errors. The compressed data obtained with aspartate aminotransferase have been fitted to the integrated rate equations that describe a variety of kinetic mechanisms. The best fit was obtained with the Ping-Pong model which is applicable to the aspartate aminotransferase reaction. Thus, progress curve analysis may be used to determine the kinetic mechanism of, and values of the kinetic parameters associated with, an enyzme-catalyzed reaction.

Aspartate Aminotransferases

Milk yield increase after anthelmintic treatment of dairy cattle related to some parameters estimating helminth infection.

On 81 farms blood samples were taken from adult dairy cattle, on pasture in October 1986 and after stabling in December 1986, to measure antibody titres against the nematodes Dictyocaulus viviparus, Cooperia spp. and Ostertagia spp., and the trematode Fasciola hepatica, and serum pepsinogen values. Faecal samples, collected in October, were examined to confirm the presence of parasites by means of egg counts and larval identifications. From December until the end of the stabling period, dry cows were either treated with albendazole or left untreated in alternate sequence of calving date. Treated cows produced 132.9 kg milk per cow per lactation more than untreated cows (P less than 0.01). Fat and protein percentage were not significantly influenced by anthelmintic treatment. The mean herd milk yield response to treatment varied from -889 to +1231 kg milk per cow per lactation. There was a significant between-herd variation in antibody titres against nematodes and in pepsinogen values. However no significant correlations between these parameters and the mean herd milk yield response to treatment were found.

Albendazole

Comparison of nonlinear pharmacokinetic parameters estimated from the sinusoidal perfusion and venous equilibrium models.

It is shown that the intrinsic and steady-state clearances and the values of Vm and Km of the Michaelis-Menten equation estimated via the sinusoidal perfusion model are different from the corresponding values estimated via the venous equilibration model. The liver blood flow rates estimated by two theories (from plasma data) are identical. The comparison was made using the single dose oral and intravenous and steady-state oral plasma concentration-time data for verapamil in six subjects previously published.

Coronary Disease