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PubMed1987

Neurotransmission parameters estimated from miniature endplate current growth phase.

A numerical model of miniature endplate current (mepc) generation was fitted to the rising phase of individual mepcs recorded at the frog neuromuscular junction, and estimates of 6 transmission parameters were obtained. Model fitting was enabled by assuming literature values for geometric parameters and determining single channel current by noise analysis, the channel closing rate constant from the mepc decay, and acetylcholine hydrolysis parameters from mepcs recorded in esterase-blocked endplates. Under control conditions, mean estimates were: number of molecules in a quantum = 29,000, diffusion coefficient = 2.8 X 10(-6) cm2s-1, endplate receptor density = 8500 micron-2, forward binding rate constant = 7.6 X 10(8) M-1s-1, equilibrium dissociation constant = 58 microM and channel opening rate constant = 8100 s-1.

Animals↗

PubMed2006

Genetic parameter estimates for serum insulin-like growth factor I concentrations, and body weight and weight gains in Angus beef cattle divergently selected for serum insulin-like growth factor I concentration.

Data for the current study were obtained from a divergent selection experiment in which the selection criterion was the average serum IGF-I concentrations of 3 postweaning blood samples collected from purebred Angus calves. Multiple-trait derivative-free REML procedures were used to obtain genetic parameter estimates for IGF-I concentrations and for BW and BW gains measured from birth to the conclusion of a 140-d postweaning performance test. Included in the analysis were 2,674 animals in the A(-1) matrix, 1,761 of which had valid records for IGF-I concentrations. Direct heritability estimates +/- SE for IGF-I concentration at d 28, 42, and 56 of the postweaning period and for mean IGF-I concentrations were 0.44 +/- 0.07, 0.51 +/- 0.08, 0.42 +/- 0.07, and 0.52 +/- 0.08, respectively. Heritability estimates for maternal genetic effects ranged from 0.10 +/- 0.05 to 0.20 +/- 0.06. The proportion of total phenotypic variance due to the maternal permanent environmental effect was essentially zero for all measures of IGF-I concentrations. Genetic correlations of IGF-I concentrations with weaning and post-weaning BW ranged from 0.07 +/- 0.12 to 0.32 +/- 0.11 and generally demonstrated an increasing trend during the postweaning period. Averaged across the various measures of IGF-I, the genetic correlation of IGF-I with preweaning gain was 0.14, whereas the genetic correlation with postweaning gain was 0.29. Genetic correlations between IGF-I and BW gain were positive during all time intervals, except between weaning and the beginning of the postweaning test and from d 84 to 112 of the postweaning period. Environmental and phenotypic correlations of IGF-I with BW and BW gains were generally positive, but small. These results indicate that postweaning serum IGF-I concentration is moderately to highly heritable and has small positive genetic, environmental, and phenotypic correlations with BW other than birth weight and with pre- and postweaning gain. Therefore, if IGF-I proves to be a biological indicator of an economically important trait (e.g., efficiency of feed use for growth) in beef cattle, it should be possible to rapidly change IGF-I concentrations via selection without significantly altering live weight or rate of gain.

Aging↗

PubMedDate not supplied

A new method to estimate parameters of pharmacokinetics with enterohepatic circulation.

A new method of estimating pharmacokinetic parameters for enterohepatic recirculation models is presented. The algorithm, based on the simplex method, assures a convergence toward the minimum minimorum; provides reliable parameters, even in large numbers; and handles up to five cycle effects in five established models: IV, EV, mono-, bi- or tricompartmental. For each model, the reabsorption rate may be considered to be slow (characterised by a rate constant with a significant value) or instantaneous (an infinite rate constant). Two examples are given to illustrate the qualities of the software that incorporates this new algorithm. The first relates to the pharmacokinetics of zinc orally given to humans; the second treats the kinetics of alpha-methylDOPA given to dogs intra-arterially (note: values of plasma concentrations have been extracted from the literature).

Enterohepatic Circulation↗

PubMed1987

Genetic parameter estimates for preweaning growth traits in Santa Gertrudis cattle.

Genetic parameters were estimated for birth weight and weaning weight from records collected on 1,894 Santa Gertrudis calves (939 bulls, 955 heifers) during the 8-yr period, 1978 through 1985. Variance and covariance components were estimated separately by sex and combined across sexes utilizing mixed-model, least-squares procedures (Henderson's Method 3). The mathematical model assumed for estimating variance and covariance components by sex included effects of year, sire-within-year and age of dam. Also, calf weaning age was included as covariate for birth weight and weaning weight. Estimates were obtained across sexes utilizing the same model, with the addition of effects of sex of calf and the sex-of-calf X age-of-dam interaction. Heritabilities and genetic and phenotypic correlations were estimated using paternal half-sib techniques. The heritability estimate for birth weight for bulls was 1.6 times larger than that for heifers (.38 +/- .12 vs .24 +/- .10). Conversely, the heritability estimate for weaning weight for heifers was 1.5 times larger than that for bulls (.45 +/- .12 vs .30 +/- .11). However, based upon their approximate standard errors, neither of these differences was significant. Heritability estimates calculated across sexes were .32 +/- .07 and .42 +/- .08 for birth weight and weaning weight, respectively. Estimates of genetic and phenotypic correlations of birth weight and weaning weight by sex were .43 +/- .21 and .31, respectively, for bulls and .33 +/- .22 and .27, respectively, for heifers. Calculated across sexes, the genetic correlation was .40 +/- .14 and the phenotypic correlation was .29.

Animals↗

PubMed1996

Ca(2+)-force relationship of frog skeletal muscle: a dynamic model for parameter estimation.

A simple mathematical model describing the dynamic connection between Ca2+ and force generation in intact skeletal muscle from the frog has been developed from isometric force responses to cytosolic Ca2+ concentration ([Ca2+]c) transients during tetanic and twitch contractions. The main element of the model is a two-state cross-bridge cycle characterized by the fractional rate of cross-bridge attachment (f(app)) and the fractional rate of cross-bridge detachment (g*). While g* is constant, f(app) is time varying and regulated by both [Ca2+]c and force. Having only four adjustable parameters, the model is mathematically unique, thereby allowing precise parameter estimation from the dynamic Ca2+ and force data. The model should be useful for developing insights into the relative importance for force generation and relaxation of 1) the size and shape of the Ca2+ transient, 2) the sensitivity of the fractional rate of cross-bridge attachment to both the [Ca2+]c and the force responses, and 3) the fractional rate of cross-bridge detachment, which is insensitive to both Ca2+ and force.

Animals↗

PubMed1997

Parameter estimation and dosage adjustment in the treatment with vancomycin of methicillin-resistant Staphylococcus aureus ocular infections.

The susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) to vancomycin (VC) is excellent, but excessive dosing of VC leads to severe side effects. In this study, we present a way of administration planning for each patient based on personal data. To this end, we employed the Sawchuck-Zaske equation to calculate VC clearance (CL) and volume of distribution (Vd) on the basis of three different plasma concentrations of VC, and we used CL and Vd values as prior information before employing the parameter estimation and dosage adjustment program to treat a patient with postsurgical endophthalmitis caused by MRSA and a patient with acute dacryocystitis also caused by MRSA. They had good remissions without any severe side effects.

Acute Disease↗

PubMed2004

The maximum-likelihood strategy for determining transcranial magnetic stimulation motor threshold, using parameter estimation by sequential testing is faster than conventional methods with similar precision.

BACKGROUND: The resting motor threshold (rMT) is the basic unit of transcranial magnetic stimulation (TMS) dosing. Traditional methods of determining rMT involve finding a threshold of either visible movement or electromyography (EMG) motor-evoked potentials, commonly approached from above and below and then averaged. This time-consuming method typically uses many TMS pulses. Mathematical programs can efficiently determine a threshold by calculating the next intensity needed based on the prior results. Within our group of experienced TMS researchers, we sought to perform an illustrative study to compare one of these programs, the Maximum-Likelihood Strategy using Parameter Estimation by Sequential Testing (MLS-PEST) approach, to a modification of the traditional International Federation of Clinical Neurophysiology (IFCN) method for determining rMT in terms of the time and pulses required and the rMT value. METHODS: One subject participated in the study. Five researchers determined the same subject's rMT on 4 separate days-twice using EMG and twice using visible movement. On each visit, researchers used both the MLS-PEST and the IFCN methods, in alternating order. RESULTS: The MLS-PEST approach was significantly faster and used fewer pulses to estimate rMT. For EMG-determined rMT, MLS-PEST and IFCN derived similar rMT, whereas for visible movement MLS-PEST rMT was higher than for IFCN. CONCLUSIONS: The MLS-PEST algorithm is a promising alternative to traditional, time-consuming methods for determining rMT. Because the EMG-PEST method is totally automated, it may prove useful in studies using rMT as a quickly changing variable, as well as in large-scale clinical trials. Further work with PEST is warranted.

Algorithms↗

PubMed2006

Optimum blood sampling time windows for parameter estimation in population pharmacokinetic experiments.

Clinical trials requiring the collection of pharmacokinetic information often specify blood samples to be taken at fixed times. This may be feasible when trial participants are in a controlled environment such as in early phase clinical trials, however it becomes problematic in trials where patients are in an out-patient clinic setting such as in late phase drug development. In such a situation it is common to take blood samples when it is convenient for all involved and may result in data that are uninformative. This paper proposes an approach to pharmacokinetic study design that allows greater flexibility as to when blood samples can be taken and still result in data that allows satisfactory parameter estimation. The sampling window approach proposed in this paper is based on determining time intervals around the D-optimum pharmacokinetic sampling times. These intervals are determined by allowing the sampling window design to result in a specified level of efficiency when compared to the fixed times D-optimum design. Several approaches are suggested for dealing with this design problem.

Blood Specimen Collection↗

PubMed1984

Statistical prediction of drug stability based on nonlinear parameter estimation.

The classical approach in Arrhenius prediction of drug stability uses two sequential steps of linear regression involving (a) a function of drug content versus time to obtain the rate constants (k) at several elevated temperatures and (b) the relationship of logarithm of mean k versus reciprocal temperature to predict the room temperature rate constant and hence the shelf-life of the drug. Uncertainties in drug content determinations are often neglected in the second regression. The classical approach also provides a wide and unsymmetrical 95% confidence interval for the predicted shelf-life. We have developed equations which allow for direct statistical prediction of shelf-life using observed values of drug content, time, and temperature. Nonlinear regression analysis was employed to provide parameter estimates of drug shelf-life and the energy of activation. The developed approach was shown to provide good estimates of shelf-life with meaningful statistics of reactions over a wide range of stability and energetics, with various kinetic orders, with different levels of noise in the data, and with different types of data structure. Comparison between the nonlinear approach and the classical approach showed that the nonlinear approach provided better mean estimates of shelf-life with much smaller and more symmetrical 95% confidence intervals than the classical approach. The method appears sufficiently robust and wide-ranging as to be potentially applicable for the prediction of the drug stability of pharmaceutical products.

Chemistry, Pharmaceutical↗

PubMed1992

Arm function after axillary dissection for breast cancer: a pilot study to provide parameter estimates.

Sixty-three women participated in a study in Calgary, Alberta to assess the rate of arm recovery and factors affecting it up to one year after axillary node dissection for breast cancer. Outcomes included objective measures of swelling, mobility, and strength, and subjective assessments of pain (at rest and with movement) and stiffness. Approximately 42% of women had residual impairment of at least one type one year after surgery, the most common problems being pain (16%) and reduced grip strength (16%). Except for lymphedema, measurements one year after surgery showed little change from measurements at 6 months, suggesting that the shorter follow-up may be appropriate for assessing the long term effects of axillary dissection. Lymphedema was the only sequela which increased over time. The results provide parameter estimates for designing studies to evaluate the role of physiotherapy after axillary dissection.

Arm↗

PubMed1995

Parameter estimation of labial movements in speech production: implications for speech motor control.

Central to theories of speech motor control are estimates on magnitudes of lip activity expressed in terms of central tendency, variability, and interrelatedness. In fact, the tenability of each of two competing theories of motor control for speech production rests solely on the observation of the predicted direction of the correlation coefficient (one positive and one negative) that indexes the relationship of concurrent lip activity. Each theory, however, predicts a relationship that is the complete opposite of the relationship predicted by the other. That is, one theory proposes that the labial system functions on the basis of complementary variation, whereas the other assumes positive covariation, or complementary modulation. In apparent contradiction, each prediction has been observed under laboratory conditions. The explanation for this apparent contradiction resides in the small sample sizes upon which each estimate was based. The minimum number of observations that are necessary to achieve accurate estimates of lip displacement parameters has remained unclear. This paper addresses three fundamental questions: (a) how many observations of on-task behavior are necessary to accurately estimate mean and variance values for the magnitude of upper lip displacement in a speech production experiment?, (b) what is the analogous number of observations for estimating the same values of lower lip displacement (together with the mandible) in the same context?, and (c) how many observations are necessary to accurately estimate the correlation coefficient indexing the relationship of lip displacements during the production of speech? Answers to these questions are accomplished through a review of estimator properties, a Monte Carlo computer simulation, and through laboratory observations.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

PubMed1992

Parameter estimation for carcass traits including growth information of Simmental beef cattle using restricted maximum likelihood with a multiple-trait model.

(Co)variance component estimates were computed for retail cuts per day of age (kilograms per day), cutability (percentage of carcass weight), and marbling score (1 through 11) using a multiple-trait sire model. Restricted maximum likelihood estimates of (co)variance components were obtained via an expectation-maximization algorithm. Carcass data consisted of 8,265 progeny records collected by U.S. Simmental producers. Growth trait information (birth weight, weaning weight, and[or] postweaning gain) for those progeny with carcass data and an additional 5,405 contemporaries formed the complete data set for analysis. A total of 420 sires were represented. Three models differing in number of traits were investigated: 1) carcass traits with growth traits, 2) carcass traits only, and 3) single trait. The final models did not include postweaning gain because of convergence problems. Parameter estimates for all three models were essentially the same. Heritability estimates were .30, .18, and .23 for retail cuts per day, cutability, and marbling score, respectively. Correlations between growth and carcass traits were low except for those with retail cuts per day, which were moderate and positive. The additional information gained by adding growth traits to the carcass-traits-only evaluation lowered prediction error variances most for retail cuts per day. Little change in prediction error variances was found for cutability and marbling score. Inclusion of growth traits in future sire evaluations for carcass traits will benefit the evaluation of retail cuts per day but have considerably less effect on cutability and marbling score.

Analysis of Variance↗

PubMed2004

Using prior knowledge in SVD-based parameter estimation for magnetic resonance spectroscopy--the ATP example.

We introduce the knowledge-based singular value decomposition (KNOB-SVD) method for exploiting prior knowledge in magnetic resonance (MR) spectroscopy based on the SVD of the data matrix. More specifically, we assume that the MR data are well modeled by the superposition of a given number of exponentially damped sinusoidal components and that the dampings alphakappa, frequencies omegakappa, and complex amplitudes rhokappa of some components satisfy the following relations: alphakappa = alpha (alpha = unknown), omegakappa = omega + (kappa- 1)delta (omega = unknown, delta = known), and rhokappa = Ckapparho (rho = unknown, ckappa = known real constants). The adenosine triphosphate (ATP) complex, which has one triple peak and two double peaks whose dampings, frequencies, and amplitudes may in some cases be known to satisfy the above type of relations, is used as a vehicle for describing our SVD-based method throughout the paper. By means of numerical examples, we show that our method provides more accurate parameter estimates than a commonly used general-purpose SVD-based method and a previously suggested prior knowledge-based SVD method.

Adenosine Triphosphate↗

PubMed2002

Body segment inertial parameter estimation for the general population of older adults.

The practical determination of accurate body segment inertial parameters for the general older adult population remains a problem, especially in estimating these parameters for women and accounting for variations in body type. A method is presented for determining the mass and center of mass location of the body segments of individuals within the general population of older adults. Effects of sex and body type on older adult mass distribution are accounted for using 32 easily obtainable body measurements. The method is based on existing results from different data sources and employs a combination of validated estimation approaches, including: body mass and segment length proportions, linear and nonlinear regression equations, and a mathematical model of the trunk. The method was applied to a validation sample of healthy, community-dwelling older adults (29 men, 50 women). Predicted body mass was 96.7+/-4.8% and 95.7+/-3.7% of measured body mass in the men and women, respectively. The estimates of body segment mass and trunk center of mass location for the sample population approximate those reported in the literature, supporting the validity of the described method. By producing practical, subject-specific estimates of body segment inertial parameters, the method should allow more accurate biomechanical analyses of the older adult population.

Age Factors↗

PubMed1998

Error structure for the HPLC analysis for atenolol, metoprolol and propranolol: a useful weighting method in parameter estimation.

Three reversed-phase high performance liquid chromatography (HPLC) methods with UV detection were developed and fully validated for the quantification of three beta-blockers: atenolol, metoprolol and propranolol. After validation, error structures for the HPLC analysis were established using a convenient and practical procedure. The mean percentage of relative standard deviation (RSD) of the experimental concentrations (C), were less than 4.29% for proportionality and less than 3.68% for precision for any of the drugs, which allowed the quantitation of beta-blockers assayed at concentrations in the range 25-0.78 micrograms.ml-1. The error structures for the HPLC analysis were: SD (micrograms.ml-1) = 5.02 x 10(-2) C for atenolol, SD (micrograms.ml-1) = 4.55 x 10(-2) + 0.63 x 10(-2) C - 7.58 x 10(-6) C3 for metoprolol and SD (micrograms.ml-1) = 2.73 x 10(-2) C - 3.49 x 10(-4) C2 for propranolol. The reciprocal of the square of the SD of the drug concentrations measured within the calibration curve could be used as weighting methods in parameter estimation by non-linear regression.

Adrenergic beta-Antagonists↗

PubMed2003

Neural-network-based parameter estimation in S-system models of biological networks.

The genomic and post-genomic eras have been blessing us with overwhelming amounts of data that are of increasing quality. The challenge is that most of these data alone are mere snapshots of the functioning organism and do not reveal the organizational structure of which the particular genes and metabolites are contributors. To gain an appreciation of their roles and functions within cells and organisms, genomic and metabolic data need to be integrated in systems models that allow the testing of hypotheses, generate experimentally testable predictions, and ultimately lead to true explanations. One type of data that is particularly well suited for such integration consists of time profiles, which show gene activities, metabolite concentrations, or protein prevalences at dense series of time points. We show with a specific example how such time series can be analyzed and evaluated, if some structural information about the data is available, even if this information is incomplete. The method consists of three components. The first is a particularly suitable mathematical modeling framework, namely Biochemical Systems Theory, in which parameters are direct indicators of the organization of the underlying phenomenon, the second is the training of an artificial neural network for data smoothing and complementation, and the third is a technique for reinterpreting differential equations in a fashion that facilitates parameter estimation. A prototype webtool for these analyses is available at https://bioinformatics.musc.edu/webmetabol/.

Biology↗

PubMed1997

Similarity or discrepancy in pharmacokinetic parameter estimation between bolus and infusion studies.

A recent study by Heatherington and Rowland showing discrepancies in steady-state volume of distribution (Vss) estimation of two barbiturates between bolus and infusion studies in rat hindlimb preparations was reviewed. Their rationale is that increasing the duration of administration may increase the accessibility for tissue distribution and thus increase Vss for compounds showing slow tissue uptake. Such a dosing-duration-dependent distribution concept is, however, inconsistent with the principle in linear kinetics that the fate or disposition function of any drug molecules is independent of time of administration and presence of other molecules. When their well-designed bolus studies were reanalyzed by including extrapolated outflow data from the last sampling time to infinity, the Vss values for the two barbiturates were found to be very similar to those obtained by the infusion method. Our analysis seems to validate a theoretical concept that parameter estimation is independent of the duration of administration in linear kinetics. A potential complication of using the bolus method to study Vss is presented.

Animals↗

PubMed1988

Effect of blood curve smearing on the accuracy of parameter estimates obtained for 82Rb/PET studies of blood-brain barrier permeability.

82Rb in conjunction with positron emission tomography (PET) has been used to estimate the blood to brain transport rate constant (K1) for Rb and the regional brain/tumour blood volume (Vb). Errors in K1 and Vb depend upon the accuracy of the measured arterial blood radioactivity and PET-monitored brain radioactivity. Arterial blood is usually sampled by placing a catheter in the radial artery and measuring the radioactivity in blood passing continuously in front of a detector or by counting discrete blood samples in a well scintillation detector. In either case, the passage of blood through catheter/pump tubing produces a smearing of the waveform as well as a delay in the arrival of radioactivity at the blood sampling site. The change in shape of the blood curve is significant for bolus-type injections and results in large errors in those model parameters which contribute substantially to the initial phase of the brain activity curve. We report here the results of computer simulations and an analysis of patient data which suggest that parameter estimation errors due to smearing and time shift may be large (greater than 50%) but that these errors can be minimised by the use of deconvolution techniques.

Blood-Brain Barrier↗