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PubMed1988

[Models of the geometry of the human ankle bone pulley: two series of geometric models for demonstrating the biomechanics of the ankle joint].

2 series of models demonstrate the geometrical shape of the human trochlea tali. We have changed step by step the shape of the 2 flanking articular facets of the trochlea, the course of the edges of the trochlea, and the length of their radii, and so we have found a model responding to the biomechanic conditions of the trochlea tali. The convex surface of this model (corresponding to the superior articular surface, i.e. the facies superior trochleae tali) is a torse, the medial flanking facet (corresponding to the medial articular facet of the trochlea, i.e. the facies malleolaris medialis) is a flat cone, the lateral flanking facet (corresponding to the lateral articular facet of the trochlea, i.e. the facies malleolaris lateralis) is a screwed (helicoidal) face. The resulting model shows the 2 completely different phases of motion in the ankle joint: During dorsiflexion (motion setting out from the neutral position towards the final position of dorsiflexion), the internal malleolus leads the talus, whereas the external malleolus is pushed outwards by the screwed lateral articular facet of the trocheal. The trochlea is moved like a hinge. In the final position of dorsiflexion, the malleoli tightly embrace the 2 flanking facets of the trochlea, whilst an obvious cleft appears dorsally and medially between the superior articular surface of the trochlea and the tibial roof (i.e. the facies articularis inferior tibiae). During plantarflexion (motion setting out from the neutral position towards the final position of plantarflexion), the external malleolus leads the talus, whereas the medial articular facet of the trochlea withdraws from the internal malleolus. The trochlea is moved like a screw. In the final position of plantarflexion, the superior articular surface of the trochlea closely contacts the tibial roof, whilst an obvious cleft appears between the medial articular facet of the trochlea and the internal malleolus.

Ankle Joint↗

PubMed1988

[Modelling and simulation of urea balance in a rat model on the condition of large intestine infusion analogous to the ultrafiltrate as a contribution to the development of an implantable intestinal hybrid kidney].

The urea kinetics in blood plasma is discussed for the animal model in rats in the development conception of an implantable artificial kidney, in which the filtration process is received energetically endogenically by a technical hemofilter whereas the ultrafiltrate procedure takes place by intestinal reabsorption and elimination of the end-products. The underlying monocompartment model contains the elements plasma, hemofilter, intestine including their urea turnover rates. Further on a special model conception is developed for the animal experimental designation of the selective urea reflecting power of the intestinal mucosa. The hemofilter-intestine-hybrid kidney-system has chanced to be in order if the experimentally ascertained quantities of the preliminary experiments will be inserted simultaneously for essential parameters in the model experiment.

Animals↗

PubMed1985

The repair-misrepair model in radiobiology: comparison to other models.

Biological phenomena related to the inactivation of eukaryotic cells by noxious agents have been formulated mathematically in the repair-misrepair (RMR) model by separately quantitating the initial submicroscopic production of molecular lesions and the later, macroscopic expression of effects in the course of cell progression and repair. This paper presents some conceptual and quantitative similarities and differences between the RMR and seven other models proposed for cellular radiobiology including: the linear-quadratic, three-lambda, cubic-survival, target theory, hit-size probability, cybernetic, and lethal-potentially lethal models. The comparison of the various approaches has shown that the RMR model can be generalized to show relationships with each.

Animals↗

PubMed1979

[Production of infarction model in dogs by several brain arteries occlusion. Part 1: Production of hemispheric non blood supply model (author's transl)].

Experimental brain infarction in model animals should most ideally be constant in the site of occurrence, be of severity that is controllable by the occlusion time of blood flow and, moreover, be reproducible at a high rate to desired extent and severity. However, among infarction models elaborated in animals so far, only thalamus infarction model in dogs which were reported by us previously have been proven to satisfy almost all of these requirements. In experiments with these model dogs we found that an extensive infarction can be produced at a high frequency in the involved hemisphere by a transient occlusion of blood flow at such intracranial levels as the internal carotid artery, the junction of the anterior cerebral artery and ophthalmic artery, the middle cerebral artery, the origin of the segment A2 of the anterior cerebral artery, and the junction of the posterior communicating artery and posterior cerebral artery. During about one hour following the releasing of the arteries approximately 2 hours occlusion, the development of severe brain edema resulted involving the whole hemisphere on the affected side invariably in all cases. This method for experimental production of brain infarction permits to control the degree of resultant brain edema by changing the duration of occlusion of blood flow, requires simple manipulations only and ensures production of a constant lesion. With these advantage it can be anticipated to prove of great benefit in the study of postischemic brain edema.

Animals↗

PubMed1979

Further observations on modelling of the cardiovascular function in the electrical model.

In 1976 the fourth type of the electrical model of the cardiovascular function was constructed, showing formal and electronic changes: inverting system, hysteresis comparator (for the valve function), simulation of the insufficiency and the stenosis of the valves. The analog values were established but they are not yet definitive. The important values are: pressure 100 mm Hg = 100mV; flow 100 ml/sec = 137 microA. The action of the heart is given by changing capacity; the contractility is characterized by systolic capacity (CS). The diastolic capacity (CD) is not yet variable (CD = 4,000 microF) and consequently the diastolic pressure is always near to zero. The pressure curves of the left ventricle and of the aorta of cardiac patients with aortic valve disease were simulated. For comparison purposes only two clinical records and electrical model simulation records are given in this paper. In the patients (only aortic stenosis is given here) left heart catheterization was carried out. A case of coronary heart disease is also shown. The curves (simulated) are satisfactory and reflect the events in the compression chamber. The values of the parameters, which were used in the stimulation, represent the analysis of the clinical curves and a functional characterization of the situation. Besides these simulations the effect of valve changes on the pressure in the left ventricle, aorta and large arteries was also studied. With the aim of extending the integrative view of the use of the electrical model, an attempt of comparing the time course of capacity changes and the time course of inner surface changes of the left ventricle was made. The cinecardioangiographic data, obtained in an invasive way, were used for the purpose of obtaining the inner surface of the left ventricle. From pressure and surface data the cardiac forces (isometric, average and also total force per minute) were calculated and compared with the normal state, taken from the literature. The total force per minute includes the sum of systolic durations per minute and characterizes the energy expenses of the heart. Further data must be obtained by different cardiographic techniques in order to obtain a solid basis for the use of indirect methods, where the electrical model would be helpful as a noninvasive integrative tool in the assessment of the cardiovascular function.

Adult↗

PubMed1982

Mathematical modelling of the reaction latency. Part III: A model of avoidance reaction latency and avoidance learning.

The linear-dynamic-stochastic model of a reaction latency as applied to avoidance experiment is presented. Reactions are classified on the basis of the model into following classes: escape, avoidance, late avoidance, three types of inter-trial responses and "no reaction". The experimental latency distribution is split into latency distributions of the escape, avoidance and late avoidance responses, providing a new insight into latency distribution. The results of fitting the model to latency measurements obtained in the avoidance conditioning experiment are presented. The same processes of the parameter changes as in the escape conditioning are discovered, one causing a latency to decrease and the other causing a latency to increase during learning. The first process affects a latency stronger than the second and, consequently, the latency decreases during learning. The second process is responsible for a decay of inter trial-responses during experiment. The value of the correlation coefficient between the threshold of avoidance reaction and the threshold of escape reaction was also estimated. Negative values of this coefficient were obtained, therefore, on the average, the greater the avoidance reaction threshold the smaller the escape one. In the course of learning the correlation coefficient tends to be equal to - 1, i.e., as a result of training, both thresholds became dependent in a functional (non-random) way. This result may provide an objective index of the "state of learning". The model provides a new tool for analysis of results of latency-based experiments.

Animals↗

PubMed1995

Model selection for extended quasi-likelihood models in small samples.

We develop a small sample criterion (AICc) for the selection of extended quasi-likelihood models. In contrast to the Akaike information criterion (AIC). AICc provides a more nearly unbiased estimator for the expected Kullback-Leibler information. Consequently, it often selects better models than AIC in small samples. For the logistic regression model, Monte Carlo results show that AICc outperforms AIC, Pregibon's (1979, Data Analytic Methods for Generalized Linear Models. Ph.D. thesis. University of Toronto) Cp*, and the Cp selection criteria of Hosmer et al. (1989, Biometrics 45, 1265-1270). Two examples are presented.

Age Factors↗

PubMed1995

Tailoring nursing models to clients' needs. Using the Roper, Logan and Tierney model after discharge.

1. The use of nursing models and the nursing process in any setting must be justified by their value for clients. 2. If no empirical evidence confirms the worth of a particular model, it is the responsibility of nurses to determine the value of the model used in their own setting. 3. Models should be adapted to the patient setting, and seen as a tool rather than applied ritualistically.

Health Services Needs and Demand↗

PubMed1977

Some properties of a "G0" -model of the cell cycle. II. Natural constraints on the theoretical model in exponential growth conditions.

The two-phase (G and C phases) model first proposed by Burns & Tannock (1970) to describe the cell cycle kinetics has the major advantage of requiring only two parameters for a complete description of the kinetic behaviour of populations that are in a steady-state, or that grow exponentially (with no cell loss from the population). Steady-state populations were examined in paper I of this series. Exponential populations with no cell loss are investigated here. The model assumes two basic kinetic states--a 'C' phase which includes S, G2, M and perhaps part of G1, and a 'G' phase which cells enter after completing the C-phase and from which either are lost or return to C-phase randomly. The model assumes that transit time through C-phase is constant for all cells in the population. An original method is described which allows the determination of two independent parameters of the model from the experimental 'fraction of labelled mitoses' (FLM) curve; From those two parameters, the ratio of G-cells among the total number of cells (NG/N) has been calculated for each cell population studied, The range of the NG/N values thus obtained is fairly restricted, and the mean NG/N value for exponential growths is not statistically different from that found in steady-states considering in that case the only sub-population of cycling cells (i.e. the cells that will undergo a further mitosis).

Animals↗

PubMed2000

Modelling in tumour biology part 1: modelling concepts and structures.

Our strategies for the treatment of cancer are constrained by our incomplete understanding of tumour biology and behaviour, and by the enormous complexity and resilience to therapeutic perturbation found in the biological world. We are obliged to simplify this complexity through the use of models and mechanistic explanations. In the first of these papers, we consider the nature of modelling mechanisms available to clinical researchers and the extent to which we rely upon them in our understanding of the nature and behaviour of tumours. In the second part, we will consider specifically how models help us to develop more effective strategies for cancer therapy.

Algorithms↗

PubMed2004

Conditional estimation for generalized linear models when covariates are subject-specific parameters in a mixed model for longitudinal measurements.

The relationship between a primary endpoint and features of longitudinal profiles of a continuous response is often of interest, and a relevant framework is that of a generalized linear model with covariates that are subject-specific random effects in a linear mixed model for the longitudinal measurements. Naive implementation by imputing subject-specific effects from individual regression fits yields biased inference, and several methods for reducing this bias have been proposed. These require a parametric (normality) assumption on the random effects, which may be unrealistic. Adapting a strategy of Stefanski and Carroll (1987, Biometrika74, 703-716), we propose estimators for the generalized linear model parameters that require no assumptions on the random effects and yield consistent inference regardless of the true distribution. The methods are illustrated via simulation and by application to a study of bone mineral density in women transitioning to menopause.

Biometry↗

PubMed2001

The mucosal invasion model: a novel in vitro model for evaluating the invasive behavior of mucocutaneous malignancies.

BACKGROUND: Prevention of regional and metastatic spread of cutaneous malignancies requires understanding the physiologic mechanism of tumor cell invasion. In vitro models are convenient for studying the in vitro invasive phenotype of normal cells, tumor cell lines, or genetically altered cells in a 3-dimensional matrix, but they should attempt to recapitulate the complex in vivo submucosal environment. A new acellular extracellular matrix, porcine submucosal matrix (PSM), is thought to accurately recapitulate the submucosal matrix. A novel in vitro model using PSM to assess mucocutaneous tumor cell invasion was studied. METHODS: The morphologic characteristics, growth, and invasive behavior of human head and neck squamous cell carcinoma (UM-SCC-1, UM-SCC-5, UM-SCC-17B, and OSC-19) cell lines were assessed on the PSM gel and compared with commonly used in vitro invasion models (type I collagen and Matrigel matrices). The invasive phenotype of canine kidney cells was also assessed on each matrix, because this cell line is known to demonstrate a characteristic in vitro invasive phenotype. RESULTS: The PSM-supported head and neck squamous cell carcinoma tumor cell line growth and single cell invasion were seen under stimulated conditions, similar to type I collagen gels. The invasive phenotype of canine kidney cells behaved similarly on PSM and collagen. Matrigel did not support growth well, and invasion occurred only superficially in isolated areas. CONCLUSION: The PSM is a good in vitro model for assessment of pharmacologic and genetic manipulations of head and neck squamous cell carcinoma tumor cell lines and has several advantages over other commonly used matrices.

Animals↗

PubMed1999

Model-based and model-free multipoint genome-wide linkage analysis of alcoholism.

We analyzed a subset of the Collaborative Study on the Genetics of Alcoholism (COGA) data set as provided by the 11th Genetic Analysis Workshop (GAW11). Linkage analyses were performed using each of the diagnostic criteria for alcoholism included in the data: the COGA criteria (DSM-III-R plus the Feighner criteria) and the narrower World Health Organization diagnosis ICD-10 criteria. Formal segregation analysis using these data was not attempted because only a subset of all the originally ascertained families was made available. Nevertheless, an attempt was made to estimate the best one-locus two-allele genetic model for these data. Model-based multipoint linkage analysis was performed using the results of our trait model fitting, and model-free multipoint linkage analysis was performed with an improved version of the Haseman and Elston linkage method for sib pairs.

Adolescent↗

PubMed1996

Analog Imagery in Mental Model Reasoning: Depictive Models

We investigated whether people can use analog imagery to model the behavior of a simple mechanical interaction. Subjects saw a static computer display of two touching gears that had different diameters. Their task was to determine whether marks on each gear would meet if the gears rotated inward. This task added a problem of coordination to the typical analog rotation task in that the gears had a physical interdependency; the angular velocity of one gear depended on the angular velocity of the other gear. In the first experiment, we found the linear relationship between response time and angular disparity that indicates analog imagery. In the second experiment, we found that people can also solve the problem through a non-analog, visual comparison. We also found that people of varying spatial ability could switch between analog and non-analog solutions if instructed to do so. In the third experiment, we examined whether the elicitation of physical knowledge would influence solution strategies. To do so, we manipulated the visual realism of the gear display. Subjects who saw the most realistic gears coordinated their transformations by using the surfaces of the gears, as though they were relying on the friction connecting the surfaces. Subjects who saw more schematic displays relied on analytic strategies, such as comparing the ratios made by the angles and/or diameters of the two gears. To explain the relationship between spatial and physical knowledge found in the experiments, we constructed a computer simulation of what we call depictive modeling. In a depictive model, general spatial knowledge and context-sensitive physical knowledge have the same ontology. This is different from prior simulations in which a non-analog representation would be needed to coordinate the analog behaviors of physical objects. In our simulation, the inference that coordinates the gear motions emerges from the analog rotations themselves. We suggest that mental depictions create a bridge between imagery and mental model research by positing the referent as the primary conceptual entity.

Journal Article↗

PubMed2000

Model Comparisons and Model Selections Based on Generalization Criterion Methodology.

The purpose of this article is to formalize the generalization criterion method for model comparison. The method has the potential to provide powerful comparisons of complex and nonnested models that may also differ in terms of numbers of parameters. The generalization criterion differs from the better known cross-validation criterion in the following critical procedure. Although both employ a calibration stage to estimate parameters, cross-validation employs a replication sample from the same design for the validation stage, whereas generalization employs a new design for the critical stage. Two examples of the generalization criterion method are presented that demonstrate its usefulness for selecting a model based on sound scientific principles out of a set that also contains models lacking sound scientific principles that are either overly complex or oversimplified. The main advantage of the generalization criterion is its reliance on extrapolations to new conditions. After all, accurate a priori predictions to new conditions are the hallmark of a good scientific theory. Copyright 2000 Academic Press.

Journal Article↗

PubMed1984

Analysis of variability in albumin content of sister hepatoma cells and a model for geometric phenotypic variability (quantitative shift model).

A model (quantitative shift model) is presented that can account for the phenomenon termed geometric phenotypic variability in which quantitative variation occurs along a square root 2-fold geometric series. The model is based on data for variability in albumin content in hepatoma cells and has three basic assumptions: (i) The albumin genes on each chromosome are active and under independent quantitative regulation. (ii) The rate of albumin gene transcription per cell is the sum of the rates of transcription of the genes of each chromosome. (iii) The mechanism that controls the rate of transcription is highly variable so that at each cell cycle there is a high probability (P = 0.1-0.3) that on the newly synthesized chromatid the rate of transcription of the albumin gene will be different from that of the old chromatid. However, if the rate is different, it will usually be either half or twice the levels of the old chromatid. A computer program was developed based on the model that can generate quantitative diversity in single cells that mimics the pattern of variability in albumin content between sister hepatoma cells, among cells in clonal colonies, and in cell populations where the periodicities in single-cell distributions are compared by Fourier transform analysis. It was determined that the rate of phenotypic variability is indirectly proportional to the magnitude of the quantitative shift in albumin content and that it can be as high as 0.3 per cell per generation. Also, the square root 2 factor in geometric phenotypic variability appears to be an average of a family of values and not the actual value of the smallest quantal shift.

Animals↗

PubMed2002

[Mechanical testing of implant properties of thoracoscopic implantation of ventral spinal stabilizing systems. Comparative study with the ISO/DIS 12189-2 corpectomy model and an improved synthetic model].

A new modular anterior fixation system MACS TL (modular anterior construct system for the thoracic and lumbar spine) has been developed for use in thoracoscopic spondylodesis. This system demonstrates high angular stability and meets the surgical requirements for an endoscopic approach. The objective of the current study was fatigue testing of the MACS TL implant system using a corpectomy model according to ISO/DIS 12189-2 and a synthetic model recently developed by Kotani et al. [6]. The MACS TL system demonstrated good mechanical properties with a high stiffness compared to the published data reviewed. The importance of dynamic testing in a corpectomy model has been demonstrated by comparing the MACS TL plate system with an early prototype, which has not yet been clinically evaluated. The corpectomy model according to Kotani et al. offers an interesting alternative to the ISO/DIS 12189-2 test method for asymmetrically designed and antero-laterally positioned spinal implants due to the unconstrained ball joint.

Biomechanical Phenomena↗

PubMed2003

Evolution of the brain tumour spheroid model: transcending current model limitations.

Tumour recurrence and the high mortality and morbidity associated with malignant brain tumours may be attributed to the failure of current therapeutic modalities (surgery, radiation and chemotherapy) to control the invasion of malignant brain tumour cells into healthy brain tissue. Several in vitro and in vivo models have been developed and used to study brain tumour invasion and cell motility. Here, we review some of the traditional in vitro models of brain tumour invasion and the latest adaptations to the widely used spheroid model. Several research groups studying the mechanisms mediating brain tumour invasion have made important contributions to the field by improving in vitro models of tumour migration and invasion. Sharing these advances will hopefully accelerate experimental discovery and the development of novel anti-invasion brain tumour therapies.

Brain Neoplasms↗