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Application of geographic information systems and remote sensing to schistosomiasis control in China.

Progress in China on developing prediction models using remote sensing, geographic information systems and climate data with historical infection prevalence and malacology databases is reviewed. Special reference is made to the effects of the Yangtze river Three Gorges dam project on environmental changes that may impact changes in the spatial and temporal distribution and abundance of Schistosoma japonicum in China, and the future success of disease control programs.

Animals↗

Extension of a state-of-the-art optimization criterion to predict co-contraction.

Most studies concerned with the prediction of muscle forces have tried to predict a physiologically reasonable, synergistic muscle behavior. In addition to the load sharing of synergistic muscles, co-contraction of antagonistic muscles also occurs. An extension to a standard quadratic criterion for the calculation of muscle forces is presented in this study. This extension however is not limited to quadratic optimization. The extension is applied to a planar, one degree of freedom model of the human knee. For this model an analytical solution is presented. With the extended criterion it was possible to predict and control the amount of co-contraction for the knee model. The enforced antagonistic muscle activity led to higher agonistic muscle activity. In the absence of an external load flexor and extensor muscles were activated. As a consequence the knee joint was preloaded. This might indicate that antagonistic muscle activity is generated to maintain or improve joint stability. In conclusion, this study presents a novel approach to predict co-contraction when using optimization techniques to determine muscle forces by introducing a shift parameter for the optimization criterion.

Humans↗

Examination of the effect of nongenetic risk factors on the familial risk of breast cancer among relatives of postmenopausal breast cancer patients.

Relatives of postmenopausal breast cancer patients have a greater risk of breast cancer than do women with no family history of the disease. However, no study has previously examined the contribution of other breast cancer risk factors to risk in these relatives, thus precluding the ability to discern between shared environment or genes as the cause of familial aggregation. We conducted a nested case-control study of 251 index case families and 234 index control families. Incident breast cancer cases occurring in 1988-1989 and cancer-free controls were selected from a prospective cohort study. A pedigree development form was mailed to identify female relatives, who were then mailed a health history questionnaire. Index cases were significantly more likely than index controls to have at least one first-degree female relative with breast cancer [odds ratio = 1.62; 95% confidence interval = 1.03-2.54] after controlling for the total number of first-degree female relatives. After excluding the index cases and controls, logistic regression models were used to predict the odds of breast cancer in sisters (n = 72 cases). Sisters of index cases had slightly, although not statistically significant, elevated risk of both early-onset (age < 50 years; odds ratio = 1.34; 95% confidence interval = 0.54-3.30) and late-onset (age > or = 50 years; odds ratio = 1.56; 95% confidence interval = 0.87-2.79) breast cancer. Adjustment for nongenetic risk factors increased the odds ratio to 1.41 and 1.81, respectively. These data suggest that risk to sisters of postmenopausal breast cancer cases may be increased for both early- and late-onset breast cancer and this risk is apparently independent of measured risk factors.

Aged↗

Dynamic selection of models for a ventilator-management advisor.

A ventilator-management advisor (VMA) is a computer program that monitors patients who are treated with a mechanical ventilator. A VMA implements a patient-specific physiologic model to interpret patient data and to predict the effects of alternative control settings for the ventilator. Because a VMA evaluates its physiologic model repeatedly during each cycle of data interpretation, highly complex models may require more computation time than is available in this time-critical application. On the other hand, less complex models may be inaccurate if they are unable to represent a patient's physiologic abnormalities. For each patient, a VMA should select a model that balances the tradeoff of prediction accuracy and computation-time complexity. I present a method to select models that are at an appropriate level of detail for time-constrained decision tasks. The method is based on a local search in a graph of models (GoM) for a model that maximizes the tradeoff of computation-time complexity and prediction accuracy. For each model under consideration, a belief network computes a probability of model adequacy given the qualitative prior information, and the goodness of fit of the model to the data provides a measure of the conditional probability of adequacy given the quantitative observations. I apply this method to the problem of model selection for a VMA. I describe an implementation of a graph of physiologic models that range in complexity from VentPlan, a simple model with 3 compartments, to VentSim, a multicompartment model with detailed airway, circulation and mechanical ventilator components.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer Simulation↗

Relationship functioning and home and work demands predict individual differences in diurnal cortisol patterns in women.

In 70 middle-class mothers of 2-year-old children, individual differences in mothers' morning cortisol levels, cortisol decreases across the day and average cortisol levels were predicted from demographic and medical control variables, maternal relationship functioning and home and work demands. For two days, salivary cortisol levels were measured in the morning immediately after wakeup, four times in the afternoon, and in the evening immediately prior to bedtime. Hierarchical linear modeling (HLM) growth curve analyses were used to estimate the intercept (early morning level), slope (steepness of decline in cortisol values across the day), and the average height of each mother's cortisol curve across the waking hours. HLM and multiple regression techniques were then used to predict individual differences in these parameters from the variables of interest. Time of day accounted for 72% of the variation in mothers' observed cortisol values across the day. After controlling for demographic and medical variables, positive relationship functioning was associated with higher morning cortisol levels and a steeper decline in cortisol across the day, while greater hours of maternal employment and a greater number of children in the household were associated with lower morning cortisol values and a less steep decline in cortisol levels across the day. Variables predicting higher morning values also predicted higher average cortisol levels, while variables predicting lower morning cortisol predicted lower average cortisol levels. The full model including selected control, relationship functioning and home and work demand variables accounted for 40% of the variance in mothers' morning cortisol values, 43% of the variance in cortisol slopes and 35% of the variability in mothers' average cortisol levels. This study presents the first evidence of associations between psychological variables and individual differences in the organization of cortisol levels across the waking day in normal adult women.

Adaptation, Psychological↗

An adaptive plasma glucose controller based on a nonlinear insulin/glucose model.

The design of plasma glucose controllers traditionally relies on linear approaches. The implementation of an appropriate nonlinear model of the insulin/glucose regulatory system into an adaptive controller should predict the insulin-dependent glucose removal more reliably and hence provide better control over a wide spectrum of insulin signals. A discretized form of the model leads to a two-step procedure. First, the measured plasma glucose levels associated with the exogenous glucose infusion rates are used in the estimation of the past removal rates which, in turn, can be expressed as a weighted sum of past insulin inputs and previous values of the removal rate. Parameters of the sum are adjusted on-line by a recursive method of estimation which features a prefiltering of data to account for a corrupting coloured process noise. The same equation is in turn used to predict the time course of the insulin-dependent fractional rate of glucose removal. The performance of the controller, tested in vivo in three pigs, is presented for various intravenous or subcutaneous rapid injections and staircase infusions of insulin. Plasma glucose is maintained at an average level of 99.9 +/- 8.7% of the target value (% set point +/- coefficient of variation). The controller reacts promptly to large and rapid variations in insulin action. Although control improves with the number of glucose measurements, the prediction of glucose removal allows for some flexibility in the monitoring of the plasma glucose. Sampling frequency varied from a 2 min interval during transient periods to 7 min as steady states were reached.

Algorithms↗

Pathophysiology and epidemiology of chronic mountain sickness.

Chronic mountain sickness, which affects permanent residents of high altitudes, is the outcome of a progressive loss of ventilatory rate which naturally occurs with age and resulting in excessive hypoxemia and polycythemia. A theoretical model predicts the progressive failure of homeostatic control of the hemoglobin concentration when the values increase above those found at sea level. This is confirmed by lack of feedback mechanism between high altitude erythrocytosis and serum erythropoietin. The results of epidemiological studies are in agreement with the physiological findings. In a male population living at 4,300 m, an increase with age of the prevalences of excessive erythrocytosis (Hb > 213 g/l), blood oxygen saturation < 83%, headaches and a high score of symptoms of chronic mountain sickness has been found. The studies suggest the possibility that in addition to an accentuated hypoxemia, the excessive erythrocytosis may also result from an overreaction of the bone marrow to a fixed level of hypoxemia in ageing individuals.

Adult↗

Predicting children's blood lead levels from exposure to school drinking water in Seattle, Washington, USA.

OBJECTIVE: Lead exposure through drinking water is of increasing interest with little known about its potential childhood health impact. In 2004, school testing in Seattle, Washington, found lead concentrations in drinking water that exceeded national guidelines (>20 ppb). On the basis of these data, we estimated potential blood lead levels (BLLs) in elementary school children to better understand the potential health risks posed by these exposures. METHODS: We used the US Environmental Protection Agency Integrated Uptake Biokinetic Model for Lead in Children to predict geometric mean BLLs. We modeled typical-case and worst-case scenarios for children in 71 elementary schools on the basis of drinking water lead concentrations results from 2004. RESULTS: The estimated geometric mean BLLs under a typical scenario for each school ranged from 1.6 to 2.5 microg/dL. The worst-case scenario predicted geometric mean BLLs ranging from 1.7 to 5.0 microg/dL. All modeling yielded predicted BLLs well below the Centers for Disease Control and Prevention's public health goal of <10 microg/dL. CONCLUSIONS: Our modeling suggests drinking water exposures up to 10-15 times the Environmental Protection Agency guideline are unlikely to result in BLLs exceeding the current guidelines of the Centers for Disease Control and Prevention in the absence of other significant exposure sources. In Seattle, elevated school drinking water lead concentrations are not a significant source of lead exposure in school-age children. Further characterization of drinking water impacts are merited only if younger-age children are consuming water or if water lead concentrations are higher than those in this study.

Child↗

Quantitative modelling and prediction of development times of the free-living stages of Ostertagia ostertagi under controlled and field conditions.

The development of the free-living stages of Ostertagia ostertagi incubated at constant temperatures from 5 to 27 degrees C and in dung pats in the field was observed. The death rates were adequately described by a single exponential functional and the distribution of times for development by a delayed gamma density function. The times of appearance of selected development stages such as maximum numbers of embryonated eggs and half the maximum number of infective larvae, were highly dependent on temperature. The relationships between these times and temperature were adequately described by the Arrhenius equation. The parameters of this equation and mean hourly temperature recorded in dung pats in the field were used to predict development times in the field. A comparison of predicted and observed times showed that an initial delay accounted for a large proportion of the time required for development in dung pats, particularly the embryonation of eggs. This delay was attributed to lack of aeration associated with high moisture content of the dung pat.

Animals↗

Measuring the impact of HIV on fertility in Africa.

OBJECTIVES: To review evidence for the impact of HIV on fertility from empirical sources pertaining to African populations and to discuss the implications for surveillance based on antenatal clinic populations. METHODS: The theoretical equivalence between the fertility rate ratio for HIV-positive to HIV-negative women and the relative odds of being infected for pregnant women compared with the general female population is demonstrated. This equivalence is used to compare fertility differentials measured in cohort studies with those calculated indirectly from antenatal clinic data. Data from case-control studies and theoretical predictions from a model of the proximate determinants of fertility and HIV incidence are used to obtain plausible explanations of the fertility differences. Estimates of population attributable change are made. RESULTS: Fertility of HIV-positive women is lower than that of HIV-negative women, in all but the youngest age-group, and the differential increases with women's age and epidemic duration. Selection for early start of sexual activity explains the reverse pattern at younger ages. Lower fertility amongst HIV-positive women causes a population attributable decline in total fertility of the order of 0.4% for each percentage point HIV prevalence in the general female population. CONCLUSIONS: In populations that do not use contraceptives, HIV-positive women have lower fertility principally as a result of foetal losses consequent to infection with HIV and coinfection with other sexually transmitted diseases; behavioural factors tend to enhance this differential. Other factors being equal, HIV prevalence estimates based on antenatal surveillance underestimate true prevalence in women in the childbearing years.

Adolescent↗

Geographic information systems as a tool for control program management for schistosomiasis in Egypt.

During a 4-year study a geographic information system (GIS) risk model was constructed for predicting the relative risk of schistosomiasis in Kafr El-Sheikh governorate, Egypt. A 1-year 1990-1991 time series on diurnal temperature difference (dT) prepared from the advanced very high resolution radiometer (AVHRR) sensor on the NOAA-11 satellite was used to develop a regional risk model for the Nile delta based on thermal-hydrological domains. A May 15, 1990 Landsat TM scene (path 177, Row 38) was used to develop a local 'village-scale' environmental risk model based on higher resolution satellite sensor data (30 m picture element size at earth surface). Four of ten classes derived from a tasseled cap (Tcap) transformation of the Landsat TM scene were shown to be significantly related to a 5-year Schistosoma mansoni prevalence database from the Ministry of Health. A risk model was developed based on dT and the proportional area of the four Tcap classes in 5 km(2) buffer zones centered on rural health unit (RHU) reporting units. Available historical data on S. mansoni and its snail host Biomphalaria alexandrina, as well as recent field collected data were gathered and incorporated as separate themes. Model validation was done using data collected on snail population bionomics-infection rates, water quality, underground water table and cercariometry at 13 hydrologically representative sites. The role of soil type, water table and water quality was studied at 79 of 154 rural health unit sites. The model permitted retrieval of relevant data by RHU point location. For the first time in Egypt, the Kafr El-Sheikh GIS schistosoma prediction model can support MOH efforts to make more accurate control program decisions based on environmental predilection sites of endemic Schistosomiasis mansoni.

Animals↗

A stochastic mathematical model of methicillin resistant Staphylococcus aureus transmission in an intensive care unit: predicting the impact of interventions.

OBJECTIVES: To estimate the transmission rate of MRSA in an intensive care unit (ICU) in an 800 bed Australian teaching hospital and predict the impact of infection control interventions. METHODS: A mathematical model was developed which consisted of four compartments: colonised and uncolonised patients and contaminated and uncontaminated health-care workers (HCWs). Patient movements, MRSA acquisition and daily prevalence data were collected from an ICU over 939 days. Hand hygiene compliance and the probability of MRSA transmission from patient to HCW per discordant contact were measured during the study. Attack rate and reproduction ratio were estimated using Bayesian methods. The impact of a number of interventions on attack rate was estimated using both stochastic and deterministic versions of the model. RESULTS: The mean number of secondary cases arising from the ICU admission of colonised patients, also called the ward reproduction ratio, R(w), was estimated to be 0.50 (95% CI 0.39-0.62). The attack rate was one MRSA transmission per 160 (95% CI 130-210) uncolonised-patient days. Results were not sensitive to uncertainty in measured model parameters (hand hygiene rate and transmission probability per contact). Hand hygiene was predicted to be the most effective intervention. Decolonisation was predicted to be relatively ineffective. Increasing HCW numbers was predicted to increase MRSA transmission, in the absence of patient cohorting. The predictions of the stochastic model differed from those of the deterministic model, with lower levels of colonisation predicted by the stochastic model. CONCLUSIONS: The number of secondary cases of MRSA colonisation within the ICU in this study was below unity. Transmission of MRSA was sustained through admission of colonised patients. Stochastic model simulations give more realistic predictions in hospital ward settings than deterministic models. Increasing staff does not necessarily lead to reduced transmission of nosocomial pathogens.

Bayes Theorem↗

Ecology of testate amoebae from mires in the Central Rhodope Mountains, Greece and development of a transfer function for palaeohydrological reconstruction.

Testate amoebae are useful environmental indicators in ecological and palaeoecological studies from peatlands. Previous quantitative studies have focused on the peatlands of Northern and Central Europe, North America, and New Zealand and have considered a relatively restricted variety of peatland types, mostly ombrotrophic or Sphagnum-dominated while more minerotrophic fens have been less studied. Here we present the first quantitative ecological study of testate amoebae from four small mesotrophic fens (pH 5.5-8.1) in the Elatia Forest, northern Macedonia province, Greece. Relationships with the environmental data were investigated using redundancy analysis and mantel tests. Transfer function models were derived using a variety of techniques. Results demonstrate that as for Sphagnum-dominated mires hydrology is the most important control on amoebae community composition. Transfer function models should enable water tables to be predicted within 2.5 cm, when data selection is used this is reduced to less than 2 cm. pH is also an important environmental control on testate amoebae communities, a transfer function model enables pH prediction within 0.4 pH units. The hydrological transfer function is the best performing such model yet produced in terms of prediction error. This study provides new data on the ecology of testate amoebae in fens, and the transfer function models should allow quantitative palaeohydrological reconstruction.

Amoeba↗

PoPS: a computational tool for modeling and predicting protease specificity.

Proteases play a fundamental role in the control of intra- and extracellular processes by binding and cleaving specific amino acid sequences. Identifying these targets is extremely challenging. Current computational attempts to predict cleavage sites are limited, representing these amino acid sequences as patterns or frequency matrices. Here we present PoPS, a publicly accessible bioinformatics tool (http://pops.csse.monash.edu.au/) which provides a novel method for building computational models of protease specificity that, while still being based on these amino acid sequences, can be built from any experimental data or expert knowledge available to the user. PoPS specificity models can be used to predict and rank likely cleavages within a single substrate, and within entire proteomes. Other factors, such as the secondary or tertiary structure of the substrate, can be used to screen unlikely sites. Furthermore, the tool also provides facilities to infer, compare and test models, and to store them in a publicly accessible database.

Amino Acid Sequence↗

PoPS: a computational tool for modeling and predicting protease specificity.

Proteases play a fundamental role in the control of intra- and extra-cellular processes by binding and cleaving specific amino acid sequences. Identifying these targets is extremely challenging. Current computational attempts to predict cleavage sites are limited, representing these amino acid sequences as patterns or frequency matrices. Here we present PoPS, a publicly accessible bioinformatics tool (http://pops.csse.monash.edu.au/) that provides a novel method for building computational models of protease specificity, which while still being based on these amino acid sequences, can be built from any experimental data or expert knowledge available to the user. PoPS specificity models can be used to predict and rank likely cleavages within a single substrate, and within entire proteomes. Other factors, such as the secondary or tertiary structure of the substrate, can be used to screen unlikely sites. Furthermore, the tool also provides facilities to infer, compare and test models, and to store them in a publicly accessible database.

Algorithms↗

Clinical pharmacokinetics of 6-hour infusion of high-dose methotrexate. Preliminary trial of monitoring high infusion doses.

Methotrexate (MTX) in serum was measured by RIA in 12 cancer patients receiving high doses of MTX (2 to 8 g/m2) in 6 hour infusions 69 treatments were studied. The peak serum level was proportional to the dose administered and was always greater than 10(-4) M. 2 elimination phases were seen: the first had a mean half-life of 2.36 h and the second a mean half-life of 16.14 h. 24 hours after beginning the infusions there were very large variations in individual serum concentrations of MTX, from 2.4 10(-6) M to 1.9 10(-5) M by 24 h after 8 g/m2. To control these variations, a mathematical model for prediction of the individual pharmacokinetic pattern of a 6 hour-infusion of high-dose MTX by kinetic analysis of a low-test dose is proposed. A program was created for an Apple III computer using toxic and therapeutic serum levels of MTX selected by the clinician. The computer program is adaptable to any infused substance for variable infusion times, thus introducing new advances over existing methods.

Adolescent↗