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The Asian Epidemic Model: a process model for exploring HIV policy and programme alternatives in Asia.

Process models offer opportunities to explore the effectiveness of different programme and policy alternatives by varying input behaviours and model parameters to reflect programmatic/policy effects. The Asian Epidemic Model (AEM) has been designed to reflect the primary groups and transmission modes driving HIV transmission in Asia. The user adjusts AEM fitting parameters until HIV prevalence outputs from the model agree with observed epidemiological trends. The AEM resultant projections are closely tied to the epidemiological and behavioural data in the country. In Thailand and Cambodia they have shown good agreement with observed epidemiological trends in surveillance populations and with changes in HIV transmission modes, AIDS cases, male:female ratios over time, and other external validation checks. By varying the input behaviours and STI trends, one can examine the impact of different prevention efforts on the future course of the epidemic. In conclusion, the AEM is a semi-empirical model, which has worked well in Asian settings. It provides a useful tool for policy and programme analysis in Asian countries.

Asia↗

A three-dimensional motion model of loads on the lumbar spine: II. Model validation.

A three-dimensional motion model has been developed that estimates loads on the lumbar spine under laboratory conditions that simulate manual materials handling conditions. Eleven subjects experienced spinal loading during an experiment in which conditions of trunk velocity, trunk torque output, and trunk asymmetric posture were varied in a series of isokinetic velocity trunk extensions. The electromyographic activity of 10 trunk muscles, subject anthropometry, and trunk kinetics were used as input to a biomechanical simulation model described in Part I of this study. The model calculated estimates of compression, shear, and torsion loading in the lumbar spine, as well as the torque production of the trunk, continuously throughout the exertion. Trunk torque estimates derived from this model were compared with measured trunk torque. The effects of trunk motion, posture, and torque level on spine loading as estimated by the model are discussed. It was concluded that this approach provides a straightforward means of assessing loading of the spine attributable to laboratory simulations of workplace conditions.

Adult↗

Economic study in surgical patients of a new model of nutrition therapy integrating hospital and home vs the conventional hospital model.

BACKGROUND: Dehospitalization is a trend in the health sector justified by humanitarian and socials aspects for the patient and relatives. From the financing institutions' perspective, whether government or third party, the positive results arise from an optimization of hospital bed use and favorable cost-benefit ratio. The "integrated home-hospital" model was created with the purpose of optimization of resources without detriment to the patients' nutritional care. The objective of this study was an economic evaluation regarding nutrition therapy of the integrated hospital-home model in comparison with an exclusively hospital model. METHODS: A retrospective controlled study, paired (age, sex, disease, and surgical procedure), was performed on 56 digestive surgery patients divided into 2 groups: study (SG; n = 30) and control (CG; n = 26). The data collected included total expenses with hospitalization, nutritional benefits, minimization cost analysis, cost-effectiveness ratio analysis, cost-benefit ratio analysis, hospital length of stay, and hospital-bed optimization. RESULTS: The patients from the SG achieved the same nutritional benefits as those in the CG, but with expenses 3 times lower (median Brazil Reals (R)$3237.18 vs R$8647.93; p < .05). The new model resulted in economic benefit to the institution, as shown by the cost-effectiveness ratio, mainly resulting from the savings of the days of hospitalization avoided. The cost-benefit ratio showed an important savings per patient for the institution (US $3100). CONCLUSIONS: The home-hospital model also reduced length of hospital stay 2.7 times and optimized the hospital bed usage, as it promoted higher hospital-bed rotation (3 times greater).

Cost-Benefit Analysis↗

B-cell depletion inhibits arthritis in a collagen-induced arthritis (CIA) model, but does not adversely affect humoral responses in a respiratory syncytial virus (RSV) vaccination model.

We report the development of a mouse B cell-depleting immunoconjugate (anti-CD22 monoclonal antibody [mAb] conjugated to calicheamicin) and its in vivo use to characterize the kinetics of CD22+ B-cell depletion and reconstitution in murine primary and secondary lymphoid tissues. The effect of B-cell depletion was further studied in a murine collagen-induced arthritis (CIA) model and a respiratory syncytial virus (RSV) vaccination model. Our results show that (1) the immunoconjugate has B-cell-specific in vitro and in vivo cytotoxicity; (2) B-cell reconstitution starts in the bone marrow and spleen around day 30 after depletion and is completed in all tissues tested by day 50; (3) B-cell depletion inhibits the development of clinical and histologic arthritis in the CIA model; (4) depletion of type II collagen antibody levels is not necessary for clinical and histologic prevention of CIA; and (5) B-cell depletion does not adversely affect memory antibody responses after challenge nor clearance of infectious virus from lungs in the RSV vaccination model. These results demonstrate for the first time that only B-cell reduction but not type II collagen antibody levels correlate with the prevention of arthritis and represent key insights into the role of CD22-targeted B-cell depletion in mouse autoimmunity and vaccination models.

Animals↗

Falls prevention within the Australian general practice data model: methodology, information model, and terminology issues.

The iterative development of the Falls Risk Assessment and Management System (FRAMS) drew upon research evidence and early consumer and clinician input through focus groups, interviews, direct observations, and an online questionnaire. Clinical vignettes were used to validate the clinical model and program logic, input, and output. The information model was developed within the Australian General Practice Data Model (GPDM) framework. The online FRAMS implementation used available Internet (TCP/IP), messaging (HL7, XML), knowledge representation (Arden Syntax), and classification (ICD10-AM, ICPC2) standards. Although it could accommodate most of the falls prevention information elements, the GPDM required extension for prevention and prescribing risk management. Existing classifications could not classify all falls prevention concepts. The lack of explicit rules for terminology and data definitions allowed multiple concept representations across the terminology-architecture interface. Patients were more enthusiastic than clinicians. A usable standards-based online-distributed decision support system for falls prevention can be implemented within the GPDM, but a comprehensive terminology is required. The conceptual interface between terminology and architecture requires standardization, preferably within a reference information model. Developments in electronic decision support must be guided by evidence-based clinical and information models and knowledge ontologies. The safety and quality of knowledge-based decision support systems must be monitored. Further examination of falls and other clinical domains within the GPDM is needed.

Accidental Falls↗

[Actuality of Wallon's emotional model: toward a "body-psychosocial" model of emotions].

Author focuses on qualitative approach of emotions with their human function. She postulates that emotions would be one of the way of the mind's body-inscription. A short presentation of the actual discussion, within psychoneurology and cognitive psychology, shows the lack of a developmental perspective. From the Wallon's emotions theory, the author presents a model that allows to go beyond this limit and to redefine the primary function of emotions: the "body-psycho-social Wallon's model" of emotions. Wallon's emotional model focuses on the interaction between body-image and psycho-social construction. This model: a) fixes the emotions into automatisms, but these automatisms are already in link with the social world (through the sense of the mother's language), b) establishes the integrative function of antagonisms (between mind and automatisms, between emotions and mind, between emotions and automatisms). This model shows that emotion's function cannot be reduce to the adaptative response to an unpredictable situation (cognitive or motor). The initial function of emotions concerns the communication system, or better, the first function of emotions is a search for action on family circle, by means of mimicry with ambient and emotional contagion. This emotional system is completely dependent (addicted) on the environment. It gives a "tool" to put in coordination with its environment: a) it favours the setting up of an instant empathy within infant and family circle, b) it makes easier the mind and motor accommodation, c) it put in the necessary plasticity for the emergence of the consciousness.

Affect↗

Nasal model and lung model machine for intranasal stent with filters efficacy evaluation.

Nasal model and lung model machine simulated human respiratory situation with cyclical air flow rate of 2 1/min. They were used to evaluate filtration efficacy of filters in an intranasal stent for laser smoke particles in the Otolaryngology Department, Ramathibodi Hospital from February to June 1998. The filters were three layers of half face mask outer filters. Each of five sets or 10 intranasal stents with filters or Whatman filters was attached at both inlet ends of the nasal model. A Whatman filter collected the maximum particle amount from 10 shots, 10 W and 0.2 s of single pulse mode carbon dioxide laser evaporative field for 5 min which was the same amount passed through filters of the intranasal stent. A high power optical microscope was used to count particle retention in each filter. The mean filtration efficacy of filters in the intranasal stent was 94.4 per cent when compared with that of the Whatman filter. A personal respiratory protective device could be applied in the human nasal vestibule to prevent polydisperse suspended particulate matter in a highly air-polluted area. The nasal model with lung model machine should be tested under different concentrations of laser smoke particles or at the main roadside.

Equipment Design↗

[Augmentation of the anti-tumor activity of regional lymph node lymphocytes and spleen cells of tumor-bearing mice by culture with T cell growth factor in vitro--a comparison of the intestinal cancer model and footpad cancer model].

The anti-tumor activity of regional lymph node lymphocytes (RLNL) of DS mice bearing syngeneic carcinoma SC42 was observed both in intestinal cancer model and in footpad cancer model, while neither spleen cells (SPLC) nor distant lymph node lymphocytes showed any activity in Winn's tumor neutralizing test. This anti-tumor activity of RLNL was tumor specific examining between SC42 and SC115. RLNL in both cancer models did not show any cytotoxic activity against SC42 measured by 51Cr release test. However, after 9 days of culture with lectin-free T cell growth factor (LF-TCGF), the cytotoxic activity against SC42 of RLNL was induced in both cancer models. Cultured SPLC showed the cytotoxic activity against SC42 only in intestinal cancer model. Any lymphocytes from normal mice showed no cytotoxic activity against SC42 after culture with LF-TCGF. Moreover, the cytotoxic activity of cultured RLNL was tumor specific between SC42 and SC115, while that of cultured SPLC was non-specific. These results indicated that RLNL was immunologically important in tumor bearing host and the immunological significance of spleen was different between intestinal cancer and cancer of other sites.

Animals↗

Hepatic clearance models: comparison of the dispersion and Goresky models in outflow profiles from multiple indicator dilution rat liver studies.

The multiple indicator dilution (MID) technique is often used for investigation of the kinetic behavior of substrates and metabolites in eliminating organs. The present study was a systematic comparison of the utility of the Goresky model (GM) (a structural model) and the mixed-boundary dispersion model (DM) (a stochastic model) in the interpretation of influx, efflux, and removal (sequestration) coefficients, with data generated from rat liver-perfusion/MID studies. Although the GM and the DM are equivalent in their descriptions of membrane transport, they differ in their classifications of the dispersion of blood-borne elements. For the DM, the dispersion is an inverse Gaussian distribution of vascular transit times; for the GM, it is accounted for by the dispersion observed among noneliminated reference indicators (e.g. labeled red blood cells, albumin, sucrose, and H2O) or the derived reference. In this study, previously published rat liver-perfusion/MID data obtained for the glutathione conjugate of bromosulfophthalein and hippuric acid, compounds that exhibit saturable carrier-mediated transport, with the GM were reanalyzed with the two-compartment DM. When the fitted values for volume and transfer coefficients were compared, good correlation was found between the fitted vascular volume for the DM and the vascular volume for the reference indicator for the GM. The influx coefficients were generally similar between the models, but improved correspondence was observed when the DM was modified to include the large-vessel transit time. In contrast, the efflux and sequestration coefficients obtained for the DM did not correspond well to those from the GM. The disagreement was due, in part, to differences in the interpretation of the late-in-time component of the reference transit time distribution curve, which was not described well by the DM. Consequently, the residence time distribution and the relative dispersion were underestimated by the DM.

Animals↗

Joint modeling of genetic association and population stratification using latent class models.

We show how latent class log-linear models can be used to test for an association between a candidate gene and a disease phenotype in a stratified population when the stratification is unobserved. The stratification may arise because of several ethnic groups or immigration and may lead to spurious associations between several loci and the disease. The information about the stratification is drawn from additional markers that are chosen to be independent of the disease and unlinked to the candidate gene and to each other within each population stratum. We use the EM algorithm to simultaneously estimate all the model parameters, including proportions of individuals in the latent population strata. The latent class model is used to test the phenotype association of single nucleotide polymorphism markers in four candidate regions in population-based case-control data selected from simulated Genetic Analysis Workshop (GAW) 12 population isolate 30. The analysis clearly demonstrates how the number of false positive associations can be reduced when the model accounts for population stratification.

Case-Control Studies↗

Generalized comparative modeling (GENECOMP): a combination of sequence comparison, threading, and lattice modeling for protein structure prediction and refinement.

An improved generalized comparative modeling method, GENECOMP, for the refinement of threading models is developed and validated on the Fischer database of 68 probe-template pairs, a standard benchmark used to evaluate threading approaches. The basic idea is to perform ab initio folding using a lattice protein model, SICHO, near the template provided by the new threading algorithm PROSPECTOR. PROSPECTOR also provides predicted contacts and secondary structure for the template-aligned regions, and possibly for the unaligned regions by garnering additional information from other top-scoring threaded structures. Since the lowest-energy structure generated by the simulations is not necessarily the best structure, we employed two structure-selection protocols: distance geometry and clustering. In general, clustering is found to generate somewhat better quality structures in 38 of 68 cases. When applied to the Fischer database, the protocol does no harm and in a significant number of cases improves upon the initial threading model, sometimes dramatically. The procedure is readily automated and can be implemented on a genomic scale.

Algorithms↗

A multi-state model for joint modelling of terminal and non-terminal events with application to Whitehall II.

Serious coronary heart disease (CHD) is a primary outcome in the Whitehall II study, a large epidemiological study of British civil servants. Both fatal (F) and non-fatal (NF) CHD events are of interest and while essentially complete information is available on F events, the observation of NF events is subject to potentially informative censoring. A multi-state model with an unobserved state is introduced for the joint modelling of F and NF events. Two model-based assumptions ensure identifiability of the model and a parameter is introduced to allow sensitivity analyses concerning the assumption linked to informative censoring. Weibull transition rates, which include dependence on explanatory variables, are used in the analysis of Whitehall II data with a particular focus on the relationship between civil service grade and CHD events.

Adult↗

Location-scale cumulative odds models for ordinal data: a generalized non-linear model approach.

Proportional odds regression models for multinomial probabilities based on ordered categories have been generalized in two somewhat different directions. Models having scale as well as location parameters for adjustment of boundaries (on an unobservable, underlying continuum) between categories have been employed in the context of ROC analysis. Partial proportional odds models, having different regression adjustments for different multinomial categories, have also been proposed. This paper considers a synthesis and further generalization of these two families. With use of a number of examples, I discuss and illustrate properties of this extended family of models. Emphasis is on the computation of maximum likelihood estimates of parameters, asymptotic standard deviations, and goodness-of-fit statistics with use of non-linear regression programs in standard statistical software such as SAS.

Humans↗

Statistical model of the hippocampal CA3 region II. The population framework: model of rhythmic activity in the CA3 slice.

A statistical model is given to describe the electrical activity patterns of large neural populations of the hippocampal CA3 region. A continuous model has been formalized to describe the statistical processes governing the interactions within and between neural fields. The system of partial differential equations contains diffusion terms which determine the evolution of second moments of the probability distribution functions. The model is supplemented with a differential description of post-synaptic potentials. The discretization procedure has been designed so as to make the discrete equations scaling invariant. Population activities as well as underlying single-cell voltages are simulated during normal and epileptiform activities in the hippocampal CA3 slice. It is demonstrated that our model can reproduce electrophysiological phenomena characteristic to both single-cell and population activities. Specifically, fully synchronized population bursts, synchronized synaptic potentials, and low amplitude population oscillation were obtained.

Action Potentials↗

Mediational analysis in HIV/AIDS research: estimating multivariate path analytic models in a structural equation modeling framework.

Mediational analyses have been recognized as useful in answering two broad questions that arise in HIV/AIDS research, those of theoretical model testing and of the effectiveness of multicomponent interventions. This article serves as a primer for those wishing to use mediation techniques in their own research, with a specific focus on mediation applied in the context of path analysis within a structural equation modeling (SEM) framework. Mediational analyses and the SEM framework are reviewed at a general level, followed by a discussion of the techniques as applied to complex research designs, such as models with multiple mediators, multilevel or longitudinal data, categorical outcomes, and problematic data (e.g., missing data, nonnormally distributed variables). Issues of statistical power and of testing the significance of the mediated effect are also discussed. Concrete examples that include computer syntax and output are provided to demonstrate the application of these techniques to testing a theoretical model and to the evaluation of a multicomponent intervention.

Data Interpretation, Statistical↗

Application of SPLINDID, a semiparametric, model-based method for pharmacogenomic modeling of mRNA dynamics.

PURPOSE: This study was conducted to evaluate the applicability of SPLINDID, a semiparametric, model-based approach for obtaining transcription rates from the pharmacodynamics of mRNA expression. METHODS: A nonparametric exponential cubic spline function was used to obtain the transcription rate profile and the dynamics of mRNA expression was fitted using compartmental approaches. The transcription rate profile and mRNA degradation parameter was estimated using maximum likelihood method of ADAPT II software. RESULTS: Data sets containing noise for mRNA levels were simulated for four diverse pharmaceutically relevant conditions: receptor nonlinearity, a model in which the variant mRNAs differing in mRNA degradation constants were transcribed and for a minimal model of the cell cycle. SPLINDID was able to fit the data sets and accurately recapitulate the transcription rate profiles normalized to the mRNA degradation rate constants. The model was also challenged using experimental data containing time profiles of cell-cycle-regulated genes. CONCLUSIONS: The SPLINDID approach is flexible in capturing complicated/complex mRNA profiles that are encountered in many experimental data sets.

Algorithms↗

Polychotomous multivariate models for coronary heart disease simulation. I. Tests of a logistic model.

Stochastic compartmental modeling techniques have been employed to simulate coronary heart disease morbidity and mortality. In the current paper, polychotomous logistic models are used to describe the relationship between risk of disease and multiple risk factors, effect modification and confounding variables. The process of estimating the parameters for two risk factors and three types of outcomes is described for a population followed for five years. A Statistical Analysis System (SAS) procedure was used to estimate risk factor coefficients based on two partial periods and on the entire five year epoch. Most of the estimated coefficients were found to be statistically significant. The model performance was evaluated by comparing the observational data with simulated outcomes using a micropopulation and Monte Carlo techniques. Two different tests of goodness of fit were used. Satisfactory fits were obtained both for the risk coefficients based on two partial periods and those based on the entire epoch. This indicates that the model is suitable for simulation of the effects of intervention strategies. The use of the entire epoch involved estimates of one half as many parameters as did the use of two partial periods. Accordingly, it is concluded that only the entire epoch need be considered for future studies of this population.

Adult↗

Modeling directed ligand passage toward enzyme active site by a 'double cellular automata' model.

It is recently proposed that directed passage of ligand on the surface of enzymes may play an important role in the process of enzyme activity, as a result of decreasing the required steps of random walking of the ligand toward the active site. Here, we revisited the approach applied by others, where a cellular automaton is designed to simulate the behavior of a ligand molecule traveling toward the active site of an enzyme. Since a cellular automaton plane is topologically equivalent to a torus surface, we recommended the use of a 'double cellular automata' to model globular proteins. With the boundary conditions applied, our model is topologically identical to a sphere. It was shown that using this model, even fewer steps are needed for a molecule to attend the active site. This assumption can lead to more realistic results in the modeling of surfaces with spherical topology.

Algorithms↗