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At least 613 records · Page 34Linked to original sources
PubMed1987

Parametrization by non-linear regression and bayesian estimation of bentazepam in a multiple dosage regimen in humans.

The plasma levels of bentazepam were determined by an HPLC technique in a total of 10 patients receiving the drug orally in pill form who were on a dosage regimen with the drug administered every 8, 12 or 24 h. Blood samples were taken three times following the administration of the first and last dose and at times, immediately after the administration of intermediate doses. The parameters corresponding to a one-compartment kinetic model were calculated in each patient by using all the data on plasma levels still corresponding to different administrations by non-linear regression and applying programs with homoscedastic, heteroscedastic and bayesian estimation. The absorption constant had mean values of 2.33, 2.18 and 2.75 h-1. The elimination constant proved to be equal to 0.10, 0.09 and 0.22 h-1 while for the apparent distribution volume mean values of 1.89, 2.89 and 0.80 l/kg were found with each of the estimation programs employed, respectively. The values found for each of the kinetic parameters and with each of the programs were subjected to the non-parametric Kruskal-Wallis test with a view to detecting the presence or absence of statistically significant differences. The discrimination of the program that yielded the best fit was performed by linear regression between the values found for the plasma calculations and those calculated theoretically at the same time with each of the programs.

Adult↗
PubMed1986

Type 1 error and power of the linear trend test in proportions under the National Toxicology Program's modified pathology protocol.

This paper investigates the relationship between the probability of detecting a statistically significant linear trend in the proportion of animals observed to have tumors for the modified pathology protocol currently being employed by The National Toxicology Program. We considered over 300 possible dose-response relationships and tested at 5% and 1% significance levels. The results indicate that a small loss in the probability of detecting a statistically significant result will occur when the modified protocol is used instead of the previous pathology protocol. This loss varies as a function of the design of the study in terms of dose and animal allocation and as a function of the steepness of the dose-response relationship. The absolute difference between the probability of a statistically significant result for the original pathology protocol and that for the modified pathology protocol never exceeded 0.03. This difference was always less than 8% of the probability of a statistically significant result for the original pathology protocol.

Animals↗
PubMed1975

[A computer program for the implicit regression of the Hill equation].

A computer program for implicit regression of the Hill equation. The fundamentals for the regression of implicit functions following the Gauss method are dealt with. Basing on these fundamentals a program for the regression of the Hill equation is described. The binding constant, the Hill coefficient and end extinction can be estimated. The mean errors of parameters were calculated in the linear model. The program was written in ALGOL 60 for the computer Robotron 300. The program is available on request.

Computers↗
PubMed1995

Supercomputer algorithms for efficient linear octree encoding of three-dimensional brain images.

We designed and implemented algorithms for three-dimensional (3-D) reconstruction of brain images from serial sections using two important supercomputer architectures, vector and parallel. These architectures were represented by the Cray YMP and Connection Machine CM-2, respectively. The programs operated on linear octree representations of the brain data sets, and achieved 500-800 times acceleration when compared with a conventional laboratory workstation. As the need for higher resolution data sets increases, supercomputer algorithms may offer a means of performing 3-D reconstruction well above current experimental limits.

Algorithms↗
PubMed1984

Fitting physiological models to data.

Methods of fitting models to experimental data obtained from biological systems are reviewed. The Michaelis-Menten model is used as the working example of a familiar and well-studied biological model. Criteria for selecting models include goodness of fit, freedom from systematic errors, and simplicity. A given model is usually fitted and the optimal parameters determined by minimization of an objective function, usually the sum of the squared errors. Freedom from systematic errors is best judged graphically. The important mathematical methods of fitting models are derived from the calculus and include linear and quadratic programming. The latter leads to minimization of the sum of squares of errors. Optimal search procedures, which also perform this minimization, are surveyed. Other properties of models, such as the proper number of parameters and whether linearization is appropriate, are discussed. The specialized problems of biological models and data are considered.

Models, Biological↗
PubMed1982

Effect of age and sex on theophylline clearance in young subjects.

The joint effects of age and gender on theophylline plasma clearance (Clp) were assessed using an analysis of covariance technique. Data from several literature sources and from our laboratory were collated for this analysis with only non-smoking subjects aged 1.3 to 30.0 years considered. The values of Clp exhibited markedly greater variability in the younger subjects, necessitating development of a weighted linear least-squares program to fit the data. The data exhibited a linear decrease in Clp with increasing age regardless of sex. A gender influence was evident over the age range of 4 to 20 years. Male Clp values tended to be higher than those of females over this age interval [25.5 ml/hr/kg higher (31%) at 4 years and 12.5 ml/hr/kg higher (22%) at 20 years]. These differences are statistically significant, and since they represent a divergence of greater than 20%, may be clinically significant as well. The statistical technique employed may be of value in future pharmacokinetic studies for the examination of multiple effects on pharmacokinetic parameters.

Adolescent↗
PubMed1998

The effect of independent collimator misalignment on the dosimetry of abutted half-beam blocked fields for the treatment of head and neck cancer.

BACKGROUND AND PURPOSE: Independent collimation conveniently allows for the junctioning of abutting fields with non-diverging beam edges. When this technique is used at the junction of multiple fields, e.g. lateral and low anterior fields in three-field head and neck set-ups, there should be a dosimetric match with no overdose or underdose at the matchline. We set out to evaluate the actual dosimetry at the central match plane. MATERIALS AND METHODS: Independent jaws were used to mimic two half-beam blocked fields abutting at the central axis. X-Ray verification film was exposed in a water-equivalent phantom and the dose at the matchline was evaluated with laser densitometry. Collimators were then programmed to force a gap or overlap of the radiation fields to evaluate the effect of jaw misalignment within the tolerance of the manufacturer's specification. Diode measurements of the field edges were also performed. Four beam energies from four different linear accelerators were evaluated. RESULTS: Small systematic inhomogeneities were found along the matchline in all linear accelerators tested. The maximum dose on the central axis varied linearly with small programmed jaw misalignments. For a gap or overlap of 2 mm between the jaws, the matchline dose increased or decreased by 30-40%. The region of overdose or underdose around the matchline is 3-4 mm wide. The discrepancy between the width of jaw separation and the width of the region of altered dose is explained by a penumbra effect. CONCLUSION: We recommend that independent jaw alignment be evaluated routinely and provide a simple method to estimate dose inhomogeneity at the match plane. If there is a field gap or overlap resulting in a clinically significant change in dosimetry, jaw misalignment should be corrected. If it cannot be corrected, part of the benefit of asymmetric collimation is lost and other methods of field junctioning may have to be considered. We routinely use a small block over the spinal cord at the mono-isocenter set-up plane for three-field head and neck treatments to prevent an overdose.

Head and Neck Neoplasms↗
PubMed1989

Analysis of progress curves for enzyme-catalysed reactions. Automatic construction of computer programs for fitting integrated rate equations.

The computer analysis of progress curves for enzyme-catalysed reactions involves a series of mathematical and computational tasks. The three most daunting of these are the derivation of an integrated rate equation, solving this equation so that the amount of product formed by the reaction at any time can be calculated, and incorporating this solution into a non-linear-regression computer program. This paper describes the basis of a computer program that greatly simplifies the problem. The proposed mechanism is specified in the familiar kinetic constant form, which is automatically translated into a program capable of fitting this mechanism to a series of experimental progress curves. The approach is illustrated for a reversible reaction with one substrate and one product, and tested with some data obtained for the fumarase reaction. A copy of the program has been deposited as Supplementary Publication SUP 50148 (13 pages) at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1989) 257, 5.

Animals↗
PubMed1979

A program package for simulation and parameter estimation in pharmacokinetic systems.

A set of programs is presented which has been developed for parameter estimation and simulation of models arising from pharmacokinetic applications. The programs can accommodate linear and nonlinear models with multiple inputs and multiple outputs. When the model is defined by differential equations, non-uniform repetitive dosage regimens can be handled. The model may also be entered in integrated form when single dose studies or uniform multiple dose studies are being considered. The programs employ a variable-step, variable-order integration routine to solve the model differential equations, and the Nelder-Mead simplex procedure to determine the parameter values which minimize a weighted least squares criterion. The programs have been written for an interactive time-sharing environment with the experimental data and model equations stored in files for future use.

Computers↗
PubMed2003

Concept and realization of a multimedia program for veterinary physiology.

A multimedia program, a non-linear system which supplements the traditional, linear way of learning (e.g. with a text book), was developed. Non-linear systems allow the direct use of information in a free sequence. A problem of these systems is the danger that the reader becomes lost in detail. Therefore, a program was constructed which tries to combine the properties of linear and non-linear teaching systems. Student groups were continuously involved during all stages of the project. The program is organized in several levels. These are: (1) choice of chapters; (2) table of contents of one chapter; (3) summary; (4) text and (5) pictures, animations, simulations and video sequences. The program can be used in different ways. In the linear mode, the reader selects via action words different levels of the program. The user can read either only on the level of the summaries or on detailed information (text, pictures, simulations and videos). In the non-linear mode the user jumps via menu items or buttons to selected pictures, simulations or a searched term. In this way, more than 3500 screen pages are integrated into a multimedia program for veterinary physiology. The program is written in TOOLBOOK, and can be used on a personal computer with Windows 95 or higher.

Animal Population Groups↗
PubMed1999

Genetic programming as an analytical tool for non-linear dielectric spectroscopy.

By modelling the non-linear effects of membranous enzymes on an applied oscillating electromagnetic field using supervised multivariate analysis methods, Non-Linear Dielectric Spectroscopy (NLDS) has previously been shown to produce quantitative information that is indicative of the metabolic state of various organisms. The use of Genetic Programming (GP) for the multivariate analysis of NLDS data recorded from yeast fermentations is discussed, and GPs are compared with previous results using Partial Least Squares (PLS) and Artificial Neural Nets (NN). GP considerably outperforms these methods, both in terms of the precision of the predictions and their interpretability.

Computational Biology↗
PubMed1985

Computer-aided construction of nucleic acid restriction maps using defined vectors.

A new algorithm is described that will rapidly produce restriction maps of cloned DNA fragments. Information concerning the vector is stored as a data file and used in constructing probable maps. As the program is based upon a permutation analysis it has two primary uses. First, preliminary restriction maps can be created from fragment length data as a starting point for further analysis. Second, existing maps can be confirmed as being highly probable, and other probable maps examined to ensure certain combinations have not been overlooked. Although primarily designed for linear vectors, the program can be used to calculate circular maps.

Algorithms↗
PubMedDate not supplied

Optimization of moist heat sterilization.

The use of different combinations of sterilization time and temperature in a pilot scale autoclave, GEV 612 AR-2 (Getinge Ab, Sweden), in optimizing the sterilization process was studied. All three programs used had the same sterilization efficacy (F0 = 15 minutes) but different sterilization temperatures (116, 121, and 126 degrees C) and total process times (98, 57, and 44 minutes). The heat distribution during the sterilization phase was, in all cases, very uniform, the greatest difference being 0.5 degrees C. Also the F0 values differed only by +/- 0.5 minutes from each other. The F0 value increases linearly with all programs until the beginning of the cooling phase. The main effect of different sterilization temperatures on the cumulative F0 curves is an increase in the slope of the curves with increasing sterilization temperature. First order temperature change constants were determined both for the heating phase and the cooling phase. The numeric values of the rate constants for the heating and the cooling phases were 0.20 +/- 0.03 and 0.046 +/- 0.005 min-1, respectively. It is concluded that the pilot autoclave used in this study controls the sterilization process very accurately. The observed variations between F0 values at different positions in the autoclave chamber are acceptable. On the basis of this study an accurately engineered and controlled autoclave is required in process optimization. It also is possible to use higher sterilization temperatures than usually suggested in pharmacopeias and thus to shorten the process time.

Hot Temperature↗
PubMed1996

Determination of alpha-methyldopa in human plasma by validated high-performance liquid chromatography with fluorescence detection.

A sensitive reversed-phase gradient elution high-performance liquid chromatographic method with fluorescence detection has been developed for the determination of alpha-methyldopa (AMD) in human plasma. Separation of the investigated compound and the 3,4-dihydroxyphenylalanine (DOPA) internal standard was achieved on a Nucleosil 7 C18 column with a 5 mM heptanesulphonic acid sodium salt containing 0.05 M potassium dihydrogenphosphate (pH 3.2)-acetonitrile mobile phase. The composition of the mobile phase was changed according to a linear gradient time program. Detection was performed at 270 nm fluorimetric excitation and 320 nm emission. The compounds were isolated from plasma by Bond-Elut C18 solid-phase extraction. The limit of quantitation was found to be 10 ng/ml plasma. The assay was validated with respect to accuracy, precision and system suitability. All validated parameters were found to be within the 20% required limits. On the basis of the sensitivity, linearity and validation parameters the developed analytical method was found to be suitable for application in a bioequivalency study.

Chromatography, High Pressure Liquid↗
PubMed1992

Concave Ferguson plots of DNA fragments and convex Ferguson plots of bacteriophages: evaluation of molecular and fiber properties, using desktop computers.

A desktop computer program evaluating physical properties of DNA and bacteriophages is presented. The analysis is based on data obtained from capillary and submarine-type agarose electrophoresis. Native molecular/particle properties and properties of the gel (or polymer) medium can be derived from electrophoresis at several gel concentrations. This is done conveniently by a computerized evaluation of the semi-logarithmic plot of mobility vs. gel concentration, designated the Ferguson plot. In application to most proteins, this plot is linear and computer programs exist to evaluate it. However, nonlinear Ferguson plots have assumed great importance in view of the fact that the plots are concave for DNA. Similarly, convex plots are important since they prevail in the electrophoresis of large particles in agarose. The computer program reported here is the first to (i) address concave Ferguson plots and (ii) allow for the evaluation of both cases using a desktop computer. Program ELPHOFIT version 2.0, a Macintosh application, is available upon request.

Bacteriophages↗