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Modeling of muscle fatigue using Hill's model.

A new model incorporating muscle fatigue has been developed to predict the effect of muscle fatigue on the force-time relationship of skeletal muscle by using the PAK-program. Differential equations in the incremental form have been implemented into Hill's muscle model. In order to describe the effect of muscle fatigue and recovery on skeletal muscle behaviors, a set of equations in terms of three phenomenological parameters which are a fatigue curve under sustained maximal activation, a recovery curve and an endurance function were developed. With reference to existing models and experimental results, the input parameters for fatigue curve under sustained maximal activation and endurance function were determined. The model has been investigated under an isometric condition. The effects of different shapes of the recovery curves have also been considered in this model. Validation of the model has been performed by comparing the predicted results with the experimental data from an existing literature.

Action Potentials↗

Bringing the Life Needs Model to life: implementing a service delivery model for pediatric rehabilitation.

This article describes the use and utility of the Life Needs Model of Pediatric Service Delivery at a regional children's rehabilitation center. The model is a transdisciplinary, evidence-based model that guides pediatric service delivery to meet the long-range goals of community participation and quality of life for children and youth with disabilities. The article describes the use of the model as a tool to assist with the development of organizational culture, strategic and operational planning, the development of therapists' expertise, and the development of community partnerships. The model also has influenced human resources practices, community relations activities, and research. The model provides needed direction to service planners about the types of services that are important to provide in a geographical region, and fills a gap in outlining the nature of services that can be encompassed in pediatric rehabilitation.

Adolescent↗

Three-dimensional kinematic modelling of the human shoulder complex--Part I: Physical model and determination of joint sinus cones.

Modelling of the human shoulder complex is essential for the multi-segmented mathematical models as well as design of the shoulder mechanism of anthropometric dummies. In Part I of this paper a three-dimensional kinematic model is proposed by utilizing the concepts of kinematic links, joints, and joint sinuses. By assigning appropriate coordinate systems, parameters required for complete quantitative description of the proposed model are identified. The statistical in-vivo data base established by Engin and Chen (1986) is cast in a form compatible with the model by obtaining a set of unit vectors describing circumductory motion of the upper arm in a torso-fixed coordinate system. This set of unit vectors is then employed in determining the parameters of a composite shoulder complex sinus of a simplified version of the proposed model. Two methods, namely the flexible tolerance and the direct methods, are formulated and tested for the determination of an elliptical cone surface for a given set of generating unit vectors. Numerical results are presented for the apex angles and orientation of the composite joint sinus cone with respect to the anatomical directions.

Biomechanical Phenomena↗

A dynamic life table model of Psorophora columbiae in the southern Louisiana rice agroecosystem with supporting hydrologic submodel. Part 2. Model validation and population dynamics.

In an earlier paper, the development of 2 simulation models designed to describe the interaction between key elements of the rice agroecosystem and the population dynamics of Psorophora columbiae were presented (Focks et al. 1988a). The objective of the work reported herein was to validate these models with field data. The first model (WaterMod) predicts soil hydrology conditions as a function of weather, agricultural practices, and soil characteristics for a variety of habitats found within the rice agroecosystem which are utilized by Ps. columbiae. Using a continuous series of hydrologic data collected in southwestern Louisiana during 1984 and 1985, WaterMod was demonstrated capable of adequately predicting runoff rates and the temporal timing of soil moisture and surface water. The second model (PcSim) simulates the population dynamics of Ps. columbiae based upon a host of variables including the output from WaterMod. This model was validated by comparisons made with density estimates from the literature on the temporal and spatial distribution of various life stages and by correspondence with light trap data gathered during the same time and location as the hydrologic data. PcSim was seen to respond appropriately to host animal densities and unusual meterological events occurring during 1984 and 1985 in southern Louisiana. A discussion is presented of the interaction between agricultural practices and certain key factors of the life history strategy of Ps. columbiae which permit the unusually successful exploitation of the rice agroecosystem by this species. A subsequent paper will use these models to evaluate current and proposed IPM strategies for this mosquito (Focks et al. 1988b).

Actuarial Analysis↗

Neural modeling and model identification.

The complexity of the nervous system poses challenging experimental and theoretical problems to the investigator. While experimental studies have provided a broad understanding of the physiological and anatomical role of neural elements, a comprehensive description of how the nervous system acquires and processes information is still lacking. Neural modeling addresses itself to the quantitative interpretation of neurophysiological experiments, to the assimilation of diverse experimental results into unified theories, and to the investigation of mechanisms of information-processing units, codes, and networks and their relation to capabilities of living systems. This review will emphasize neural models which can be tested by physiological or psychophysical experiments and will include the identification of model parameters based on experimental measurements. An overview of neural firing models, neural interaction models, neural variability and coding, design of input-output experiments for model identification, and description of small network interactions through multiunit and gross potential recording will be included.

Action Potentials↗

Comparison of two prospective rate-setting models: the DRG and PIR models.

The article compares two statistical prospective hospital reimbursement models: the diagnosis-related group (DRG) model and the prospective individualized reimbursement (PIR) model. Both models are applied to the same variables from the same data set, a random sample of 10,000 hospital discharges in Maryland in 1983. For comparative purposes, the two statistical models are allowed to differ only in their treatment of the predictive variable, "patient age." The criteria of comparison and results (DRG and PIR, respectively) are: number of patient groups required (469 and 337); accuracy of prediction of length of stay (38 percent and 45 percent of the total variation is explained by the models); correction for sampling bias (0 and 2.4 percent additional explained variation); and accuracy of prediction of total charges ($526 and $262 average error per patient).

Adolescent↗

A finite element model of skin deformation. II. An experimental model of skin deformation.

Skin flap design has traditionally been based on geometric models which ignore the elastic properties of skin and its subcutaneous attachments. This study reviews the theoretical and experimental mechanics of skin and soft tissues (I) and proposes a mathematical model of skin deformation based on the finite element method (III). Finite element technique facilitates the modeling of complex structures by analyzing them as an aggregate of smaller elements. This paper gives the results of an animal model developed to study the deformation and mechanical properties of skin, including its viscoelastic properties (hysteresis, creep, and stress relaxation). A new skin extensometer, constructed with digital stepper motors and controlled with a microcomputer, is described to measure these properties for both skin and its subcutaneous attachments. Deformation grids quantitated from photographs with a digitalizing tablet are presented, and computer software is introduced to standardize and analyze them (II). The mathematical model is used to simulate wound closures such as the ellipse and rectangular advancement flap. In addition, a series of mathematical experiments performed to simulate deformation of a strip of skin are described; the relationships between the various elastic constants are investigated; and a comparison of these simulations with actual deformation is presented. Limitations of the model and areas for future investigation are discussed (III).

Animals↗

A finite element model of skin deformation. III. The finite element model.

Skin flap design has traditionally been based on geometric models which ignore the elastic properties of skin and its subcutaneous attachments. This study reviews the theoretical and experimental mechanics of skin and soft tissues (I) and proposes a mathematical model of skin deformation based on the finite element method (III). Finite element technique facilitates the modeling of complex structures by analyzing them as an aggregate of smaller elements. This paper gives the results of an animal model developed to study the deformation and mechanical properties of skin, including its viscoelastic properties (hysteresis, creep, and stress relaxation). A new skin extensometer, constructed with digital stepper motors and controlled with a microcomputer, is described to measure these properties for both skin and its subcutaneous attachments. Deformation grids quantitated from photographs with a digitalizing tablet are presented, and computer software is introduced to standardize and analyze them (II). The mathematical model used to simulate wound closures such as the ellipse and rectangular advancement flap. In addition, a series of mathematical experiments performed to simulate deformation of a strip of skin are described; the relationships between the various elastic constants are investigated; and a comparison of these simulations with actual deformation is presented. Limitations of the model and areas for future investigation are discussed (III).

Animals↗

[Study of brain edema by an infusion edema Model--the method and characteristics of the model].

In this report, we have described the way of making the infusion edema model, physiological changes of various parameters during this procedure, distribution of water content in white and gray matter and the light and electron microscopic findings of this edema model, for the further understanding of vasogenic edema of the brain. To make the infusion edema model, 25-G needle was stereotaxically inserted into the left frontal white matter of the cat brain. Through the polyethylene catheter with three way stop cock, this catheter was connected to the pressure transducer and slow infusion pump. By this way, we can monitor the pressure of infusing fluid into the white matter. Normal saline was infused with initial rate of 0.75 microliter/min for the first 2 hours. The inflow rate was increased to 1.5 microliter/min for the next one hour, and then changed to 3.0 microliters/min for maintenance inflow rate. The total amount of infused volume was 0.5 ml in this study. During making the infusion edema model, blood pressure and PaCO2 changed little. Intracranial pressure slightly increased from 5.8 to 15.1 mmHg. Pressure volume index (PVI) changed from 0.74 to 0.64, suggesting the changes of intracranial compliance. The water content measured by specific gravimetric technique showed nearly the same water contents and distribution of edema fluid in the white matter of the cat as in the cryogenic injury model. Pathological findings of this infusion edema model demonstrated that the infused liquid was accumulated in the extracellular space of white matter without damaging the tight junction, and endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Application of the four-parameter logistic model to bioassay: comparison with slope ratio and parallel line models.

Bioassays with a quantitative response showing a sigmoid log-dose relationship can be analysed by fitting a non-linear dose-response model directly to the data. It is demonstrated that the four-parameter logistic model, previously applied to immunoassay (Healy 1972), is applicable to the free fat cell bioassay of insulin (Moody, Stan, Stan and Gliemann 1974). It is shown that the standard slope ratio and parallel line models for bioassay can be considered as approximations to the logistic in the extreme dose regions, while the parallel line model can be expected to fit in the middle region. The full statistical analysis of the four-parameter logistic model applied to a general assay design is described. An APL computer program has been developed to facilitate the calculations, which include non-linear curve-fitting, tests of goodness of fit and parallelity, as well as point and interval estimates of the relative potency. Examples of free fat cell bioassays of insulin that have been analysed according to these methods are given. Efficient estimation of the potency calls for concentrating the doses in the region with the steepest slope of the dose-response curve. With respect to testing the parallelity and to allow for assay-to-assay variability and unpredictable potencies, it may be preferable to use an assay design with doses distributed over a wide range and to apply a dose-response model which, like the four-parameter logistic, is capable of fitting over the whole feasible dose range.

Biological Assay↗

Mathematical modelling of reaction latency: the structure of the models and its motivation.

The basic structural assumptions concerning the dynamic models of the reaction latency are presented. The linear dynamic stochastic model of the reaction latency is considered as a special case of dynamic model. The biological motivation for using these models are outlined. These models express the reaction latency as a first access time of the random threshold of a certain stochastic process. This approach was used in modelling the reaction latency in escape and avoidance experiments (the results will be presented in subsequent papers).

Animals↗

Testing the fit of a regression model via score tests in random effects models.

This paper considers testing the goodness-of-fit of regression models. Emphasis is on a goodness-of-fit test for generalized linear models with canonical link function and known dispersion parameter. The test is based on the score test for extra variation in a random effects model. By choosing a suitable form for the dispersion matrix, a goodness-of-fit test statistic is obtained which is quite similar to test statistics based on non-parametric kernel methods. We consider the distribution of the test statistic and discuss the choice of the dispersion matrix. The testing method can handle models with continuous and discrete covariates. Corrections for bias when parameters are estimated are available and extensions to models with unknown dispersion parameters, and more general nonlinear models are discussed. The proposed goodness-of-fit method is demonstrated in a simulation study and on real data of bone marrow transplant patients. The individual contributions of observations to the test statistic are used to perform residual analyses.

Age Factors↗

The effect of an education and feedback intervention on group-model and network-model health maintenance organization physician prescribing behavior.

The authors evaluated the effect of an educational and feedback intervention on H2-blocker prescribing patterns and determined, if such effects differed for network- versus group-model health maintenance organization (HMO) physicians and in academic versus nonacademic settings. Physicians were randomized to receive an educational memorandum alone or combined with feedback regarding their individual prescribing behavior. The memo suggested preferred use of an H2-blocker (cimetidine) that would be less expensive to the HMO. Prescribing was monitored during the 6 months before and after the intervention. The study was undertaken at the primary care practices of a mixed group- and network-model university-affiliated HMO. Thirty group-model (at two academic and four nonacademic sites) and 33 network-model (all in full-time private practice) primary care physicians participated in the study. The analysis utilized weighted and unweighted analysis of covariance of the change in physicians' cimetidine-prescribing rates between the baseline and study periods. A significant response to the intervention was noted among academic and nonacademic group-model HMO physicians, but not among network physicians (adjusted mean absolute prescribing changes of +9.9% and +8.9% versus -2.8%, P = .02). There was no difference in prescribing change based on type of intervention (education versus feedback). The authors conclude that a simple passive educational intervention can be effective at changing group-model HMO physician behavior.

Cimetidine↗

Adaptive modeling in a mammalian skeletal model system.

Juvenile BALB/c mice were used as a model system to test the effects of various loading and exercise regimens on the growth and development of femora. Six treatments and three controls were used to document changes in geometric, mechanical, and material properties of the femora associated with strength. In each age-matched experiment, body weight and the strength, length, anterior and posterior diameters, cross-sectional area, moments of inertia in the anteroposterior and lateromedial directions, cortical wall thickness, and mineral content of the femora were assessed and found to vary significantly among treatment groups. An adaptive interpretation of these data was provided by calculating Pearson correlation coefficients between moment at failure (one measure of strength) and each geometric, mechanical and material property of the femora that contributes to strength. We make the assumption that at the termination of the experiment the greater the coordination between changes in strength and changes in the parameters that contribute to strength (the greater the number of correlations), the more adaptively modeled the femora are. Adaptive modeling here refers to the manner in which the femora grow and develop (adapt) under a given treatment regimen. Absolute strength of whole femora was reflected by our measure of adaptive modeling in all groups with one exception. In each experiment, the voluntary exercise controls were the most adaptively modeled. The least adaptively modeled groups also showed a general retardation of growth. It appears that juvenile mouse femora demonstrate a wide range of responses to different conditions of loading and exercise and that some of these changes are likely permanent. Moreover, at least two major variables--1) mechanical loading and 2) glucocorticoid mediated psychological stress--appear to contribute to the differences seen between the treatment groups.

Adaptation, Physiological↗

Indirect pharmacodynamic response models do not require any parametric pharmacokinetic model to be fitted to effect-time data.

Indirect response models (IRM) represent one of the possible ways to explain and quantitatively describe a delayed pharmacodynamic effect at non-steady-state conditions. The standard way to get estimates of pharmacodynamic (PD) parameters of IRM consists of two steps. First, an appropriate parametric pharmacokinetic (PK) model (compartmental, polyexponential, etc.) is to be fitted to plasma concentration-time data, and then IRM is fitted to PD data having PD model as an input. In the present work it is demonstrated that a simple piecewise function which consists in interpolation lines connecting concentration-time points can be used as a universal nonparametric PK model thereby allowing to skip the first step. MS Excel spreadsheets implementing this PK model and four known versions of IRM are presented. The usefulness of the approach is demonstrated by fitting IRMs to simulated data as well as to real PK/PD data of warfarin and terbutaline. Estimates of IRM parameters obtained with the nonparametric PK model were close to that published in the literature.

Models, Biological↗

Novel semi-automated methodology for developing highly predictive QSAR models: application for development of QSAR models for insect repellent amides.

Conventional 3D-QSAR models are built using global minimum conformations or quantum-mechanics based geometry-optimized conformations as bioactive conformers. QSAR models developed using the global minima as bioactive conformers, employing the GFA, PLS and G/PLS methodologies, gave good non-validated r(2) (0.898, 0.868 and 0.922) and performed well on an internal validation test with leave-one-out correlation q(2) (LOO) (0.902, 0.726 and 0.924), leave-10%-out correlation q(2) (L10O) (0.874, 0.728 and 0.883) and leave-20%-out q(2) (L20O) (0.811, 0.716 and 0.907). However, they showed poor predictive ability on an external data set with best predictive r(2) (Pred-r(2)) of 0.349, 0.139 and 0.204 respectively. A novel methodology to mine bioactive conformers, from clusters of conformations with good 3D-spatial representation around pharmacophoric moiety, furnishes highly predictive 3D-QSAR models. The best QSAR model (model A) showed r(2) of 0.989, q(2) (LOO) of 0.989, q(2) (L10O) of 0.980, q(2) (L20O) of 0.963 and Pred-r(2) on eight test compounds of 0.845. The methodology is based on mimicking the multi-way Partial Least Squares (PLS) technique by performing several automated sequential PLS analyses. The poses/shapes of the mined bioactive conformers provide valuable insight into the mechanism of action of the insect repellents. All of the repetitive tasks were automated using Tcl-based Cerius2 scripts.

Algorithms↗

Pairwise fitting of mixed models for the joint modeling of multivariate longitudinal profiles.

A mixed model is a flexible tool for joint modeling purposes, especially when the gathered data are unbalanced. However, computational problems due to the dimension of the joint covariance matrix of the random effects arise as soon as the number of outcomes and/or the number of used random effects per outcome increases. We propose a pairwise approach in which all possible bivariate models are fitted, and where inference follows from pseudo-likelihood arguments. The approach is applicable for linear, generalized linear, and nonlinear mixed models, or for combinations of these. The methodology will be illustrated for linear mixed models in the analysis of 22-dimensional, highly unbalanced, longitudinal profiles of hearing thresholds.

Auditory Threshold↗