SEARCH · PubMed Health

Results for “Model”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources

PubMed2005

A multi-group model of Schistosoma japonicum transmission dynamics and control: model calibration and control prediction.

Previously we formulated a quantitative model to characterize site-specific schistosomiasis transmission. In this paper, we present a procedure to calibrate the model to data collected in endemic villages of south-western Sichuan, China, with the objective of reducing parametric uncertainty to allow the model to describe local transmission with relative confidence. A Bayesian approach using local epidemiological data and expert opinion is employed to calibrate the model. Results indicate that, after calibration, the output uncertainty is reduced substantially. The calibrated model is then used for prediction of the effects of different intervention options. Simulations reflect a bimodal transmission in both human (early summer and early fall) and snail (late summer and late fall) infections in this area, for which there is some field evidence. Also shown in the simulations are relatively high reinfection rates following chemotherapy in these endemic villages. These results suggest that a sustainable control strategy is essential in reducing transmission, and that transmission can be reduced by chemotherapy, focal snail (e.g. snail clusters) control, and egg control. Our work demonstrates the feasibility of characterizing site-specific schistosomiasis transmission using a mathematical model and a calibration approach that integrates diverse field data, and the use of the calibrated model to design control strategies.

Animals↗

PubMed2002

Glottal flow through a two-mass model: comparison of Navier-Stokes solutions with simplified models.

A new numerical model of the vocal folds is presented based on the well-known two-mass models of the vocal folds. The two-mass model is coupled to a model of glottal airflow based on the incompressible Navier-Stokes equations. Glottal waves are produced using different initial glottal gaps and different subglottal pressures. Fundamental frequency, glottal peak flow, and closed phase of the glottal waves have been compared with values known from the literature. The phonation threshold pressure was determined for different initial glottal gaps. The phonation threshold pressure obtained using the flow model with Navier-Stokes equations corresponds better to values determined in normal phonation than the phonation threshold pressure obtained using the flow model based on the Bernoulli equation. Using the Navier-Stokes equations, an increase of the subglottal pressure causes the fundamental frequency and the glottal peak flow to increase, whereas the fundamental frequency in the Bernoulli-based model does not change with increasing pressure.

Air Pressure↗

PubMed2002

Absorption and metabolism of flavonoids in the caco-2 cell culture model and a perused rat intestinal model.

The purpose of present study was to determine the intestinal absorption and metabolism of genistein and its analogs to better understand the mechanisms responsible for their low oral bioavailability. The Caco-2 cell culture model and a perfused rat intestinal model were used for the study. In both models, permeabilities of aglycones (e.g., genistein) were comparable to well absorbed compounds, such as testosterone and propranolol. In the Caco-2 model, permeabilities of aglycones were at least 5 times higher (p < 0.05) than their corresponding glycosides (e.g., genistin), and the vectorial transport of aglycones was similar (p > 0.05). In contrast, vectorial transport of glucosides favored excretion (p < 0.05). Limited hydrolysis of glycosides was observed in the Caco-2 model, which was completely inhibited (p < 0.05) by 20 mM gluconolactone, a broad specificity glycosidase inhibitor. In the perfused rat intestinal model, genistin was rapidly hydrolyzed (about 40% in 15 min) in the upper intestine but was not hydrolyzed at all in the colon. Aglycones were rapidly absorbed (P*(eff) > 1.5), and absorbed aglycones underwent extensive (40% maximum) phase II metabolism via glucuronidation and sulfation in the upper small intestine. Similar to the hydrolysis, recovery of conjugated genistein was also region-dependent, with jejunum having the highest and colon the lowest (p < 0.05). This difference in conjugate recovery could be due to the difference in the activities of enzymes or efflux transporters, and the results of studies tend to suggest that both of these factors were involved. In conclusion, genistein and its analogs are well absorbed in both intestinal models, and therefore, poor absorption is not the reason for its low bioavailability. On the other hand, extensive phase II metabolism in the intestine significantly contributes to its low bioavailability.

Animals↗

PubMed2006

Use of probabilistic modeling within a physiologically based pharmacokinetic model to predict sulfamethazine residue withdrawal times in edible tissues in swine.

The presence of antimicrobial agents in edible tissues of food-producing animals remains a major public health concern. Probabilistic modeling techniques incorporated into a physiologically based pharmacokinetic (PBPK) model were used to predict the amounts of sulfamethazine residues in edible tissues in swine. A PBPK model for sulfamethazine in swine was adapted to include an oral dosing route. The distributions for sensitive parameters were determined and were used in a Monte Carlo analysis to predict tissue residue times. Validation of the distributions was done by comparison of the results of a Monte Carlo analysis to those obtained with an external data set from the literature and an in vivo pilot study. The model was used to predict the upper limit of the 95% confidence interval of the 99th percentile of the population, as recommended by the U.S. Food and Drug Administration (FDA). The external data set was used to calculate the withdrawal time by using the tolerance limit algorithm designed by FDA. The withdrawal times obtained by both methods were compared to the labeled withdrawal time for the same dose. The Monte Carlo method predicted a withdrawal time of 21 days, based on the amounts of residues in the kidneys. The tolerance limit method applied to the time-limited data set predicted a withdrawal time of 12 days. The existing FDA label withdrawal time is 15 days. PBPK models can incorporate probabilistic modeling techniques that make them useful for prediction of tissue residue times. These models can be used to calculate the parameters required by FDA and explore those conditions where the established withdrawal time may not be sufficient.

Animals↗

PubMed1999

Undermodeling affects minimal model indexes: insights from a two-compartment model.

The classic (hereafter cold) and the labeled (hereafter hot) minimal models are powerful tools to investigate glucose metabolism. The cold model provides, from intravenous glucose tolerance test (IVGTT) data, indexes of glucose effectiveness (SG) and insulin sensitivity (SI) that measure the effect of glucose and insulin, respectively, to enhance glucose disappearance and inhibit endogenous glucose production. The hot model provides, from hot IVGTT data, indexes of glucose effectiveness (SG*) and insulin sensitivity (SI*) that, respectively, measure the effects of glucose and insulin on glucose disappearance only. Recent reports call for a reexamination of some of the assumptions of the minimal models. We have previously pointed out the criticality of the single-compartment description of glucose kinetics on which both the minimal models are founded. In this paper we evaluate the impact of single-compartment undermodeling on SG, SI*, and by using a two-compartment model to describe the glucose system. The relationships of the minimal model indexes to the analogous indexes measured with the glucose clamp technique are also examined. Theoretical analysis and simulation studies indicate that cold indexes are more affected than hot indexes by undermodeling. In particular, care must be exercised in the physiological interpretation of SG, because this index is a local descriptor of events taking place in the initial portion of the IVGTT. As a consequence, SG not only reflects glucose effect on glucose uptake and production but also the rapid exchange of glucose between the accessible and nonaccessible glucose pools that occurs in the early part of the test.

Glucose↗

PubMed1999

Modeling the influence of body size on V(O2) peak: effects of model choice and body composition.

This study examined the bivariate relationship between peak oxygen uptake (V(O2) peak); l/min) and body size in adult men (n = 1,314, age 17-66 yr), using both "simple" and "full" iterative nonlinear allometric models. The simple model was described by V(O2) peak = M(b) (or FFM(b)) exp(c SR-PA) exp(a + d age) epsilon (where M is body mass in kg; FFM is fat-free mass in kg; SR-PA is self-reported physical activity; epsilon is a multiplicative error term; and exp indicates natural antilogarithms). The full model was described by V(O2) peak = M(b) (or FFM(b)) exp(c SR-PA) exp(a + d age) + e (epsilon), where e is a permitted Y-intercept term. The M exponent obtained from simple allometry was 0.65 [95% confidence interval (CI), 0.59-0.71], suggestive of a curvilinear relationship constrained to pass through the origin. This "zero Y-intercept" assumption was examined via the full allometric model, which revealed an M exponent of 1.00 (95% CI, 0.7-1.31), together with a positive Y-intercept term (e) of 1.13 (95% CI, 0.54-1.73). The FFM exponents were not significantly different from unity in either the simple or full allometric models. It appears that the curvilinearity of the simple allometric model (using total M) is fictitious and is due to the inappropriate forcing of the regression line through the origin. Utilizing FFM as the body-size variable revealed a linear relationship between body size and V(O2) peak, irrespective of model choice. We conclude that the population mass exponent for V(O2) peak is close to unity.

Adolescent↗

PubMedDate not supplied

Genetic analysis combining path analysis with regressive models: the TAU model of multifactorial transmission.

We have extended regressive models by incorporating a simple path model (the TAU model). This was achieved for both class A and class D regressive models by expressing the residual correlations in the regressive models in terms of parameters of the path model. We have presented explicit solutions for path coefficients in terms of the residual correlations. These methods were applied to a French-Canadian family study on body mass index. It was found that the estimate of pseudopolygenic heritability was robust under class A (t2 = 0.28) and class D (t2 = 0.26) models.

Body Mass Index↗

PubMed2001

The Gaussian derivative model for spatial-temporal vision: I. Cortical model.

How do we see the motion of objects as well as their shapes? The Gaussian Derivative (GD) spatial model is extended to time to help answer this question. The GD spatio-temporal model requires only two numbers to describe the complete three-dimensional space-time shapes of individual receptive fields in primate visual cortex. These two numbers are the derivative numbers along the respective spatial and temporal principal axes of a given receptive field. Nine transformation parameters allow for a standard geometric association of these intrinsic axes with the extrinsic environment. The GD spatio-temporal model describes in one framework the following properties of primate simple cell fields: motion properties, number of lobes in space-time, spatial orientation. location, and size. A discrete difference-of-offset-Gaussians (DOOG) model provides a plausible physiological mechanism to form GD-like model fields in both space and time. The GD model hypothesizes that receptive fields at the first stage of processing in the visual cortex approximate 'derivative analyzers' that estimate local spatial and temporal derivatives of the intensity profile in the visual environment. The receptive fields as modeled provide operators that can allow later stages of processing in either a biological or machine vision system to estimate the motion as well as the shapes of objects in the environment.

Animals↗

PubMedDate not supplied

Community blood supply model: development of a new model to assess the safety, sufficiency, and cost of the blood supply.

BACKGROUND: Through a combination of predonation donor screening and donated unit testing, the blood supply is safer than ever. However, as a result of increasingly stringent screening measures, one of the greatest threats may be an insufficient supply. The balance between safety and adequacy of the blood supply has not received enough attention. STUDY DESIGN AND METHODS: The authors developed a model to allow for empirical investigation of the determinants of a safe and sufficient supply. The model is a cohort simulation of allogeneic whole-blood donation, with the population of presenting donors stratified into 8 age and gender groups because the probability of donor and donation deferral varies by these characteristics. Parameters are estimated from year 2000 Blood Centers of Pacific (BCP) data. The model includes cost parameters, which were estimated using BCP expenditure data. The main outcomes are the number of transfusable units of blood and the unit cost of procurement. RESULTS: The model tracks the production of a supply of blood, highlighting the influence of demographic characteristics, predonation deferral, underweight collection of blood units, and associated costs. The authors sought to establish model validity by showing that modeled results closely mimic the outcomes and costs observed by blood bank administrators. CONCLUSION: The model was developed to evaluate blood safety and policy decisions; it can be used to assess the impact of predonation deferrals, such as expanded European travel deferral for variant Creutzfeldt-Jakob disease, or the impact of new testing strategies, such as nucleic acid testing for West Nile virus.

Blood Donors↗

PubMed2006

Development of the isolated dual perfused rat liver model as an improved reperfusion model for transplantation research.

The Isolated Perfused Liver (IPL) model is a widely used and appreciated in vitro method to demonstrate liver viability and metabolism. Reperfusion is performed in a controlled setting, however, via the portal vein only. To study transplant related questions concerning bile and transport of bile, the in vitro Isolated dual Perfused Liver model is revisited. The IdPL is an in vitro reperfusion model, using both portal vein and hepatic artery. Livers from 12 Wistar rats were flushed with University of Wisconsin-organ preservation solution, procured and reperfused in either the conventional IPL-model (n = 6) or the new IdPL-model (n = 6). Liver injury, assessed by the release of aspartate amino transferase and lactate dehydrogenase, showed similar levels during both IPL and I dPL reperfusion, only alanine amino transferase showed an improvement. Cumulative bile production showed an improvement: 176.3 +/- 8.4 in the IdPL compared to 126.1 +/- 12.2 microg/g-liver in the IPL (p < 0.05). Clearance of phenol red (PR) and taurocholic acid (TC) remained similar. At 90 minutes reperfusion the PR clearance showed 0.11 +/- 0.01 and 0.11 +/- 0.02 mg/30min/g-liver and the TC clearance 1.01 +/- 0.10 and 1.01 +/- 0.07 micromol/ml/30min/g-liver in the IPL and IdPL, respectively. Increasing the reperfusion time beyond the normally used 90 minutes resulted in a significant increase in transaminases and LDH and a decrease in bile production, liver morphology remained intact and glycogen content was appropriate. In conclusion, the IdPL-model showed similar or better results than the IPL-model, but the liver could not endure an extended reperfusion time using the IdPL.

Animals↗

PubMed2001

Model-based analysis of oligonucleotide arrays: model validation, design issues and standard error application.

BACKGROUND: A model-based analysis of oligonucleotide expression arrays we developed previously uses a probe-sensitivity index to capture the response characteristic of a specific probe pair and calculates model-based expression indexes (MBEI). MBEI has standard error attached to it as a measure of accuracy. Here we investigate the stability of the probe-sensitivity index across different tissue types, the reproducibility of results in replicate experiments, and the use of MBEI in perfect match (PM)-only arrays. RESULTS: Probe-sensitivity indexes are stable across tissue types. The target gene's presence in many arrays of an array set allows the probe-sensitivity index to be estimated accurately. We extended the model to obtain expression values for PM-only arrays, and found that the 20-probe PM-only model is comparable to the 10-probe PM/MM difference model, in terms of the expression correlations with the original 20-probe PM/MM difference model. MBEI method is able to extend the reliable detection limit of expression to a lower mRNA concentration. The standard errors of MBEI can be used to construct confidence intervals of fold changes, and the lower confidence bound of fold change is a better ranking statistic for filtering genes. We can assign reliability indexes for genes in a specific cluster of interest in hierarchical clustering by resampling clustering trees. A software dChip implementing many of these analysis methods is made available. CONCLUSIONS: The model-based approach reduces the variability of low expression estimates, and provides a natural method of calculating expression values for PM-only arrays. The standard errors attached to expression values can be used to assess the reliability of downstream analysis.

Cluster Analysis↗

PubMed2001

A computational model for estimating the mechanics of horizontal flapping flight in bats: model description and validation.

We combine three-dimensional descriptions of the movement patterns of the shoulder, elbow, carpus, third metacarpophalangeal joint and wingtip with a constant-circulation estimation of aerodynamic force to model the wing mechanics of the grey-headed flying fox (Pteropus poliocephalus) in level flight. Once rigorously validated, this computer model can be used to study diverse aspects of flight. In the model, we partitioned the wing into a series of chordwise segments and calculated the magnitude of segmental aerodynamic forces assuming an elliptical, spanwise distribution of circulation at the middle of the downstroke. The lift component of the aerodynamic force is typically an order of magnitude greater than the thrust component. The largest source of drag is induced drag, which is approximately an order of magnitude greater than body form and skin friction drag. Using this model and standard engineering beam theory, we calculate internal reaction forces, moments and stresses at the humeral and radial midshaft during flight. To assess the validity of our model, we compare the model-derived stresses with our previous in vivo empirical measurements of bone strain from P. poliocephalus in free flapping flight. Agreement between bone stresses from the simulation and those calculated from empirical strain measurements is excellent and suggests that the computer model captures a significant portion of the mechanics and aerodynamics of flight in this species.

Animals↗

PubMed2005

Population pharmacokinetic-pharmacodynamic modeling of TF-505 using extension of indirect response model by incorporating a circadian rhythm in healthy volunteers.

The pharmacokinetic-pharmacodynamic (PK-PD) relationship of the newly developed drug, (-)-(S)-4-[1-[4-[1-(4-isobutylphenyl)butoxy]benzoyl]indolizin-3-yl]butyric acid (TF-505), was characterized via a population approach in early human study. Healthy volunteers were divided into six groups. The groups received four single doses (25, 50, 75 or 100 mg) and 2 multiple doses (12.5 or 25 mg) of TF-505, respectively. Dihydrotestosterone (DHT) data were collected to assess TF-505 pharmacodynamics. Population PK/PD modeling of TF-505 was performed via mixed-effects modeling using the NONMEM software package. The final PK-PD model incorporates a two-compartment PK model and an extended indirect PD model. The population PK parameters were 0.197 h(-1) for the k(a), 0.0678 h(-1) for k(e), 12.5 l for V(c), 0.0645 h(-1) for k(12), 0.0723 h(-1) for k(21). Extension of indirect response model by incorporating a time-dependent periodic function for k(in) takes into account the chronopharmacologic rhythms (I(max): 0.706+/-0.297, IC(50): 1.01+/-1.64 (microg/ml), k(out): 0.221+/-0.0486 (h(-1)), R(m): 20.4+/-8.08 (% h(-1)), R(amp): 5.06+/-3.43 (% h(-1)), T(z): 5.01+/-0.407 (h) (Population mean+/-S.E.)). R(m) is the mean DHT synthesis rate, R(amp) is the amplitude of the DHT synthesis rate, and T(z) is the acrophase time, signifying maximum synthesis rate. The present study represents a successful population PK-PD model using the full data from early human studies. The population parameters thus obtained could provide useful indicators for the determination of dosage regimens in exploratory studies in patient populations.

Adult↗

PubMed2003

Modeling the training-performance relationship using a mixed model in elite swimmers.

PURPOSE: The aim of this study was to model the relationship between training and performance in 13 competitive swimmers, over three seasons, and to identify individual and group responses to training. METHODS: A linear mixed model was used as an alternative to the Banister model. Training effect on performance was studied over three training periods: short-term, the average of training load accomplished during the 2 wk preceding each performance of the studied period; mid-term, the average of training load accomplished during weeks 3, 4, and 5 before each performance; and long-term, weeks 6, 7, and 8. RESULTS: Cluster analysis identified four groups of subjects according to their reactions to training. The first group corresponded to the subjects who responded well to the long-term training period, the second group to the long- and mid-term periods, the third to the short- and mid-term periods, and the fourth to the combined periods. In the model, the intersubject differences and the evolution over the three seasons were statistically significant for the identified groups of swimmers. Influence of short-term training was negative on performance in the four groups, whereas mid- and long-term training had, on the average, a positive effect in three groups out of four. Between seasons 1 and 3, the effect of mid-term training declined, whereas the effect of long-term training increased. The fit between real and modeled performances was significant for all swimmers (0.15 </= r2 </= 0.65; P </= 0.01). CONCLUSION: The mixed model described a significant relationship between training and performance both for individuals and for groups of swimmers. This relationship was different over the 3 yr. Personalized training schedules could be prescribed on the basis of the model results.

Adult↗

PubMed2005

The mdr1a-/- mouse model of spontaneous colitis: a relevant and appropriate animal model to study inflammatory bowel disease.

There are many types of colitis models in animals that researchers use to elucidate the mechanism of action of human inflammatory bowel disease (IBD). These models are also used to test novel therapeutics and therapeutic treatment regimens. Here, we will review the characteristics of the mdr1a -/- model of spontaneous colitis that we believe make this model an important part of the IBD researcher's toolbox. We will also share new data that will reinforce the fact that this model is relevant in the study of IBD. Mdr1a -/- mice lack the murine multiple drug resistance gene for P-glycoprotein 170 that is normally expressed in multiple tissues including intestinal epithelial cells. These mice spontaneously develop a form of colitis at around 12 wk of age. The fact that the complexity of this model mirrors the complexity of disease in humans, as well as recent literature that links MDR1 polymorphisms in humans to Crohn's Disease and Ulcerative Colitis, makes this an appropriate animal model to study.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed1999

Individual causal models and population system models in epidemiology.

A group of individuals behaves as a population system when patterns of connections among individuals influence population health outcomes. Epidemiology usually treats populations as collections of independent individuals rather than as systems of interacting individuals. An appropriate theoretical structure, which includes the determinants of connections among individuals, is needed to develop a "population system epidemiology." Infection transmission models and sufficient-component cause models provide contrasting templates for the needed theoretical structure. Sufficient-component cause models focus on joint effects of multiple exposures in individuals. They handle time and interactions between individuals in the definition of variables and assume that populations are the sum of their individuals. Transmission models, in contrast, model interactions among individuals over time. Their nonlinear structure means that population risks are not simply the sum of individual risks. The theoretical base for "population system epidemiology" should integrate both approaches. It should model joint effects of multiple exposures in individuals as time related processes while incorporating the determinants and effects of interactions among individuals. Recent advances in G-estimation and discrete individual transmission model formulation provide opportunities for such integration.

Causality↗

PubMed1992

A computer model to predict the effects of level of nutrition on composition of empty body gain in beef cattle: II. Evaluation of the model.

A computer model developed to predict composition of empty body gain of beef cattle fed at different levels of nutrition was evaluated with data from one unpublished and seven published experiments. These experiments used several breeds of beef cattle growing at rates that varied from negative to fast and various combinations of these growth rates. There was close agreement between observed and simulated absolute treatment means for fatness, except when animals were fed diets low in protein. In this case, experimental animals fed inadequate protein grew at slower rates and became fatter than contemporaries fed adequate protein, whereas the model predicted the opposite. Ability of the model to predict effects of nutrition not associated with changes in BW was evaluated using the proportion of residual variation in experimental fat percentage accounted for by the model, after fitting linear and quadratic terms for empty BW. The model accounted for 13.8 to 56.2% of the residual variation in observed fatness in four experiments in which significant differences in fatness were observed among nutritional treatments after accounting for differences in empty BW. Regression of observed fatness on model-simulated fatness resulted in regression coefficients that were positive and close to 1 in these four experiments. This suggests that the model can accurately predict some of the effects of nutrition on fatness that are not associated with changes in empty BW.

Adipose Tissue↗

PubMed2001

A mechanistic model of whole-tract digestion and methanogenesis in the lactating dairy cow: model development, evaluation, and application.

Dietary intervention to reduce methane emissions from lactating dairy cattle is both environmentally and nutritionally desirable due to the importance of methane as a causative agent in global warming and as a significant loss of feed energy. Reliable prediction systems for methane production over a range of dietary inputs could be used to develop novel dietary regimes for the limitation of feed energy loss to methane. This investigation builds on previous attempts at modeling methanogenesis and involves the development of a dynamic mechanistic model of wholerumen function. The model incorporates modifications to certain ruminal fermentation parameters and the addition of a postruminal digestive element. Regression analysis showed good agreement between observed and predicted results for experimental data taken from the literature (r2 = 0.76, root mean square prediction error = 15.4%). Evaluation of model predictions for experimental observations from five calorimetry studies (67 observations) with lactating dairy cows at the Centre for Dairy Research, in Reading, U.K., shows an underprediction (2.1 MJ/d) of methane production (r2 = 0.46, root mean square prediction error = 12.4%). Application of the model to develop diets for minimizing methanogenesis indicated a need to limit the ratio of lipogenic to glucogenic VFA in the rumen and hindgut. This may be achieved by replacing soluble sugars in the concentrate with starch or substituting corn silage for grass silage. On a herd basis, the model predicted that increasing dietary energy intake per cow can minimize the annual loss of feed energy through methane production. The mechanistic model is a valuable tool for predicting methane emissions from dairy cows.

Animal Feed↗