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Prognostic factors and outcome after different types of resection for temporal lobe epilepsy.

OBJECT: It is unknown whether different resection strategies for temporal lobe epilepsy (TLE) produce alterations in seizure control or neuropsychological performance. METHODS: A series of 321 patients who underwent surgery for TLE between 1989 and 1997 was submitted to a uni- and multifactorial analysis of clinical, electrophysiological, neuroimaging, neuropsychological, and surgical factors to determine independent predictors of outcome. Until 1993, most patients with TLE underwent standard anterior temporal lobectomy (ATL); beginning in 1993, surgical procedures were increasingly restricted to lesions detected on magnetic resonance (MR) imaging and the presumed epileptogenic foci: for example, amygdalohippocampectomy (AH) or lesionectomy/corticectomy began to be used more often. The mean follow-up duration in this study was 38 months. Two hundred twenty-seven patients were classified as seizure free (70.7%), and 36 patients had rare and nondisabling seizures (11.2%); these groups were summarized as having good seizure control (81.9%). Twenty-four patients attained more than 75% improvement (7.5%), and no worthwhile improvement was seen in 34 cases (10.6%); these groups were summarized as having unsatisfactory seizure control (18.1%). On unifactorial analysis the following preoperative factors were associated with good seizure control (p < 0.05): single and concordant lateralizing focus on electroencephalography studies, low seizure frequency, absence of status epilepticus, concordant lateralizing memory deficit, clear abnormality on MR images, suspected ganglioglioma or dysembryoplastic neuroepithelial tumor (DNT), and absence of dysplasia on MR images. Stepwise logistic regression revealed a model containing five factors that were predictive for good seizure control (p < 0.1): 1) clear abnormality on MR images; 2) absence of status epilepticus; 3) MR imaging-confirmed ganglioglioma or DNT; 4) concordant lateralizing memory deficit; and 5) absence of dysplasia on MR images. Seizure outcome was mainly correlated with diagnosis and clinical factors. No significant differences were found regarding different resection types performed for comparable tumors. Neuropsychological testing revealed better postoperative results after limited resections compared with standard ATL, especially with regard to attention level, verbal memory, and calculated total neuropsychological performance. CONCLUSIONS: Different strategies for surgical approaches in TLE result in equally good outcomes. Seizure outcome is mainly dependent on the diagnosis and clinical factors, whereas the neuropsychological results are more beneficial after resections limited to an epileptogenic lesion and focus.

Adolescent↗

Correcting the QT interval for changes in HR in pre-clinical drug development.

OBJECTIVES: Estimation of possible cardiovascular side effects belongs to the safety assessment of every drug candidate. Drug-induced prolongation of the QT interval can result in life-threatening ventricular arrhythmia. In pre-clinical drug development, animal experiments are used to study this possible effect. Researchers have become aware that correction formulae derived for human beings are not applicable to animal experiments. METHODS: We investigated some of the proposed models by comparing the outcomes of the analyses on the same data. The data was derived from telemetry measurements on Labrador dogs. We propose the use of both the correlation with heart rate (or RR interval) and a measure of predictive performance. As a sufficiently large number of observations were available, the data was subdivided into a training and a test set. The training set serves to estimate the respective parameters while the test set is used to determine the performance of the model. Here, a kind of PRESS statistic was used. Next, the models were considered for treated animals, using the estimated parameters. Both positive and negative controls were used. CONCLUSIONS: Most models under consideration performed quite well. These models eliminated the correlation for the most part and were reasonably predictive. Furthermore, they reliably differentiate between positive and negative controls. The next steps in identifying the best correction will be to consider additional compounds as well as other species to validate our current results.

Animals↗

User-friendly models of the costs and efficacy of tsetse control: application to sterilizing and insecticidal techniques.

An interactive programme, incorporating a deterministic model of tsetse (Diptera: Glossinidae) populations, was developed to predict the cost and effect of different control techniques applied singly or together. Its value was exemplified by using it to compare: (i) the sterile insect technique (SIT), involving weekly releases optimized at three sterile males for each wild male, and (ii) insecticide-treated cattle (ITC) at 3.5/km(2). The isolated pre-treatment population of adults was 2500 males and 5000 females/km(2); if the population was reduced by 90%, its growth potential was 8.4 times per year. However, the population expired naturally when it was reduced to 0.1 wild males/km(2), due to difficulties in finding mates, so that control measures then stopped. This took 187 days with ITC and 609 days with SIT. If ITC was used for 87 days to suppress the population by 99%, subsequent control by SIT alone took 406 days; the female population increased by 48% following the withdrawal of ITC and remained above the immediate post-suppression level for 155 days; the vectorial capacity initially increased seven times and remained above the immediate post-suppression level for 300 days. Combining SIT and ITC after suppression was a little faster than ITC alone, provided the population had not been suppressed by more than 99.7%. Even when SIT was applied under favourable conditions, the most optimistic cost estimate was 20-40 times greater than for ITC. Modelling non-isolated unsuppressed populations showed that tsetse invaded approximately 8 km into the ITC area compared to approximately 18 km for SIT. There was no material improvement by using a 3-km barrier of ITC to protect the SIT area. In general, tsetse control by increasing deaths is more appropriate than reducing births, and SIT is particularly inappropriate. User-friendly models can assist the understanding and planning of tsetse control. The model, freely available via http://www.tsetse.org, allows further exploration of control strategies with user-specified assumptions.

Animals↗

[Psychic drugs: predicting therapeutic effects and doses by test models with normal subjects (author's transl)].

Pharmacopsychology is concerned with the effects of drugs on "psychic" processes. It is attempted to demonstrate approaches which meet the criteria of scientific methodology. These approaches are based upon observation of somatic and/or behavioral changes. The steps from "naive" observation to the generation of objective data consist mainly of strict control of the observational situation and of technical refinement of the observation methods. Two kinds of pharmacopsychological models in healthy volunteers are described: models of normal and models of abnormal behaviour. Their relevance for the prediction of therapeutic drug effects and dosage is discussed. Possible new approaches are demonstrated: a) utilization of feedback form clinical investigation to control the relevance of pharmacopsychological models and, b) the concept of symptomatic volunteers, who are shown to be more suitable models than non-selected subjects.

Behavior↗

Applicability of two surgical-site infection risk indices to risk of sepsis in surgical patients.

OBJECTIVE: To compare the ability of the Study of the Efficacy of Nosocomial Infection Control (SENIC) and the National Nosocomial Infection Surveillance (NNIS) indices to predict the development of nosocomial sepsis in subjects undergoing surgery. DESIGN: 1-year prospective case-control study. SETTING: A tertiary-care center in Spain. PATIENTS: Cases were surgical patients with nosocomial sepsis defined using the criteria of the Consensus Conference on Sepsis, identified by daily prospective surveillance. METHODS: Controls were randomly selected from the daily list of surgical inpatients. Data were prospectively collected. To determine whether either index added explanatory information to the other, two methods were used. The first method involved computing a set of residuals for both variables. Residuals and primary variables were introduced in logistic regression models. The second method evaluated both indices with the Goodman-Kruskal (G) nonparametric coefficient. RESULTS: 99 cases and 97 controls were included. After controlling for confounders, both the SENIC index (P<.001) and the NNIS index (P=.04) showed a significant trend. Residuals of the SENIC index added discriminating ability to the NNIS index, whereas residuals of the NNIS index did not improve the prediction ability of the SENIC index. Similar results were yielded by the G statistic: the SENIC index showed higher predictive power than the NNIS index (G=0.56 vs G=0.41). CONCLUSIONS: Both indices performed about equally well for discriminating risk of nosocomial sepsis. The SENIC index had a somewhat better ability than the NNIS index only when the number of discharge diagnoses (not truly a predictive factor) were involved in the calculation of the SENIC index.

Case-Control Studies↗

Transmission assumptions generate conflicting predictions in host-vector disease models: a case study in West Nile virus.

This review synthesizes the conflicting outbreak predictions generated by different biological assumptions in host-vector disease models. It is motivated by the North American outbreak of West Nile virus, an emerging infectious disease that has prompted at least five dynamical modelling studies. Mathematical models have long proven successful in investigating the dynamics and control of infectious disease systems. The underlying assumptions in these epidemiological models determine their mathematical structure, and therefore influence their predictions. A crucial assumption is the host-vector interaction encapsulated in the disease-transmission term, and a key prediction is the basic reproduction number, R(0). We connect these two model elements by demonstrating how the choice of transmission term qualitatively and quantitatively alters R(0) and therefore alters predicted disease dynamics and control implications. Whereas some transmission terms predict that reducing the host population will reduce disease outbreaks, others predict that this will exacerbate infection risk. These conflicting predictions are reconciled by understanding that different transmission terms apply biologically only at certain population densities, outside which they can generate erroneous predictions. For West Nile virus, R(0) estimates for six common North American bird species indicate that all would be effective outbreak hosts.

Animals↗

Executive neurocognitive functioning and neurobehavioral systems indicators in borderline personality disorder: a preliminary study.

It is argued that borderline personality disorder (BPD) represents the interaction of underlying neurobehavioral systems that are reflected principally in the phenotypic constructs of positive emotion, negative emotion, and nonaffective constraint (Depue & Lenzenweger, 2001). This preliminary and exploratory study sought to examine predictions made from the Depue-Lenzenweger model with respect to controlled (effortful) information processing in BPD. It was hypothesized that (a) BPD subjects may display deficits on tasks that require controlled information processing (sustained attention, spatial working memory, and executive functioning), (b) they may reveal elevated negative emotion as well as decreased positive emotion and nonaffective constraint, and (c) nonaffective constraint should be substantially inversely associated with accurate performance on controlled information processing tasks. The results of this study, which examined 24 BPD diagnosed individuals and 68 normal adults, found support for each of these predictions in relation to performance on the Wisconsin Card Sorting Test. The implications of these results for further experimental psychopathology investigations of BPD as well as further refinement of theoretical models of the disorder are discussed.

Adult↗

Parental body mass index: a predictor of childhood obesity?

Cross-sectional data of 210 Chinese children aged three to 16 years, of whom 29 (13.8%) were obese, and their biological parents were statistically assessed whether the body mass index (BMI = weight/height2) of the parents were predictive of childhood obesity. Using the logistic regression and proportional hazards models to predict the probability of obesity and to control for potential confounding due to the age and sex of the children, families with one parent having a BMI score of 25 or higher were 3.7 times, and families with two such parents were five times more likely to have an obese child than families with no such parent. Childhood obesity was more markedly correlated with the mother's BMI than with the father's BMI. These findings were all stochastically significant (p < 0.05) inspite of the modest sample size. One in two parents with an obese child did not perceive their child to be overweight and 62% of the parents with an obese child did not want their child to lose weight.

Adolescent↗

Theoretical model for predicting rates of nitrosamine and nitrosamide formation in the human stomach.

A mathematical model has been developed to estimate the rates of formation of nitrosamines and nitrosamides in the human stomach, under a variety of physiological and environmental conditions. The model combines a detailed description of the kinetics of N-nitrosation with mass balance equations which account for gastric emptying, dilution and absorption. The simulations were based on a typical schedule of dietary inputs, and included variations in gastric pH and in the volume of the stomach contents over a 24-h period. Consideration of these transient phenomena allowed a distinction to be made between amines or amides present in the diet and in gastric or salivary secretions. A comparison of the theoretical results with available data on the nitrosation of proline suggests that the model accurately predicts gastric rates of nitrosamine formation under control conditions, and correctly represents the strong catalytic effects of thiocyanate and the inhibitory effects of ascorbic acid or ascorbate ion. The results further suggest that nitrosoproline (NPro) excretion is not an accurate index of gastric nitrosation under physiological (low-dose) conditions, even when corrections are made for dietary intake of NPro. The predicted rates of formation of N-nitrosodimethylamine (NDMA), even for a diet high in dimethylamine, were found to be a factor of approximately 10(2) to 10(3) lower than published estimates of the dietary exposure to preformed NDMA. Thus, these findings do not support the hypothesis that gastric formation of NDMA from dietary dimethylamine poses a serious additional health risk. The results are presented in a graphical and tabular form which makes it possible to readily estimate the rates of formation of other nitrosamines or nitrosamides in the stomach, under various assumed conditions.

Ascorbic Acid↗

Motor mechanisms of balance during quiet standing.

The purpose of this paper is to highlight the motor mechanisms involved in balance as the human, as a biped, continuously defends against gravitational and internal forces to maintain a safe posture. The search for these mechanisms needs precise and valid 3D measurements including both limbs plus valid biomechanical models. The literature shows the need for two force platforms to separate the mechanisms at the ankle and hip (load/unload mechanism). Also, precise measures ( approximately 0.03 mm) of markers on a multi-segment 3D bilateral model are required to record the minute trajectories of all segments and joints. The controlled variable, center-of-mass, is seen to be virtually in phase with the controlling variable, the center-of-pressure, which suggests a 0th order system where a simple series elastic spring could maintain balance. The first model involves a mass/spring/damper of medial/lateral balance: the stiffness was varied with stance width and the predicted sway from a spring controlled inverted pendulum closely matched the experimentally measured stiffness and sway. The second was a non-linear model of the plantarflexor series elastic elements which resulted in three closely validated predictions of anterior/posterior balance: the locus of the gravitational load line, the predicted ankle moment and the ankle stiffness at the operating point.

Adult↗

Metabolic control analysis of monoclonal antibody synthesis.

A general route for protein synthesis in eukaryotic cells has been proposed and applied to monoclonal antibody (MAb) synthesis. It takes into account transcription of the gene, binding of ribosomes to mRNA, and polypeptide elongation including binding to SRP (signal recognition particles) and SRP-receptor, competing translocation, folding and glycosylation, assembly of the heavy and light chains in a tetrameric protein and Golgi processing and secretion. A comprehensive model was built on the basis of the proposed pathway. The model takes into account the mechanism of each step. Metabolic control analysis (MCA) principles were applied to the general pathway using the proposed model, and control coefficients were calculated. The results show a shared flux control (of both pathway flux and flux ratio at the branch) among different steps, i.e., transcription, folding, glycosylation, translocation and building blocks synthesis. The steps sharing the control depend on the concentration of building blocks, pathway flux and levels of OST (oligosacharyl transferase), BiP (heavy chain binding protein) and PDI (protein disulfide isomerase). Model predictions compare well with experimental data for MAb synthesis, explaining the control structure of the route and the heterogeneity of the product and also addressing future targets for improvement of the production rate of MAbs.

Antibodies, Monoclonal↗

Pinning stationary planar fronts in diffusion-convection-reaction systems.

This paper considers various strategies for controlling a stationary planar front solution, in a rectangular domain with a diffusion-reaction distributed system, by pinning the solution to one or few points and using actuators with the simplest possible spatial dependence. We review previous results obtained for one-dimensional diffusion-reaction (with or without convection) systems, for which we applied two approaches: an approximate model reduction to a form that follows the front position while approximating the front velocity, and linear stability analysis. We apply the same two approaches for the planar fronts. The approximate model reduction allows us to analyze qualitatively various control strategies and to predict the critical width below which the control mode of the one-dimensional system is sufficient. These results are corroborated by linear analysis of a truncated model with the spectral methods representation, using concepts of finite and infinite zeros of linear multidimensional systems.

Journal Article↗

Factors affecting the monetary return from programmes for synchronising oestrus in dairy cows with gonadotrophin-releasing hormone and prostaglandin F2alpha.

Synchronisation, using a combination of gonadotrophin-releasing hormone and prostaglandin F2alpha injections, is commonly used to control the reproductive cycle of dairy cows. A simple model that could predict the monetary return from synchronisation would be a valuable tool in determining whether it would be worthwhile. This study used data from three controlled clinical trials to investigate the effects of six factors (interval between calving and synchronisation, 21-day submission rate, number of cows synchronised, average age, pregnancy rate of non-synchronised cows and season) on the return from synchronisation. The results suggests that the herd's submission and pregnancy rates, the time between calving and synchronisation, and the number of cows synchronised can all significantly affect the return from synchronisation, but only time since calving significantly affected the return in all three trials. They also suggest that there is no simple linear relationship between these factors and the return from synchronisation.

Age Factors↗

Social support and mortality in an elderly community population.

A community sample made in the fall of 1972 in Durham County, North Carolina, and that consisted of 331 persons 65 years of age and older was assessed for adequacy of social support along three parameters: roles and available attachments, perceived social support, and frequency of social interaction. This approach to the assessment of social support complements previous approaches to the measurement of social support which have not compared with the various components of the construct. Mortality status, the outcome variable, was determined 30 months after the initial assessment. The crude relative risks of mortality were 1.96 for impaired roles and available attachments, 3.86 for impaired perceived social support, and 2.72 for impaired frequency of social interaction. Ten potential confounding variables-age, sex, race, economic status, physical health status, self-care capacity, depressive symptoms, cognitive functioning, stressful life events, and cigarette smoking-were controlled using binary linear regression analysis. The estimates of relative mortality risk were 2.04, 3.40, and 1.88, respectively, for impaired roles and available attachments, impaired perceived social support, and impaired frequency of social interaction when the control variables were included in a regression model. Therefore, these three parameters of social support significantly predicted 30-month mortality in both crude and controlled analyses in a community sample of older adults.

Activities of Daily Living↗

Thermo-kinetics study of laser-induced desorption of self-assembled monolayers from gold: case of laser micropatterning.

Laser-induced desorption of self-assembled monolayers (SAMs) from gold surfaces within context of the direct laser patterning methodology was investigated through combining results of a heat diffusion thermal model with desorption kinetics of alkanethiol SAMs. It was found that contrast plots of experimental scanning electron microscopy (SEM) images, which are correlated to surface coverage of SAMs desorbed after laser irradiation, agreed with the theoretically predicted surface composition of SAMs. The surface composition of SAM was then interpreted in terms of the wetting property of the resulting surface. The effect of incident laser beam power and size on the final spatial coverage of SAMs on the surface and feature sizes was investigated both experimentally and by modeling. Theoretical modeling and experimental evidence showed that the resulting feature sizes are wider when the surface is heated by a laser of higher power. Increasing the laser beam size results in broadening of feature sizes. Considering the correlation of the theoretical and experimental results, we concluded that the feature sizes are controllable in a predictable way (using the presented thermal-kinetics model) through varying laser beam power and beam size.

Journal Article↗

The impact of intimate partner violence on decisions to leave dating relationships: a test of the investment model.

This study explored the impact of violence exposure on investment-model constructs within a sample of college women involved in heterosexual dating relationships. Results generally supported the "common sense" hypothesis, suggesting that violence negatively impacts satisfaction for and commitment to one's relationship and is positively associated with intentions to leave. Exposure to psychological abuse uniquely impacted intentions to leave relationships above and beyond other model factors, suggesting that this may be a particularly important factor in determining college women's decisions. In a series of analyses examining the investment model within each of two groups (e.g., those exposed or not exposed to physical violence), results showed that the model predicted victimized women's decisions to leave as well as it predicted nonvictimized women's decisions. Taken together, results of this study suggest that victimized women base their relationship termination decisions on the same information as nonvictimized women do.

Adult↗

The relationship of post-acute home care use to Medicaid utilization and expenditures.

RESEARCH OBJECTIVES: To describe the use of post-acute home care (PAHC) and total Medicaid expenditures among hospitalized nonelderly adult Medicaid eligibles and to test whether health services utilization rates or total Medicaid expenditures were lower among Medicaid eligibles who used PAHC compared to those who did not. STUDY POPULATION: 5,299 Medicaid patients aged 18-64 discharged in 1992-1996 from 29 hospitals in the Cleveland Health Quality Choice (CHQC) project. DATA SOURCES: Linked Ohio Medicaid claims and CHQC medical record abstract data. DATA EXTRACTION: One stay per patient was randomly selected. DESIGN: Observational study. To control for treatment selection bias, we developed a model predicting the probability (propensity) a patient would be referred to PAHC, as a proxy for the patient's need for PAHC. We matched 430 patients who used Medicaid-covered PAHC ("USE") to patients who did not ("NO USE") by their propensity scores. Study outcomes were inpatient re-admission rates and days of stay (DOS), nursing home admission rates and DOS, and mean total Medicaid expenditures 90 and 180 days after discharge. PRINCIPAL FINDINGS: Of 3,788 medical patients, 12.1 percent were referred to PAHC; 64 percent of those referred used PAHC. Of 1,511 surgical patients, 10.9 percent were referred; 99 percent of those referred used PAHC. In 430 pairs of patients matched by propensity score, mean total Medicaid expenditures within 90 days after discharge were $7,649 in the USE group and $5,761 in the NO USE group. Total Medicaid expenditures were significantly higher in the USE group compared to the NO USE group for medical patients after 180 days (p < .05) and surgical patients after 90 and 180 days (p < .001). There were no significant differences for any other outcome. Sensitivity analysis indicates the results may be influenced by unmeasured variables, most likely functional status and/or care-giver support. CONCLUSIONS: Thirty-six percent of the medical patients referred to PAHC did not receive Medicaid-covered services. This suggests potential underuse among medical patients. The high post-discharge expenditures suggest opportunities for reducing costs through coordinating utilization or diverting it to lower-cost settings. Controlling for patients' need for services, PAHC utilization was not associated with lower utilization rates or lower total Medicaid expenditures. Medicaid programs are advised to proceed cautiously before expanding PAHC utilization and to monitor its use carefully. Further study, incorporating non-economic outcomes and additional factors influencing PAHC use, is warranted.

Acute Disease↗

Kinematic models of the buccal mass of Aplysia californica.

The feeding behavior of the marine mollusc Aplysia californica is an intensively studied model system for understanding the neural control of behavior. Feeding movements are generated by contractions of the muscles of the buccal mass. These muscles are internal and cannot be visualized during behavior. In order to infer the movements of the muscles of the buccal mass, two kinematic models were constructed. The first kinematic model assumed that the complex consisting of the pincer-like radula and the underlying odontophore was spherical in shape. In this model, the radula/odontophore was moved anteriorly or posteriorly and the more superficial buccal muscles (I1/I3 and I2) were fitted around it. Although the overall buccal mass shapes predicted by this model were similar to those observed in vivo during protraction, the shapes predicted during retraction were very different. We therefore constructed a second kinematic model in which the shape of the radula/odontophore was based on the shapes assumed by those structures in vitro when they were passively forced into protraction, rest or retraction positions. As each of these shapes was rotated, the second kinematic model generated overall shapes of the buccal mass that were similar to those observed in vivo during swallowing and tearing, and made predictions about the antero-posterior length of the buccal mass and the relative location of the lateral groove. These predictions were consistent with observations made in vivo and in vitro. The kinematic patterns of intrinsic buccal muscles I1 and I2 in vivo were estimated using the second model. Both models make testable predictions with regard to the functions and neural control of intrinsic buccal muscles I2 and I3.

Animals↗