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PubMed1999

Modeling of surface myoelectric signals--Part I: Model implementation.

The relationships between the parameters of active motor units (MU's) and the features of surface electromyography (EMG) signals have been investigated using a mathematical model that represents the surface EMG as a summation of contributions from the single muscle fibers. Each MU has parallel fibers uniformly scattered within a cylindrical volume of specified radius embedded in an anisotropic medium. Two action potentials, each modeled as a current tripole, are generated at the neuromuscular junction, propagate in opposite directions and extinguish at the fiber-tendon endings. The neuromuscular junctions and fiber-tendon endings are uniformly scattered within regions of specified width. Muscle fiber conduction velocity and average fiber length to the right and left of the center of the innervation zone are also specified. The signal produced by MU's with different geometries and conduction velocities are superimposed. Monopolar, single differential and double differential signals are computed from electrodes placed in equally spaced locations on the surface of the muscle and are displayed as functions of any of the model's parameters. Spectral and amplitude variables and conduction velocity are estimated from the surface signals and displayed as functions of any of the model's parameters. The influence of fiber-end effects, electrode misalignment, tissue anisotropy, MU's location and geometry are discussed. Part II of this paper will focus on the simulation and interpretation of experimental signals.

Action Potentials↗

PubMed2006

Bayesian feature and model selection for Gaussian mixture models.

We present a Bayesian method for mixture model training that simultaneously treats the feature selection and the model selection problem. The method is based on the integration of a mixture model formulation that takes into account the saliency of the features and a Bayesian approach to mixture learning that can be used to estimate the number of mixture components. The proposed learning algorithm follows the variational framework and can simultaneously optimize over the number of components, the saliency of the features, and the parameters of the mixture model. Experimental results using high-dimensional artificial and real data illustrate the effectiveness of the method.

Algorithms↗

PubMed2006

Comparing the predictive value of neural network models to logistic regression models on the risk of death for small-cell lung cancer patients.

Cancer is one of the leading causes of mortality in the developed world, and prognostic assessment of cancer patients is indispensable in medical care. Medical researchers are accustomed to using regression models to predict patient outcomes. Neural networks have been proposed as an alternative with great potential. Nonetheless, empirical evidence remains lacking to support the application of this technique as the appropriate method to investigate cancer prognosis. Utilizing data on patients from two National Cancer Institute of Canada clinical trials, we compared predictive accuracy of neural network models and logistic regression models on risk of death of limited-stage small-cell lung cancer patients. Our results suggest that neural network and logistic regression models have similar predictive accuracy. The distributions of individual predicted probabilities are very similar. On occasion, however, the prediction pairs are quite different, suggesting that they do not always give the same interpretations of the same variables.

Adult↗

PubMed1995

A model of the active site of dipeptidyl peptidase IV predicted by comparative molecular field analysis and molecular modelling simulations.

A molecular model of the active site of the serine protease dipeptidyl peptidase IV (DPP IV or CD26) has been developed on the basis of comparative molecular field analysis (CoMFA) of competitive inhibitors and by force field calculations. By application of CoMFA experimentally obtained inhibition constants Ki have been successfully predicted. The resulting steric and electrostatic coefficients of CoMFA were used for the development of the molecular model. The main assumptions of the model are the recognition of substrates or inhibitors by the side chains of a tyrosine (S1-position) and a tryptophan residue (S2-position). The model helps us to understand a multitude of experimental data regarding the substrate specificity of this enzyme as well as results obtained by genetic engineering experiments by other authors. General conclusions concerning a new family of serine proteases are drawn and discussed.

Binding Sites↗

PubMed1994

Homology modelling of the catalytic domain of human furin. A model for the eukaryotic subtilisin-like proprotein convertases.

A model is presented for the three-dimensional structure of the catalytic domain of the human serine proteinase furin and its interaction with model substrates. This homology model is based on the crystal structures of subtilisin BPN' and thermitase in complex with the inhibitor eglin, and it also applies to other members of the eukaryotic subtilisin-like proprotein convertases. Predictions are made of the general protein fold, inserted loops, disulfide bonds, Ca(2+)-binding sites and salt bridges. A detailed prediction of the substrate-binding region attempts to explain the basis of specificity for multiple basic residues preceding the cleavage site. Specific acidic residues in the S1, S2 and S4 subsites of the substrate-binding region of furin are identified which appear to be of particular importance, while residues of the S2', S3, S5 and S6 subsites may also contribute to substrate binding. Based on this model, protein engineering can be employed not only to test the predicted enzyme-substrate interactions, as demonstrated for human furin, but, equally importantly, to design proprotein convertases with a desired specificity, or to design novel substrates or inhibitors.

Amino Acid Sequence↗

PubMed1991

Moving muscles with microchips, mathematics and models: an update on the 'reverse' model.

This paper reviews the current status of our computer model for the management of strabismus and its future direction. Vector analysis was first used in the 1950s for the assessment of strabismus. Robinson's model was the first computer simulation of ocular motility. Using physiological principles and anatomical approximations, Robinson's model sought to predict the strabismic pattern to be expected from a given injury. The Kault/Stark 'reverse' model works in the opposite direction, to first simulate the given strabismic pattern and then advise the surgery required to restore orthophoria. The surgeon is able to 'trial' various operations and compare the expected postoperative results. An automated system is currently being developed to ease the difficulty in measuring the position of the eyes in all nine positions of gaze. This paper includes three illustrative case reports.

Adolescent↗

PubMed1978

Choice of ascertainment model I. Discrimination between single-proband models by means of birth order data.

A statistical method for choosing between ascertainment models for human family data has been constructed. The families are assumed to have been ascertained through a single proband each and the birth number of the proband among the affected children is recorded. If the proband is the eldest affected child in each family the so-called complete ascertainment model has to be used. If each affected child has the same probability of being the proband, the so-called single ascertainment model should be used. In intermediate cases a third ascertainment model should be used.

Birth Order↗

PubMed2006

Random change point model for joint modeling of cognitive decline and dementia.

We propose a joint model for cognitive decline and risk of dementia to describe the pre-diagnosis phase of dementia. We aim to estimate the time when the cognitive evolution of subjects in the pre-dementia phase becomes distinguishable from normal evolution and to study whether the shape of cognitive decline depends on educational level. The model combines a piecewise polynomial mixed model with a random change point for the evolution of the cognitive test and a log-normal model depending on the random change point for the time to dementia. Parameters are estimated by maximum likelihood using a Newton-Raphson-like algorithm. The expected cognitive evolution given age to dementia is then derived and the marginal distribution of dementia is estimated to check the log-normal assumption.

Algorithms↗

PubMed1985

The Beavers-Timberlawn model of family competence and the circumplex model of family adaptability and cohesion: separate, but equal?

An empirical examination of the association between instruments measuring the Beavers-Timberlawn Model of family competence and the Circumplex Model of adaptability and cohesion is presented. Even when triangulated measures were utilized to control for the divergent methods of data collection traditionally employed to operationalize these models of family health, family competence as measured by the Beavers-Timberlawn Family Evaluation Scales was either minimally (mothers) or not associated at all (fathers and children) with balanced and thereby optimal dimensions of adaptability and cohesion as measured by the Family Adaptability and Cohesion Evaluation Scales. Methodological and substantive explanations for the surprising lack of association between measures of these two prominent family assessment models are explored and short- and long-range implications for the growth and practice of family therapy are discussed.

Adaptation, Psychological↗

PubMed2005

Improving predictive modeling in pediatric drug development: pharmacokinetics, pharmacodynamics, and mechanistic modeling.

A workshop was conducted on November 18-19, 2004, to address the issue of improving predictive models for drug delivery to developing humans. Although considerable progress has been made for adult humans, large gaps remain for predicting pharmacokinetic/pharmacodynamic (PK/PD) outcome in children because most adult models have not been tested during development. The goals of the meeting included a description of when, during development, infants/children become adult-like in handling drugs. The issue of incorporating the most recent advances into the predictive models was also addressed: both the use of imaging approaches and genomic information were considered. Disease state, as exemplified by obesity, was addressed as a modifier of drug pharmacokinetics and pharmacodynamics during development. Issues addressed in this workshop should be considered in the development of new predictive and mechanistic models of drug kinetics and dynamics in the developing human.

Adult↗

PubMed1996

A quantitative model of the "effective" signal processing in the auditory system. I. Model structure.

This paper describes a quantitative model for signal processing in the auditory system. The model combines a series of preprocessing stages with an optimal detector as the decision device. The present paper gives a description of the various preprocessing stages and of the implementation of the optimal detector. The output of the preprocessing stages is a time-varying activity pattern to which "internal noise" is added. In the decision process, a stored temporal representation of the signal to be detected (template) is compared with the actual activity pattern. The comparison amounts to calculating the correlation between the two temporal patterns and is comparable to a "matched filtering" process. The detector itself derives the template at the beginning of each simulated threshold measurement from a suprathreshold value of the stimulus. The model allows one to estimate thresholds with the same signals and psychophysical procedures as those used in actual experiments. In the accompanying paper [Dau et al., J. Acoust. Soc. Am. 99, 3623-3631 (1996)] data obtained for human observers are compared with the optimal-detector model for various masking conditions.

Auditory Perception↗

PubMed2005

Drosophila: a "model" model system to study neurodegeneration.

The fruit fly, Drosophila melanogaster, is a powerful model genetic organism that has been used since the turn of the previous century in the study of complex biological problems. In the last decade, numerous researchers have focused their attention on understanding neurodegenerative diseases by utilizing this model system. Numerous Drosophila mutants have been isolated that profoundly affect neural viability and integrity of the nervous system with age. Additionally, many transgenic strains have been developed as models of human disease conditions. We review the existing Drosophila neurodegenerative mutants and transgenic disease models, and discuss the role of the fruit fly in therapeutic development for neurodegenerative diseases.

Animals↗

PubMed1998

Minimal model of oscillations and waves in the Limax olfactory lobe with tests of the model's predictive power.

Propagating waves are observed in the olfactory or procerebral (PC) lobe of the terrestrial mollusk, Limax maximus. Wave propagation is altered by cutting through the various layers of the PC lobe both parallel and transverse to the direction of wave propagation. We present a model for the PC lobe based on two layers of coupled cells. The top layer represents the cell layer of the PC lobe, and the bottom layer corresponds to the neuropil of the PC lobe. To get wave propagation, we induce a coupling gradient so that the most apical cells receive a greater input from neighbors than the basal cells. The top layer in the model is composed of oscillators coupled locally, whereas the bottom layer is comprised of oscillators with global coupling. Odor stimulation is represented by an increase in the strength of coupling between the two layers. This model allows us to explain a number of experimental observations: 1) the intact PC lobe exhibits regular propagating waves, which travel from the apical to the basal end; 2) there is a gradient in the local frequency of slices cut transverse to the axis of wave propagation, with apical slices oscillating faster than basal slices; 3) with partial cuts through the cell layer or the neuropil layer, the apical and basal ends remain tightly coupled; 4) removal of the neuropil layer does not prevent wave propagation in the cell layer; 5) odor stimulation causes the waves to collapse and the cells in the PC lobe oscillate synchronously; and 6) by allowing a single parameter to vary in the model, we capture the reversal of waves in low chloride medium.

Animals↗

PubMed1992

Modelling survivorship kinetics: a two-parameter model.

A mathematical model of survivorship kinetics is presented. It takes into account both deterministic and stochastic aspects of survival curves. Earlier reports [Piantanelli: Arch Gerontol Geriatr 1986;5:107-118; Piantanelli: Ann NY Acad Sci 1988; 521:99-109] described a model capable of making distinct predictions on the mean and standard deviation of an index of physiological function, fitting data even in the tail of survivorship curves, and accounting for the selection of the cohort at advanced ages. However, it contains four parameters whose biological interpretation is unclear. In the present paper we propose a modification of the model which maintains the main characteristics of the previous one and, in addition, results in two significant improvements. First, the number of free parameters is reduced to only two, making much easier both their estimation and interpretation, particularly when the model is applied to data from various animal groups manipulated in different ways. Second, it is possible to relate the parameters to well-defined deterministic and stochastic factors: specifically, a deterministic component describing the environmental and genetic influence on physiological functions, and a stochastic component representing the fluctuating interactions of the living organism and its environment.

Aging↗

PubMedDate not supplied

A new model of bilateral hemispheric ischemia in the rat--three vessel occlusion model.

A new model of bilateral hemispheric ischemia was created in the rat by occluding the common carotid arteries and the basilar artery; this resulted in consistent and severe impairment of the cerebral blood flow. The procedure for producing this model is described, and the results of EEG and autoradiography obtained by this model are compared to those obtained by the four-vessel occlusion model.

Animals↗

PubMed1995

Therapeutic models of psychopathology. Part I: Introduction, overview of the model, and personality organization.

Part I of this paper introduces an integrated model of psychopathology that may be used as a guide for formulating a more specific model for patients in psychotherapy. This model considers the influence of biological and environmental factors in development, as well as the influence of the current environment on the psychological structure of the adult. It is compatible with a broader biological context and with current scientific thinking about the functioning of the human mind. Key principles in the development and functioning of the psychological organization of the individual are introduced. The central concept of Psychological Organization and the major dimensions of motivation, models of self and other, and information processing are discussed in detail.

Defense Mechanisms↗

PubMed2001

Pharmacodynamic modeling of lansoprazole using an indirect irreversible response model.

A mechanism-based pharmacokinetic/pharmacodynamic model was used to assess lansoprazole effects on gastric pH. The irreversible inactivation of the H+/K+-ATPase enzyme by lansoprazole controls the secretion rate of H+ ions and gastric pH values. The basal circadian rhythm of gastric acid production was taken into account as well as the effects of food intake. A model was applied to multiple-dose data from a crossover study of four dosage regimens of lansoprazole in two groups of normal male subjects. Model parameters were estimated by nonlinear regression and were compared to historical values reported in the literature. The predicted mean gastric ion concentration was 23.2 mM (pH 1.6) with the peak time at 12.6 hours (8:30 p.m.), and the half-time for H+ removal from the stomach averaged 1.7 hours. The estimated half-life of gastric food removal was 0.8 hours. The rate constant for normal H+/K+-ATPase degradation was 0.045 h(-1). The pharmacodynamic parameter describing lansoprazole action on gastric acid secretion was the second-order enzyme inactivation constant, which averaged 0.16 microg(-1) x L x h(-1). The parameters obtained for both the baseline and drug treatment data were consistent with the literature and physiologically relevant with the exception of effective food volume, which was large presumably due to buffer effects. The model successfully incorporated the physiological regulation of gastric acid production, the effects of food on gastric acid, and the effects of multiple-dosing regimens of lansoprazole on gastric acid production to give reasonable profiles of gastric pH.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1994

A comparison of two nursing models: Allen's developmental health model and Newman's theory of health as expanding consciousness.

Allen's developmental health model and Newman's theory of health as expanding consciousness are compared here with respect to their goals, theoretical influences, general orientations, and conceptualizations of the metaparadigm concepts of person, health, environment and nursing. While development of each of these models began around the same time (early 1970s) and each emphasizes health as the central concept, clear differences and relatively few similarities are evident. Each proposes that health is a process which evolves over time, yet conceptualization of these processes lies at the heart of the distinctiveness of the models. For Allen, health is a phenomenon of the family which can be developed through the learning of healthy behavior (coping and development skills). In Newman's view, health is not developed through behavior change but reflects increasing awareness of one's unitary pattern of interaction with the universe. Both models contribute to nursing science in a unique way by offering alternative perspectives of health and nursing and, for Allen, considering the family as the unit of concern.

Consciousness↗