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PubMed1977

Quantitative analysis of biological marker synthesis in tumor cell cycle.

A quantitative relationship between tumor cell number and biologic marker concentration has been investigated and characterized by the previously developed discrete-time kinetic model for the study of cell kinetics. Here, this model is further expanded to cope with both cell cycle kinetics and biologic marker synthesis. A synchronized tumor-cell population is examined to determine the time course of the synthesis of markers in relation to cell cycle. The DNA content distributions, measured by flow microfluorometry, are analyzed by use of the model, and the cell age distribution is extracted. The average marker content per cell in cell cycle is measured for each time sequence in synchronized cell populations. The model, incorporating the cell age distribution and the average marker content per cell in cell cycle, enables one to generate the marker content distribution, from which the cell number is estimated from the marker concentration. The model performance is further evaluated with Chinese hamster ovary cells, and their polyamine content and the total polyamine concentration during synchronization is calculated and related to the total cell number.

Cell Division↗

PubMed2005

Health state values for the HUI 2 descriptive system: results from a UK survey.

This paper reports the results of a study to estimate a statistical health state valuation model for a revised version of the Health Utilities Index Mark 2, using Standard Gamble health state preference data. A sample of 51 health states were valued by a sample of the 198 members of the UK general population. Models are estimated for predicting health state valuations for all 8000 states defined by the revised HUI2. The recommended model produces logical and significant coefficients for all levels of all dimensions in the HUI2. These coefficients appear to be robust across model specifications. This model performs well in predicting the observed health state values within the valuation sample and for a separate validation sample of health states. However, there are concerns over large prediction errors for two health states in the valuation sample. These problems must be balanced against concerns over the validity of using the VAS based health state valuation data of the original HUI2 valuation model.

Data Collection↗

PubMed2006

Which extrauterine pelvic masses are difficult to correctly classify as benign or malignant on the basis of ultrasound findings and is there a way of making a correct diagnosis?

OBJECTIVES: To determine which extrauterine pelvic masses are difficult to correctly classify as benign or malignant on the basis of ultrasound findings, and to determine if the use of logistic regression models for calculation of individual risk of malignancy would improve the diagnostic accuracy in difficult tumors. METHODS: In a prospective, international, European multicenter study involving nine centers, 1066 women with a pelvic mass judged to be of extrauterine origin underwent transvaginal ultrasound examination by an experienced ultrasound examiner before surgery. A standardized examination technique and predefined definitions of ultrasound characteristics were used. On the basis of subjective evaluation of ultrasound findings, the examiner classified each mass as being certainly benign, probably benign, unclassifiable, probably malignant or certainly malignant. Even when the examiner found the mass unclassifiable (i.e. difficult mass) he or she was obliged to state whether the mass was more likely to be benign or malignant. Borderline tumors were classified as malignant. RESULTS: There were 90 (8%) unclassifiable masses. Multiple logistic regression analysis showed papillary projections, >10 locules in a cyst without solid components, low-level echogenicity of cyst fluid, and moderate vascularization as assessed subjectively at color Doppler examination to be ultrasound variables independently associated with unclassifiable mass. Borderline malignant tumors (n = 55) proved to be most difficult to assess with only 47% being correctly classified (i.e. classified as malignant), 29% being incorrectly classified (i.e. classified as benign) and 24% being unclassifiable vs. 90% of non-borderline tumors being correctly classified, 3% being incorrectly classified and 8% being unclassifiable (P < 0.0001). Papillary cystadeno(fibro)mas, myomas and cases of struma ovarii were also more common among the unclassifiable masses than among the classifiable ones (5.6% vs. 1.1%, P = 0.008; 4.4% vs. 0.9%, P = 0.02; 4.4% vs. 0.2%, P = 0.0006). No ultrasound variable or clinical variable (including CA 125) entered a logistic regression model to predict malignancy in difficult masses. A model could be constructed for difficult masses containing papillary projections but this model performed no better than subjective evaluation of the ultrasound image. Sensitivity and specificity of subjective evaluation with regard to malignancy in the group of unclassifiable masses were 56% (14/25) and 77% (50/65) vs. 91% (220/241) and 97% (712/735) in the classifiable masses. CONCLUSIONS: Borderline tumors cause great diagnostic difficulties, but so do papillary cystadeno(fibro)mas, struma ovarii and some myomas. Logistic regression models do not solve the diagnostic problem in difficult pelvic masses.

Adnexa Uteri↗

PubMed2005

Homology modelling and active-site-mutagenesis study of the catalytic domain of the pneumococcal phosphorylcholine esterase.

Streptococcus pneumoniae is among the major human pathogens. Several interactions of this bacterium with its host appear to have been mediated by bacterial cell wall components. Specifically, phosphorylcholine residues covalently attached to teichoic and lipoteichoic acids serve as anchors for many surface-located proteins (choline-binding proteins CBPs), including cell-adhesion and virulence factors, and are also recognized by host response components through choline-binding receptors. In this study, we have performed modelling of the catalytic domain of pneumococcal phosphorylcholine esterase (Pce), a modular enzyme that is capable of removing phosphorycholine residues from teichoic and lipoteichoic acids, remodelling their distribution on the bacterial envelope. We wish to contribute to the structural knowledge of Pce. In this pursuit, 3D models of Pce have been established by homology modelling, using the X-ray structure of enzymes from the alpha/beta metallo-lactamase family fold as templates. Theoretical models of pneumococcal phosphorylcholine esterase (Pce) catalytic modules obtained by homology modelling, and corresponding docking studies employed to find out the residues involved in the binding of Zn ions, are discussed according to mutational studies and ab initio calculations. The presence of a binuclear Zn cluster in the catalytic domain of Pce and a likely coordination model are proposed.

Amino Acid Sequence↗

PubMed2005

Modeling inorganic aerosols and their response to changes in precursor concentration in Mexico City.

Based on data from the 1997 Investigación sobre Materia Particulada y Deterioro Atmosférico-Aerosol and Visibility Evaluation Research (IMADA-EVER) campaign and the inorganic aerosol model ISORROPIA, the response of inorganic aerosols to changes in precursor concentrations was calculated. The aerosol behavior is dominated by the abundance of ammonia and thus, changes in ammonia concentration are expected to have a small effect on particle concentrations. Changes in sulfate and nitrate are expected to lead to proportional reductions in inorganic fine particulate matter (PM2.5). Comparing the predictions of ISORROPIA with the observations, the lowest bias and error are achieved when the aerosols are assumed to be in the efflorescence branch. Including crustal species reduces the bias and error for nitrate but does not improve overall model performance. The estimated response of inorganic PM2.5 to changes in precursor concentrations is affected by the inclusion of crustal species in some cases, although average responses are comparable with and without crustal species. Observed concentrations of particle chloride suggest that gas phase concentrations of hydrogen chloride may not be negligible, and future measurement campaigns should include observations to test this hypothesis. Our ability to model aerosol behavior in Mexico City and, thus, design control strategies, is constrained primarily by a lack of observations of gas phase precursors. Future campaigns should focus in particular on better understanding the temporal and spatial distribution of ammonia concentrations. In addition, gas phase observations of nitric acid are needed, and a measure of particle water content will allow stable versus metastable aerosol behavior to be distinguished.

Aerosols↗

PubMed2006

Landscape history, fragmentation, and patch occupancy: models for a forest bird with limited dispersal.

We developed and tested patch occupancy models for an endemic understory bird with limited dispersal ability, the Chucao Tapaculo (Scelorchilus rubecula), in two South American temperate rain forest landscapes that differed in levels and duration of forest loss. We assessed cover changes since 1961 in each landscape and surveyed patches for Chucao Tapaculo occupancy. We then developed incidence-based predictive models independently for each landscape and tested each model reciprocally in the alternative study area. We thereby assessed the domain of model applicability and identified those predictor variables with general effects and those that varied between the two landscapes. The two models were consistent regarding variable selection, and predictive accuracy of each model was high in the landscape where training data were collected. However, the models differed substantially in the magnitudes of effects related to patch size, with larger unoccupied patches observed in the landscape with the more advanced stage of fragmentation. Due to this discrepancy, each model performed poorly when applied to the alternative landscape, potentially reflecting the contrasting stages of habitat loss. Although it was impossible to dissociate effects of level and duration of forest loss, we viewed the landscapes as representing two extremes along a continuum of fragmentation, providing insights into potential trajectories for portions of the biome where deforestation is occurring. Further, our data suggest that static equilibrium models developed from distribution patterns in recently fragmented landscapes may overestimate persistence when used as a forecasting tool, or when extrapolated to alternative landscapes where fragmentation is more advanced. Thus, we suggest that landscapes used as standards for model building should be selected with caution. We recommend that distribution patterns be obtained from landscapes where fragmentation is advanced, preferably with histories of fragmentation long enough that time-delayed extinctions already would have occurred.

Animals↗

PubMed2004

Prediction of splice sites with dependency graphs and their expanded bayesian networks.

MOTIVATION: Owing to the complete sequencing of human and many other genomes, huge amounts of DNA sequence data have been accumulated. In bioinformatics, an important issue is how to predict the complete structure of genes from the genomic DNA sequence, especially the human genome. A crucial part in the gene structure prediction is to determine the precise exon-intron boundaries, i.e. the splice sites, in the coding region. RESULTS: We have developed a dependency graph model to fully capture the intrinsic interdependency between base positions in a splice site. The establishment of dependency between two position is based on a chi2-test from known sample data. To facilitate statistical inference, we have expanded the dependency graph (which is usually a graph with cycles that make probabilistic reasoning very difficult, if not impossible) into a Bayesian network (which is a directed acyclic graph that facilitates statistical reasoning). When compared with the existing models such as weight matrix model, weight array model, maximal dependence decomposition, Cai et al.'s tree model as well as the less-studied second-order and third-order Markov chain models, the expanded Bayesian networks from our dependency graph models perform the best in nearly all the cases studied. AVAILABILITY: Software (a program called DGSplicer) and datasets used are available at http://csrl.ee.nthu.edu.tw/bioinf/ CONTACT: cclu@ee.nthu.edu.tw.

Bayes Theorem↗

PubMed2002

Tropomyosin 3 expression leads to hypercontractility and attenuates myofilament length-dependent Ca(2+) activation.

Tropomyosin (TM), an integral component of the thin filament, is encoded by three striated muscle isoforms: alpha-TM, beta-TM, and TPM 3. Although the alpha-TM and beta-TM isoforms are well characterized, less is known about the function of the TPM 3 isoform, which is predominantly found in the slow-twitch musculature of mammals. To determine its functional significance, we ectopically expressed this isoform in the hearts of transgenic mice. We generated six transgenic mouse lines that produce varying levels of TPM 3 message with ectopic TPM 3 protein accounting for 40-60% of the total striated muscle tropomyosin. The transgenic mice have normal life spans and exhibit no morphological abnormalities in their sarcomeres or hearts. However, there are significant functional alterations in cardiac performance. Physiological assessment of these mice by using closed-chest analyses and a work-performing model reveals a hyperdynamic effect on systolic and diastolic function. Analysis of detergent-extracted fiber bundles demonstrates a decreased sensitivity to Ca(2+) in force generation and a decrease in length-dependent Ca(2+) activation with no detectable change in interfilament spacing as determined by using X-ray diffraction. Our data are the first to demonstrate that TM isoforms can affect sarcomeric performance by decreasing sensitivity to Ca(2+) and influencing the length-dependent Ca(2+) activation.

Actin Cytoskeleton↗

PubMed2003

Effective use of human simulators in surgical education.

BACKGROUND: We initiated a teaching module utilizing a human simulator midway through 2001-2002 to improve student skills specific to the evaluation of patients in shock during a required clerkship in surgery for fourth-year medical students. We tested the hypothesis that student skills would improve after implementation of this module and identified factors that predicted student performance. MATERIALS AND METHODS: Students (n = 86) chose one of two hospital sites for a clerkship that focuses on the care of acutely ill surgical patients. A case-based lecture focusing on the diagnosis and management of a patient in shock was replaced midway through the academic year by a simulator session with a computerized life-sized mannequin. A standardized clinical final evaluation (OSCE) was used to assess student skills. We evaluated the effect of the simulator session and other factors on student exam performance using univariate and multivariate analysis. RESULTS: The site of the clerkship and the simulator session were significant factors affecting the OSCE score identified by ANOVA, P < 0.05. A stepwise multiple regression analysis testing the effect of simulator module, site, time of year, prior NBME subject exam, and prior OSCE during the third year clerkship identified that the simulator module was the only independent factor that modeled performance on all shock stations, P < 0.01. CONCLUSIONS: In a clerkship that already emphasized faculty facilitated case-based learning, the use of a teaching module employing a human simulator significantly improved test scores. This study supports the efficacy of human simulators to improve student skills related to the management of complex critically ill patients.

Clinical Clerkship↗

PubMed1999

Modeling of air pollution and its relationship with mortality and morbidity in Madrid, Spain.

OBJECTIVE: Evaluation of the association between air pollution and mortality and morbidity is becoming ever more complex owing to changes in inner-city air pollution, marked by decreasing values for all main pollutants save those associated with traffic. This has led to the need for the study of new epidemiological scenarios in which most pollutants are below guideline values. Nonetheless, the health effects are significant. METHODS: This report presents the results of a statistically based model for real-time forecasting of mortality and morbidity in Madrid, with meteorological and pollution series serving as inputs. RESULTS AND CONCLUSIONS: Not only did the models perform well with correlation coefficients between predicted and observed values (r = 0.683 for mortality, r = 0.681 for morbidity), but they enabled quantification of the impact of air pollution on mortality and morbidity (with increases ranging from 1. 8% to 12% for mortality and from 2.3% to 18% for morbidity for a 25-microg/m(3) increase in pollutants). Moreover, attention should be drawn to the observation that the model proved to be easy to implement and operate on a routine basis.

Air Pollution↗

PubMed1994

Time series forecasts of emergency department patient volume, length of stay, and acuity.

STUDY HYPOTHESIS: Time series analysis can provide accurate predictions of emergency department volume, length of stay, and acuity. DESIGN: Prospective stochastic time series modeling. SETTING: A university teaching hospital. INTERVENTIONS: All patients seen during two sequential years had time of arrival, discharge, and acuity recorded in a computer database. Time series variables were formed for patients arriving per hour, length of stay, and acuity. Prediction models were developed from the year 1 data and included five types: raw observations, moving averages, mean values with moving averages, seasonal indicators with moving averages, and autoregressive integrated moving averages. Forecasts from each model were compared with observations from the first 25 weeks of year 2. Model accuracy was tested on residuals by autocorrelation functions, periodograms, linear regression, and confidence intervals of the variance. RESULTS: There were 42,428 patients seen in year 1 and 44,926 in year 2. Large periodic variations in patient volume with time of day were found (P < .00001). The models based on arithmetic means or seasonal indices with a single moving average term gave the most accurate forecasts and explained up to 42% of the variation present in the year 2 test series. No time series model explained more that 1% of the variation in length of stay or acuity. CONCLUSION: Time series analysis can provide powerful, accurate short-range forecasts of future ED volume. Simpler models performed best in this study. Time series forecasts of length of stay and patient acuity are not likely to contribute additional useful information for staffing and resource allocation decisions.

Emergency Service, Hospital↗

PubMed1993

Digital models for arterial pressure and respiratory waveforms.

Digital models for arterial pressure pulse (APP) and respiratory volume waveforms (RVW) are proposed for efficient representation of these signals. When these signals are discrete cosine transformed (DCT), the pole-zero technique of Steiglitz-McBride (SM) gave system functions of much lower order than those obtained directly from the signals. The DCT of a bell-shaped biphasic wave needed two poles and two zeros. Based on this, the model order is fixed by the number of distinct peaks in the magnitude spectrum of the transformed APP/RVW signal. The partial fraction expansion (PFE) of the system function allowed delineation of component waves present in the time signal. The angles of model poles and zeros enabled easy determination of several important features from both of these signals. The model performance is evaluated using the normalized root mean-square error (NRMSE). A Bayes classifier using the pole angles as the feature vector performed satisfactorily when a limited number of RVW's recorded under deep and rapid maneuver are classified into normal (n) and abnormal (ab) categories of respiratory pathways.

Algorithms↗

PubMed2004

Enhanced wet deposition estimates using modeled precipitation inputs.

Effective assessments of linkages between atmospheric deposition and sensitive aquatic and terrestrial ecosystems require a knowledge of spatial patterns in deposition of greater resolution than currently available using point estimates and two-dimensional surface algorithms. A high resolution wet deposition model was developed for the Eastern U.S.A. by incorporating daily precipitation measurements from National Oceanic and Atmospheric Administration (NOAA) monitoring sites located within the Eastern U.S.A.; topographic variables, including elevation, slope, and aspect that affect the amount and distribution of precipitation across the region; and precipitation chemistry data from National Atmospheric Deposition Program (NADP) sites within and adjacent to the region. Model performance, which was tested against independent measurements from three physiographic regions of the eastern U.S.A., revealed a statistically significant reduction in interpolation error compared to traditional two-dimensional surface algorithms.

Air Pollutants↗

PubMed1999

Effects of an organized critical care service on outcomes and resource utilization: a cohort study.

OBJECTIVE: To determine whether the presence of an on-site, organized, supervised critical service improves care and decreases resource utilization. DESIGN: The study compared two patient cohorts admitted to a surgical intensive care unit during the same period of time. The study cohort was cared for by an on-site critical care team supervised by an intensivist. The control cohort was cared for by a team with patient care responsibilities in multiple sites supervised by a general surgeon. The main outcome measures were duration of stay, resource utilization, and complication rate. SETTING: Study patients were general surgical patients in an academic medical center. RESULTS: Despite having higher Acute Physiology and Chronic Health Evaluation II scores, patients cared for by the critical care service spent less time in the surgical intensive care unit, used fewer resources, had fewer complications and had lower total hospital charges. The difference between the two cohorts was most evident in patients with the worst APACHE II score. CONCLUSIONS: Critical care interventions are expensive and have a narrow safety margin. It is essential to develop structured and validated approaches to study the delivery of this resource. In this study, the critical care service model performed favorably both in terms of quality and cost.

APACHE↗

PubMed2000

Three-dimensional geometric modeling of the cochlea using helico-spiral approximation.

In this paper, the three-dimensional geometry of the human cochlea is modeled by the helico-spiral seashell model. The 3-D helico-spiral model, the generalized representation of the Archimedian spiral model, provides a framework for measuring cochlear features based on consistent estimation of model parameters. Nonlinear least square minimization based algorithms are developed for the identification of rotation, center and intrinsic parameters of the helico-spiral representation. Two algorithms are designed for the rotation axis aligned to the modiolar axis: one is more susceptible in the presence of noise, while the other allows applicability to two-dimensional data sets. The estimated center and intrinsic parameters allow the calculation of length, height and angular positions needed for frequency mapping of multichannel cochlear implant electrodes. Model performance is evaluated with numerically synthesized curves with different levels of added random noise, histologic data and real human cochlear spiral computed tomography data.

Algorithms↗

PubMed2004

Development and field validation of a biotic ligand model predicting chronic copper toxicity to Daphnia magna.

In this study, we developed a toxicity model predicting the long-term effects of copper on the reproduction of the cladoceran Daphnia magna that is based on previously reported toxicity tests in 35 exposure media with different water chemistries. First, it was demonstrated that the acute copper biotic ligand model (BLM) for D. magna could not serve as a reliable basis for predicting chronic copper toxicity. Consequently, BLM constants for chronic exposures were derived by multiple regression analysis of 21-d median effective concentrations (EC50s; expressed as Cu2+ activity) versus physicochemistry from a large toxicity dataset and the results of an additional experiment in which the individual effect of sodium on copper toxicity was investigated. The effect of sodium on chronic toxicity (log K NaBL = 2.91) seemed to be similar to its effect on acute toxicity (log K NaBL = 3.19). However, in contrast to the acute BLM, no significant calcium, magnesium, or combined competition effect was observed, and an increase in proton competition and bioavailability of CuOH+ and CuCO3 complexes was noted. Some indirect evidence was also found for some limited toxicity of complexes of copper with two of three tested types of dissolved organic matter. Because the latter was only a minor effect, this factor was not included in the chronic Cu BLM. The newly developed model performed well in predicting 21-d EC50s and no-observed-effect concentrations in natural water samples: 79% of the toxicity threshold values were predicted within a factor of two of the observed values. It is clear, however, that more research is needed to provide information on the exact mechanisms that have resulted in different BLM constants for chronic exposures (as opposed to acute exposures). It is suggested that the developed model can contribute to the improvement of risk assessment procedures of copper by incorporating bioavailability of copper in these regulatory exercises.

Animals↗

PubMed1994

Acute behavioral toxicity of pyridostigmine or soman in primates.

Effects of a peripherally active carbamate (pyridostigmine bromide) and a centrally active organophosphate (OP) nerve agent (soman) on performance by rhesus monkeys of a compensatory tracking (primate equilibrium platform, or PEP) task were measured using a balanced Latin-square design to determine the ED50 for pyridostigmine (0.66 mg/kg) and the up-and-down (titration) method to determine the ED50 for soman (2.50 micrograms/kg). We concluded that the PEP performance model is a sensitive and reliable indicator of anticholinesterase (anti-ChE) behavioral toxicity. We also found that soman, an irreversible inhibitor of acetylcholinesterase (AChE), is more than 100 times more behaviorally disruptive than the reversible peripheral inhibitor pyridostigmine, as indicated by the difference in ED50 doses expressed in molar terms. Soman's behavioral toxicity is severe at levels of serum cholinesterase inhibition (70-80%) at which pyridostigmine does not significantly affect performance. As a prophylactic treatment for OP agent poisoning, pyridostigmine has a substantial safety factor, since behavioral toxicity becomes significant only at approximately four times the proposed therapeutic dose.

Animals↗

PubMed1988

An application of logit models in analysing the behaviour of pedestrians and car drivers on pedestrian crossings.

A multinomial logit model is used to examine pedestrian and driver reaction to "encounters" occurring on pedestrian crossings. The probabilities of a driver braking or weaving, and of a pedestrian continuing to cross in response to an encounter are identified for a variety of pedestrian, environmental, and traffic conditions. Results indicate that the most important explanatory variables included pedestrian distance from kerb, city size, number of pedestrians simultaneously crossing, vehicle speed, and vehicle platoon size. It is felt that the model performed well, should be applied in further studies, and could be a useful technique for identifying the most hazardous situations and locations within an area, for planning relevant safety measures, and for national research for developing traffic legislation.

Accidents, Traffic↗