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Predictive models of short- and long-term survival in patients with nonbiliary cirrhosis.

The limited number of donor organs has placed a burden on the medical community to improve patient selection and timing of liver transplantation (LT). We aim to evaluate short- and long-term survival of 124 consecutive patients with a diagnosis of nonbiliary cirrhosis. Seventeen clinical, biochemical, functional, and hemodynamic parameters were computed. Patient survival was evaluated in the short term (3 months) by logistic regression, and the predictive power of the model was evaluated using receiver operating characteristic curves and the log likelihood ratio. For the long-term (up to 5 years) prognosis, the Cox proportional model was used. During follow-up, 54 patients died and 20 patients underwent LT. In the short-term study, the Model for End-Stage Liver Disease score (including bilirubin level, international normalized ratio [INR], and creatinine level) was as predictive as our score, which contained only two independent indicators (bilirubin and creatinine levels). In the long-term study, three independent variables (albumin level, INR, and creatinine level) emerged from the Cox model, and patients were classified into three survival-risk groups according to a prognostic index (PI): -1.039 x albumin (grams per deciliter) + 1.909 x log(e) INR + 1.207 x log(e) serum creatinine (milligrams per deciliter). Survival probabilities at 1 and 5 years were 89% and 80%, 63% and 52%, and 23% and 10% with a low, medium, and high PI, respectively. The validation study using the split-sample technique and data from independent patients confirmed that a high PI (>-2.5) identifies patients with a poor prognosis within 5 years. We thus have shown and validated that risk for death at the short and long term of patients with nonbiliary cirrhosis can be predicted with great accuracy using models containing a few simple and easily obtained objective variables, and these survival models are useful tools in clinical decision making, especially in deciding to list patients for LT and prioritization on the liver waiting list.

Female↗

Cat lung hemodynamics: comparison of experimental results and model predictions.

Commonly, attempts have been made to learn about the structure and function of the pulmonary vascular bed from measurements of arterial and venous pressures and blood flow rate under steady-state conditions (e.g., from pressure vs. flow data) or dynamic conditions (e.g., from vascular occlusion data). Zhuang et al. (J. Appl. Physiol. 55: 1341-1348, 1983) have presented a detailed model of steady-state cat lung hemodynamics based on direct measurements of anatomical and elasticity data. This model provides an opportunity to better understand the information content of the hemodynamic data. Therefore, in the present study we carried out a series of steady-state and dynamic experiments on isolated cat lungs. We then compared the results with those predicted by the model. We found that the model provided a good fit to the steady-state data. However, to fit the dynamic data, some modifications were necessary to account for the viscous behavior of the vessel walls and to move the first moment of the distribution of vascular resistance toward the arterial end of the vascular bed relative to that of the distribution of vascular compliance. Due to the sensitivity of the vascular resistance to small changes in vessel diameters and branching ratio, the modifications in morphometry represent small changes in morphometric data and are probably within the range of uncertainty in such data. The modifications had little effect on the steady-state model simulations but substantially improved the dynamic model simulations, suggesting that the dynamic data are quite sensitive to small changes in the relative distributions of vessel diameters and elasticity.

Animals↗

A single-degree-of-freedom dynamic model predicts the range of human responses to impulsive forces produced by power hand tools.

The human operator is modelled as a single-degree-of-freedom dynamic mechanical system for predicting the response to impulsive torque reaction forces produced by rotating spindle power hand tools such as nutrunners or screwdrivers. The model uses mass, spring and damping elements to represent the standing operator supporting the tool in the hand. It was hypothesized that these mechanical elements are affected by work location and vary among individuals. These elements were ascertained by measuring the resulting frequency and amplitude of a freely oscillating defined mechanical system when externally loaded using maximal effort to oppose its motion. Twenty-five subjects (13 female, 12 male) participated in the full factorial experiment that measured the effects of gender, vertical and horizontal work location for various tool shapes (in-line, pistol, right angle), and orientations (horizontal and vertical). The mean operator stiffness decreased from 1721 to 1195 N/m when the horizontal work location increased from 30 to 90 cm in front of the ankles for a pistol-grip handle used on a vertical surface. Males had greater mass moment of inertia of (0.0099 kg m2) than females (0.0072 kg m2) for an in-line handle used on a horizontal surface. Internal validation by independently measuring apparatus torque found that the model satisfactorily explained the measured operator dynamics with an average error of 2.86%. Group variance reflects the range of operator capacities to react against power hand tool generated forces for the sample group and therefore it may also be useful for understanding the range of capacities among a group of operators performing similar tasks.

Adult↗

Mechanistic model predicts a U-shaped relation of radon exposure to lung cancer risk reflected in combined occupational and US residential data.

A mechanistically based cytodynamic two-stage (CD2) cancer model was shown recently to predict both ecologic US county data and underground-miner data on lung-cancer mortality (LCM) vs radon concentration, indicating biological plausibility of the apparent negative dose-response relation exhibited by the ecologic data. To further investigate this hypothesis, the CD2 model was fitted to combine age-specific LCM data vs estimated radon-exposure in white females of age 40+ years in 2821 US counties during 1950-1954 using new estimates of county-specific mean residential radon exposure, and in five cohorts of underground nonsmoking miners. The negative association of radon levels and corresponding county-level LCM rates apparent in women dying in 1950-1954 (11% of whom never smoked) was also apparent in women of age 60+ years (5% of whom never smoked). The CD2 fit obtained to the combined residential and occupational data was found to predict the combined data using biologically plausible parameter values, and also to predict inverse dose-rate effects exhibited in nonsmoking miner data to which the CD2 model was not fit. These results are consistent with the hypothesis that residential radon exposure has a nonlinear U-shaped relation to LCM risk, and that current linear extrapolation models substantially overestimate such risk.

Adult↗

A predictive model for combined temperature and water activity on microbial growth during the growth phase.

An empirical and generalized model is presented, based on a modified Arrhenius equation, for predicting the combined effect of temperature and water activity on the growth rate of bacteria. When it was applied to seven separate sets of wide ranging published results, spanning some 50 years and including a spore-former and a silage micro-organism, predictions explained between 92.9 and 99.0% of the variation in the results with an overall mean of 96.6%. Advantages over existing models are that it is relatively easy to fit to data using least squares regression and requires only five coefficients. These, together with its simplicity and demonstrated wide application, will facilitate its practical use.

Bacteria↗

Dopamine and the mechanisms of cognition: Part I. A neural network model predicting dopamine effects on selective attention.

BACKGROUND: Dopamine affects neural information processing, cognition, and behavior; however, the mechanisms through which these three levels of function are affected have remained unspecified. We present a parallel-distributed processing model of dopamine effects on neural ensembles that accounts for effects on human performance in a selective attention task. METHODS: Task performance is stimulated using principles and mechanisms that capture salient aspects of information processing in neural ensembles. Dopamine effects are simulated as a change in gain of neural assemblies in the area of release. RESULTS: The model leads to different predictions as a function of the hypothesized location of dopamine effects. Motor system effects are simulated as a change in gain over the response layer of the model. This induces speeding of reaction times but an impairment of accuracy. Cognitive attentional effects are simulated as a change in gain over the attention layer. This induces a speeding of reaction times and an improvement of accuracy, especially at very fast reaction times and when processing of the stimulus requires selective attention. CONCLUSIONS: A computer simulation using widely accepted principles of processing in neural ensembles can account for reaction time distributions and time-accuracy curves in a selective attention task. The simulation can be used to generate predictions about the effects of dopamine agonists on performance. An empirical study evaluating these predictions is described in a companion paper.

Attention↗

Integrating neuronal coding into cognitive models: predicting reaction time distributions.

Neurophysiological studies have examined many aspects of neuronal activity in terms of neuronal codes and postulated roles for these codes in brain processing. There has been relatively little work, however, examining the relationship between different neuronal codes and the behavioural phenomena associated with cognitive processes. Here, predictions about reaction time distributions derived from an accumulator model incorporating known neurophysiological data in temporal lobe visual areas of the macaque are examined. Results from human experimental studies examining the effects of changing stimulus orientation, size and contrast are consistent with the model, including qualitatively different changes in reaction time distributions with different stimulus manipulations. The different changes in reaction time distributions depend on whether the image manipulation changes neuronal response latency or magnitude and can be related to parallel or serial cognitive processes respectively. The results indicate that neuronal coding can be productively incorporated into computational models to provide mechanistic accounts of behavioural results related to cognitive phenomena.

Acoustic Stimulation↗

Applying Ockham's razor to pancreatitis prognostication: a four-variable predictive model.

OBJECTIVE: We sought to develop a simple yet accurate prognostic scoring system to determine the severity of acute pancreatitis at admission. SUMMARY BACKGROUND DATA: Because acute pancreatitis has a variable and frequently unpredictable course, identifying individuals at greatest risk for significant, life-threatening complications and stratifying their care appropriately remain a concern. Previous prognostic scoring systems predict severity reasonably well but are limited by time constraints, are unwieldy to use, or both. METHODS: Data from the international phase III trial of the platelet-activating factor receptor-antagonist Lexipafant were used to develop a 4-variable prognostic model. We then compared the model's ability to predict the severity of acute pancreatitis with the Ranson, Glasgow, and APACHE II systems. RESULTS: The model (BALI), which included BUN >or=25 mg/dL, Age >or=65 years, LDH >or=300 IU/L, and IL-6 >or=300 pg/mL, measured at admission, was similar to the Ranson, Glasgow, and APACHE II systems in its ability to identify increased mortality from acute pancreatitis. The receiver operating characteristic curve area for the BALI model was >or=0.82 +/- 0.03 (mean +/- SD) versus 0.75 +/- 0.04 (Ranson), 0.80 +/- 0.03 (Glasgow), and 0.79 +/- 0.03 (APACHE II). Furthermore, at a prevalence of 15%, the positive and negative predictive values for increased mortality were similar for all systems. CONCLUSION: The prognostic ability of the BALI 4-variable model was similar to the Ranson, Glasgow, and APACHE II systems but is unique in its simplicity and ability to accurately predict disease severity when used at admission or anytime during the first 48 hours of hospitalization.

APACHE↗

Evaluation of a predictive model for Clostridium perfringens growth during cooling.

Proper temperature control is essential in minimizing Clostridium perfringens germination, growth, and toxin production. The U.S. Department of Agriculture Food Safety and Inspection Service offers two options for the cooling of meat products: follow a standard time-temperature schedule or validate that alternative cooling regimes result in no more than a 1-log CFU/g increase of C. perfringens and no growth of Clostridium botulinum. The Juneja 1999 model for C. perfringens growth during cooling may be helpful in determining whether the C. perfringens performance standard has been achieved, but this model has not been extensively validated. The objective of this study was to validate the Juneja 1999 model under a variety of temperature situations. The Juneja 1999 model for C. perfringens growth during cooling is fail safe when low (<1 log CFU/ml) or high (>3 log CFU/ml) observed increases occur during exponential cooling. The Juneja 1999 model consistently underpredicted growth at intermediate observed increases (1 to 3 log CFU/ml). The Juneja 1999 model also underpredicted growth whenever exponential cooling took place at two different rates in the first and second portions of the cooling process. This error may be due to faster than predicted growth of C. perfringens cells during cooling or to an inaccuracy in the Juneja 1999 model.

Clostridium perfringens↗

Dynamic nonlinear cochlear model predictions of click-evoked otoacoustic emission suppression.

A comprehensive set of results from 2-click suppression experiments on otoacoustic emissions (OAEs) have been presented by Kapadia and Lutman [Kapadia, S., Lutman, M.E., 2000a. Nonlinear temporal interactions in click-evoked otoacoustic emissions. I. Assumed model and polarity-symmetry. Hear. Res. 146, 89-100]. They found that the degree of suppression of an OAE evoked by a test click varied systematically with the timing and the level of a suppressor click, being greatest for suppressor clicks occurring some time before the test click, particularly at lower levels of suppression. Kapadia and Lutman also showed that although the general shape of the graph of suppression against suppressor click timing could be predicted by a static power law model, this did not predict the asymmetry with respect to the timing of the suppressor click. A generalised automatic gain control (AGC) is presented as a simple example of a dynamic nonlinear system. Its steady state nonlinear behaviour, as quantified by its level curve, and its dynamic behaviour, as quantified by its transient response, can be independently set by the feedback gain law and detector time constant, respectively. The previously reported suppression results, with the asymmetry in the timing, are found to be predicted better by such an AGC having a level curve with a slope of about 0.5 dB/dB, and a detector time constant of about twice the period at the characteristic frequency. Although this gives adequate predictions for high suppression levels, it under predicts the suppression and the asymmetry for lower levels. Further research is required to establish whether simple peripheral feedback models can explain OAE suppression of this type.

Acoustic Stimulation↗

Non-linear viscoelastic models predict fingertip pulp force-displacement characteristics during voluntary tapping.

We evaluated whether lumped-parameter non-linear viscoelastic models of human fingertip tissue can describe fingertip force-displacement characteristics during a range of rapid, dynamic tapping tasks. Eight human subjects tapped with their index finger on the surface of a rigid load cell while an optical system tracked fingertip position using an infra-red LED attached to the fingernail. Four different tapping conditions were tested: normal and high-speed taps with a relaxed hand, and normal and high-speed taps with the other fingers co-contracted. A non-linear viscoelastic model comprised of an instantaneous stiffness function and viscous relaxation function was capable of predicting fingertip tissue force response due to measured pulp compression under these four different loading conditions. The model could successfully reconstruct very rapid (less than 5 ms) force transients, and forces occurring over time periods greater than 100 ms, with errors of 10%. Model parameters varied by less than 20% over the four conditions, despite almost 3-fold differences in average forces and 38% differences in fingertip velocities. Energy dissipation by the fingertip averaged 81%, and varied little (<3%) across conditions, despite a 1. 5-fold range of energy input. The ability of a lumped-parameter model to describe fingertip force-displacement characteristics during a range of conditions contributes both to understanding the transmission of force through the fingertip to the musculoskeletal system and to predicting the stimulation of mechano-receptors located within the fingertip.

Adult↗

ECOSIMP2 model: prediction of CO2 concentration changes and carbon status in closed ecosystems.

The ECOSIMP2 model, simulating the Plant-Soil-Atmosphere interactions, was developed as a tool for the management of an experimental artificial ecosystem. It consists in three main carbon compartments for production, consumption and decomposition of the biomass. The main biological parameters concern photosynthesis (apparent Km, CO2 compensation point), the harvest index, the rate of consumption, and the kinetics of litter decomposition. From realistic assumptions of kinetics of soil compartments, a steady-state case was obtained, simulating a terrestrial ecosystem. The stability of the atmospheric CO2 concentration was studied after a virtual enclosure of the system in a 20-m high greenhouse. In natural lighting the conditions of stability are severe because of the small size of the atmospheric compartment which amplifies any imbalance between carbon fluxes. The positive consequence of that amplification for research on artificial ecosystems was emphasized.

Atmosphere↗

A criterion-referenced multidimensional job-related model prediction capability to perform occupations among persons with chronic pain.

OBJECTIVE: The purpose of this prospective study was an exploration of the construct of the criterion-referenced multidimensional job-related model (CMVA) aimed for predicting patients' with chronic pain capability to perform occupations. METHODS: The study samples were 1) participants (n=84) who at present were not performing employed work (median sick-listing period 12 months) because of chronic pain and 2) participants (n = 104) who at present were performing employed work at least 20 hours of a workweek. The participants had experiences of 40 different occupations classified into five of the occupational categories of Jist's Enhanced Dictionary of Occupational Titles. Data were collected through ten assessment instruments and a structured interview, comprising 54 variables and 465 items. Data were analyzed using multiple regression with forward entering of variables. RESULTS: The CMVA model (Adjusted R^2 0.777, F (4, 183) = 164.067; p<0.001) was able to explain 78% of the variance. CMVA contained the aspects; "the work demands-variable, the person-variable of work life values, the environment-variable of social support and the two occupational performances-variables; self-perceived capability to perform work tasks/the simulated work tasks". CONCLUSIONS: The construct of CMVA was robust suggesting that among persons with chronic pain, the predictors focusing on their capability to perform occupations are of great importance.

Journal Article↗

Grading scores and survivorship functions in liver cirrhosis: a comparative statistical analysis of various predictive models.

In a group of followed-up liver cirrhotics we evaluated the reliability of prognostic estimates predicted on the basis of a previously described multivariate statistical model (MSM). In the same subjects we also compared theoretical survival estimates obtained by fitting some other liver cirrhosis grading scores (Child-Turcotte's, McCormick's and Orrego's) to prognostic purposes. No statistical difference between actual and MSM-estimated survivorship functions was found (employing a life-table method with Logrank test), thus confirming the prognostic reliability of this multivariate classification model. Such a global and prognosis-correlated index may be recommendable both for comparing different groups of patients, and for assessing treatment effectiveness. Or results also substantially confirm the other investigated classificative methods such as reliable liver cirrhosis severity indexes, although their use for prognostic purposes seems to be less suitable.

Actuarial Analysis↗

Predictive modelling of growth of Listeria monocytogenes. The effects on growth of NaCl, pH, storage temperature and NaNO2.

The effect of NaCl concentration (5.0 115.0 g/l). pH value (4.0-7.2), temperature (1-35 degrees C) and NaNO2 concentration (0 200 mg/l) on the growth responses of Listeria monocytogenes, in laboratory medium was investigated. The growth curves generated within this matrix of conditions were fitted using the function of Baranyi and Roberts (1994) and the growth responses modelled using a quadratic polynomial to produce response surfaces. Growth curves could then be regenerated for any set of conditions within the experimental matrix and values predicted for the growth rate, doubling time, lag time and time to 1000-fold increase. The model was validated using data from published literature and was found to give realistic predictions for doubling times in foods, including meat and meat products, milk, dairy products and vegetables. Predictions from this model (Baranyi and Roberts. 1994) compared favourably with those from the models of Buchanan and Phillips (1990), Murphy et al. (1996) and the Food MicroModel.

Hydrogen-Ion Concentration↗

A predictive model for the combined effect of pH, sodium chloride and storage temperature on the growth of Brochothrix thermosphacta.

Growth of Brochothrix thermosphacta was observed under ranges of pH (5.6-6.8), NaCl (0.5-8.0% w/v) and incubation temperature (1-30 degrees C). In order to compare different approaches, two models were used to fit growth curves to viable count data, and to calculate parameters from those fitted curves. Growth responses as a function of pH, NaCl and temperature were described with a quadratic function which was then used to predict growth within the limits where growth was observed. The predictions of the model show good agreement with published observations from other laboratories.

Cell Division↗

Uncertainties in pharmacokinetic modeling for perchloroethylene: II. Comparison of model predictions with data for a variety of different parameters.

In this paper we compare expectations derived from 10 different human physiologically based pharmacokinetic models for perchloroethylene with data on absorption via inhalation, and concentrations in alveolar air and venous blood. Our most interesting finding is that essentially all of the models show a time pattern of departures of predictions of air and blood levels relative to experimental data that might be corrected by more sophisticated model structures incorporating either (a) heterogeneity of the fat compartment (with respect to either perfusion or partition coefficients or both) or (b) intertissue diffusion of perchloroethylene between the fat and muscle/VRG groups. Similar types of corrections have recently been proposed to reduce analogous anomalies in the fits of pharmacokinetic models to the data for several volatile anesthetics. A second finding is that models incorporating resting values for alveolar ventilation in the region of 5.4 L/min seemed to be most compatible with the most reliable set of perchloroethylene uptake data.

Biological Transport, Active↗

Importance of glucose per se to intravenous glucose tolerance. Comparison of the minimal-model prediction with direct measurements.

Glucose disappearance after an oral or intravenous challenge is a function of the effects of both endogenously secreted insulin and of glucose itself. We previously introduced the term "glucose effectiveness," or SG, defined as the ability of glucose per se to enhance its own disappearance independent of an increment in plasma insulin. The present investigation, performed in conscious dogs, was undertaken to quantify this glucose effect by minimal-model-based analysis of insulin and glucose dynamics after a frequently sampled intravenous glucose tolerance test (FSIGT). The values from the standard FSIGT were then compared with direct measurements obtained from experiments in which the dynamic insulin response to glucose was suppressed with somatostatin (SRIF). In addition, we examined SG values from the modified FSIGT protocol, which involves both glucose and tolbutamide injections. Protocol l (N = 9): FSIGTs were performed and the glucose and insulin data were analyzed by computer. KG was 2.65 +/- 0.28 min-1, S1 was 4.09 +/- 0.34 X 10(4) min-1/(microU/ml), and SG was 0.033 +/- 0.004 min-1. Protocol II (N = 6): FSIGTs were performed on animals in which SRIF was infused (0.8 micrograms/min X kg) to obliterate the dynamic insulin response to glucose injection. Before the FSIGt, insulin and glucagon were infused intraportally to reattain basal glycemia. Without dynamic insulin, KG was reduced to 0.96 +/- 0.18 min-1 (P less than 0.0001). However, SG, estimated from the exponential rate of fall of plasma glucose in the absence of dynamic insulin, was similar to the standard FSIGTs: 0.025 +/- 0.004 (P greater than 0.25). Protocol III (N = 6): modified FSIGTs were performed using glucose and tolbutamide injections for a better estimate of model parameters. Model parameters Sl and SG, and the KG were not different from standard FSIGTs (P greater than 0.3). In fact, the value of SG (0.028 +/- 0.003 min-1) was nearly identical to the direct measure from protocol II. Therefore, the effect of glucose per se on glucose decline, estimated by modeling the standard and modified FSIGTs, was confirmed by a direct measurement with the endogenous insulin response suppressed with SRIF. Also, the time course of the insulin effect to enhance net glucose disappearance from plasma [Ieff(t)] was calculated from the data of protocol II, and was the same as the time course predicted by the model. These studies demonstrate the ability of the computer modeling approach to separate insulin-dependent and glucose-dependent glucose disappearance, and represent a direct confirmation of the minimal model.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗