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PubMed1996

Development of an atmospheric 222Rn concentration model using a hydrodynamic meteorological model: II. Three-dimensional research-purpose model.

This paper describes a new type of three-dimensional numerical model for 222Rn transport in an atmospheric boundary layer. The model is a combination of a prognostic hydrodynamic meteorological model including a turbulence closure model and an atmospheric diffusion model for 222Rn. The first part provides the second part with the meteorological conditions needed for calculations of the 222Rn transport and diffusion. The model is capable of giving consideration to horizontal source distribution, complex terrain, and non-uniform and non-steady atmosphere. The model's results were compared with 222Rn field measurements in a mountain-valley area and represented qualitatively a typical diurnal variation of the 222Rn concentration in nocturnal drainage flows. The model was also applied to the transport of 222Rn in a seacoast area. These results indicated that the model could be effective as a research tool for numerical analysis of 222Rn behavior under various atmospheric conditions.

Air Pollutants, Radioactive↗
PubMed2006

From spiking neurons to rate models: a cascade model as an approximation to spiking neuron models with refractoriness.

A neuron that is stimulated repeatedly by the same time-dependent stimulus exhibits slightly different spike timing at each trial. We compared the exact solution of the time-dependent firing rate for a stochastically spiking neuron model with refractoriness (spike response model) with that of an inhomogeneous Poisson process subject to the same stimulus. To arrive at a mapping between the two models we used alternatively (i) a systematic parameter-free Volterra expansion of the exact solution or (ii) a linear filter combined with nonlinear Poisson rate model (linear-nonlinear Poisson cascade model) with a single free parameter. Both the cascade model and the second-order Volterra model showed excellent agreement with the exact rate dynamics of the spiking neuron model with refractoriness even for strong and rapidly changing input. Cascade rate models are widely used in systems neuroscience. Our method could help to connect experimental rate measurements to the theory of spiking neurons.

Action Potentials↗
PubMed2006

Ordinal regression model and the linear regression model were superior to the logistic regression models.

OBJECTIVE: Ordinal scales often generate scores with skewed data distributions. The optimal method of analyzing such data is not entirely clear. The objective was to compare four statistical multivariable strategies for analyzing skewed health-related quality of life (HRQOL) outcome data. HRQOL data were collected at 1 year following catheterization using the Seattle Angina Questionnaire (SAQ), a disease-specific quality of life and symptom rating scale. STUDY DESIGN AND SETTING: In this methodological study, four regression models were constructed. The first model used linear regression. The second and third models used logistic regression with two different cutpoints and the fourth model used ordinal regression. To compare the results of these four models, odds ratios, 95% confidence intervals, and 95% confidence interval widths (i.e., ratios of upper to lower confidence interval endpoints) were assessed. RESULTS: Relative to the two logistic regression analysis, the linear regression model and the ordinal regression model produced more stable parameter estimates with smaller confidence interval widths. CONCLUSION: A combination of analysis results from both of these models (adjusted SAQ scores and odds ratios) provides the most comprehensive interpretation of the data.

Adolescent↗
PubMed2000

Analysis of urea nitrogen and creatinine kinetics in hemodialysis: comparison of a variable-volume two-compartment model with a regional blood flow model and investigation of an appropriate solute kinetics model for clinical application.

To investigate an appropriate solute kinetics model for clinical application, we analyzed urea nitrogen (UN) and creatinine (Cr) kinetics by a variable-volume two-compartmental model (2CM) and a regional blood flow model (RBF) in 44 hemodialysis patients with varying proportions of first compartmental volume and regional volume (p(1)). Solute kinetics could not be solved in some of the patients with higher p(1) values, and there were more solution failures by the RBF than by the 2CM. The solute generation rate (g) and solute distribution volume in the dry state (V(D)) increased with increases in p(1) in both models, but there were some differences between the two models. When g was normalized by V(D), it became relatively constant, irrespective of the p(1) value or model used (0.133 +/- 0.029 mg/min/l by the 2CM and 0.132 +/- 0.029 mg/min/l by the RBF for UN; 0.0200 +/- 0.0049 mg/min/l by the 2CM and 0.0198 +/- 0.0048 mg/min/l by the RBF for Cr). The intercompartmental mass transfer coefficient (K(c); liters/min) calculated by the 2CM decreased as p(1) increased (K(c) = -1.77.p(1) + 1.16, p < 0.0001, R = 0.999 for UN; K(c) = -0.847.p(1) + 0.556, p < 0.0001, R = 1.000 for Cr). The systemic blood flow (Q(sys); liters/min) calculated by the RBF also decreased as p(1) increased (Q(sys) = -11.1.p(1) + 6.21, p < 0.0005, R = 1.000 for UN; Q(sys) = -5.22.p(1) + 2.90, p < 0.001, R = 0.999 for Cr). Since the RBF more frequently failed to solve the solute kinetics and since there was a difference in its Q(sys) values for UN and Cr, the 2CM was considered to be a superior model. When p(1) was extremely low, the 2CM could be transformed into a modified variable-volume one-compartment model (1CM) which presented a similar g/V(D) (0.133 +/- 0.029 for UN; 0.0200 +/- 0.0048 for Cr). This modified 1CM was considered to satisfy appropriate conditions for clinical application, since it is simpler than the 2CM and provides useful information on the dialysis dose.

Aged↗
PubMed2001

Investigation of 5-FU disposition after oral administration of capecitabine, a triple-prodrug of 5-FU, using a physiologically based pharmacokinetic model in a human cancer xenograft model: comparison of the simulated 5-FU exposures in the tumour tissue between human and xenograft model.

The nonlinear pharmacokinetics of capecitabine, a triple prodrug of 5-FU preferentially activated in tumour tissues, was investigated in human cancer xenograft models. A physiologically based pharmacokinetic (PBPK) model integrating the activation process of capecitabine to 5-FU and 5-FU elimination was constructed to describe the concentration/time profiles of capecitabine and its three metabolites, including 5-FU, in blood and organs. All the biochemical parameters (enzyme kinetic parameters, plasma protein binding and tissue binding of capecitabine and its metabolites) integrated in this model were measured in vitro. The simulated curves for the blood and tumour concentrations of capecitabine and its metabolites can basically describe the observed values. A simple prodrug of 5-FU, doxifluridine, is known to be activated to 5-FU to some extent in the gastrointestinal (GI) tract, causing diarrhoea, which is the dose limiting side effect of doxifluridine. Consequently, the therapeutic index (the ratio of 5-FU AUC in the tumour to that in GI) after the administration of effective dose capecitabine was predicted by this PBPK model and found to be five times and 3000 times greater than that of doxifluridine and 5-FU, respectively. This was compatible with the previous result for the difference in the ratio of the toxic dose to the minimum effective dose between capecitabine and doxifluridine, suggesting that 5-FU preferentially accumulates in tumour tissue after oral administration of capecitabine compared with the other drugs (doxifluridine and 5-FU). The 5-FU AUC in tumour tissue of human cancer xenograft models at the minimum effective dose was comparable with those estimated for humans at the clinical dose. In addition, the predicted therapeutic indices at the respective doses were correlated well between humans and mice (xenograft model). These results suggest that the 5-FU AUC in human tumour tissue at its clinically effective dose can be predicted based on the PBPK model inasmuch as the 5-FU AUC in a human cancer xenograft model at its effective dose may be measured or simulated.

Administration, Oral↗
PubMed1983

Family models: comparing and contrasting the Olson Circumplex Model with the Beavers Systems Model.

There is an increasing interest in and need for family models. One such model is the Olson Circumplex Model, previously reported in this journal (18). This model is compared and contrasted with the Beavers Systems Model, which was also developed from empirical data and has had extensive use in family assessment. Though both are cross-sectional, process-oriented, and capable of providing structure for family research, we believe there are certain short-comings in the Olson model that make it less clinically useful than the Beavers Systems Model. These include definitional problems and a total reliance on curvilinear dimensions with a grid approach to family typology that does not acknowledge a separation/individuation continuum. Our model avoids these deficiencies and includes a continuum of functional competence that reflects the development and differentiation of many living systems, including the family.

Adaptation, Psychological↗
PubMed1991

Two models of brief strategic therapy: the MRI model and the de Shazer model.

This paper presents and compares two models of brief strategic therapy: the MRI model, and the de Shazer model. Both models were implemented simultaneously in a community mental health child clinic. Each model is presented, and then illustrated by a case study. Apparent are the benefits that can be gained through exposure to each model, and the point that premature integration of the models might detract from the processes. The staff members' experience with the two models, and the differences in the therapist attitude are discussed.

Child↗
PubMed2003

Fitting genetic models to twin data with binary and ordered categorical responses: a comparison of structural equation modelling and Bayesian hierarchical models.

We compare Bayesian methodology utilizing free-ware BUGS (Bayesian Inference Using Gibbs Sampling) with the traditional structural equation modelling approach based on another free-ware package, Mx. Dichotomous and ordinal (three category) twin data were simulated according to different additive genetic and common environment models for phenotypic variation. Practical issues are discussed in using Gibbs sampling as implemented by BUGS to fit subject-specific Bayesian generalized linear models, where the components of variation may be estimated directly. The simulation study (based on 2000 twin pairs) indicated that there is a consistent advantage in using the Bayesian method to detect a "correct" model under certain specifications of additive genetics and common environmental effects. For binary data, both methods had difficulty in detecting the correct model when the additive genetic effect was low (between 10 and 20%) or of moderate range (between 20 and 40%). Furthermore, neither method could adequately detect a correct model that included a modest common environmental effect (20%) even when the additive genetic effect was large (50%). Power was significantly improved with ordinal data for most scenarios, except for the case of low heritability under a true ACE model. We illustrate and compare both methods using data from 1239 twin pairs over the age of 50 years, who were registered with the Australian National Health and Medical Research Council Twin Registry (ATR) and presented symptoms associated with osteoarthritis occurring in joints of the hand.

Bayes Theorem↗
PubMed2004

Geo-referenced multimedia environmental fate model (G-CIEMS): model formulation and comparison to the generic model and monitoring approaches.

A spatially resolved and geo-referenced dynamic multimedia environmental fate model, G-CIEMS (Grid-Catchment Integrated Environmental Modeling System) was developed on a geographical information system (GIS). The case study for Japan based on the air grid cells of 5 x 5 km resolution and catchments with an average area of 9.3 km2, which corresponds to about 40,000 air grid cells and 38,000 river segments/catchment polygons, were performed for dioxins, benzene, 1,3-butadiene, and di-(2-ethyhexyl)phthalate. The averaged concentration of the model and monitoring output were within a factor of 2-3 for all the media. Outputs from G-CIEMS and the generic model were essentially comparable when identical parameters were employed, whereas the G-CIEMS model gave explicit information of distribution of chemicals in the environment. Exposure-weighted averaged concentrations (EWAC) in air were calculated to estimate the exposure ofthe population, based on the results of generic, G-CIEMS, and monitoring approaches. The G-CIEMS approach showed significantly better agreement with the monitoring-derived EWAC than the generic model approach. Implication for the use of a geo-referenced modeling approach in the risk assessment scheme is discussed as a generic-spatial approach, which can be used to provide more accurate exposure estimation with distribution information, using generally available data sources for a wide range of chemicals.

Benzene↗
PubMed2006

Dynamic modelling and analysis of biochemical networks: mechanism-based models and model-based experiments.

Systems biology applies quantitative, mechanistic modelling to study genetic networks, signal transduction pathways and metabolic networks. Mathematical models of biochemical networks can look very different. An important reason is that the purpose and application of a model are essential for the selection of the best mathematical framework. Fundamental aspects of selecting an appropriate modelling framework and a strategy for model building are discussed. Concepts and methods from system and control theory provide a sound basis for the further development of improved and dedicated computational tools for systems biology. Identification of the network components and rate constants that are most critical to the output behaviour of the system is one of the major problems raised in systems biology. Current approaches and methods of parameter sensitivity analysis and parameter estimation are reviewed. It is shown how these methods can be applied in the design of model-based experiments which iteratively yield models that are decreasingly wrong and increasingly gain predictive power.

Algorithms↗
PubMed1996

Development of an atmospheric 222Rn concentration model using a hydrodynamic meteorological model: I. One-dimensional practical model.

A one-dimensional numerical model for 222Rn transport in an atmospheric boundary layer was developed. The model consists of two parts: a prognostic hydrodynamic model including a turbulence closure model and an atmospheric diffusion model for 222Rn. The first part predicts meteorological conditions to provide the second part with vertical turbulence conditions which affects the vertical motion of 222Rn near the Earth's surface. Calculations with the model are compared with 222Rn concentrations measured during a variety of meteorological conditions, from clear days with high radiation and low winds to cloudy days of low radiation with high winds. The model's results represent well the typical diurnal variations of the 222Rn concentrations.

Air Pollutants, Radioactive↗
PubMed1998

Model-based, goal-oriented, individualised drug therapy. Linkage of population modelling, new 'multiple model' dosage design, bayesian feedback and individualised target goals.

This article examines the use of population pharmacokinetic models to store experiences about drugs in patients and to apply that experience to the care of new patients. Population models are the Bayesian prior. For truly individualised therapy, it is necessary first to select a specific target goal, such as a desired serum or peripheral compartment concentration, and then to develop the dosage regimen individualised to best hit that target in that patient. One must monitor the behaviour of the drug by measuring serum concentrations or other responses, hopefully obtained at optimally chosen times, not only to see the raw results, but to also make an individualised (Bayesian posterior) model of how the drug is behaving in that patient. Only then can one see the relationship between the dose and the absorption, distribution, effect and elimination of the drug, and the patient's clinical sensitivity to it; one must always look at the patient. Only by looking at both the patient and the model can it be judged whether the target goal was correct or needs to be changed. The adjusted dosage regimen is again developed to hit that target most precisely starting with the very next dose, not just for some future steady state. Nonparametric population models have discrete, not continuous, parameter distributions. These lead naturally into the multiple model method of dosage design, specifically to hit a desired target with the greatest possible precision for whatever past experience and present data are available on that drug--a new feature for this goal-oriented, model-based, individualised drug therapy. As clinical versions of this new approach become available from several centers, it should lead to further improvements in patient care, especially for bacterial and viral infections, cardiovascular therapy, and cancer and transplant situations.

Anti-Arrhythmia Agents↗
PubMed1993

[From multiple regression analysis to logistic model, proportional hazard model and log linear model. Its concept and application].

Recently logistic model, proportional hazard model and log linear model have been used frequently in the medical literatures. Here, each model is reviewed briefly from basics to its application, pointing out pitfalls in its application, some of which are common to any regression analysis. The logistic model is especially useful for the analysis of retrospective data where odds ratio is utilized to evaluate the outcome probability. On the other hand, proportional hazard model is useful when we analyze censored data, utilizing hazard function. Log linear model has been used where contingency table has more than three independent variables, the situation where its applicability in clinical medicine is wide. Familiarity with these statistical methods would enable us to evaluate data more effectively and efficiently and ultimately to read literature more easily.

Models, Statistical↗
PubMed2005

Association between psychosocial job characteristics and insomnia: an investigation using two relevant job stress models--the demand-control-support (DCS) model and the effort-reward imbalance (ERI) model.

BACKGROUND AND PURPOSE: The details of risky psychosocial job characteristics related to insomnia are unclear, although potential relationships between the two have been suggested. The study objective was to clarify these relationships by using the demand-control-support (DCS) model and the effort-reward imbalance (ERI) model. PATIENTS AND METHODS: A cross-sectional questionnaire survey was conducted with 1081 middle-aged (39 years and older) workers in a corporate group of electric products in Osaka, Japan. The study variables included insomnia symptoms (non-refreshing sleep, difficulty falling asleep, frequent sleep disruption, and early morning arousal) and psychosocial job characteristics which were evaluated using the DCS and ERI models, gender, age, disease, sleep-related factors, occupational status, and health practices. RESULTS: ERI [odds ratio (95% confidence interval): 2.27 (1.43, 3.60)], overcommitment [1.86 (1.40, 2.47)], and high job strain [1.55 (1.12, 2.15)] were independently associated with insomnia. The odds ratio of insomnia for individuals with high job strain was increased by adding ERI or overcommitment. CONCLUSIONS: The ERI and DCS models describe the adverse psychosocial job characteristics related to insomnia. Simultaneously employing these two models is more useful than employing a single model to identify workers at risk of insomnia. The conceptual framework derived from the job stress models assists in defining preventive measures for insomnia in workers.

Adult↗
PubMed1997

Using models to explore whole-body metabolism and accessing models through a model library.

A model is a mathematical representation of a system that can be used to explore the system in a number of ways: to determine the system's internal connections, to calculate properties of the system such as flow rates and pool sizes, and to make predictions about the system's behavior under different conditions. The use of modeling to explore whole-body metabolism is demonstrated using a compartmental model of zinc kinetics as an example. Because models are useful tools for exploring systems, a facility called a "model library" is being established on the Internet to provide access to working versions of published models.

Animals↗
PubMed2004

Modeling of dry sliding friction dynamics: from heuristic models to physically motivated models and back.

After giving an overview of the different approaches found in the literature to model dry friction force dynamics, this paper presents a generic friction model based on physical mechanisms involved in the interaction of a large population of surface asperities and discusses the resulting macroscopic friction behavior. The latter includes the hysteretic characteristic of friction in the presliding regime, the velocity weakening and strengthening in gross-sliding regime, the frictional lag and the stick-slip behavior. Out of the generic model, which is shown to be a good, but rather computationally intensive, simulation tool, a simpler heuristic model, which we call the generalized Maxwell-slip friction, is deduced. This model is appropriate for quick simulation and control purposes being easy to implement and to identify. Both of the generic and heuristic model structures are compared, through simulations, with each other and with experimental data.

Journal Article↗
PubMed2006

Animal models for the study of squamous cell carcinoma of the upper aerodigestive tract: a historical perspective with review of their utility and limitations. Part A. Chemically-induced de novo cancer, syngeneic animal models of HNSCC, animal models of transplanted xenogeneic human tumors.

Understanding the complex histological, genetic and molecular changes that lead to malignant transformation of squamous epithelia of the head and neck will likely guide the development of methods for improved diagnosis, monitoring and treatment of head and neck squamous cell carcinoma (HNSCC). The development and use of animal models that closely mimic the histopathology and molecular pathogenesis of HNSCC in humans would greatly expand the research possibilities and provide a means of testing potential therapeutic agents. However, many available animal models of HNSCC fall short of this objective. In order for investigators to select the appropriate model to answer scientific questions, it is important to understand the benefits and limitations of available animal models for the study of HNSCC. The purpose of this work is to give an overview of the most pertinent animal models of HNSCC, and to discuss future directions of research in this field.

Animals↗
PubMedDate not supplied

NADH-Regulated metabolic model for growth of Methylosinus trichosporium OB3b. Model presentation, parameter estimation, and model validation.

A biochemical model is presented that describes growth of Methylosinus trichosporium OB3b on methane. The model, which was developed to compare strategies to alleviate NADH limitation resulting from cometabolic contaminant conversion, includes (1) catabolism of methane via methanol, formaldehyde, and formate to carbon dioxide; (2) growth as formaldehyde assimilation; and (3) storage material (poly-beta-hydroxybutyric acid, PHB) metabolism. To integrate the three processes, the cofactor NADH is used as central intermediate and controlling factor-instead of the commonly applied energy carrier ATP. This way a stable and well-regulated growth model is obtained that gives a realistic description of a variety of steady-state and transient-state experimental data. An analysis of the cells' physiological properties is given to illustrate the applicability of the model. Steady-state model calculations showed that in strain OB3b flux control is located primarily at the first enzyme of the metabolic pathway. Since no adaptation in V(MAX) values is necessary to describe growth at different dilution rates, the organism seems to have a "rigid enzyme system", the activity of which is not regulated in response to continued growth at low rates. During transient periods of excess carbon and energy source availability, PHB is found to accumulate, serving as a sink for transiently available excess reducing power.

Biotechnology↗