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PubMed1980

Local contrast and maintained generalization.

Pigeons received variable-interval reinforcement for key pecking during presentations of horizontal and vertical line-orientation stimuli, while pecks during five intermediate orientations were extinguished. Lowest peck rates were observed during presentations of negative stimuli adjacent to the positive orientations while peck rate during 45 degrees (the intermediate negative orientation) was relatively high, i.e., there were negative contrast shoulders. When peck rates were manipulated in the positive orientations, peck rate in neithboring orientations changed in the opposite direction. Contrast shoulders faded after prolonged training. A second type of contrast, local contrast, was correlated with similarity of preceding stimulus and different average peck rates during different stages of the discrimination process. The data suggest that sequential local contrast accompanying the formation of a discrimination contributes to the form of generalization gradients. Blough's model of stimulus control predicts the changes in gradient form described here, but may not accurately depict the underlying process responsible for gradient form.

Animals↗

PubMed1997

Phasic temperature control appraised with the Ceres-Wheat model.

Phasic control refers to the specification of a series of different environmental conditions during a crop's life cycle, with the goal of optimizing some aspect of productivity. Because of the enormous number of possible scenarios, phasic control is an ideal situation for modeling to provide guidance prior to experiments. Here we use the Ceres-Wheat model, modified for hydroponic growth chambers, to examine temperature effects. We first establish a baseline by running the model at constant temperatures from 10 degrees C to 30 degrees C. Grain yield per day peaks at 15 degrees C at a value that is 25% higher than the yield at the commonly used 23 degrees C. We then show results for phasic control limited to a single shift in temperature and, finally, we examine scenarios that allow each of the five phases of the life cycle to have a different temperature. Results indicate that grain yield might be increased by 15-20% over the best yield at constant temperature, primarily from a boosted harvest index, which has the additional advantage of less waste biomass. Such gains, if achievable, would help optimize food production for life support systems. Experimental work should first verify the relationship between yield and temperature, and then move to selected scenarios of phasic control, based on model predictions.

Biomass↗

PubMed2006

Prediction of distal radius fracture in children, using a biomechanical impact model and case-control data on playground free falls.

OBJECTIVES: To assess the ability of a biomechanical impact model to predict the likelihood of distal radius fracture in children using data gathered for a previous epidemiological case-control study of falls from playground equipment. METHODOLOGY: Factor of Risk (FR) values were generated for each of selected subjects from the case-control study using a biomechanical model. Logistic regression curves were fitted to examine the relationship between the FR values and the probability of radius fracture. RESULTS: Forty-five cases and thirty-one controls were selected. The logistic regression analyses showed a significant association between the probability of fracture and FR. CONCLUSIONS: The biomechanical model distinguished between children who fractured their distal radius and those who did not. The model can be used to test how risk factors, such as fall height and ground surface type, affect physical stresses transmitted through the arm and their relation to the fracture tolerance of the distal radius.

Accidental Falls↗

PubMed2000

A model for evaluating intervention strategies to control salmonella in the poultry meat production chain.

A model of the transmission of salmonella through the poultry meat production chain is developed, to predict the effects of intervention strategies for salmonella control. The model first describes the situation before intervention in terms of salmonella prevalences at flock level and some transmission parameters. After single control measures are translated into effects on these transmission parameters, the effects of sets of control measures (intervention strategies), can be calculated with the model. As research data are lacking, the model input parameters were derived from expert opinion. As an example, the effects of two intervention strategies proposed for the Dutch poultry industry are predicted. A sensitivity analysis is performed to indicate where the most effective control measures may be expected. Additionally, the reliability of the model predictions is studied by an uncertainty analysis. The use of the model as a tool for policy makers deciding about salmonella control strategies is discussed.

Animal Husbandry↗

PubMed2003

Founder control and coexistence in a simple model of asymmetric competition for light.

Size asymmetry in plant light acquisition complicates predictions of competitive outcomes in light-limited communities. We present a mathematically tractable model of asymmetric competition for light and discuss its implications for predicting outcomes of competition during establishment in two-, three-, and many-species communities. In contrast to the resource-reduction model of symmetric competition for a single resource, the model we present predicts that outcomes of asymmetric competition for light will sometimes depend on the timing of establishment and the consequent hierarchy among species in canopy position. Competitive outcomes in the model depend on the minimum light requirements (L(c)) and self-shading of species lower in the canopy compared to the light available (L(out)(*)) beneath species higher in the canopy. Succession progresses towards species with decreasing values for L(c), but arrested successions occur when initial dominants have relatively high values for L(c) but low values for L(out)(*), leading to founder control. A theoretically limitless number of species may coexist in competition for light when dominance is founder controlled. These model predictions have implications for an array of applied ecological questions, including methods to control invasive species in light-limited restored ecosystems.

Biomass↗

PubMed2006

A Process Analytical Technology approach to near-infrared process control of pharmaceutical powder blending: Part II: Qualitative near-infrared models for prediction of blend homogeneity.

The successful implementation of near-infrared spectroscopy (NIRS) in process control of powder blending requires constructing an inclusive spectral database that reflects the anticipated voluntary or involuntary changes in processing conditions, thereby minimizing bias in prediction of blending behavior. In this study, experimental design was utilized as an efficient way of generating blend experiments conducted under varying processing conditions such as humidity, blender speed and component concentration. NIR spectral data, collected from different blending experiments, was used to build qualitative models for prediction of blend homogeneity. Two pattern recognition algorithms: Soft Independent Modeling of Class Analogies (SIMCA) and Principal Component Modified Bootstrap Error-adjusted Single-sample Technique (PC-MBEST) were evaluated for qualitative analysis of NIR blending data. Optimization of NIR models, for the two algorithms, was achieved by proper selection of spectral processing, and training set samples. The models developed were successful in predicting blend homogeneity of independent blend samples under different processing conditions.

Algorithms↗

PubMed1992

A longitudinal analysis of adherence and health status in childhood diabetes.

Applied structural equation modeling to a longitudinal data set of 193 youngsters with insulin-dependent diabetes mellitus assessed on two occasions, an average of 1.65 years apart. Six adherence constructs, Injection, Exercise, Diet Type, Testing-Eating Frequency, Calories Consumed, and Concentrated Sweets, were quantified from 24-hr recall interviews conducted with mother and child. Glycemic control was indexed by glycosylated hemoglobin (HA1C); lipid metabolism was indexed by fasting triglyceride levels (TRIG). The relationship of each adherence construct to metabolic control was tested separately. Patient age and disease duration served as exogenous variables in all models. Testing-Eating Frequency was associated with HA1C and Injection was associated with TRIG; in both cases better adherence was associated with better metabolic control. However, the standardized regression weights and variance accounted for were small. Patient age was a predictor of both adherence and metabolic control; older youngsters were less adherent and were in worse metabolic control. Inspection of models for younger versus older children suggested that age-homogeneous models improved prediction, but adherence and metabolic control linkages remained weak. Suggestions for refining the model are provided.

Blood Glucose↗

PubMed2004

The biology and engineering of stem-cell control.

There is significant interest in studying stem cells, both to elucidate their basic biological functions during development and adulthood as well as to learn how to utilize them as new sources of specialized cells for tissue repair. Whether the motivation is basic biology or biomedical application, however, progress will hinge upon learning how to better control stem-cell function at a quantitative and molecular level. There are several major challenges within the field, including the identification of new signals and conditions that regulate and influence cell function, and the application of this information towards the design of stem-cell bioprocesses and therapies. Both of these efforts can significantly benefit from the synthesis of biological data into quantitative and increasingly mechanistic models that not only describe, but also predict, how a stem cell's environment can control its fate. This review will briefly summarize the history and current state of the stem-cell biology field, but will then focus on the development of predictive models for stem-cell control. Early models formulated on the assumption that cell fate was decided by stochastic, cell-intrinsic processes have gradually evolved into hybrid deterministic-stochastic models with increasingly finer molecular resolution that accounts for environmental regulation. As our understanding of cellular control mechanisms expands from the cell surface and towards the nucleus, these efforts may culminate in the development of a stem-cell culture programme, or a series of signals to provide to the cells as a function of time to guide them along a desired developmental trajectory.

Animals↗

PubMed1992

A model of the volumetrically-controlled hemodialysis circuit.

We developed a model that predicts the hemodynamics of the volumetrically-controlled circuit used to administer high flux hemodialysis. The equations simulate the entire blood side of the circuit so that blood and dialysate pressures can be predicted from a knowledge of circuit component and patient characteristics. An alternative method of computation has also been devised which permits measured circuit pressures to be used to predict patient blood access pressure, dialyzer resistance to flow and membrane hydraulic conductivity. Success of the model was evaluated by measuring both circuit pressure and component characteristics. The model successfully predicted circuit pressures when measured component characteristics were employed as model inputs. Conversely, the model accurately predicted circuit component characteristics when measured pressures were employed as inputs (8 patients, 30 dialyses). Specific predictions of the model include the following. Elevations of patient blood access pressure will cause blood and dialysate pressures to rise equivalently without affecting the rate of back-filtration or location of pressure equilibrium along the dialyzer axis. Elevated hematocrit is predicted to increase circuit pressures to a degree that is similar to a poorly functioning blood access, however, high hematocrit markedly augments back-filtration and moves the point of pressure equilibrium toward the dialyzer entrance. We conclude that the model provides a predictive tool that can be used to optimize circuit design. Alternatively, the model can be used to separate the influence of a poorly functioning patient access from other factors which can elevate circuit pressures.

Blood Flow Velocity↗

PubMed2006

Predictive performance of three multivariate difficult tracheal intubation models: a double-blind, case-controlled study.

We performed a case-controlled, double-blind study to examine the performance of three multivariate clinical models (Wilson, Arné, and Naguib models) in the prediction of unanticipated difficult intubation. The study group consisted of 97 patients in whom an unanticipated difficult intubation had occurred. For each difficult intubation patient, a matched control patient was selected in whom tracheal intubation had been easily accomplished. Postoperatively, a blinded investigator evaluated both patients. The clinical assessment included the patient's weight, height, age, Mallampati score, interincisor gap, thyromental distance, thyrosternal distance, neck circumference, Wilson risk sum score, history of previous difficult intubation, and diseases associated with difficult laryngoscopy or intubation. The Naguib model was significantly more sensitive (81.4%; P < 0.0001) than the Arné (54.6%) or Wilson (40.2%) models. Both the Naguib (76.8%) and Arné (74.7%) model classified more intubations correctly (P = 0.01) than the Wilson model (66.5%). The specificity of Arné, Wilson, and Naguib model was 94.9%, 92.8%, and 72.2%, respectively (P < 0.0001). The corresponding area under the receiver operating characteristic curve was 0.87, 0.79, and 0.82, respectively. Our new model for prediction of difficult intubation was developed using logistic regression and includes thyromental distance, Mallampati score, interincisor gap, and height. This model is 82.5% sensitive and 85.6% specific with an area under the receiver operating characteristic curve of 0.90.

Adult↗

PubMed1994

Radiosurgery dose distributions: theoretical impact of inhomogeneities on lesion control.

OBJECTIVE: To develop a mathematical model to predict the impact of dose heterogeneities on tumor/lesion control during radiosurgery. It is necessary to be able to estimate these effects in order to quantitatively and objectively assess competing treatment plans. METHODS: Target cells are assumed to be uniformly distributed throughout the lesion. The control rate for the entire lesion is assumed to be the product of the control probabilities for each subregion within the target volume. The lesion control probability (LCP) for each region is assumed to equal EXP (the number of surviving target cells within the subregion), as predicted by Poisson statistics. Subregions of variable size are assumed to receive variable doses, and the impact of this dose heterogeneity on the LCP is calculated based on the single-fraction radiation cell survival curve predicted by the single-hit multitarget model. RESULTS: The impact of a dose heterogeneity on LCP is related to three variables: the LCP predicted with uniform irradiation, the volume of the lesion that is irradiated to a new dose, and the magnitude of the dose change relative to the slope of the single-fraction radiation cell survival curve of (delta D/Dzero). The calculations predict that the detrimental effect of underdosing regions of the lesion can, in some instances, be offset by escalating the dose to other subregions within the target volume. In this regard, the "average" dose delivered to the lesion rather than the minimum dose may be most predictive of the lesion control probability. In some situations, escalating the dose to part of the lesion may improve the lesion control rate. CONCLUSION: These calculations quantify the theoretical impact of dose heterogeneities on lesion control rate and may be very useful when comparing competing treatment plans.

Dose-Response Relationship, Radiation↗

PubMed2005

Force level independent representations of predictive grip force-load force coupling: a PET activation study.

The existence of forward internal models is a fundamental principle in theories of predictive motor control. There are indications that internal models are represented in the cerebellum. So far, no conclusive data exist on automated procedures involving predictive motor behavior. In particular, it is unknown whether single or multiple task-specific internal models handle the broad range of behavioral situations in which they occur. Using H2(15)O PET in eight subjects, we examined predictive motor control in an automated grip force-load force coupling task at three differing load force levels. In the experimental condition, subjects pulled a grasped object against an isometric resistance while simultaneously producing anticipatory grip forces. There were three control conditions (pull force isolated; grip force isolated; motor rest). A 2 x 2 factorial design was chosen to reveal the interaction effect of grip force-pull force coupling. The factors were pull force (with/without) and grip force (with/without). Grip and load forces were well matched between experimental and control conditions. Conjunction inference and interaction analyses identified force coupling related activity in the ipsilateral posterior cerebellum that was independent of force levels. Interaction effects were also identified in the anterior cingulate and frontal association regions, the right caudate nucleus, and the left lingual gyrus. These data demonstrate the existence of modular representations for predictive force coupling, with the ipsilateral cerebellum playing a major role. Moreover, the data implicate that the representations for predictive force control are applicable to a range of different environmental affordances.

Brain↗

PubMed1988

Gastrointestinal nematode parasites and the stability and productivity of intensive ruminant grazing systems.

This paper uses mathematical models, describing the transmission dynamics of directly transmitted gastrointestinal nematode parasites of sheep and cattle, to examine the impact of these parasites on the stability and productivity of ruminant grazing systems. Current models of the ecology of grass growth under grazing, and the epidemiology of trichostrongylid nematode parasites of ruminants, are combined in a formulation that captures the general features of the plant - (ruminant) herbivore - parasite interaction. The simplest case, in which herbivore numbers are constant and not food limited (the norm for many agricultural systems) is considered in detail. The effect of gastrointestinal parasitism in reducing herbivore feeding rates is shown to act as a potential density-dependent constraint on the parasite's infection rate. The process is manifested in the model as a progressive linearization of the relation between herbivore feeding rate and plant density at the parasite equilibrium. This effect acts to stabilize the dynamics of the model grazing system and significantly affects its predictions about the impact of parasite control and the pattern of host productivity. Model predictions are discussed in the light of relevant field observations, and areas for future research are identified.

Animal Feed↗

PubMed2003

Controlling incision-induced distortion of nasal septal cartilage: a model to predict the effect of scoring of rabbit septa.

Cartilage can be shaped by scoring. In an exploratory study in living adult animals, this phenomenon was demonstrated in cartilage of the nasal septum. Bending was observed immediately after superficial scoring of the cartilage surface, and the cartilage always warped in the direction away from the scored side. The scored piece of cartilage still showed its initially distorted shape 10 weeks after primary surgery. In ex vivo experiments, a clear relation between incision depth and bending of septal cartilage was observed. Under these controlled conditions, the variation between different septa was small. Deformation of the septal specimens was increased by introducing single superficial incisions deepening to half the thickness of the cartilage. A positive correlation between incision depth and bending was demonstrated. A model was used to accurately predict the degree of bending of the cartilage after making an incision of a particular depth. Hence, the effect of cartilage scoring can be predicted. Because the results of this controlled study showed excellent reproducibility for different septa, it is expected that this model can be extrapolated to human nasal septum cartilage. This would enable the surgeon to better predict the result of cartilage scoring, either preoperatively or perioperatively.

Animals↗

PubMed1995

Fast freeze-fixation/freeze-substitution reveals the secretory membranes of the gastric parietal cell as a network of helically coiled tubule. A new model for parietal cell transformation.

The parietal cell of the gastric mucosa undergoes rapid morphological transformation when it is stimulated to produce hydrochloric acid. In chemically fixed cells, this process is seen as a reduction in number of cytoplasmic 'tubulovesicles' as the apical surface of the cell progressively invaginates to increase the secretory surface area. It is widely believed that the tubulovesicles represent stored secretory membrane in the cytoplasm of the unstimulated cell, which is incorporated into the apical membrane upon stimulation, because they share H+,K+-ATPase activity with the apical membrane. However, fusion of tubulovesicles with the apical membrane concomitant with parietal cell activation has never been convincingly demonstrated. We have used fast freeze-fixation and freeze-substitution to study stages of morphological transformation in these cells. Tubulovesicles were not seen in the cytoplasm of any of our cryoprepared cells. Instead, the cytoplasm of the unstimulated cell contained numerous and densely packed helical coils of tubule, each having an axial core of cytoplasm. The helical coils were linked together by connecting tubules, lengths of relatively straight tubule. Lengths of straight connecting tubule also extended from coils lying adjacent to the apical and canalicular surfaces and ended at the apical and canaliculus membranes. Immunogold labelling with alpha- and beta-subunit-specific antibodies showed that the gastric H+,K+-ATPase was localized to the membranes of this tubular system, which therefore represented the configuration of the secretory membrane in the cytoplasm of the unstimulated parietal cell. Stimulation of the cells with histamine and isobutylmethylxanthine lead to modification of the tubular membrane system, correlated with progressive invagination of the apical membrane. The volume of the tubule lumen increased and, as this occurred, the tight spiral twist of the helical coils was lost, indicating that tubule distension was accounted for by partial unwinding. This exposed the cores of cytoplasm in the axes of the coils as rod-shaped elements of a three-dimensional reticulum, resembling a series of microvilli in random thin sections. Conversely, treatment with the H2 antagonist cimetidine caused severe contraction of the tubular membrane system and intracellular canaliculi. Our results indicate that tubulovesicles are an artifact of chemical fixation; consequently, they cannot have a role in parietal cell transformation. From our findings we propose an alternative model for morphological transformation in the parietal cell. This model predicts cytoskeleton-mediated control over expansion and contraction of the tubular membrane network revealed by cryopreparation. The model is compatible with the localization of cytoskeletal components in these cells.

Animals↗

PubMed2000

A simplified model for predicting malaria entomologic inoculation rates based on entomologic and parasitologic parameters relevant to control.

Malaria transmission intensity is modeled from the starting perspective of individual vector mosquitoes and is expressed directly as the entomologic inoculation rate (EIR). The potential of individual mosquitoes to transmit malaria during their lifetime is presented graphically as a function of their feeding cycle length and survival, human biting preferences, and the parasite sporogonic incubation period. The EIR is then calculated as the product of 1) the potential of individual vectors to transmit malaria during their lifetime, 2) vector emergence rate relative to human population size, and 3) the infectiousness of the human population to vectors. Thus, impacts on more than one of these parameters will amplify each other's effects. The EIRs transmitted by the dominant vector species at four malaria-endemic sites from Papua New Guinea, Tanzania, and Nigeria were predicted using field measurements of these characteristics together with human biting rate and human reservoir infectiousness. This model predicted EIRs (+/- SD) that are 1.13 +/- 0.37 (range = 0.84-1.59) times those measured in the field. For these four sites, mosquito emergence rate and lifetime transmission potential were more important determinants of the EIR than human reservoir infectiousness. This model and the input parameters from the four sites allow the potential impacts of various control measures on malaria transmission intensity to be tested under a range of endemic conditions. The model has potential applications for the development and implementation of transmission control measures and for public health education.

Animals↗

PubMed1990

Approximation of various canine left ventricular end-systolic relations by a cylinder model.

Assuming a linear end-systolic force-length relation and a cylindrical geometry of the left ventricle (LV), we have developed a mathematical model (cylinder model) and derived formulas for LV end-systolic force-diameter (Fes-Des), stress-diameter (Ses-Des), pressure-diameter (Pes-Des), and pressure-cylinder volume (Pes-Ves) relations. To assess the validity of this model for the study of the intact LV, eight healthy beagles were instrumented with ultrasonic crystals to measure LV diameter and wall thickness and a micromanometer to measure LV pressures. Preload was altered by vena caval occlusion. Contractility was increased by addition of Ca2+. Fes-Des relation was nearly linear under control contractility, whereas after addition of Ca2+ this relation became concave toward the diameter axis. Linear approximation was more accurate for this relation than for the Pes-Des and Pes-Ves relations in control contractility. Predictions from the model formulas more accurately reproduced observed data in the Pes-Des (P less than 0.01) and Pes-Ves (P less than 0.001) relations than those from linear regression equations, whereas the model predictions for the Ses-Des relation were as accurate as those of a linear regression equation. Although the slope of the Fes-Des relation increased with inotropic stimulation, diameter intercepts of this relation did not change. Thus the present results obtained under control contractility were consistent with assumptions of the model. This cylinder model might provide reasonable approximations for various canine LV end-systolic relations.

Animals↗

PubMed2004

A new system for the prediction of drug absorption using a pH-controlled Caco-2 model: evaluation of pH-dependent soluble drug absorption and pH-related changes in absorption.

One purpose of this study was to develop a new system for the prediction of pH-dependent soluble drug absorption that takes into account the physiological condition of the gastrointestinal tract. Another purpose was to establish several models of different gastric acidities: a normal gastric acidity model, a low gastric acidity model (a model of achlorhydria), a temporarily elevated gastric acidity model (a model of a case in which an acidic drug was coadministered to temporarily elevate gastric acidity in the case of low gastric acidity), a weak antacid model (a model of a case in which a weak antacid drug, such as an H(2) receptor antagonist, was coadministered to temporarily elevate pH up to 6), and a strong antacid model (a model of a case in which a strong antacid drug, such as magnesium hydroxide, was coadministered to temporarily elevate pH up to 8.0). These models were used to evaluate variation in pH-related absorption in humans. Dipyridamole preparation (Persantin tablets) and glibenclamide preparation (Euglucon tablets), both poorly water-soluble and pH-dependent soluble drugs, were chosen as model drugs to determine whether absorption is altered by changes in levels of gastric acid. The extent of absorption of dipyridamole was remarkably lower when gastric pH was continuously elevated to 6.0, whereas it was increased when gastric pH temporarily decreased to 1.8. The extent of absorption of glibenclamide increased dramatically when gastric pH temporarily increased to 8.0, but did not change when gastric pH temporarily increased to 6.0. These results are consistent with reported results obtained in clinical studies. The results suggest that pH-related variations in absorption in humans can be accurately predicted using our new system.

Caco-2 Cells↗