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Modeling the dry-weather tidal cycling of fecal indicator bacteria in surface waters of an intertidal wetland.

Recreational water quality at beaches in California and elsewhere is often poor near the outlets of rivers, estuaries, and lagoons. This condition has prompted interest in the role of wetlands in modulating surface water concentrations of fecal indicator bacteria (FIB), the basis of water quality standards internationally. A model was developed and applied to predict the dry-weather tidal cycling of FIB in Talbert Marsh, an estuarine, intertidal wetland in Huntington Beach, California, in response to loads from urban runoff, bird feces, and resuspended sediments. The model predicts the advection, dispersion and die-off of total coliform, Escherichia coli, and enterococci using a depth-integrated formulation. We find that urban runoff and resuspension of contaminated wetland sediments are responsible for surface water concentrations of FIB in the wetland. Model predictions show that urban runoff controls surface water concentrations at inland sites and sediment resuspension controls surface water concentrations near the mouth. Direct wash-off of bird feces into the surface water is not a significant contributor, although bird feces can contribute to the sediment bacteria load. The key parameters needed to accurately predict FIB concentrations, using a validated hydrodynamic model, are: the load due to urban runoff, sediment erodibility parameters, and sediment concentrations and surface water die-off rates of enteric bacteria. In the present study, literature values for sediment erodibility and water column die-off rates are used and average concentrations of FIB are predicted within 1/2 log unit of measurements. Total coliform are predicted more accurately than E. coli or enterococci, both in terms of magnitude and tidal variability. Since wetland-dependent animals are natural sources of FIB, and FIB survive for long periods of time and may multiply in wetland sediments, these results highlight limitations of FIB as indicators of human fecal pollution in and near wetlands.

California↗

Development of a GPC-based sliding mode controller.

This article presents a sliding mode controller that uses a generalized predictive controller in the reaching mode. The proposed predictive sliding mode controller is developed from a first-order-plus-deadtime model that represents a good approximation to many chemical processes. The predictive sliding mode controller has six tuning parameters and the tuning rules are given in the paper. Four simulation examples show the features of the proposed controller, which overcomes some of the disadvantages of sliding mode control and generalized predictive control strategies.

Algorithms↗

Interaction between surgical procedure for repairing retinal detachment and clinical risk factors for proliferative vitreoretinopathy.

PURPOSE: To asses risk factors of proliferative vitreoretinopathy (PVR) and a model for predicting it. METHODS: Observational, case-control. 335 patients with non-complicated retinal detachment (RD) were included: 134 developed PVR (Cases); 201 patients did not (Controls). Risk factors for PVR were identified by multivariate analysis. Influence of variables was assayed according to the surgical approach. By logistic regression analysis a model to predict the risk of developing PVR and odds ratio (OR) values for each clinical factor were estimated. RESULTS: Risk was higher in patients > 70 years and with intraocular pressure lower than 14 (OR: 3.84; CI 95%: 2.04-7.30) and in retinal breaks larger than "1 clock hour" (OR: 2.54; CI: 1.28-5.05), extended retinal detachments (OR: 4.01; CI: 1.98-8.10) and reinterventions (OR: 1.55; CI: 1.14-9.22). Scleral surgery also was a risk factor (OR: 3.89; CI: 2.12-7.14) and aphakia/pseudophakia when scleral surgery is performed (OR: 3.33; CI: 1.54-7.22). A model to predict PVR was proposed with these results. CONCLUSIONS: Surgical approach modifies risk factors of PVR, and should be taken into account to improve the models for predicting it.

Adolescent↗

A model of scale effects in mammalian quadrupedal running.

Although the effects of body size on mammalian locomotion are well documented, the underlying mechanisms are not fully understood. Here, we present a computational model of the mechanics, control and energetics that unifies some well-known scale effects in running quadrupeds. The model consists of dynamic, physics-based simulations of six running mammals ranging in size from a chipmunk to a horse (0.115-676 kg). The 'virtual animals' are made up of rigid segments (head, trunk and four legs) linked by joints and are similar in morphology to particular species. In the model, each stance limb acts as a spring operating within a narrow range of stiffness, forward motion is powered and controlled by active hip and shoulder torques, and metabolic cost is predicted from the time course of supporting body weight. Model parameters that are important for stability (joint stiffnesses, limb-retraction times and target positions and velocities of the limbs) are selected such that (i) running kinematics (aerial height, forward speed and body pitch) is smooth and periodic and (ii) overall leg stiffness is in agreement with published data. Both trotting and galloping gaits are modeled, and comparisons across size are made at speeds that are physiologically similar among species. Model predictions are in agreement with data on vertical stiffness, limb angles, metabolic cost of transport, stride frequency, peak force and duty factor. This work supports the idea that a single, integrative model can predict important features of running across size by employing simple strategies to control overall leg stiffness. More broadly, the model provides a quantitative framework for testing hypotheses that relate limb control, stability and metabolic cost.

Animals↗

Regulation of herpesvirus replication by subcellular compartmentalization.

The transcriptional regulation of herpesvirus gene expression has been well documented. A second model is proposed that is superimposed on regulation at the transcriptional level. The regulation is post-translational in nature. Three examples of the model are found in viral DNA replication, capsid assembly, and the cleavage and packaging of DNA into capsids. For each example, at least one viral protein depends upon an interaction with a second viral protein for transport into the nucleus. A model is proposed whereby these protein-protein interactions control the efficiency of these processes by the formation of the appropriate protein complexes in the cytoplasm. The model predicts that these interactions impose a necessary control and that mechanisms to bypass this control would deleteriously affect virus replication. It is probable that level of regulation extends for each of these processes among other herpesviruses.

DNA, Viral↗

Development and validation of a 3-D model to predict knee joint loading during dynamic movement.

The purpose of this study was to develop a subject-specific 3-D model of the lower extremity to predict neuromuscular control effects on 3-D knee joint loading during movements that can potentially cause injury to the anterior cruciate ligament (ACL) in the knee. The simulation consisted of a forward dynamic 3-D musculoskeletal model of the lower extremity, scaled to represent a specific subject. Inputs of the model were the initial position and velocity of the skeletal elements, and the muscle stimulation patterns. Outputs of the model were movement and ground reaction forces, as well as resultant 3-D forces and moments acting across the knee joint. An optimization method was established to find muscle stimulation patterns that best reproduced the subject's movement and ground reaction forces during a sidestepping task. The optimized model produced movements and forces that were generally within one standard deviation of the measured subject data. Resultant knee joint loading variables extracted from the optimized model were comparable to those reported in the literature. The ability of the model to successfully predict the subject's response to altered initial conditions was quantified and found acceptable for use of the model to investigate the effect of altered neuromuscular control on knee joint loading during sidestepping. Monte Carlo simulations (N = 100,000) using randomly perturbed initial kinematic conditions, based on the subject's variability, resulted in peak anterior force, valgus torque and internal torque values of 378 N, 94 Nm and 71 Nm, respectively, large enough to cause ACL rupture. We conclude that the procedures described in this paper were successful in creating valid simulations of normal movement, and in simulating injuries that are caused by perturbed neuromuscular control.

Adult↗

Maintenance of equilibrium point control during an unexpectedly loaded rapid limb movement.

Two experiments investigated whether the equilibrium point hypothesis or the mass-spring model of motor control subserves positioning accuracy during spring loaded, rapid, bi-articulated movement. For intact preparations, the equilibrium point hypothesis predicts response accuracy to be determined by a mixture of afferent and efferent information, whereas the mass-spring model predicts positioning to be under a direct control system. Subjects completed a series of load-resisted training trials to a spatial target. The magnitude of a sustained spring load was unexpectedly increased on selected trials. Results indicated positioning accuracy and applied force varied with increases in load, which suggests that the original efferent commands are modified by afferent information during the movement as predicted by the equilibrium point hypothesis.

Humans↗

Planning chemotherapy based schistosomiasis control: validation of a mathematical model using data on Schistosoma haematobium from Pemba, Tanzania.

A mathematical model, based on a deterministic differential equation framework, has been developed to predict the impact of community chemotherapy programmes for human schistosomiasis. Here, this model is validated using data collected from a long-term control programme for urinary schistosomiasis on the island of Pemba, Zanzibar, United Republic of Tanzania, initiated in 1986 and still ongoing, in which schoolchildren were offered praziquantel chemotherapy every 6 months. Prevalence of infection and blood in urine were monitored in all the schools (total 26000 children from 60 schools) and more detailed data were collected in selected evaluation schools. Model predictions were run by using the initial prevalence as input. The predictions were very close to the observed decreases in prevalence and in prevalence of blood in urine. The correspondence improved further when the data were combined, going from single school level to district, and when the entire data set was combined. The accuracy of the predictions suggests that this model could be used as a tool to predict the consequences of chemotherapy control programmes. It is currently in press as a Windows software package under the name of 'EpiSchisto'.

Adolescent↗

Prediction of physical aging in controlled-release coatings: the application of the relaxation coupling model to glassy cellulose acetate.

The effect of physical aging on both the water transport properties and the mechanical properties of glassy cellulose acetate was investigated. Results indicate a reduction in the mechanical rate of relaxation as well as a reduction in the water permeability as the glass ages. A model which describes the low-frequency relaxation behavior of condensed, amorphous systems is used to quantitate the mechanical relaxation data. Systematic changes in key parameters from this model signify alterations in the microscopic or short-range structure as the glass physically ages. Predictions from this model correlate quite closely with the observed water permeability reductions and thus indicate that the transport properties of glassy polymers are dependent on the structure of the glass. This approach may provide further insight into the effects of nonequilibrium behavior on pharmaceutically important properties and may serve as a basis for predicting aging and permeability changes in controlled-release dosage forms.

Cellulose↗

An engineered epigenetic transgene switch in mammalian cells.

In multicellular systems cell identity is imprinted by epigenetic regulation circuits, which determine the global transcriptome of adult cells in a cell phenotype-specific manner. By combining two repressors, which control each other's expression, we have developed a mammalian epigenetic circuitry able to switch between two stable transgene expression states after transient administration of two alternate drugs. Engineered Chinese hamster ovary cells (CHO-K1) showed toggle switch-specific expression profiles of a human glycoprotein in culture, as well as after microencapsulation and implantation into mice. Switch dynamics and expression stability could be predicted with mathematical models. Epigenetic transgene control through toggle switches is an important tool for engineering artificial gene networks in mammalian cells.

Alkaline Phosphatase↗

Interactions between eye and head control signals can account for movement kinematics.

Advances in understanding the neural control of saccades (visual orienting movements made when the head is prevented from moving) stem largely from early modeling efforts which provided a framework for developing and testing hypotheses about the relationships between neural activity and observed behaviors. When the head is free to move, visual orienting is often accomplished with coordinated movements of the eyes and head. A recent description of the temporal progression (i.e., kinematics) of these movements led to the hypothesis that eye and head control signals interact. This hypothesis is now formalized as a control systems model which accounts for existing data and makes explicit predictions about the neural control of orienting gaze shifts.

Animals↗

Polymer size and concentration effects on the size of gold nanoparticles capped by polymeric thiols.

Gold nanoparticles stabilized by thiol-terminated poly(ethylene glycol) monomethyl ethers with molecular weights ranging from 350 to 2000 have been prepared at thiol-to-gold molar ratios ranging from 3:1 to 1:8. Particle size distributions have been constructed for these particles from transmission electron microscopy images of hundreds of particles for each variation in synthetic conditions. The mean diameters of these particles range from 1.5 to 3.2 nm, with a slight increase in particle size with decreasing thiol content; these particles are smaller than those prepared using alkanethiols at similar thiol-to-gold ratios. Particles prepared under thiol-poor conditions exhibit much greater polydispersity than those prepared under thiol-rich conditions and include numerically rare large-particle outliers that contain much of the gold in the sample. The mean diameters of the gold nanoparticles decrease slightly with increasing polymer weight, especially under thiol-rich conditions. A simple model is developed to predict the trends in nanoparticle diameter that would result were the polymer's steric bulk protecting the nanoparticles from additional growth the principal factor controlling nanoparticle size in this system. This model predicts a much stronger dependence on thiol concentration than has been experimentally observed and a dependence on polymer molecular weight opposite to that experimentally observed. This suggests that the polymers' steric bulk is not the principal reason that these polymers yield smaller nanoparticles than alkanethiols at similar thiol-to-gold ratios. It is instead proposed that polar polymers may yield small nanoparticles by accelerating particle nucleation via coordination between functional groups in the polymer and atomic gold.

Gold↗

Model of human/liquid cooling garment interaction for space suit automatic thermal control.

The Wissler human thermoregulation model was augmented to incorporate simulation of a space suit thermal control system that includes interaction with a liquid cooled garment (LCG) and ventilation gas flow through the suit. The model was utilized in the design process of an automatic controller intended to maintain thermal neutrality of an exercising subject wearing a liquid cooling garment. An experimental apparatus was designed and built to test the efficacy of specific physiological state measurements to provide feedback data for input to the automatic control algorithm. Control of the coolant inlet temperature to the LCG was based on evaluation of transient physiological parameters that describe the thermal state of the subject, including metabolic rate, skin temperatures, and core temperature. Experimental evaluation of the control algorithm function was accomplished in an environmental chamber under conditions that simulated the thermal environment of a space suit and transient metabolic work loads typical of astronaut extravehicular activity (EVA). The model was also applied to analyze experiments to evaluate performance of the automatic control system in maintaining thermal comfort during extensive transient metabolic profiles for a range of environmental temperatures. Finally, the model was used to predict the efficacy of the LCG thermal controller for providing thermal comfort for a variety of regiments that may be encountered in future space missions. Simulations with the Wissler model accurately predicted the thermal interaction between the subject and LCG for a wide range of metabolic profiles and environmental conditions and matched the function of the automatic temperature controller for inlet cooling water to the LCG.

Algorithms↗

A model of tsetse-transmitted animal trypanosomiasis.

The data needed to develop analytical models of trypanosomiasis transmission have become available only recently. By making some simplifying assumptions, models of the dynamics of the disease in vector, cattle and wild mammal populations can be constructed in order to determine criteria for successful disease control by mass and targetted chemotherapy, and by vector control. The heterogeneity in transmission due to tsetse fly feeding preferences and the variability of immunological characteristics among the vertebrate hosts account for differences in prevalence of Trypanosoma vivax and T. congolense, and also lead to an increase in the basic reproductive rates of the parasites and a corresponding decrease in the vector population density threshold for disease eradication or persistence. The long life-span of the vectors relative to the duration of the parasites' developmental period lead to high infection rates in the vector and high values of R0. The efficacy of chemotherapeutic regimes depends on the relationship between treatment rate and the duration of prophylaxis conferred by the drugs used. The model's predictions of the effects of vector control are shown to be in broad agreement with published field data for Mkwaja Ranch, Tanzania. Vector control programmes are frequently blighted by reinvasion, and the implications of this are discussed in terms of a model for fly immigration. With immigration of vectors, the disease is always endemic, though the infection rate in the fly population is modified by the effect of differential mortalities inside and outside the controlled area on cohorts of incubating flies. Sensitivity analysis of the model, using Monte-Carlo methods, enables an assessment of the relative importance of the parameters to be made. The results emphasize the need for studies of the wild animal reservoir to be carried out alongside entomological surveys. The relative accuracy with which field measurements need to be made in order to minimize the uncertainty in predictions of trypanosomiasis prevalence is discussed.

Animals↗

Predictive modeling of mixed microbial populations in food products: evaluation of two-species models.

Predictive microbiology is an emerging research domain in which biological and mathematical knowledge is combined to develop models for the prediction of microbial proliferation in foods. To provide accurate predictions, models must incorporate essential factors controlling microbial growth. Current models often take into account environmental conditions such as temperature, pH and water activity. One factor which has not been included in many models is the influence of a background microflora, which brings along microbial interactions. The present research explores the potential of autonomous continuous-time/two-species models to describe mixed population growth in foods. A set of four basic requirements, which a model should satisfy to be of use for this particular application, is specified. Further, a number of models originating from research fields outside predictive microbiology, but all dealing with interacting species, are evaluated with respect to the formulated model requirements by means of both graphical and analytical techniques. The analysis reveals that of the investigated models, the classical Lotka-Volterra model for two species in competition and several extensions of this model fulfill three of the four requirements. However, none of the models is in agreement with all requirements. Moreover, from the analytical approach, it is clear that the development of a model satisfying all requirements, within a framework of two autonomous differential equations, is not straightforward. Therefore, a novel prototype model structure, extending the Lotka-Volterra model with two differential equations describing two additional state variables, is proposed to describe mixed microbial populations in foods.

Evaluation Studies as Topic↗

Effect of overall time when radiotherapy includes teletherapy and brachytherapy: a mathematical model.

By expanding the linear quadratic equations to allow for the interval of time between teletherapy and brachytherapy in a model which assumes continual exponential tumour regression following teletherapy, the loge cell kill resulting from brachytherapy is found to depend on radiosensitivity, tumour regression rate (lambda) and tumour clonogen doubling time (Tp). When lambda is relatively small the precise timing of brachytherapy following teletherapy is shown to influence the tumour cure probabilities. The model predicts a reduction in tumour control if brachytherapy is delayed when lambda values are small and Tp values are short, but when Tp values are long, deferral of brachytherapy may be advantageous. By differential calculus the occurrence of a minimum value of log cell kill can be found. Application of these concepts may improve the results of clinical radiotherapy.

Brachytherapy↗

On-line multi-analyzer monitoring of biomass, glucose and acetate for growth rate control of a Vibrio cholerae fed-batch cultivation.

In situ near-infrared (NIR) spectroscopy and in-line electronic nose (EN) mapping were used to monitor and control a cholera-toxin producing Vibrio cholerae fed-batch cultivation carried out with a laboratory method as well as with a production method. Prediction models for biomass, glucose and acetate using NIR spectroscopy were developed based on spectral identification and partial-least squares (PLS) regression resulting in high correlation to reference data (standard errors of prediction for biomass, glucose and acetate were 0.20 gl(-1), 0.26 gl(-1) and 0.28 gl(-1)). A compensation algorithm for aerated bioreactor disturbances was integrated in the model computation, which in particular improved the prediction by the biomass model. First, the NIR data were applied together with EN in-line data selected by principal component analysis (PCA) for generating a trajectory representation of the fed-batch cultivation. A correlation between the culture progression and EN signals was demonstrated, which proved to be beneficial in monitoring the culture quality. It was shown that a deviation from a normal cultivation behavior could easily be recognized and that the trajectory was able to alarm a bacterial contamination. Second, the NIR data indicated the potential of predicting the concentration of formed cholera toxin with a model prediction error of 0.020 gl(-1). Third, the on-line biomass prediction based on the NIR model was used to control the overflow metabolism acetate formation of the V. cholerae culture. The controller compared actual specific growth rate as estimated from the prediction with the critical acetate formation growth rate, and from that difference adjusted the glucose feed rate.

Acetates↗

Gender differences in outcomes in an HMO-based substance abuse treatment program.

This study examined gender differences in treatment outcomes and outcomes predictors among 155 men and 81 women attending a gender-sensitive substance abuse treatment program. Bivariate analyses indicated women improved more than men in social/family and daily functioning domains, but differences disappeared after controlling for baseline characteristics. Multivariate models predicting treatment outcomes revealed that, across Addiction Severity Index domains, outcomes for men were predicted primarily by mental health and medical conditions, severity of the substance abuse problem, and treatment com- pletion. For women, in addition to treatment completion, outcomes were more likely to be predicted by social, socio-demographic, and life-history characteristics. For abstinence outcomes, women who completed treatment were 9 times as likely to be abstinent at 7-month follow-up as other women; men who completed were 3 times more likely to be abstinent than other men. Women with more severe psychiatric status and those who felt their life was out of control were less likely to be abstinent, as were men who lived alone. Clinicians targeting such factors differentially for men and women may enhance the effectiveness of treatment.

Adult↗