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PubMed1981

Issues in filariasis--a century of enquiry and a century of failure.

A great deal is known about the biology of the filarial parasites infecting man and of their transmission, their clinical manifestations, their treatment and their control but many more people are infected with Bancroftian filariasis and onchocerciasis today than more than 100 years ago when Manson discovered the first live cycle. There has been some success in the control of the Simulium vectors of onchocerciasis in parts of Africa and mass chemotherapy has helped to reduce Bancroftian filariasis in a few Pacific Islands but the main endemic areas have seen no benefit from all the advance in the techniques for controlling these diseases. There is an obvious need for more research to find better tools that are less hazardous to the environment and more acceptable to the affected communities. Fortunately the combined resources of the United Nations Development Programme, the World Bank for Development and the World Health Organization in the setting up of the Special Programme for Research and Training in Tropical Diseases has stimulated a renewed interest in these problems. An obvious area for further research is on the epidemiology of the disease with special emphasis on transmission of the parasites to help with the development of predictive models which might assist in the design and evaluation of control programmes. There is a need for novel approaches to kill the vectors and for the development of more effective and less hazardous drugs. There is a need for immunologists to try to produce vaccines which will help to consolidate other methods of control but of more immediate values will be the production of more specific immunological diagnostic tests and methods for modifying the immunopathology processes caused by the disease and accentuated by treatment. But whatever new tools are produced it is still true to say that control measures will be effective only if there is active cooperation by the affected communities. It is therefore essential that laboratory research is supplemented with research on human behaviour in relation to the transmission of the diseases and also on the acceptability of control measures if we are to avoid the disappointments of many other antiparasitic control campaigns.

Animals↗

PubMed2006

Evaluation of four modelling techniques to predict the potential distribution of ticks using indigenous cattle infestations as calibration data.

Efficient tick and tick-borne disease control is a major goal in the efforts to improve the livestock industry in developing countries. To gain a better understanding of the distribution and abundance of livestock ticks under changing environmental conditions, a country-wide field survey of tick infestations on indigenous cattle was recently carried out in Tanzania. This paper evaluates four models to generate tick predictive maps including areas between the localities that were surveyed. Four techniques were compared: (1) linear discriminant analysis, (2) quadratic discriminant analysis, (3) generalised regression analysis, and (4) the weights-of-evidence method. Inter-model comparison was accomplished with a data-set of adult Rhipicephalus appendiculatus ticks and a set of predictor variables covering monthly mean temperature, relative humidity, rainfall, and the normalised difference vegetation index (NDVI). The data-set of tick records was divided into two equal subsets one of which was utilised for model fitting and the other for evaluation, and vice versa, in two independent experiments. For each locality the probability of tick occurrence was predicted and compared with the proportion of infested animals observed in the field; overall predictive success was measured with mean squared difference (MSD). All models exhibited a relatively good performance in configurations with optimised sets of predictors. The linear discriminant model had the least predictive success (MSD>or=0.210), whereas the accuracy increased in the quadratic discriminant (MSD>or=0.197) and generalised regression models (MSD>or=0.173). The best predictions were gained with the weights-of-evidence model (MSD>or=0.141). Theoretical as well as practical aspects of all models were taken into account. In summary, the weights-of-evidence model was considered to be the best option for the purpose of predictive mapping of the risk of infestation of Tanzanian indigenous cattle. A detailed description of the implementation of this model is provided in an annex to this paper.

Animals↗

PubMed2004

A growth-controlled model of the shape of a sunflower head.

A mathematical model is presented which predicts the shape of a sunflower receptacle (or the compact receptacle of various other taxa) and the pattern of its floral parts (florets) from the time of their initiation to maturity. The model assumes that the expansion and curving of the receptacle surface is just sufficient to accommodate the development of the florets, thus minimizing the quantity of plant tissue involved. The model assumes a fixed angular separation (divergence) between successive florets, an S-shaped (sigmoidal) growth function followed by each florets, and a fixed time delay (period) between the initiation of successive florets. It is further assumes that the shape and relative position occupied by the florets on the receptacle surface are invariant in time. By this theory, the shape of the receptacle surface is fully determined once the mathematical form of the growth function is specified. Using the logistic growth function, the theory is tested against the measured shapes of plant receptacles from different taxa at various points in their development. The least-squares adjusted fits to the theory are, in most cases, very good indeed.

Helianthus↗

PubMed2003

Irritability following abstinence from cocaine predicts euphoric effects of cocaine administration.

This study evaluated the association between negative affective symptoms during initial abstinence and euphorigenic response to experimentally administered cocaine. Cocaine-dependent individuals achieved 5 days of abstinence in a hospital setting. Forty milligrams of cocaine was given intravenously on the fifth day of abstinence, and participants were asked to rate the subjective effects produced by the drug. The associations between irritability, self-reported depression, and the subjective "high" produced by cocaine were evaluated. Increased levels of irritability and depression both correlated positively and statistically significantly with heightened response to experimentally administered cocaine as indexed by self-reported subjective "high." The positive association between irritability and subjective "high" remained after controlling for self-reported depressive symptoms. The opponent process model predicts that increased levels of negative affect should be associated with diminished euphoric response to cocaine; however, the opposite was observed. If these findings are replicated in a larger sample, then it may be necessary to reconsider the applicability of the opponent process model to cocaine addiction in humans.

Adult↗

PubMed2006

Use of artificial neural network black-box modeling for the prediction of wastewater treatment plants performance.

A reliable model for any wastewater treatment plant is essential in order to provide a tool for predicting its performance and to form a basis for controlling the operation of the process. This would minimize the operation costs and assess the stability of environmental balance. This process is complex and attains a high degree of nonlinearity due to the presence of bio-organic constituents that are difficult to model using mechanistic approaches. Predicting the plant operational parameters using conventional experimental techniques is also a time consuming step and is an obstacle in the way of efficient control of such processes. In this work, an artificial neural network (ANN) black-box modeling approach was used to acquire the knowledge base of a real wastewater plant and then used as a process model. The study signifies that the ANNs are capable of capturing the plant operation characteristics with a good degree of accuracy. A computer model is developed that incorporates the trained ANN plant model. The developed program is implemented and validated using plant-scale data obtained from a local wastewater treatment plant, namely the Doha West wastewater treatment plant (WWTP). It is used as a valuable performance assessment tool for plant operators and decision makers. The ANN model provided accurate predictions of the effluent stream, in terms of biological oxygen demand (BOD), chemical oxygen demand (COD) and total suspended solids (TSS) when using COD as an input in the crude supply stream. It can be said that the ANN predictions based on three crude supply inputs together, namely BOD, COD and TSS, resulted in better ANN predictions when using only one crude supply input. Graphical user interface representation of the ANN for the Doha West WWTP data is performed and presented.

Evaluation Studies as Topic↗

PubMed2004

Endofullerenes with metal atoms inside as precursors of nuclei of single-walled carbon nanotubes.

Thermodynamic estimations have been made which show that amorphous carbon cannot be the source of single-walled carbon nanotube growth during carbon/metal vapor condensation. Thus the source of carbon material for nanotube growth seems to be small carbon clusters into gas phase or clusters in the adsorbed state on the nanotube surface. Kinetic analysis of carbon/metal vapor condensation in the arc process was performed and showed that metal vapor becomes supersaturated at temperatures that are close to the temperature of the highest rate of fullerene shell formation. A new model of the nucleation of single-walled carbon nanotubes is proposed. In the model an endometallofullerene serves as the precursor of a nanotube nucleus, and the nucleus itself forms as an adduct arising after metal atoms attach to the endofullerene shell. The relative efficiencies of La/Ni, Gd/Ni, Ce/Ni, and Pr/Ni catalysts, in comparison with Y/Ni catalyst, were measured, and their high efficiency in buckytube formation was demonstrated. This fact was explained by the double action of a metal catalyst in buckytube nucleus formation. First, metal takes part in the formation of endometallofullerenes. Second, the metal atoms attach to the endofullerene shell to transform an endofullerene into a nanotube nucleus. The high performance of bimetallic catalysts lies in adjusting the values of two metal concentrations separately for each of these purposes. In accordance with observations, the proposed model predicts increasing size of endofullerenes with increasing concentration of the metal that controls endofullerene formation.

Carbon↗

PubMed2003

Time-dependent predictors of primary cardiac arrest in patients with acute myocardial infarction.

To understand predictors of cardiac arrest early in acute myocardial infarction (AMI), for the Thrombolytic Predictive Instrument, we developed a multivariable regression model predicting primary cardiac arrest using time-dependent variables based on a case-control study of emergency department (ED) patients with AMI: 65 cases with sudden cardiac arrest and 258 without cardiac arrest. Within the first hour of AMI symptom onset, adjusting for age, systolic blood pressure, serum potassium, and infarct size, increased risk of cardiac arrest was associated with electrocardiographic prolonged QTc interval and a greater sum of ST-segment elevation. After 1 hour, the effect of ST-segment elevation was much reduced and the effect of the QTc interval was reversed, so prolonged QTc appeared protective. Accordingly, for patients presenting 30 minutes after chest pain onset, compared with a QTc of 0.44, the risk for cardiac arrest for patients with QTc of 0.50 was more than doubled (odds ratio [OR] 2.20, 95% confidence intervals [CI] 1.17 to 4.13), whereas for those presenting after an hour, it was much lower (e.g., at 1.5 hours, OR 0.21, 95% CI 0.06 to 0.73). Patients presenting 30 minutes after chest pain onset with a sum of ST elevation of 20 mm had a threefold higher risk than patients with a sum of ST elevation of 5 mm (OR 3.37, 95% CI 1.83 to 6.20). However, if presenting 1.5 hours after chest pain onset, the risk was barely elevated (OR 1.18; 95% CI 1.09 to 1.29). Thrombolytic therapy was protective, halving the odds of cardiac arrest (OR 0.51, 95% CI 0.27 to 0.93). Thus, the relation of prolonged QTc interval and substantial ST segment elevation to cardiac arrest in AMI may be obscured because patients with these risks are more likely to die soon after AMI onset, before ED presentation, and are thereby unavailable for study. Those with prolonged QTc or substantial ST elevation who survive the initial 1.5-hour period are those less susceptible to these risks.

Aged↗

PubMed2000

Mathematical modeling of the human body during water replacement and dehydration: body water changes.

A model of the human body that integrates the variables involved in temperature regulation and blood gas transport within the cardiovascular and respiratory systems is presented here. It expands upon previous work to describe the competition between skin and muscles when both require increased blood flows during exercise and/or heat stress. First, a detailed study of the control relations used to predict skin blood flow was undertaken. Four other control relations employed in the model were also examined and modified as indicated by empirical results found in literature. Internal responses to exercise and/or heat stress can affect both thermoregulation and the cardiorespiratory system. Dehydration was studied in addition to complete water replacement during similar environmental and exercise situations. Control relations for skin blood flow and evaporative heat loss were modified and a water balance was added to study how the loss of water through sweat can be limiting. Runoff from sweating as a function of relative humidity was introduced along with evaporation, and these results were compared to data to validate the model.

Body Temperature Regulation↗

PubMed2002

Modeling a full-scale primary sedimentation tank using artificial neural networks.

Modeling the performance of full-scale primary sedimentation tanks has been commonly done using regression-based models, which are empirical relationships derived strictly from observed daily average influent and effluent data. Another approach to model a sedimentation tank is using a hydraulic efficiency model that utilizes tracer studies to characterize the performance of model sedimentation tanks based on eddy diffusion. However, the use of hydraulic efficiency models to predict the dynamic behavior of a full-scale sedimentation tank is very difficult as the development of such models has been done using controlled studies of model tanks. In this paper, another type of model, namely artificial neural network modeling approach, is used to predict the dynamic response of a full-scale primary sedimentation tank. The neuralmodel consists of two separate networks, one uses flow and influent total suspended solids data in order to predict the effluent total suspended solids from the tank, and the other makes predictions of the effluent chemical oxygen demand using data of the flow and influent chemical oxygen demand as inputs. An extensive sampling program was conducted in order to collect a data set to be used in training and validating the networks. A systematic approach was used in the building process of the model which allowed the identification of a parsimonious neural model that is able to learn (and not memorize) from past data and generalize very well to unseen data that were used to validate the model. Theresults seem very promising. The potential of using the model as part of a real-time process control system isalso discussed.

Forecasting↗

PubMed1998

GABA receptor subunit mRNA expression in brain of conflict, yoked control and control rats.

Animal conflict models have been used for years as a preclinical screen for predicting anxiolytic therapeutic efficacy. Anxiolytics, including benzodiazepines, increase punished responding. This suggests that the punished behavior may be mediated by the GABA receptor. To evaluate this hypothesis, we performed in situ hybridization histochemistry studies of GABA receptor subunits (alpha1-alpha4) and synthetic enzymes glutamic acid decarboxylase (GAD65 and GAD67) in four groups of rats: conflict (punishment), yoked controls (rats shocked without conflict training history), fixed interval only controls (rats that worked for food but were not shocked) and untreated controls. With conflict behavioral training, bilateral reduction of mRNA for the GABAA alpha1 subunit was seen relative to controls in the cortex, thalamus and hippocampus. In contrast, alteration of alpha2 mRNA levels appeared only in the yoked control group, with increased levels seen in the thalamus and cortex and decreased levels in the hippocampus. There were no differences in the alpha2 mRNA level between the control and the conflict behavioral trained animals. Further, no significant differences were found between groups in the mRNA levels for the alpha3 subunit, alpha4 subunit, GAD65, and GAD67. These results suggest that the behaviors related to conflict and uncontrollable aversive stimuli (yoked control group) are accompanied and perhaps mediated by selective changes in the GABAA alpha1 or alpha2 subunits, respectively. These findings highlight the potential usefulness of the conflict model as a means of elucidating the biological underpinnings of anxiety disorder. Published by Elsevier Science B.V. All rights reserved.

Animals↗

PubMed1993

Human standing posture: multi-joint movement strategies based on biomechanical constraints.

We developed a theoretical framework for studying coordination strategies in standing posture. The framework consists of a musculoskeletal model of the human lower extremity in the sagittal plane and a technique to visualize, geometrically, how constraints internal and external to the body affect movement. The set of all feasible accelerations (i.e., the "feasible acceleration set" or FAS) that muscles can induce at positions near upright were calculated. We found that musculoskeletal mechanics dictate that independent control of joints is relatively difficult to achieve. When muscle activations are constrained so the knees stay straight, to approximate the typical postural response to perturbation, the corresponding subset of the feasible acceleration set greatly favors a combination of ankle and hip movement in the ratio 1:3 (called the "hip strategy"). Independent control of these two joints remains difficult to achieve. When near the boundary of instability, the orientation and shape of this subset show that the movement strategy necessary to maintain stability, without taking a step, is quite restricted. Hypothesizing that regulation of center-of-mass position is crucial to maintaining balance, we examined the feasible set of center-of-mass accelerations. When the knees must be kept straight, the acceleration of the center of mass is severely limited vertically, but not horizontally. We also found that the "ankle strategy", involving rotation about the ankles only, requires more muscle activation than the "hip strategy" for a given amount of horizontal acceleration. Our model therefore predicts that the hip strategy is most effective at controlling the center of mass with minimal muscle activation ("neural effort").

Ankle Joint↗

PubMed1998

Temperament and novelty seeking in adolescent substance use: convergence of dimensions of temperament with constructs from Cloninger's theory.

This study investigated the convergence of temperament dimensions with constructs from C. R. Cloninger's (1987a) theory using data from a sample of 949 adolescents (M age = 13.6 years). Substantial convergence was found, and both types of constructs were related in predicted ways to self-regulation variables and adolescent substance use. Structural modeling procedures tested a mediational model for substance use; results showed mediation through self-control, academic competence, negative life events, and deviant peer affiliations. Interactions indicated that substance use could be predicted from a balance of systems for good control and poor control. Poor self-control was present for dimensions implicated in both externalizing and internalizing disorders. Results are discussed with reference to self-regulation models of substance use and the comorbidity of substance abuse and mental disorder.

Adaptation, Psychological↗

PubMed2004

Nonlinear mixed-effects model for the dissolution assays of drugs.

Sustained or controlled release delivery systems can achieve predictable and reproducible drug release rates. With the aim of optimizing the bioavailability of conventional drugs with minimum side effects, new drug delivery systems continue to attract much attention. This research has been addressed to investigate in vitro metoclopramide release behavior from inert polymeric matrix tablets. Model-dependent and model-independent approaches are commonly used to investigate the release process and a fitted model results for each experimental condition. The aim of this work was to study the release characterization of the whole batch, therefore, we have developed a population model, taking into account the differences between tablets, experimental conditions, heterogeneity, and autocorrelation of residuals. The study of dissolution profiles was carried out using a mixed-effect model, which has provided a satisfactory tool for this kind of data.

Models, Chemical↗

PubMed2004

Is a "loss of balance" a control error signal anomaly? Evidence for three-sigma failure detection in young adults.

Given that a physical definition for a loss of balance (LOB) is lacking, the hypothesis was tested that a LOB is actually a loss of effective control, as evidenced by a control error signal anomaly (CEA). A model-reference adaptive controller and failure-detection algorithm were used to represent central nervous system decision-making based on input and output signals obtained during a challenging whole-body planar balancing task. Control error was defined as the residual generated when the actual system output is compared with the predicted output of the simple first-order polynomial system model. A CEA was hypothesized to occur when the model-generated control error signal exceeded three standard deviations (3sigma) beyond the mean calculated across a 2-s trailing window. The primary hypothesis tested was that a CEA is indeed observable in 20 healthy young adults (ten women) performing the following experiment. Seated subjects were asked to balance a high-backed chair for as long as possible over its rear legs. Each subject performed ten trials. The ground reaction force under the dominant foot, which constituted the sole input to the system, was measured using a two-axis load cell. Angular acceleration of the chair represented the one degree-of-freedom system output. The results showed that the 3sigma algorithm detected a CEA in 94% of 197 trials. A secondary hypothesis was supported in that a CEA was followed in 93% of the trials by an observable compensatory response, occurring at least 100 ms later, and an average of 479 ms, later. Longer reaction times were associated with low velocities at CEA, and vice versa. It is noteworthy that this method of detecting CEA does not rely on an external positional or angular reference, or knowledge of the location of the system's center of mass.

Adolescent↗

PubMed2001

NO chemical events in the human airway during the immediate and late antigen-induced asthmatic response.

A wealth of evidence supports increased NO (NO.) in asthma, but its roles are unknown. To investigate how NO participates in inflammatory airway events in asthma, we measured NO. and NO. chemical reaction products [nitrite, nitrate, S-nitrosothiols (SNO), and nitrotyrosine] before, immediately and 48 h after bronchoscopic antigen (Ag) challenge of the peripheral airways in atopic asthmatic individuals and nonatopic healthy controls. Strikingly, NO(3)(-) was the only NO. derivative to increase during the immediate Ag-induced asthmatic response and continued to increase over 2-fold at 48 h after Ag challenge in contrast to controls [P < 0.05]. NO(2)(-) was not affected by Ag challenge at 10 min or 48 h after Ag challenge. Although SNO was not detectable in asthmatic airways at baseline or immediately after Ag, SNO increased during the late response to levels found in healthy controls. A model of NO. dynamics derived from the current findings predicts that NO. may have harmful effects through formation of peroxynitrite, but also subserves an antioxidant role by consuming reactive oxygen species during the immediate asthmatic response, whereas nitrosylation during the late asthmatic response generates SNO, safe reservoirs for removal of toxic NO. derivatives.

Adult↗

PubMed2001

Stigma as a barrier to recovery: Adverse effects of perceived stigma on social adaptation of persons diagnosed with bipolar affective disorder.

OBJECTIVE: The purpose of this study was to evaluate the effect of concerns about stigma on social adaptation among persons with a diagnosis of bipolar affective disorder. METHODS: The sample comprised 264 persons who were consecutively admitted to a psychiatric inpatient or outpatient service at a university-affiliated hospital and who met research diagnostic criteria for bipolar I disorder, bipolar II disorder, or schizoaffective disorder, manic type. Patients were evaluated with use of the Schedule for Affective Disorders and Schizophrenia, Lifetime Version (SADS-L), the Brief Psychiatric Rating Scale (BPRS), and a measure of perceived stigma. Social adjustment was measured at baseline and seven months later with the Social Adjustment Scale (SAS). RESULTS: As predicted, patients who had concerns about stigma showed significantly more impairment at seven months on the social leisure subscale but not on the SAS extended family subscale, after baseline SAS score and symptom level had been controlled for. More refined models using SAS-derived factors as dependent variables indicated that concerns about stigma predicted higher avoidance of social interactions with persons outside the family and psychological isolation at seven-month follow-up, after baseline SAS and BPRS scores had been controlled for. CONCLUSIONS: Concerns about the stigma associated with mental illness reported by patients during an acute phase of bipolar illness predicted poorer social adjustment seven months later with individuals outside the patient's family. Greater attention to patients' concerns about stigma is needed from both researchers and clinicians.

Adaptation, Psychological↗

PubMed1999

Predicting malaria infection in Gambian children from satellite data and bed net use surveys: the importance of spatial correlation in the interpretation of results.

In line with the renewed World Health Organization Global Malaria Control Strategy, we have advocated the use of satellite imagery by control services to provide environmental information for malaria stratification, monitoring, and early warning. To achieve this operationally, appropriate methodologies must be developed for integrating environmental and epidemiologic data into models that can be used by decision-makers for improved resource allocation. Using methodologies developed for the Famine Early Warning Systems and spatial statistics, we show a significant association between age related malaria infection in Gambian children and the amount of seasonal environmental greenness as measured using the normalized difference vegetation index derived from satellite data. The resulting model is used to predict changes in malaria prevalence rates in children resulting from different bed net control scenarios.

Animals↗

PubMed2005

Experimental and in silico analyses of glycolytic flux control in bloodstream form Trypanosoma brucei.

A mathematical model of glycolysis in bloodstream form Trypanosoma brucei was developed previously on the basis of all available enzyme kinetic data (Bakker, B. M., Michels, P. A. M., Opperdoes, F. R., and Westerhoff, H. V. (1997) J. Biol. Chem. 272, 3207-3215). The model predicted correctly the fluxes and cellular metabolite concentrations as measured in non-growing trypanosomes and the major contribution to the flux control exerted by the plasma membrane glucose transporter. Surprisingly, a large overcapacity was predicted for hexokinase (HXK), phosphofructokinase (PFK), and pyruvate kinase (PYK). Here, we present our further analysis of the control of glycolytic flux in bloodstream form T. brucei. First, the model was optimized and extended with recent information about the kinetics of enzymes and their activities as measured in lysates of in vitro cultured growing trypanosomes. Second, the concentrations of five glycolytic enzymes (HXK, PFK, phosphoglycerate mutase, enolase, and PYK) in trypanosomes were changed by RNA interference. The effects of the knockdown of these enzymes on the growth, activities, and levels of various enzymes and glycolytic flux were studied and compared with model predictions. Data thus obtained support the conclusion from the in silico analysis that HXK, PFK, and PYK are in excess, albeit less than predicted. Interestingly, depletion of PFK and enolase had an effect on the activity (but not, or to a lesser extent, expression) of some other glycolytic enzymes. Enzymes located both in the glycosomes (the peroxisome-like organelles harboring the first seven enzymes of the glycolytic pathway of trypanosomes) and in the cytosol were affected. These data suggest the existence of novel regulatory mechanisms operating in trypanosome glycolysis.

Animals↗