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PubMed2006

Untangling the health disparities of teen pregnancy.

PURPOSE: The purpose of this secondary analysis is to determine whether a developmental maturity model differentially predicts pregnancy for African American, Puerto Rican, and Mexican inner-city teens. DESIGN AND METHODS: This is a secondary analysis of data from a case control study that tested a model of developmental maturity and teen pregnancy with 183 pregnant and never-pregnant pairs of inner-city teens matched on age, ethnicity, and freshman cohort. RESULTS: The models differentially predict pregnancy for the separate ethnic groups, with sexual behaviors being the most important factors regardless of ethnicity. PRACTICE IMPLICATIONS: The health disparities of teen pregnancies may not decrease unless patterns of dating/sexual behaviors are reversed.

Adolescent↗

PubMed1994

Differentiated intestinal epithelial cell lines as in vitro models for predicting the intestinal absorption of drugs.

The oral absorption of a compound is a critical factor for the future of the compound as a drug. This absorption is mainly controlled by the passage across the intestinal epithelium. Thus, the prediction of the intestinal absorption by means of an in vitro model may represent a powerful tool for the early selection of molecules during the process of drug development. In the present study, the differentiated human intestinal epithelial cell line HT29-18-C1, was grown on permeable filters in dual chambers. These cells formed tight monolayers that were used to measure in vitro the transepithelial permeability coefficient (Pc) of various molecules. The results were compared with in vivo data of oral absorption. A threshold value of in vitro permeability of 2 x 10(-6) cm/s was found. Molecules having a permeability coefficient higher than this value were absorbed orally more than 80%, while drugs with Pc values lower than 2 x 10(-6) cm/s were poorly absorbed. By mathematical simulation, it was found that this Pc value, when extrapolated to the surface area and volume of the small intestine, corresponds to an absorption of 80% for a compound with a transit time through the small intestine of 5 h. This demonstrates the predictive utility of the threshold value of the permeability coefficient derived from the in vitro model of intestinal epithelium.

Cell Line↗

PubMed2004

Concepts and tools for predictive modeling of microbial dynamics.

Description of microbial cell (population) behavior as influenced by dynamically changing environmental conditions intrinsically needs dynamic mathematical models. In the past, major effort has been put into the modeling of microbial growth and inactivation within a constant environment (static models). In the early 1990s, differential equation models (dynamic models) were introduced in the field of predictive microbiology. Here, we present a general dynamic model-building concept describing microbial evolution under dynamic conditions. Starting from an elementary model building block, the model structure can be gradually complexified to incorporate increasing numbers of influencing factors. Based on two case studies, the fundamentals of both macroscopic (population) and microscopic (individual) modeling approaches are revisited. These illustrations deal with the modeling of (i) microbial lag under variable temperature conditions and (ii) interspecies microbial interactions mediated by lactic acid production (product inhibition). Current and future research trends should address the need for (i) more specific measurements at the cell and/or population level, (ii) measurements under dynamic conditions, and (iii) more comprehensive (mechanistically inspired) model structures. In the context of quantitative microbial risk assessment, complexity of the mathematical model must be kept under control. An important challenge for the future is determination of a satisfactory trade-off between predictive power and manageability of predictive microbiology models.

Bacteria↗

PubMed2005

Prediction of theophylline clearance in CCl4-treated rats using in vivo CYP1A2 and CYP3A2 contents assessed with the PKCYP test.

We previously established a method to predict the drug metabolism capacity of injured liver based on pharmacokinetic estimation of the amount of cytochrome P450 (CYP) in vivo (PKCYP test), by introducing the apparent liver-to-blood free concentration gradient in vivo (qg) as a parameter. Here we show that the amount of CYP3A2 in CCl(4)-treated rats can be estimated appropriately by applying the PKCYP test using midazolam (MDZ) as a probe, assuming that the qg value in control rats does not change. We applied the results to predict the clearance of theophylline as a model drug with a physiologically based pharmacokinetic model. Male Sprague-Dawley rats were pretreated with CCl4, and the amount of CYP (A-CYP(vivo)) was quantified by Western blotting. The qg value of MDZ was determined in control rats and used to estimate the amounts of CYP3A2 in CCl4-treated rats; the result agreed well with the observed values. The qg value of CYP3A2 estimated with MDZ as a probe was used together with our previously reported value for CYP1A2 (theophylline metabolism in the liver is known to be almost entirely mediated by CYP3A2 and CYP1A2) to predict the total body clearance (CL(tot)) of theophylline in CCl4-treated rats. The predicted CL(tot) was about one-third of the observed value, which was considered acceptable. The time-course of theophylline concentration in serum simulated with a physiologically-based pharmacokinetic model agreed well with the observed values. Thus, the PKCYP test using MDZ as a probe can be used to predict the amount of CYP3A2 and the CL(tot) of theophylline in CCl4-treated rats.

Animals↗

PubMed2003

Investigating multiple components of attitude, subjective norm, and perceived control: an examination of the theory of planned behaviour in the exercise domain.

The presence of two subcomponents within each theory of planned behaviour (TPB) concept of attitude (affective and instrumental), subjective norm (injunctive and descriptive), and PBC (self-efficacy and controllability) has been widely supported. However, research has not examined whether the commonality of variance between these components (i.e. a general factor) or the specificity of variance within the subcomponents influences intention and behaviour. Therefore, the purpose of this study was to examine the optimal conceptualization of either two subcomponents or a general common factor for each TPB concept within an omnibus model. Further, to test whether conceptualizations may differ by population even within the same behavioural domain, we examined these research questions with 300 undergraduates (M age = 20) and 272 cancer survivors (M age = 61) for exercise behaviour. Results identified that a general subjective norm factor was an optimal predictive conceptualization over two separate injunctive and descriptive norm components. In contrast, a specific self-efficacy component, and not controllability or a general factor of PBC, predicted intention optimally for both samples. Finally, optimal models of attitude differed between the populations, with a general factor best predicting intention for undergraduates but only affective attitude influencing intention for cancer survivors. The findings of these studies underscore the possibility for optimal tailored interventions based on population and behaviour. Finally, a discussion of the theoretical ambiguity of the PBC concept led to suggestions for future research and possible re-conceptualization.

Adolescent↗

PubMedDate not supplied

Hypothesis: set-points and long-term control of arterial pressure. A theoretical argument for a long-term arterial pressure control system in the brain rather than the kidney.

1. It has been hypothesised that the 'set-point' for the long-term control of mean arterial (MAP) resides within the kidney. In this model, the set-point of the 'chronic renal function curve' establishes the steady state relationship between renal perfusion pressure and urinary excretion of sodium and water, which, in turn, affects blood volume and cardiac output. The 'renal-MAP set-point' theory predicts that the kidney controls MAP to maintain its own excretory function and that long-term regulation of blood volume and cardiac output are paramount to the regulation of arterial pressure. 2. An alternative hypothesis is proposed in which the 'set-point' for the long-term control of MAP resides within the central nervous system (CNS) rather than the kidney. In contrast with the 'renal-MAP set-point' model, the 'CNS-MAP set-point' model dictates that the brain controls MAP to maintain cerebral blood flow and CNS function. 3. The 'CNS-MAP set-point hypothesis' predicts that long-term regulation of MAP is paramount to the regulation of blood volume and cardiac output. It is proposed that the 'CNS-MAP set-point' system operates independently of the arterial baroreceptor reflex, which is a short-term controller of MAP. 4. The precise mechanisms by which the CNS 'senses' MAP are complex and remain to be discovered. The MAP 'sensor' likely involves integration of hormone levels linked to body fluid homeostasis and osmoreceptor and baroreceptor inputs. It is also proposed that an as yet undiscovered 'central baroreceptor' exists within the brain itself. 5. The 'CNS-MAP set-point hypothesis' predicts that many forms of experimental and essential hypertension are due to a primary shift in the CNS-MAP set-point.

Animals↗

PubMed1995

Cold water immersion simulations using the Wissler Texas Thermal Model: validation and sensitivity analysis.

BACKGROUND: Wissler's Texas Thermal Model (TM) has been used to simulate the effects of thermal stresses on individuals under a variety of conditions. As part of a U.S. Navy effort to develop integrated protection garments, TM was modified to predict tolerance to cold water immersion (CWI) with garments with clo values less than 0.1 (15). METHODS: With these modifications, TM predictions were validated using experimental data obtained from 39 males and females during anti-exposure suit CWI assessments. Data analyses were based on changes in rectal (Tre) and various skin temperatures (Tsk). A sensitivity analysis was also performed to determine which TM parameters were most affected during simulated CWI. The condition tested was head-out immersion in 4.4 degrees C water by a 72.6 kg man (10 mm mean skinfold thickness). RESULTS: For most of the subject pool, the estimated change in Tre, chest, thigh, calf, and arm temperatures were not statistically different from experimental values. However, TM predictions were less accurate with respect to female responses. Based on thermal end points, TM predictions indicated that the following body segments were most sensitive to changes in insulation level (ordered from most to least important): chest and abdomen, leg, head, and arm. The physical parameters mean skinfold thickness, basal metabolic rate, body weight, and exercise metabolic rate had the most impact on TM predictions. CONCLUSIONS: The relative benefit of increased insulation on individual body segments was identified to aid garment design. Further, the relative importance of model physical parameters was identified so that judicious initial conditions could be selected to ensure that only garment design changes would be reflected in model predictions.

Abdomen↗

PubMed2000

Subject specific coordination of two- and one-joint muscles during landings suggests multiple control criteria.

The target article, thoughtfully constructed by Dr. Prilutsky, effectively synthesizes available data on multijoint movements regarding coordination patterns of major two- and one-joint muscles, provides evidence for an optimization criterion that predicts critical features of muscle activation patterns, and explores the functional consequences of muscle coordination. This work also provides a clear set of definitions and an organizational framework that is currently needed for a productive interdisciplinary discussion regarding the underlying control mechanisms used during realistic multijoint movements. Although identification of an optimization criterion that predicts muscle recruitment strategies would greatly simplify control logic required for rehabilitation and musculoskeletal modeling, our experimental data during landings indicate more than one criterion may exist. Preliminary review of our experimental landing data suggests the rules identified by Prilutsky apparently hold for some subjects during portions of the landing movements. The presence of more than one muscle activation pattern used to achieve the same NJMs demonstrates there may be more than one optimization criterion that predicts critical features of muscle activation patterns. The functional consequences of more than one control criterion may also prove to be an asset, particularly when adapting to different environmental constraints.

Biomechanical Phenomena↗

PubMed2006

Construction of an in vitro bistable circuit from synthetic transcriptional switches.

Information processing using biochemical circuits is essential for survival and reproduction of natural organisms. As stripped-down analogs of genetic regulatory networks in cells, we engineered artificial transcriptional networks consisting of synthetic DNA switches, regulated by RNA signals acting as transcription repressors, and two enzymes, bacteriophage T7 RNA polymerase and Escherichia coli ribonuclease H. The synthetic switch design is modular with programmable connectivity and allows dynamic control of RNA signals through enzyme-mediated production and degradation. The switches support sharp and adjustable thresholds using a competitive hybridization mechanism, allowing arbitrary analog or digital circuits to be created in principle. As an example, we constructed an in vitro bistable memory by wiring together two synthetic switches and performed a systematic quantitative characterization. Good agreement between experimental data and a simple mathematical model was obtained for switch input/output functions, phase plane trajectories, and the bifurcation diagram for bistability. Construction of larger synthetic circuits provides a unique opportunity for evaluating model inference, prediction, and design of complex biochemical systems and could be used to control nanoscale devices and artificial cells.

Escherichia coli↗

PubMed1997

Traumatic myiasis of sheep in Europe: a review.

The two most important fly species causing traumatic cutaneous myiasis of sheep in Europe are Wohlfahrtia magnifica (Diptera: Sarcophagidae), which causes a form of myiasis known as wound myiasis, mainly in southern and eastern Europe, and Lucilia sericata (Diptera: Calliphoridae), which causes sheep strike, mainly in the middle latitudes of Europe. Other calliphorid blow-flies play a role mainly as secondary agents of myiasis, but in northern latitudes the L. caesar/illustris group are primary agents. Infestation levels vary greatly from region to region depending on a wide range of factors related to the composition of the parasite fauna, the host, animal husbandry and control practices, climate and geography. In some areas of Europe there have been recent increases in the incidence of traumatic myiasis due to changes in some of the previously mentioned factors. However, in other areas the incidence of myiasis is apparently low. More studies are needed to resolve this unclear situation and to explain regional differences. A number of areas for future research are highlighted including predicting the impact of environmental change, population modelling and development of novel control strategies.

Animal Husbandry↗

PubMed2006

Computational model explains high activity and rapid cycling of Rho GTPases within protein complexes.

Formation of multiprotein complexes on cellular membranes is critically dependent on the cyclic activation of small GTPases. FRAP-based analyses demonstrate that within protein complexes, some small GTPases cycle nearly three orders of magnitude faster than they would spontaneously cycle in vitro. At the same time, experiments report concomitant excess of the activated, GTP-bound form of GTPases over their inactive form. Intuitively, high activity and rapid turnover are contradictory requirements. How the cells manage to maximize both remains poorly understood. Here, using GTPases of the Rab and Rho families as a prototype, we introduce a computational model of the GTPase cycle. We quantitatively investigate several plausible layouts of the cycling control module that consist of GEFs, GAPs, and GTPase effectors. We explain the existing experimental data and predict how the cycling of GTPases is controlled by the regulatory proteins in vivo. Our model explains distinct and separable roles that the activating GEFs and deactivating GAPs play in the GTPase cycling control. While the activity of GTPase is mainly defined by GEF, the turnover rate is a sole function of GAP. Maximization of the GTPase activity and turnover rate places conflicting requirements on the concentration of GAP. Therefore, to achieve a high activity and turnover rate at once, cells must carefully maintain concentrations of GEFs and GAPs within the optimal range. The values of these optimal concentrations indicate that efficient cycling can be achieved only within dense protein complexes typically assembled on the membrane surfaces. We show that the concentration requirement for GEF can be dramatically reduced by a GEF-activating GTPase effector that can also significantly boost the cycling efficiency. Interestingly, we find that the cycling regimes are only weakly dependent on the concentration of GTPase itself.

Amino Acid Sequence↗

PubMed1988

Predicting cost for new HMO subscribers.

The purpose of the project was to develop a model for predicting costs for potential new HMO subscribers, using available cost data from fiscal year 1985 for current enrollees of a large HMO. Regression analysis of aggregated clinic, referral, and hospital cost data using a log transformation of cost indicated that 20 percent of the variation in cost could be explained by sex and coverage type of the subscriber, compared with 7 percent explainable by a simple comparison of costs for single versus family subscribers. Subscriber age, while by itself a significant and nonlinear predictor of cost, was not significant when controlled for coverage type. Application of the model to 28 large companies yielded predicted costs well correlated with observed costs (r = .75, p less than .01). Prediction was significantly better for companies with low observed mean costs than for companies with high observed mean costs.

Adult↗

PubMed2006

Improving caregiver well-being delays nursing home placement of patients with Alzheimer disease.

OBJECTIVE: To determine the effectiveness of a counseling and support intervention for spouse caregivers in delaying time to nursing home placement of patients with Alzheimer disease (AD), and identify the mechanisms through which the intervention accomplished this goal. METHODS: We conducted a randomized controlled trial of an enhanced counseling and support intervention compared to usual care. Participants were a referred volunteer sample of 406 spouse caregivers of community-dwelling patients who had enrolled in the study over a 9.5-year period. The intervention consisted of six sessions of individual and family counseling, support group participation, and continuous availability of ad hoc telephone counseling. Structured questionnaires were administered at baseline and at regular follow-up intervals, every 4 months for the first year and every 6 months thereafter. Cox proportional hazard models were used to test the effects of the intervention on the time to nursing home placement for the patients after controlling for multiple time-invariant and time-dependent predictors of placement. RESULTS: Patients whose spouses received the intervention experienced a 28.3% reduction in the rate of nursing home placement compared with usual care controls (hazard ratio = 0.717 after covariate adjustment, p = 0.025). The difference in model-predicted median time to placement was 557 days. Improvements in caregivers' satisfaction with social support, response to patient behavior problems, and symptoms of depression collectively accounted for 61.2% of the intervention's beneficial impact on placement. CONCLUSION: Greater access to effective programs of counseling and support could yield considerable benefits for caregivers, patients with Alzheimer disease, and society.

Aged↗

PubMed2001

Body weight setpoint, metabolic adaption and human starvation.

A biological setpoint for fatness has been proposed in the medical literature. This body weight setpoint functions as a point of stable equilibrium. In an underfed state, with resulting weight loss, the body will reduce the relative energy expenditure by metabolic adaption which reduces the rate of weight loss. Previous mathematical models of energy expenditure and weight loss dynamics have not addressed this setpoint mechanism. The setpoint model has been proposed to quantify this biological process and is unique in predicting energy expenditure during weight loss as a function of the setpoint fat-free mass ratio and setpoint energy expenditure, eliminating the various controlling characteristics such as age, gender and heredity. The model is applied to the seminal Minnesota human semistarvation experiment and is used to predict weight vs time on an individual basis and the caloric requirements for weight maintenance at the reduced weight. Comparison is made with the Harris-Benedict equations and the Brody-Kleiber (W3/4) law.

Adaptation, Physiological↗

PubMed2004

Bayesian analysis of binary prediction tree models for retrospectively sampled outcomes.

Classification tree models are flexible analysis tools which have the ability to evaluate interactions among predictors as well as generate predictions for responses of interest. We describe Bayesian analysis of a specific class of tree models in which binary response data arise from a retrospective case-control design. We are also particularly interested in problems with potentially very many candidate predictors. This scenario is common in studies concerning gene expression data, which is a key motivating example context. Innovations here include the introduction of tree models that explicitly address and incorporate the retrospective design, and the use of nonparametric Bayesian models involving Dirichlet process priors on the distributions of predictor variables. The model specification influences the generation of trees through Bayes' factor based tests of association that determine significant binary partitions of nodes during a process of forward generation of trees. We describe this constructive process and discuss questions of generating and combining multiple trees via Bayesian model averaging for prediction. Additional discussion of parameter selection and sensitivity is given in the context of an example which concerns prediction of breast tumour status utilizing high-dimensional gene expression data; the example demonstrates the exploratory/explanatory uses of such models as well as their primary utility in prediction. Shortcomings of the approach and comparison with alternative tree modelling algorithms are also discussed, as are issues of modelling and computational extensions.

Algorithms↗

PubMed1978

Biomechanical models for vibration feedthrough to hands and head for a semisupine pilot.

A series of tracking experiments under vibration has been carried out on the AMRL/BBV shaker facilities covering three axes of vibration with sinusoidal and random waveforms and different control stick configurations. Based on this and other data, a lumped-parameter biomechanical model has been evolved to suit the needs of aircraft control system designers for the new generation of low-altitude, high-speed bombers and highly maneuverable fighters. This paper shows that measured vibration feedthrough to hands and head can be adequately described by this model when linearized about the appropriate configuration of display, posture, and control. The model includes effects of: semisupine torso; sliding hip, plus rocking chest supported on a compliant buttocks/seat; head bobbing on an articulated neck; upper arm and forearm links plus grip-interface compliance, driven by an active neuromuscular system; elbow rest (optional); and stick "feel system" dynamics. Examples are given of the model's application to predict effects of: a 65 degrees semisupine seat, apparent impedance increase of a control stick under pilot control, and a sliding arm rest.

Aerospace Medicine↗

PubMed1998

Artificial neural networks as models of stimulus control.

We evaluate the ability of artificial neural network models (multilayer perceptrons) to predict stimulus-response relationships. A variety of empirical results are considered, such as generalization, peak shift (supernormality) and stimulus intensity effects. The networks were trained on the same tasks as the animals in the experiments considered. The subsequent generalization tests on the networks showed that the model replicates correctly the empirical results. We conclude that these models are valuable tools in the study of animal behaviour. (c) 1998 The Association for the Study of Animal Behaviour.

Journal Article↗

PubMed2002

State detection and control of overloads in the anaerobic wastewater treatment using fuzzy logic.

The two-stage anaerobic wastewater pre-treatment was modelled and controlled. The biological state of the reactors could be predicted using a fuzzy logic system and based upon this, proper control actions were taken automatically in order to avoid an overload. The system was designed to handle very strong fluctuations in the concentration of the substrate and the volumetric loading rate. Hydrogen concentration together with methane concentration, gas production rate. pH and the filling level of the acidification buffer tank were used as input variables for the fuzzy logic system. The manipulated variables were the flow rate from the acidification buffer tank into the methane reactor, the temperature and pH of both reactors, the circulation rate of the fixed bed reactor, back flow from the methane reactor into the acidification, and the control of the feed into the acidification buffer tank. The developed control system was successfully tested on a fully automated lab scale two-stage anaerobic digester. Different types of wastewater from food processing industries were successfully applied. Even a restart of feeding with very high COD concentrations (100 gl(-1) after several days of stand by was handled successfully. Effluent concentrations could be kept low without using TOC, COD or equivalent measurements.

Bacteria, Anaerobic↗