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PubMed2004

Assessment of basic human performance resources predicts the performance of virtual ureterorenoscopy.

PURPOSE: Regardless of training, innate ability may influence the acquisition of endoscopic skills. Until recently objective methods to assess innate ability have not been available. We compared objective measures of human basic performance resources (BPRs) using nonlinear causal resource analysis (NCRA) and expert rated endoscopic performance of medical students on a virtual reality (VR) simulator. MATERIALS AND METHODS: BPRs were measured in 18 medical students (group 1) using 13 validated tests. BPR results were compared to the results of ureteroscopic skills assessment on the VR simulator. An NCRA model was devised to predict performance based on BPRs and the limiting performance resource (LPR). The same BPRs were measured in a second group of 14 medical students (group 2). Using the model created from group 1 performance of VR ureterorenoscopy was predicted based on LPR for each student in group 2. Predicted performance was compared to rated performance. RESULTS: The average difference in score between 2 expert raters was 7.2%. The average difference in predicted score based on the NCRA model and rated score was only 8.0%. In 9 of the 14 group 2 subjects (63%) the performance prediction by NCRA was in excellent agreement (+/-10%) with the expert rating on the VR simulation. NCRA over predicted performance in 2 subjects (14%) and under predicted performance in 3 (21%). CONCLUSIONS: Objective prediction of ureteroscopic performance in the VR environment using LPRs (measures of innate ability) for each subject is possible and practical using new measurement and modeling methods. The selection of surgical candidates, training and the educational curriculum could be impacted.

Clinical Competence↗
PubMed2005

The absence of delayed graft function is predicted by the presence of manganese-superoxide dismutase in distal tubules of renal allografts.

BACKGROUND: Acute tubular necrosis (ATN) in renal allograft biopsies correlates poorly with delayed graft function (DGF). Factors involved in the pathogenesis of DGF were evaluated in biopsies in an attempt to refine the recognition of DGF. METHODS: Anti-cubulin and anti-AE-1/AE-3 antibodies identified proximal and distal tubules, respectively. The terminal deoxynucleotide transferase-mediated dUTP nick-end labeling technique and active caspase-3 staining were used to demonstrate apoptosis. Antibodies against superoxide dismutase (SOD) were used as markers of the protective tubular response. Tubular regeneration was evaluated using anti-ki 67 and antivimentin antibodies. RESULTS: Of a total of 40 biopsies, 9 were associated with DGF. ATN was seen in 16 biopsies; 5 were associated with DGF. The finding of ATN in the biopsy of a graft predicted DGF in only 56% of cases. Absence of distal caspase-3 staining predicted the absence of ATN in 87% of cases. The presence of caspase-3 predicted ATN in 54% of cases. The detection of manganese-SOD in distal tubules predicts the absence of DGF in 76% of the cases. CONCLUSIONS: The use of immunohistochemical staining on posttransplant renal biopsies improved its predictive value with respect to ATN and DGF: The absence of active caspase-3 in distal tubular epithelium predicts the absence of ATN in 87% of cases, whereas its presence predicts ATN in 54% of cases. The presence of manganese-SOD in distal tubules predicts the absence of DGF in 76% of cases.

Biopsy↗
PubMed1995

Predicting patterns of epicardial potentials during ventricular fibrillation.

Ventricular fibrillation (VF) is a fatal cardiac arrhythmia, characterized by uncoordinated propagation of activation wavefronts in the ventricular myocardium. Short-term predictions of epicardial potential fields during VF in pigs were attempted using linear techniques, and prediction accuracy was measured at various stages during sustained episodes. VF was induced in five pigs via premature electrical stimulation. Unipolar electrograms were recorded from an epicardial array of 506 electrodes in a 22 x 23 array with 1-mm spacing. Optimal spatial basis functions (modes) and time-varying weighting coefficients were found using the Karhunen-Loeve decomposition. Linear autoregressive (AR) models incorporating the dynamics of only a few spatial modes led to predicted patterns that were qualitatively similar to observed patterns. Predictions were made 0.256 s into the future, based on 0.768 s of past data, over an area of approximately 5 cm2 on the ventricular epicardium. The mean squared error of predictions varied from as much as 1.23 to as little as 0.14, normalized to the variance of the actual data. Inconsistency in long-term forcasts is partly due to the limitations of linear AR models. Changes in predictability, however, were consistent. Predictability varied inversely with spatial complexity, as measured by the mean squared error of a five-mode approximation. Predictability also increased significantly during the first minute of VF.

Algorithms↗
PubMed2004

Prediction of myelinated nerve fiber stimulation thresholds: limitations of linear models.

Computer models of neurons are used to simulate neural behavior, and are important tools for designing neural prostheses. Computation time remains an issue when simulating large numbers of neurons or applying models to real time applications. Warman et al. developed a method to predict excitation thresholds for axons using linear models and a predetermined critical voltage. We calculated threshold prediction error as a function of the location of an extracellular electrode using two different axon models to examine further threshold prediction using linear models. Threshold prediction error was low (<3% error) under the conditions examined by Warman et al., but under more general conditions, threshold prediction error was as high as 23.6%. Linear models were limited as effective tools for single fiber threshold prediction because accuracy was dependent on the nonlinear and linear models used, and any parameter that affected the extracellular potential distribution. Threshold prediction could be improved by appropriately choosing the membrane conductance of the linear model, but determination of an optimal conductance was computationally expensive. Finally, although single fiber threshold prediction error was partially masked when considering the input-output (I/O) properties of populations of axons, relatively large errors still occurred in population I/O curves generated with linear models.

Axons↗
PubMed2003

SiteLight: binding-site prediction using phage display libraries.

Phage display enables the presentation of a large number of peptides on the surface of phage particles. Such libraries can be tested for binding to target molecules of interest by means of affinity selection. Here we present SiteLight, a novel computational tool for binding site prediction using phage display libraries. SiteLight is an algorithm that maps the 1D peptide library onto a three-dimensional (3D) protein surface. It is applicable to complexes made up of a protein Template and any type of molecule termed Target. Given the three-dimensional structure of a Template and a collection of sequences derived from biopanning against the Target, the Template interaction site with the Target is predicted. We have created a large diverse data set for assessing the ability of SiteLight to correctly predict binding sites. SiteLight predictive mapping enables discrimination between the binding and nonbinding parts of the surface. This prediction can be used to effectively reduce the surface by 75% without excluding the binding site. In 63% of the cases we have tested, there is at least one binding site prediction that overlaps the interface by at least 50%. These results suggest the applicability of phage display libraries for automated binding site prediction on three-dimensional structures. For most effective binding site prediction we propose using a random phage display library twice, to scan both binding partners of a given complex. The derived peptides are mapped to the other binding partner (now used as a Template). Here, the surface of each partner is reduced by 75%, focusing their relative positions with respect to each other significantly. Such information can be utilized to improve docking algorithms and scoring functions.

Algorithms↗
PubMed2002

Contact order and ab initio protein structure prediction.

Although much of the motivation for experimental studies of protein folding is to obtain insights for improving protein structure prediction, there has been relatively little connection between experimental protein folding studies and computational structural prediction work in recent years. In the present study, we show that the relationship between protein folding rates and the contact order (CO) of the native structure has implications for ab initio protein structure prediction. Rosetta ab initio folding simulations produce a dearth of high CO structures and an excess of low CO structures, as expected if the computer simulations mimic to some extent the actual folding process. Consistent with this, the majority of failures in ab initio prediction in the CASP4 (critical assessment of structure prediction) experiment involved high CO structures likely to fold much more slowly than the lower CO structures for which reasonable predictions were made. This bias against high CO structures can be partially alleviated by performing large numbers of additional simulations, selecting out the higher CO structures, and eliminating the very low CO structures; this leads to a modest improvement in prediction quality. More significant improvements in predictions for proteins with complex topologies may be possible following significant increases in high-performance computing power, which will be required for thoroughly sampling high CO conformations (high CO proteins can take six orders of magnitude longer to fold than low CO proteins). Importantly for such a strategy, simulations performed for high CO structures converge much less strongly than those for low CO structures, and hence, lack of simulation convergence can indicate the need for improved sampling of high CO conformations. The parallels between Rosetta simulations and folding in vivo may extend to misfolding: The very low CO structures that accumulate in Rosetta simulations consist primarily of local up-down beta-sheets that may resemble precursors to amyloid formation.

Algorithms↗
PubMed2001

Genomic-scale comparison of sequence- and structure-based methods of function prediction: does structure provide additional insight?

A function annotation method using the sequence-to-structure-to-function paradigm is applied to the identification of all disulfide oxidoreductases in the Saccharomyces cerevisiae genome. The method identifies 27 sequences as potential disulfide oxidoreductases. All previously known thioredoxins, glutaredoxins, and disulfide isomerases are correctly identified. Three of the 27 predictions are probable false-positives. Three novel predictions, which subsequently have been experimentally validated, are presented. Two additional novel predictions suggest a disulfide oxidoreductase regulatory mechanism for two subunits (OST3 and OST6) of the yeast oligosaccharyltransferase complex. Based on homology, this prediction can be extended to a potential tumor suppressor gene, N33, in humans, whose biochemical function was not previously known. Attempts to obtain a folded, active N33 construct to test the prediction were unsuccessful. The results show that structure prediction coupled with biochemically relevant structural motifs is a powerful method for the function annotation of genome sequences and can provide more detailed, robust predictions than function prediction methods that rely on sequence comparison alone.

Algorithms↗
PubMedDate not supplied

Ranking of hair dye substances according to predicted sensitization potency: quantitative structure-activity relationships.

Allergic contact dermatitis following the use of hair dyes is well known. Many chemicals are used in hair dyes and it is unlikely that all cases of hair dye allergy can be diagnosed by means of patch testing with p-phenylenediamine (PPD). The objectives of this study are to identify all hair dye substances registered in Europe and to provide their tonnage data. The sensitization potential of each substance was then estimated by using a quantitative structure-activity relationship (QSAR) model and the substances were ranked according to their predicted potency. A cluster analysis was performed in order to help select a number of chemically diverse hair dye substances that could be used in subsequent clinical work. Various information sources, including the Inventory of Cosmetics Ingredients, new regulations on cosmetics, data on total use and ChemId (the Chemical Search Input website provided by the National Library of Medicine), were used in order to identify the names and structures of the hair dyes. A QSAR model, developed with the help of experimental local lymph node assay data and topological sub-structural molecular descriptors (TOPS-MODE), was used in order to predict the likely sensitization potential. Predictions for sensitization potential were made for the 229 substances that could be identified by means of a chemical structure, the majority of these hair dyes (75%) being predicted to be strong/moderate sensitizers. Only 22% were predicted to be weak sensitizers and 3% were predicted to be extremely weak or non-sensitizing. Eight of the most widely used hair dye substances were predicted to be strong/moderate sensitizers, including PPD - which is the most commonly used hair dye allergy marker in patch testing. A cluster analysis by using TOPS-MODE descriptors as inputs helped us group the hair dye substances according to their chemical similarity. This would facilitate the selection of potential substances for clinical patch testing. A patch-test series with potent, frequently used, substances representing various chemical clusters is suggested. This may prove useful in diagnosing PPD-negative patients with symptoms of hair dye allergy and would provide some clinical validation of the QSAR predictions.

Allergens↗
PubMed2005

Prediction of drug disposition in infants and children by means of physiologically based pharmacokinetic (PBPK) modelling: theophylline and midazolam as model drugs.

AIMS: To create a general physiologically based pharmacokinetic (PBPK) model for drug disposition in infants and children, covering the age range from birth to adulthood, and to evaluate it with theophylline and midazolam as model drugs. METHODS: Physiological data for neonates, 0.5-, 1-, 2-, 5-, 10- and 15-year-old children, and adults, of both sexes were compiled from the literature. The data comprised body weight and surface area, organ weights, vascular and interstitial spaces, extracellular body water, organ blood flows, cardiac output and glomerular filtration rate. Tissue: plasma partition coefficients were calculated from rat data and unbound fraction (f u) of the drug in human plasma, and age-related changes in unbound intrinsic hepatic clearance were estimated from CYP1A2 and CYP2E1 (theophylline) and CYP3A4 (midazolam) activities in vitro. Volume of distribution (V dss), total and renal clearance (CL and CL R) and elimination half-life (t(1/2)) were estimated by PBPK modelling, as functions of age, and compared with literature data. RESULTS: The predicted V dss of theophylline was 0.4-0.6 l kg(-1) and showed only a modest change with age. The median prediction error (MPE) compared with literature data was 3.4%. Predicted total CL demonstrated the time-course generally reported in the literature. It was 20 ml h(-1) kg(-1) in the neonate, rising to 73 ml h(-1) kg(-1) at 5 years and then decreasing to 48 ml h(-1) kg(-1) in the adult. Overall, the MPE was - 4.0%. Predicted t(1/2) was 18 h in the neonate, dropping rapidly to 4.6-7.2 h from 6 months onwards, and the MPE was 24%. The predictions for midazolam were also in good agreement with literature data. V dss ranged between 1.0 and 1.7 l kg(-1) and showed only modest change with age. CL was 124 ml h(-1) kg(-1) in the neonate and peaked at 664 ml h(-1) kg(-1) at 5 years before decreasing to 425 ml h(-1) kg(-1) in the adult. Predicted t(1/2) was 6.9 h in the neonate and attained 'adult' values of 2.5-3.5 h from 1 year onwards. CONCLUSIONS: A general PBPK model for the prediction of drug disposition over the age range neonate to young adult is presented. A reference source of physiological data was compiled and validated as far as possible. Since studies of pharmacokinetics in children present obvious practical and ethical difficulties, one aim of the work was to utilize maximally already available data. Prediction of the disposition of theophylline and midazolam, two model drugs with dissimilar physicochemical and pharmacokinetic characteristics, yielded results that generally tallied with literature data. Future use of the model may demonstrate further its strengths and weaknesses.

Adolescent↗
PubMed1994

Predictive value of specific risk factors, symptoms and signs, in diagnosing obstructive sleep apnoea and its severity.

A positive diagnosis of obstructive sleep apnoea (OSA) is based on a combination of characteristic symptoms and polysomnographic findings. The present study evaluated the specificity and sensitivity of several risk factors, signs and symptoms in predicting an Apnoea Index in 86 patients referred to the sleep laboratory with suspected OSA. All 86 subjects completed a detailed questionnaire, were interviewed, underwent a brief physical examination, and then a whole-night polysomnographic study. Stepwise multiple regression analysis revealed that self reporting on apnoeas, neck circumference index (NCI), age, and a tendency to fall asleep unintentionally, were all significant positive predictors of apnoea index (AI), explaining 41.8% of the variability. The sensitivity of the model for predicting OSA (taking OSA as AI > 10) was 92.2%, specificity was 18.2% and the positive predictive value was 76.6%. Raising the cut-off AI values resulted in decreased sensitivity and increased specificity. Applying the predicting equation of AI to another group of 50 patients referred to the sleep laboratory with suspected OSA revealed similar results. However, running the equation on 105 offspring of OSA patients who did not complain of OSA-associated symptoms resulted in 32% sensitivity and 94% specificity in predicting OSA. It is concluded that questionnaires, interviews and physical examination, can only vaguely predict AI, and cannot replace polysomnographic recordings. However, the low rates of false negative in predicting AI > 10, and the low rates of false positive in predicting AI > 50, can be used for specific purposes.

Journal Article↗
PubMed2005

Predicting progressive hepatic fibrosis stage on subsequent liver biopsy in chronic hepatitis C virus infection.

Retrospective cross-sectional studies indicate that 20% with chronic hepatitis C virus (HCV) infection become cirrhotic within 20 years. Known risk factors for advanced hepatic fibrosis include age at time of infection, male sex, excess alcohol consumption and cytokine polymorphisms. Prospective study to assess and identify factors predictive of change in hepatic fibrosis stage in chronic HCV infection by interval protocol liver biopsy was performed. One hundred and five patients with paired liver biopsy specimens separated by a mean 41 months were recruited from a cohort of 823 HCV carriers. Five per cent developed worsening hepatic fibrosis by more than two stages. In 43% there was no change in fibrosis stage. Excessive alcohol intake currently (P = 0.037) or previously (P = 0.07) predicted progression. In contrast, always having a normal alanine transaminase (P = 0.038) and always being negative in serum for HCV RNA (P =0.067) predicted no progression. Three models were developed to predict outcome. Progressive fibrosis was predicted by baseline fibrosis (P = 0.018), steatosis (P = 0.02) and age (P = 0.017). The rate of progressive fibrosis was predicted by baseline fibrosis (P = 0.0002), steatosis (P =0.039) and lobular inflammation (P = 0.09). Fibrosis stage on the second biopsy was predicted by baseline fibrosis alone (P = 0.01). The rate of progression varies widely. Alcohol misuse is an important co-factor. Progressive fibrosis can be predicted at first liver biopsy, where baseline fibrosis is most critical, allowing targeted therapy for those with early disease and a significant risk of progression.

Adult↗
PubMed1980

Prediction of the surface-interior diagram of globular proteins by an empirical method.

The number of amino acid residues in contact with a residue in a globular protein is a simple and good measure to show the relative location of the residue on the surface or in the interior of the protein. The contact number is estimated as the number of C alpha atoms within a sphere of radius r (8 A) centered at the C alpha atom of a given residue. The prediction of a diagram (the plot of the contact number against the residue number) from a given amino acid sequence may be meaningful as an alternative to the secondary-structure prediction currently performed. Parameter values are determined empirically using the observed contact numbers calculated from known structures of 39 proteins. In order to assess the real efficiency of the method, the prediction has been performed in the following way; all the proteins are divided into two groups; one group is used to derive parameter sets and the other serves to test the prediction accuracy. The test reveals that the parameter sets empirically determined are biased significantly towards the data base, the extent of which is roughly proportional to the number of parameter terms included. The results show that an adequate smoothing of a parameter set is the best way to reduce the extent of biasing towards the data base and to give the best prediction for 'unknown' proteins. The prediction accuracy finally obtained is about 0.4 (or roughly 70%), on the average, measured by the correlation coefficient between the predicted and observed diagrams. This value is of the same order as the accuracy in the current predictions of secondary structures.

Amino Acid Sequence↗
PubMed1993

Prediction of transmembrane beta-strands from hydrophobic characteristics of proteins.

The assembly of outer-membrane proteins consisting of beta-strands as transmembrane segments is somewhat more complex when compared to the assembly of inner membrane proteins having alpha-helices as transmembrane parts. This is probably due to the difference in the amino acid sequences of the transmembrane part strands and helices. Because of this feature, most predictive schemes which are successful in predicting transmembrane helical segments fail to predict transmembrane strand segments. Here we propose a new predictive scheme for forecasting the transmembrane strand segments in outer-membrane proteins with the use of the general surrounding hydrophobicity scale developed both for the globular and membrane proteins in the preceding article. Two major features of the scheme are (i) that it does not solely depend on the amphipathic character of a sequence segment while identifying it as a transmembrane strand, and it is capable of predicting strands in varied lengths, a facility to reflect the variation in the membrane surfaces. This scheme predicts the transmembrane beta-strands in porin from R. capsulatus at 76% accuracy (giving due weights to over- and under-predictions when compared to X-ray results). The predicted beta-structure contents in OmpA, porin from E. coli and maltoporin compared with the Raman spectroscopic results at 95% level. These accuracy levels are far superior than the levels obtained from other existing methods. Apart from the above four proteins for which experimental informations are available, ten other outer-membrane proteins, for which there is no information about their secondary structure, are considered in the forecast. The results are analysed and the common features in the folds of the set of fourteen outer-membrane proteins are deduced.

Amino Acid Sequence↗
PubMed2004

Predicting the need for ventilation in term and near-term neonates.

OBJECTIVE: To determine whether the need for respiratory support can be predicted by oxygen requirement within the first 72 h in term and near-term infants. METHODS: To mimic the population of infants that would often be delivered outside a tertiary centre we studied a retrospective cohort of infants > or = 32 weeks requiring oxygen, divided into three groups: cot oxygen only, nasal continuous positive airway pressure (NCPAP) only, or intermittent positive pressure ventilation (IPPV). We recorded each infant's peak fraction of inspired oxygen (FiO2)--i.e. FiO2 in the first 72 h in the cot oxygen only group or maximum FiO2 prior to commencing the highest level of respiratory support. The peak FiO2 was used as a diagnostic test to predict any respiratory support or IPPV--sensitivity and specificity were calculated and receiver operating characteristic (ROC) curves plotted (FiO2 0.21-1.00) to identify the best balance point for prediction. RESULTS: The cohort included 592 infants: 516 cot oxygen only, 46 NCPAP only and 30 IPPV. The proportion ventilated increased with increasing peak FiO2--above 0.45 the proportion of infants ventilated exceeded 50%. To predict any respiratory support, the cut-point balancing sensitivity and specificity was a FiO2 > or = 0.35-58/136 required respiratory support (sensitivity = 0.76, specificity = 0.85, positive predictive value (PPV) = 43%, negative predictive value (NPV) = 96%). To predict IPPV the cut-point was a FiO2 > or = 0.5-28/47 treated with IPPV (sensitivity = 0.93, specificity = 0.97, PPV = 60%, NPV = 100%). CONCLUSION: The need for respiratory support can be predicted by oxygen requirement within the first 72 h in term and near-term infants with reasonable sensitivity and excellent specificity.

Blood Gas Analysis↗
PubMed2006

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↗
PubMed2000

How useful is uterine artery Doppler flow velocimetry in the prediction of pre-eclampsia, intrauterine growth retardation and perinatal death? An overview.

OBJECTIVE: To evaluate the clinical usefulness of Doppler analysis of the uterine artery velocity waveform in the prediction of pre-eclampsia and its associated complications of intrauterine growth retardation and perinatal death. DESIGN: Quantitative systematic review of observational diagnostic studies using online searching of the MEDLINE database coupled with scanning of the bibliographies of primary and review articles including known unpublished studies. MATERIAL: Twenty-seven studies involving 12,994 subjects stratified into population subgroups at low and high risk of developing pre-eclampsia and its complications. OUTCOME MEASURES: The outcome measures studied were: 1. the development of pre-eclampsia; 2. intrauterine growth retardation; and 3. perinatal death. The main meta-analyses were the flow velocity waveform ratio +/- diastolic notch derived by transabdominal Doppler ultrasound as the measurement parameter. The analyses were conducted using likelihood ratio as a measure of diagnostic accuracy. A likelihood ratio of 1 indicates that the test has no predictive value for the outcome. Prediction for the outcome event is considered conclusive with likelihood ratios of > 10 or < 0 x 1 for a positive and negative test result, respectively. Moderate prediction can be achieved with likelihood ratios of 5-10 and 0 x 1-0 x 2 whereas likelihood ratios values of 1-5 and 0 x 2-1 would generate only minimal prediction. RESULTS: In the low risk population a positive test result, predicted pre-eclampsia with a pooled likelihood ratio of 6 x 4 (95% CI 5 x 7-7 x 1), while a negative test result had a pooled likelihood ratio of 0 x 7 (95% CI 0 x 6-0 x 8). For intrauterine growth retardation the pooled likelihood ratio was 3 x 6 (95% CI 3 x 2-4 x 0) for a positive test result and 0 x 8 (95% CI 0 x 8-0 x 9) for a negative test result. Using perinatal death as outcome measure, the pooled likelihood ratio was 1 x 8 (95% CI 1 x 2-2 x 9) for a positive test result and 0 x 9 (95% CI 0 x 8-1 x 1) for a negative test result. In the high risk population a positive test result predicted pre-eclampsia with a pooled likelihood ratio of 2 x 8 (95% CI 2 x 3-3 x 4), while a negative test had a likelihood ratio of 0 x 8 (95% CI 0 x 7-0 x 9). For intrauterine growth retardation the pooled likelihood ratio was 2 x 7 (95% CI 2 x 1-3 x 4) for a positive test result and 0 x 7 (95% CI 0 x 6-0 x 9) for a negative result. For perinatal death the pooled likelihood ratio was 4 x 0 (95% CI 2 x 4-6 x 6) for a positive test result and 0 x 6 (95% CI 0 x 4-0 x 9) for a negative result. CONCLUSION: Uterine artery Doppler flow velocity has limited diagnostic accuracy in predicting pre-eclampsia, intrauterine growth retardation and perinatal death.

Arteries↗
PubMed1997

Utility of the lethargic (lh/lh) mouse model of absence seizures in predicting the effects of lamotrigine, vigabatrin, tiagabine, gabapentin, and topiramate against human absence seizures.

PURPOSE: Traditional methods of preclinical screening have predicted the effects of a putative antiepileptic drug (AED) against human absence seizures by testing its efficacy against clonic seizures in the high-dose pentylenetetrazole (PTZ) model. This high-dose PTZ model correctly predicted the efficacy of ethosuximide (ESM), benzodiazepines, and valproate (VPA) and the lack of efficacy of phenytoin (PHT) and carbamazepine (CBZ). However, the high-dose PTZ model erred in predictions for (a) phenobarbital (PB) (PTZ: efficacy; human: nonefficacy); (b) lamotrigine (LTG) (PTZ: nonefficacy; human: efficacy); (c) vigabatrin (VGB) (PTZ: nonefficacy; human: proabsence effect); and (d) tiagabine (TGB) (PTZ: efficacy; human: possible proabsence). It also appears to have erred in predictions for gabapentin (GBP) (PTZ: efficacy) and topiramate (TPM) (PTZ: efficacy). Because the lh/lh genetic model of absence seizures correctly predicted effects of ESM, clonazepam, VPA, PHT, CBZ, and PB against human absence seizures, we performed this study to test the predictive utility of the lh/lh model for LTG, VGB, TGB, GBP, and TPM. METHODS: Bipolar recording electrodes were implanted bilaterally into frontal neocortex of 8-week-old male lh/lh mice. With the exception of VGB, vehicle or drugs were administered intraperitoneally (i.p.) on alternating days, and an EEG was used to record effects on seizure frequency. With VGB, vehicle was administered i.p. on day 1, and gradually increasing doses of VGB were administered on successive days. Drug and vehicle effects were compared in corresponding 15-min epochs of the 150-min period after administration. RESULTS: LTG (4.8-144 micromol/kg) significantly (p < 0.04) reduced seizure frequency (by 65%) compared with vehicle. In contrast, VGB (0.35-11 mmol/kg) and TGB (0.27-27 micromol/kg) significantly increased seizure frequency (300-700%) and seizure duration (1,700-1,800%; p < 0.001). GBP (18 micromol/kg to 1.8 mmol/kg) and TPM (8.9-295 micromol/kg) had no significant effect on seizure frequency. CONCLUSIONS: In contrast to the high-dose PTZ model, the lh/lh model correctly predicted the antiabsence effect of LTG, the possible proabsence effects of VGB and TGB, and the lack of effect of GBP and TPM. The lh/lh model appears to be superior to the high-dose PTZ model in predicting efficacy of putative AEDs against human absence seizures.

Acetates↗
PubMed2006

Evaluating the contributions of state-of-the-art assessment techniques to predicting memory outcome after unilateral anterior temporal lobectomy.

PURPOSE: Although anterior temporal lobectomy (ATL) is an effective treatment for many patients with medically refractory temporal lobe epilepsy (TLE), one risk associated with this procedure is postsurgical decline in memory. A substantial number of past studies examined factors that predict memory decline after surgery, but few have investigated multiple predictors simultaneously or considered measures that are currently in use. METHODS: This study compared the relative contributions made by presurgical neuropsychological test scores, MRI-based hippocampal volumetric analysis, and Wada test results to predicting memory outcome after ATL in a group of 87 patients. RESULTS: Logistic regression analyses indicated that noninvasive procedures (neuropsychological testing and MRI) made significant contributions to improving the prediction of memory outcome in this sample. The results from the Wada procedure did not significantly improve prediction once these other factors were considered. The only exception was in predicting memory for visual information after a delay, in which Wada results improved prediction accuracy from 78% to 81%. CONCLUSIONS: Current neuropsychological tests and MRI volumetric measures predict changes in verbal and visual memory after ATL. The relatively small change in correct classification rates when Wada memory scores are considered calls into question the benefits of using Wada test results to predict memory outcome when the results of noninvasive procedures are available.

Anterior Temporal Lobectomy↗