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Neural networks as predictors of outcomes in alcoholic patients with severe liver disease.

We developed and evaluated neural networks as predictors of outcomes in alcoholic patients with severe liver disease using commonly available clinical and laboratory values. Hospital charts of 144 patients were reviewed. Nine variables (five laboratory, four clinical) were recorded along with in-hospital death or survival. Data were organized into separate development and validation sets. Neural network predictions of survival were compared with those of the Maddrey discriminant function and logistic regression models developed on the same data. Model performance was evaluated by comparing areas under receiver-operating characteristic (ROC) curves and the distributions of model scores. Survivors had significantly different laboratory and clinical characteristics, the most important being a higher prothrombin time, lower bilirubin, and lower incidence of encephalopathy. Neural network performance was significantly better than that of the Maddrey score (ROC areas, 81.5% vs. 73.8%; P = .04). The ROC area for neural networks was similar to that of logistic regression (ROC area 78.2%; P = .3), but the neural networks were more successful in classifying patients into low- and high-risk groups (P < .001). A neural network score with laboratory data from hospital-day 7 improved prognostic accuracy further to 84.3%. After adjusting for baseline risk, the neural network change in illness severity was still a significant predictor of mortality (P = .001). Neural networks using clinical and laboratory data showed a high prognostic accuracy for predicting mortality in alcoholic patients with severe liver disease.

Adult↗

Studies of parallel barrier performance by acoustical modeling.

An investigation is presented into the performance of parallel barrier configurations, using acoustical scale modeling. A realistic geometry is investigated, with the source being positioned over a paved roadway and the receiver over grass-covered ground. The grass-covered ground surface was properly modeled in terms of its impedance. Results were obtained for a range of barrier types, and demonstrate that frequency dependent effects are evident in barrier insertion loss data. In most cases, the barrier on the far side of the source did not significantly affect sound levels at the receiver. The most effective barrier design was found to be that of a gradual grass-covered slope up to an upright, thin barrier.

Acoustics↗

Occupational performance measures: a review based on the guidelines for the client-centred practice of occupational therapy.

In 1987, Health and Welfare Canada and the Canadian Association of Occupational Therapists Task Force recommended that work go forward to develop an outcome measure for occupational therapy which reflects the Occupational Performance Model. The first step in this process was to review critically those outcome measures which assess occupational performance and that are currently available in the literature. This paper will present the review process, describe in more detail eight assessments that fulfilled many of the review criteria, discuss the limitations of these measures using the "Guidelines for the Client-centred Practice of Occupational Therapy as the framework, and make recommendations for the development of a new outcome measure for use in occupational therapy.

Activities of Daily Living↗

Performance optimization of left ventricular assistance. A computer model study.

Performance of temporary parallel left ventricular assistance was investigated and the theoretic conditions leading to optimal behavior of the mechanical system were explored. Computer models of nonpulsatile and pulsatile left ventricular assist devices (LVADs) were incorporated into a previously reported closed-loop simulation of the canine cardiovascular system. Assuming the assisted heart was capable of recovery, LVAD performance was assessed based on both myocardial oxygen balance and cardiac output. With a synchronous LVAD, and operating in a counterpulsation mode, these variables were sensitive to the phasing of pump ejection. Maximum reduction in cardiac oxygen consumption, maximum increase in oxygen availability, and maximum increase in cardiac output with the atrio-aortic device were obtained when pump ejection immediately followed aortic valve closure. These variables were directly proportional to the magnitude of bypass volume. The pulsatile asynchronous and nonpulsatile LVAD models affected oxygen balance in a similar manner, but neither performed so well as the synchronous model when equal bypass volumes were used. Ventricular uptake of blood provided a further 27% decrease in oxygen consumption and further 78% increase in oxygen availability than atrial uptake. In summary, the model predicted that the pulsatile synchronous LVAD, filling from the ventricle during heart systole and ejecting into either the ascending or descending aorta just after ventricular systole, would be most beneficial to both myocardial oxygen balance and cardiac output.

Animals↗

Validation of a calibrated prediction model for response to growth hormone treatment in an independent cohort.

BACKGROUND: Prediction models, e.g. for prediction of response to growth hormone treatment, need validation in appropriate independent cohorts, comparing predicted and observed outcomes. In a previous validation of a model for predicting the first-year response to growth hormone treatment in children with idiopathic growth hormone deficiency, overfitting was observed. We modified the prediction formula and now report validation of this modified model. PATIENTS AND METHODS: The modified and original prediction models were applied to a group of patients selected from Lilly's GeNeSIS database using the same inclusion and exclusion criteria as for the original model. For both prediction methods, observed first-year height velocity was plotted vs. predicted height velocity in a calibration plot. For a valid prediction, the regression line should correspond to the line of identity (observed outcome is equal to predicted outcome); the regression lines for each prediction model were tested for significant differences from this line of identity. RESULTS: The number of patients fulfilling the criteria was 226. The regression line in the calibration plot of the modified model was not significantly different from the line of identity (p = 0.43), in contrast to the original model (p < 0.001). For the modified model the mean (SD) prediction error was -0.11 (2.05) cm/year and for the original model 0.28 (2.11) cm/year. CONCLUSION: The modified prediction method, obtained after calibration of the original model, performs well in an independent patient sample and gives more accurate predictions than the original model.

Body Height↗

Structure selection for protein kinase docking and virtual screening: homology models or crystal structures?

There is currently far more sequence information than structural information available, and the ability to use homology models for virtual screening applications is desirable in many cases where structures have not yet been solved. This review focuses on the application of protein kinase homology models for virtual screening use. In addition to reviewing previous cases in which kinase homology models have been used in inhibitor design, we present new data - useful for template selection in homology modeling applications - indicating that the template structure with the highest sequence or structural similarity with the target structure may not always be the best choice. This new work explored the simple hypothesis that better results might be obtained for docking a ligand to a target receptor using a homology model of the target created from a different kinase template co-crystallized with the ligand, than from a crystal structure of the actual kinase target that is unliganded or bound to an unrelated ligand. This hypothesis was tested in docking studies of staurosporine with eight different kinases: AutoDock was used to dock staurosporine to homology models of each kinase created from staurosporine-bound template structures, and the results were compared with docking staurosporine to crystal structures of the target kinase that were obtained in complex with a non-staurosporine ligand or no ligand. It was found that the homology models performed as well as or better than the crystal structures, suggesting that using a homology model created from a template crystallized with a representative ligand may in some cases be a preferred approach, especially in virtual screening experiments that focus on enriching for members of a particular inhibitor class.

Crystallography, X-Ray↗

Prospective evaluation of a logistic model based on sonographic morphologic and color Doppler findings developed to predict adnexal malignancy.

To assess prospectively a logistic model based on sonographic morphologic and color Doppler findings, which had been developed to predict adnexal malignancy, 167 consecutive and unselected patients (mean age, 45.7 yr; range, 17 to 81 yr; 113 [67.7%] premenopausal and 54 [32.3%] postmenopausal) diagnosed as having an adnexal mass and scheduled for surgery were prospectively included in this study. All patients were evaluated by transvaginal color Doppler ultrasonography. The probability of adnexal malignancy was estimated prior to surgery, applying a logistic model developed previously. A probability of malignancy greater than 75% was considered to assess model performance. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for the model. In all cases definitive histopathologic diagnosis was obtained. One hundred and twenty-five (74.9%) benign and 42 (25.1%) malignant tumors were found. The sensitivity, specificity, positive predictive value, and negative predictive value of the model were 85.7% (95% confidence intervals, 71.4% to 94.6%), 100% (95% confidence intervals, 97.1% to 100%), 100% (95% confidence intervals, 90.3% to 100%), and 95.4% (95% confidence intervals, 90.3% to 98.3%), respectively. Overall accuracy was 96.4% (95% confidence intervals, 91.3% to 98.7%). Our results confirm the validity of the proposed logistic model in predicting adnexal malignancy.

Adnexal Diseases↗

Changes in stomatal conductance and net photosynthesis during phenological development in spring wheat: implications for gas exchange modelling.

Gas exchange was measured from 1 month before the onset of anthesis until the end of grain filling in field-grown spring wheat, Triticum aestivum L., cv. Vinjett, in southern Sweden. Two g ( s ) models were parameterised using these data: one Jarvis-type multiplicative g ( s ) model (J-model), and one combined stomatal-photosynthesis model (L-model). In addition, the multiplicative g ( s ) model parameterisation for wheat used within the European Monitoring and Evaluation Programme (EMEP-model) was tested and evaluated. The J-model performed well (R (2)=0.77), with no systematic pattern of the residuals plotted against the driving variables. The L-model explained a larger proportion of the variation in g ( s ) data when observations of A (n) were used as input data (R (2)=0.71) compared to when A (n) was modelled (R (2)=0.53). In both cases there was a systematic model failure, with g (s) being over- and underestimated before and after anthesis, respectively. This pattern was caused by the non-parallel changes in g ( s ) and A (n) during plant phenological development, with A (n) both peaking and starting to decline earlier as compared to g ( s ). The EMEP-model accounted for 41% of the variation in g ( s ) data, with g ( s ) being underestimated after anthesis. We conclude that, under the climatic conditions prevailing in southern Scandinavia, the performance of the combined stomatal-photosynthesis approach is hampered by the non-parallel changes in g ( s ) and A (n), and that the phenology function of the EMEP-model, having a sharp local maximum at anthesis, should be replaced by a function with a broad non-limiting period after anthesis.

Carbon Dioxide↗

Probabilistic gas and bubble dynamics models of decompression sickness occurrence in air and nitrogen-oxygen diving.

Probabilistic models of the occurrence of decompression sickness (DCS) with instantaneous risk defined as the weighted sum of bubble volumes in each of three parallel-perfused gas exchange compartments were fit using likelihood maximization to the subset of the USN Primary Air and N2-O2 database [n = 2,383, mean P(DCS) = 5.8%] used in development of the USN LE1 probabilistic models. Bubble dynamics with one diffusible gas in each compartment were modeled using the Van Liew equations with the nucleonic bubble radius, compartmental volume, compartmental bulk N2 diffusivity, compartmental N2 solubility, and the N2 solubility in blood x compartmental blood flow as adjustable parameters. Models were also tested that included the effects of linear elastic resistance to bubble growth in one, two, or all three of the modeled compartments. Model performance about the training data and separate validation data was compared to results obtained about the same data using the LE1 probabilistic model, which was independently implemented from published descriptions. In the most successful bubble volume model, BVM(3), diffusion significantly slows bubble growth in one of the modeled compartments, whereas mechanical resistance to bubble growth substantially accelerates bubble resolution in all compartments. BVM(3) performed generally on a par with LE1, despite inclusion of 12 more adjustable parameters, and tended to provide more accurate incidence-only estimates of DCS probability than LE1, particularly for profiles in which high fractional O2 gas mixes are breathed. Values of many estimated BVM(3) parameters were outside of the physiologic range, indicating that the model emerged from optimization as a mathematical descriptor of processes beyond bubble formation and growth that also contribute to DCS outcomes. Although incomplete as a mechanistic description of DCS etiology, BVM(3) remains applicable to a wider variety of decompressions than LE1 and affords a conceptual framework for further refinements motivated by mechanistic principles.

Decompression Sickness↗

Can the clinical history distinguish between organic and functional dyspepsia?

CONTEXT: Upper gastrointestinal symptoms occur in 40% of the population. An accurate diagnosis would help rationalize investigation and treatment. OBJECTIVE: To systematically review the literature of the accuracy of primary care physicians, gastroenterologists, or computer models in diagnosing organic dyspepsia. DATA SOURCES: A search of Cochrane Controlled Trials Register (December 2003), MEDLINE (1966-December 2003), EMBASE (1988-December 2003), and CINAHL (1982-December 2003) for studies that reported on cohorts of patients attending for endoscopy that had symptoms, clinical opinion, or both recorded before investigation. STUDY SELECTION: Studies that prospectively compared the diagnosis reached by a clinician, computer model, or both with results of upper gastrointestinal endoscopy in adult patients with upper gastrointestinal symptoms. DATA EXTRACTION: Two authors independently assessed studies (n = 79) for eligibility and abstracted data for estimating likelihood ratios (LRs) of clinical opinion, computer models, or both in diagnosing an organic cause for dyspepsia. DATA SYNTHESIS: Fifteen studies were identified that evaluated 11 366 patients, with 4817 patients (42%) classified as having organic dyspepsia. The computer models performed similarly to the clinician; therefore, the 2 approaches were combined. The diagnosis reached by the clinician or computer model suggesting organic dyspepsia had an LR of 1.6 (95% confidence interval [CI], 1.4-1.8), and a negative result decreased the likelihood of organic dyspepsia (LR, 0.46; 95% CI, 0.38-0.55). A diagnosis of peptic ulcer disease performed similarly with an LR of 2.2 (95% CI, 1.9-2.6), but an evaluation that suggested the absence of peptic ulcer disease had an LR of 0.45 (95% CI, 0.38-0.53). A clinical history suggesting esophagitis had an LR of 2.4 (95% CI, 1.9-3.0) vs a negative history that had an LR of 0.50 (95% CI, 0.42-0.60). CONCLUSION: Neither clinical impression nor computer models that incorporated patient demographics, risk factors, history items, and symptoms adequately distinguished between organic and functional disease in patients referred for endoscopic evaluation of dyspepsia.

Diagnosis, Computer-Assisted↗

Diagnostic cost groups (DCGs) and concurrent utilization among patients with substance abuse disorders.

OBJECTIVE: To assess the performance of Diagnostic Cost Groups (DCGs) in explaining variation in concurrent utilization for a defined subgroup, patients with substance abuse (SA) disorders, within the Department of Veterans Affairs (VA). DATA SOURCES: A 60 percent random sample of veterans who used health care services during Fiscal Year (FY) 1997 was obtained from VA administrative databases. Patients with SA disorders (13.3 percent) were identified from primary and secondary ICD-9-CM diagnosis codes. STUDY DESIGN: Concurrent risk adjustment models were fitted and tested using the DCG/HCC model. Three outcome measures were defined: (1) "service days" (the sum of a patient's inpatient and outpatient visit days), (2) mental health/substance abuse (MH/SA) service days, and (3) ambulatory provider encounters. To improve model performance, we ran three DCG/HCC models with additional indicators for patients with SA disorders. DATA COLLECTION: To create a single file of veterans who used health care services in FY 1997, we merged records from all VA inpatient and outpatient files. PRINCIPAL FINDINGS: Adding indicators for patients with mild/moderate SA disorders did not appreciably improve the R-squares for any of the outcome measures. When indicators were added for patients with severe SA who were in the most costly category, the explanatory ability of the models was modestly improved for all three outcomes. CONCLUSIONS: Modifying the DCG/HCC model with additional markers for SA modestly improved homogeneity and model prediction. Because considerable variation still remained after modeling, we conclude that health care systems should evaluate "off-the-shelf" risk adjustment systems before applying them to their own populations.

Adult↗

The evaluation of preprocessing choices in single-subject BOLD fMRI using NPAIRS performance metrics.

This work proposes an alternative to simulation-based receiver operating characteristic (ROC) analysis for assessment of fMRI data analysis methodologies. Specifically, we apply the rapidly developing nonparametric prediction, activation, influence, and reproducibility resampling (NPAIRS) framework to obtain cross-validation-based model performance estimates of prediction accuracy and global reproducibility for various degrees of model complexity. We rely on the concept of an analysis chain meta-model in which all parameters of the preprocessing steps along with the final statistical model are treated as estimated model parameters. Our ROC analog, then, consists of plotting prediction vs. reproducibility results as curves of model complexity for competing meta-models. Two theoretical underpinnings are crucial to utilizing this new validation technique. First, we explore the relationship between global signal-to-noise and our reproducibility estimates as derived previously. Second, we submit our model complexity curves in the prediction versus reproducibility space as reflecting classic bias-variance tradeoffs. Among the particular analysis chains considered, we found little impact in performance metrics with alignment, some benefit with temporal detrending, and greatest improvement with spatial smoothing.

Adult↗

Evaluation of spectrofluorometry as a tool for estimation in fed-batch fermentations.

Native culture fluorescence was investigated as an additional source of information for predicting biomass and glucose concentrations in a fed-batch fermentation of Alcaligenes eutrophus. Partial least squares (PLS) regression and a feed forward neural network (FFNN) coupled with principle component analysis (PCA) were each used to model the kinetics of the fermentation. Data from three fermentations was combined to form a training set for model calibration and data from a fourth fermentation was used as the testing set. The fluorescent soft-sensors were compared with a previously developed feed forward neural network soft-sensor model which used oxygen uptake rate (OUR), carbon dioxide evolution rate (CER), aeration rate, feed rate, and fermentor volume to estimate biomass and glucose concentrations. The best model performance for predicting both biomass and glucose concentrations was achieved using the native fluorescence-based models. Real data predictions of the biomass concentration in the testing set were obtained using both the PLS and FFNN PCA modeling utilizing fluorescence measurements plus the rate of change of the fluorescence measurements. Accurate predictions of the glucose concentration in the testing set were obtained using the FFNN PCA modeling technique utilizing the rate of change of the fluorescence measurements. Substrate exhaustion was indicated qualitatively by a first-order PLS model utilizing the rate of change of fluorescence measurements. These results indicate that native culture fluorescence shows promise for providing additional valuable information to enhance predictive modeling which cannot be extracted from other easily acquired measurements.

Algorithms↗

Modeling the dishabituation hierarchy: the role of the primordial hippocampus.

We present a neural model for the organization and neural dynamics of the medial pallium, the toad's homolog of mammalian hippocampus. A neural mechanism, called cumulative shrinking, is proposed for mapping temporal responses from the anterior thalamus into a form of population coding referenced by spatial positions. Synaptic plasticity is modeled as an interaction of two dynamic processes which simulates acquisition and both short-term and long-term forgetting. The structure of the medial pallium model plus the plasticity model allows us to provide an account of the neural mechanisms of habituation and dishabituation. Computer simulations demonstrate a remarkable match between the model performance and the original experimental data on which the dishabituation hierarchy was based. A set of model predictions is presented, concerning mechanisms of habituation and cellular organization of the medial pallium.

Animals↗

Risk adjusting capitation: applications in employed and disabled populations.

Risk adjustment may be a sensible strategy to reduce selection bias because it links managed care payment directly to the costs of providing services. In this paper we compare risk adjustment models in two populations (public employees and their dependents, and publicly-insured low income individuals with disabilities) in Washington State using two statistical approaches and three health status measures. We conclude that a two-part logistic/GLM statistical model performs better in populations with large numbers of individuals who do not use health services. This model was successfully implemented in the employed population, but the managed care program for the publicly insured population was terminated before risk adjustment could be applied. The choice of the most appropriate health status measure depends on purchasers' principles and desired outcomes.

Adolescent↗

Young children's ability to understand a model as a spatial representation.

Children's ability to understand that a real environment can be represented in a symbolic form (i.e., by a model) is an important developmental achievement. Researchers have claimed that children who are just 3 years of age appreciate models as representations. This research was based on tasks that involved having young children use a model to locate a hiding place in an actual room. In this article, however, we point out the difficulties in interpreting previous model tasks, and we describe two studies that showed that young 3-year-olds could perform model tasks successfully when the hiding place they were looking for was a unique place in the model (and room). When the hiding place was unique, the children had to note only that place and they needed no further knowledge about the relationship between the model and the room. When the hiding place was one of two identical places, however, the children needed to take spatial relationships into account to distinguish the correct place, and young 3-year-olds were unable to do this. Four-year-olds were able to use spatial relationships to distinguish identical places when the model was aligned with the space it represented, but they had difficulty when the model was not aligned. Five-year-olds could use spatial relationships effectively between one model space and another whether or not the model was aligned.

Child↗

Model evaluation and spatial interpolation by Bayesian combination of observations with outputs from numerical models.

Constructing maps of dry deposition pollution levels is vital for air quality management, and presents statistical problems typical of many environmental and spatial applications. Ideally, such maps would be based on a dense network of monitoring stations, but this does not exist. Instead, there are two main sources of information for dry deposition levels in the United States: one is pollution measurements at a sparse set of about 50 monitoring stations called CASTNet, and the other is the output of the regional scale air quality models, called Models-3. A related problem is the evaluation of these numerical models for air quality applications, which is crucial for control strategy selection. We develop formal methods for combining sources of information with different spatial resolutions and for the evaluation of numerical models. We specify a simple model for both the Models-3 output and the CASTNet observations in terms of the unobserved ground truth, and we estimate the model in a Bayesian way. This provides improved spatial prediction via the posterior distribution of the ground truth, allows us to validate Models-3 via the posterior predictive distribution of the CASTNet observations, and enables us to remove the bias in the Models-3 output. We apply our methods to data on SO2 concentrations, and we obtain high-resolution SO2 distributions by combining observed data with model output. We also conclude that the numerical models perform worse in areas closer to power plants, where the SO2 values are overestimated by the models.

Air Pollution↗

Risk adjustment for measuring health outcomes: an application in VA long-term care.

An empirically derived risk adjustment model is useful in distinguishing among facilities in their quality of care. We used Veterans Affairs (VA) administrative databases to develop and validate a risk adjustment model to predict decline in functional status, an important outcome measure in long-term care, among patients residing in VA long-term care facilities. This model was used to compare facilities on adjusted and unadjusted rates of decline. Predictors of decline included age, time between assessments, baseline functional status, terminal illness, pressure ulcers, pulmonary disease, cancer, arthritis, congestive heart failure, substance-related disorders, and various neurologic disorders. The model performed well in the development and validation databases (c statistics, 0.70 and 0.68, respectively). Risk-adjusted rates and rankings of facilities differed from unadjusted ratings. We conclude that judgments of facility performance depend on whether risk-adjusted or unadjusted decline rates are used. Valid risk adjustment models are therefore necessary when comparing facilities on outcomes.

Aged↗