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PubMed2005

Process-oriented dose assessment model for 14C due to releases during normal operation of a nuclear power plant.

Swedish nuclear utility companies are required to assess doses due to releases of radionuclides during normal operation. In 2001, calculation methods used earlier were updated due to new authority regulations. The isotope (14)C is of special interest in dose assessments due to the role of carbon in the metabolism of all life forms. Earlier, factors expressing the ratio between concentration of (14)C in air and in various plants were used. In order to extend the possibility to take local conditions into account, a process-oriented assessment model for uptake of carbon and doses from releases of (14)C to air was developed (POM(14)C). The model uses part of DAISY which has been developed to model the turnover of carbon in crops. [Hansen, S., Jensen, H.E., Nielsen, N.E., Svendsen, H., 1993. Description of the Soil Plant System Model DAISY, Basic Principles and Modelling Approach. Simulation Model for Transformation and Transport of Energy and Matter in the Soil Plant Atmosphere System. Jordbruksförlaget, The Royal Veterinary and Agricultural University, Copenhagen, Denmark]. The main objectives were to test model performance of the former method, and to investigate if taking site specific parameters into account to a greater degree would lead to major differences in the results. Several exposure pathways were considered: direct consumption of locally grown cereals, vegetables, and root vegetables, as well as consumption of milk and meat from cows having eaten fodder cereals and green fodder from the area around the nuclear plant. The total dose of the earlier model was compared with that of POM(14)C. The result of the former was shown to be slightly higher than the latter, but POM(14)C confirmed that the earlier results were of a reasonable magnitude. When full account of local conditions was taken, e.g. as regards solar radiation, temperature, and concentration of (14)C in air at various places in the surroundings of each nuclear plant, a difference in dose between sites of approximately one order of magnitude was found.

Air Pollutants, Radioactive↗

PubMed1992

Does a cognitive map guide choices in the radial-arm maze?

Fifteen rats performed in a standard radial-arm maze task (Experiment 1) and in a modified task with a set of forced choices and a 15-min retention interval prior to completion of the maze (Experiment 2). In addition to the standard measure of choice in the radial-arm maze, orientation toward arms was measured and considered to constitute go-no-go "microchoice" decisions. Rats investigated but rejected many arms. A model of choice was developed in which it was assumed that choice decisions about arms were made independently and that microchoices were not selectively guided toward baited arms. The model performed nearly as well as the rats. These results place important limitations on the theory that choice behavior in the radial-arm maze is guided by a cognitive map.

Animals↗

PubMed2001

Organ system failures prediction model in intensive care patients with acute renal failure treated with dialysis.

OBJECTIVE: To evaluate the organ system failures hospital mortality predictions in critically ill patients with acute renal failure requiring dialysis. DESIGN: Prospective, cohort study. SETTING: Intensive care units in a tertiary care university hospital in Taiwan. PATIENTS: A total of 112 patients admitted to the intensive care units with acute renal failure who required dialysis from January 1999 through December 1999. INTERVENTIONS: Collection of information necessary to compute the number of failed organs. MEASUREMENTS AND RESULTS: Of the 112 patients studied, 75 were men and 37 were women. The mean age of survivors and non-survivors was 58.59 +/- 19.91 years and 58.76 +/- 19.62 years. The overall mortality rate was 67%. There were no significant differences between survivors and non-survivors in terms of age, gender, or indication for dialysis. The cause of death in the majority of patients was related to organ system failure during the 24 hours immediately preceding the initiation of acute hemodialysis, and carry mortality rates exceeding 83% with the coexistence of four or more failed organs. The area under the organ system failures prediction model receiver operating characteristic curve equaled 0.772 +/- 0.046. CONCLUSION: We conclude that mortality rate for acute renal failure in intensive care unit patients continues to be high. Organ system failures prediction model performed well and simple in its ability to identify patients who die in hospital. Mortality rate increases as number of failed organ increases.

Acute Kidney Injury↗

PubMed1994

The simulation of discrete vessel effects in experimental hyperthermia.

The ability of two simple thermal models to predict experimentally measured in vivo temperature profiles was compared. These comparisons were done both with and without the inclusion of separate, discrete blood vessels. The two tissue models were: 1) Pennes' Bio-Heat Transfer equation (BHTE), and 2) an effective thermal conductivity equation (ETCE). The experimental temperature data were measured (Moros, 1990; Moros et al., 1993) in the thighs of anesthetized greyhound dogs under hyperthermic conditions generated by scanned focused ultrasound. Blood vessels were added to the thermal models in counter-current pairs transiting the model domain. The blood vessels in both models were assumed to have a constant heat transfer coefficient, and an axially varying mixed mean temperature. The vessel locations were determined a posteriori, via inspection of the experimental temperature data. Least square error fits of the predicted model temperatures to the experimental temperature data were obtained by adjusting both (a) the mass flow rate within and (b) the position of each blood vessel, and (c) the value of either the perfusion parameter (W) in the BHTE or the effective thermal conductivity parameter (Keff) in the ETCE. When small numbers (3-4) of blood vessel pairs were included, both of the models showed significant improvement in their ability to predict the experimental temperatures. Although both models performed well in terms of predicting temperatures near large vessels, the BHTE had a statistically significant better ability to predict the complete set of measured temperatures at all locations.

Angiography, Digital Subtraction↗

PubMed2005

Glenohumeral joint loading in tetraplegia during weight relief lifting: a simulation study.

BACKGROUND: The incidence of shoulder complaints in wheelchair users is high and the etiology is poorly understood. The goal of this study was to examine the effect of lesion level and isolated triceps muscle paresis on the internal load on the shoulder by simulation. METHODS: Kinematic and kinetic profiles from four able-bodied subjects and four subjects with tetraplegia were used as input for an inverse dynamics biomechanical model. The model was modified to simulate lesion level and triceps muscle paresis. FINDINGS: The simulations resulted in a significantly higher (+56%) glenohumeral contact force (P=0.037) for tetraplegic profiles than for able-bodied profiles. The model modifications to simulate lesion level only had a minor effect (+7%) on the calculated glenohumeral contact force. More simulations were successful at lower triceps force levels for tetraplegic profiles compared to able-bodied profiles (P=0.012). The muscle forces at the simulated T1 lesion were not significantly higher in tetraplegic profiles compared to able-bodied profiles. INTERPRETATION: The glenohumeral contact force for the tetraplegic profiles is mainly higher due to different task performance. Model modifications only have a minor effect on the calculated glenohumeral contact force. For able-bodied profiles the triceps force seems to be an important factor. The high internal load at the shoulder recommends new techniques of weight relief lifting and proper training of the arm-shoulder muscles in rehabilitation.

Arm↗

PubMed2001

Quantitative classification of life-style types in predaceous phytoseiid mites.

Classification of species into different functional groups based on biological criteria has been a difficult problem in ecology. The difficulty mainly arises because natural classification patterns are not necessarily mutually exclusive. The more group characteristics overlap, the more difficult it is to identify the membership of a species in the overlapping portions of any two groups. In this paper, we present an application of discriminant analysis by creating classification models from life history and morphological data for two specialist and two generalist life-styles type of predaceous phytoseiid mites. Two stages can be distinguished in our method: life-style group membership assignment and trait variable evaluation. We use a Bayesian framework to create a classifier system to locate or assign species within a mixture of trait distributions. The method assumes that a mixture of trait distributions can represent the multiple dimensions of biological data. The mixture is most evident near the boundaries between groups. Because of the complexity of analytical solution, an iterative method is used to estimate the unknown means, variances, and mixing proportion between groups. We also developed a criterion based on information theory to evaluate model performance with different combinations of input variables and different hypotheses. We present a working example of our proposed methods. We apply these methods to the problem of selecting key species for inoculative release and for classical introductions of biological pest control agents.

Animals↗

PubMed2004

The role of perceptual bias in complex figure recall.

Several studies have demonstrated that constructional and organizational abilities affect how well visual stimuli are remembered. The purpose of the present study was to determine whether perceptual bias, independent of constructional ability, influenced visual memory performance. Participants were 118 normal adults who were administered the Rey-Osterrieth Complex Figure (ROCF) and a similarity judgement task requiring then to decide which of two hierarchically constructed comparison figures most resemble a standard figure. The initial steps of a multiple regression analysis indicated that delayed recall of the ROCF was directly related to copy accuracy, inversely related to age, and better in males than females. In the final step of the regression model, performance on the similarity judgement task also predicted ROCF recall, with a more global perceptual bias predicting better recall. Results indicate that even when copy accuracy and demographic variables are accounted for, components of visual perception influence how well visual stimuli are encoded and recalled. Findings are consistent with research correlating global processing and spatial ability, and suggest that in addition to copy ability and organization, visuoperceptual bias must be considered as a moderator variable when interpreting performance as a visual memory test.

Adult↗

PubMed2006

An adaptive visual neuronal model implementing competitive, temporally asymmetric Hebbian learning.

A novel depth-from-motion vision model based on leaky integrate-and-fire (I&F) neurons incorporates the implications of recent neurophysiological findings into an algorithm for object discovery and depth analysis. Pulse-coupled I&F neurons capture the edges in an optical flow field and the associated time of travel of those edges is encoded as the neuron parameters, mainly the time constant of the membrane potential and synaptic weight. Correlations between spikes and their timing thus code depth in the visual field. Neurons have multiple output synapses connecting to neighbouring neurons with an initial Gaussian weight distribution. A temporally asymmetric learning rule is used to adapt the synaptic weights online, during which competitive behaviour emerges between the different input synapses of a neuron. It is shown that the competition mechanism can further improve the model performance. After training, the weights of synapses sourced from a neuron do not display a Gaussian distribution, having adapted to encode features of the scenes to which they have been exposed.

Algorithms↗

PubMed2006

A multimarker model to predict outcome in tamoxifen-treated breast cancer patients.

PURPOSE: This study was designed to produce a model to predict outcome in tamoxifen-treated breast cancer patients based on clinicopathologic features and multiple molecular markers. EXPERIMENTAL DESIGN: This was a retrospective study of 324 stage I to III female breast cancer patients treated with tamoxifen for whom standard clinicopathologic data and tumor tissue microarrays were available. Nine molecular markers were studied by semiquantitative immunohistochemistry and/or fluorescence in situ hybridization. Cox proportional hazards analysis was used to determine the contributions of each variable to disease-specific and overall survival, and machine learning was used to produce a model to predict patient outcome. RESULTS: On a univariate basis, the following features were significantly associated with worse survival: high pathologic tumor or nodal class, histologic grade, epidermal growth factor receptor, ERBB2, MYC, or TP53; absent estrogen receptor (ER) or progesterone receptor; and low BCL2. CCND1 and CDKN1B did not reach statistical significance. On a multivariate basis, nodal class, ER, and MYC were statistically significant as independent factors for survival. However, the benefit of ER-positive status was moderated by BCL2, ERBB2, and progesterone receptor. BCL2 and TP53 also interacted as an independent risk factor. A kernel partial least squares polynomial model was developed with an area under the receiver operating characteristic curve of 0.90. CONCLUSIONS: Our data show the predictive value of BCL2, ERBB2, MYC, and TP53 in addition to the standard hormone receptors and clinicopathologic features, and they show the importance of conditional interpretation of certain molecular markers. Our multimarker predictive model performed significantly better than standard guidelines.

Aged↗

PubMed1991

Simultaneous modeling of the pharmacokinetics and methemoglobin pharmacodynamics of an 8-aminoquinoline candidate antimalarial (WR 238605).

Methemoglobin (MHb) formation can be a clinically significant and dose-limiting side effect of 8-aminoquinoline antimalarials. MHb may also protect against cyanide poisoning. A two-compartment pharmacokinetic model, linked to a sigmoid Emax pharmacodynamic model, was developed to predict the MHb levels after administration of 8-[(4-amino-1-methylbutyl)amino]-2,6-dimethoxy-4-methyl-5-[(3- trifluoromethyl)phenoxy] quinoline succinate (WR 238605 succinate), a primaquine analogue. Six healthy male beagle dogs received four daily doses of 6.0 mg/kg (base) orally. Forty plasma drug concentrations and 19 MHb levels (effect) were determined over 7 weeks on each dog. Compartmental and noncompartmental pharmacokinetic and parametric and nonparametric pharmacodynamic analyses were performed. Model parameters (mean +/- SD) included a Vss/f of 18.5 +/- 2.8 L/kg, CL/f of 83 +/- 24 ml/hr/kg, terminal elimination t1/2 of 169.7 +/- 52.0 hr, t1/2keo of 123.0 +/- 22.4 hr, an Emax of 31.3 +/- 15.9% MHb, an EC50 of 596 +/- 128 ng/ml, and a sigmoidicity coefficient (n) of 1.94 +/- 0.47. The model was then validated in three additional dogs given three different dosing regimens. It predicted the peak plasma concentrations and MHb levels and the times of their occurrence well. This model could be useful for dose and sampling time selection in further animal studies and initial human phase I clinical testing.

Aminoquinolines↗

PubMedDate not supplied

Development and validation of a kinetic model for enzymatic saccharification of lignocellulosic biomass.

A multireaction kinetic model was developed for closed-system enzymatic hydrolysis of lignocellulosic biomass such as corn stover. Three hydrolysis reactions were modeled, two heterogeneous reactions for cellulose breakdown to cellobiose and glucose and one homogeneous reaction for hydrolyzing cellobiose to glucose. Cellulase adsorption onto pretreated lignocellulose was modeled via a Langmuir-type isotherm. The sugar products of cellulose hydrolysis, cellobiose and glucose, as well as xylose, the dominant sugar prevalent in most hemicellulose hydrolyzates, were assumed to competitively inhibit the enzymatic hydrolysis reactions. Model parameters were estimated from experimental data generated using dilute acid pretreated corn stover as the substrate. The model performed well in predicting cellulose hydrolysis trends at experimental conditions both inside and outside the design space used for parameter estimation and can be used for in silico process optimization.

Carbohydrates↗

PubMed2001

Modelling nitrogen transformations in surface flow wastewater treatment wetlands in Sweden.

The purpose of this study was to describe and compare the fate of nitrogen (N) in two Swedish wastewater treatment wetlands in the cities of Oxelösund and Hässleholm. Specifically, we wanted to see if a fairly simple model, developed with regard to common data availability, could satisfactorily describe the concentration dynamics at the outlet from the wetlands. A first-order area-based model, with two alternative expressions for temperature dependence, was set up to describe three major processes: ammonification, nitrification and denitrification. The N concentration dynamics at the outlet of the Oxelösund wetland was not satisfactorily described, R2(NH4+-N) = 0.33 and R2(NO3(-)-N) = 0.10, while the modelled concentrations corresponded quite well with measured concentrations in the Hässleholm wetland, R2(NH4+-N) = 0.83 and R2(NO3(-)-N) = 0.58. The NO3(-)-N concentrations, in both wetlands, could be slightly better described when introducing a temperature coefficient as an additional free parameter. The explained variances reported above were achieved when the model was calibrated individually for the two wetlands, when the resulting (optimised) reaction rate coefficients for each of the three processes were quite different between the two wetlands. To improve model performance, the rate equations may have to be changed to include factors in addition to concentration and temperature, such as dissolved oxygen and hydraulic efficiency. It may also be important to include other processes, such as plant uptake/decay and ammonia volatilisation.

Ammonia↗

PubMed2002

Assessing vegetation exposure to ozone: is it possible to estimate AOT40 by passive sampling?

A statistical model for estimating AOT40 from time-integrated concentration data is presented and validated. AOT40 is a numerical index that describes the ozone exposure of ecosystems in terms of the hourly accumulated exposure over a threshold of 40 ppb. A rather simple model formulation was achieved by approximating the frequency distribution of hourly concentrations by the Gaussian probability distribution. The model represents a relationship between a time-averaged ozone concentration and the corresponding AOT40. Time-averaged concentration data are obtained when employing the passive sampling technique. For testing the method, passive sampling data with a 14-day sampling time were simulated by averaging continuous monitoring data. Data from eight background stations in Europe were used for calibration and testing. In spite of the simplifying assumption, the model performed well for the accumulated exposure when tested against independent data. The results show that it is possible to obtain a reasonable estimate of AOT40 even in the absence of continuous data, if the time-averaged concentration can be measured reliably.

Air Pollutants↗

PubMedDate not supplied

Prediction of human intestinal absorption of drug compounds from molecular structure.

The absorption of a drug compound through the human intestinal cell lining is an important property for potential drug candidates. Measuring this property, however, can be costly and time-consuming. The use of quantitative structure-property relationships (QSPRs) to estimate percent human intestinal absorption (%HIA) is an attractive alternative to experimental measurements. A data set of 86 drug and drug-like compounds with measured values of %HIA taken from the literature was used to develop and test a QSPR mode. The compounds were encoded with calculated molecular structure descriptors. A nonlinear computational neural network model was developed by using the genetic algorithm with a neural network fitness evaluator. The calculated %HIA (cHIA) model performs wells, with root-mean-square (rms) errors of 9.4%HIA units for the training set, 19.7%HIA units for the cross-validation (CV) set, and 16.0%HIA units for the external prediction set.

Humans↗

PubMed2006

Probing the structure-function relationship of polyene macrolides: engineered biosynthesis of soluble nystatin analogues.

Although polyene macrolides are efficient antifungal agents with fungicidal mode of action, their use in medical practice is problematic due to their low solubility and significant human toxicity. In an attempt to address the solubility problem, we have obtained two analogues of nystatin with hydroxy groups at positions C31 and C33 through manipulation of the nystatin polyketide synthase in the producing organism Streptomyces noursei. Structures of the analogues were confirmed by nuclear magnetic resonance (NMR), and their solubility was found to be more than 2000 times higher than that of nystatin. However, both analogues were shown to have lost antifungal activity, implying that the integrity of the hydrophobic polyene region of the nystatin molecule is crucial for the fungicidal action. NMR data and computer modeling performed for the new analogues suggested conformational changes together with a significantly increased structural disorder, which may account for both increased solubility and the loss of activity.

Antifungal Agents↗

PubMed2005

Surgical outcomes for patients aged 80 and older: morbidity and mortality from major noncardiac surgery.

OBJECTIVES: To gather information about surgical outcomes for patients in their 80s and 90s. DESIGN: Prospective cohort study. SETTING: Veterans Affairs Medical Centers. PARTICIPANTS: Patients (26,648 aged >/=80; 568,263 aged <80) enrolled in the Veterans Affairs National Surgical Quality Improvement Project (NSQIP) who had noncardiac surgery between 1991 and 1999. METHODS: Data were collected prospectively from medical records and healthcare providers. Detailed information was collected about patients' preoperative status, intraoperative experience, and postoperative outcomes. Postoperative outcomes were survival status at 30 days (deaths from any cause occurring during hospitalization and after hospital discharge were captured) and the occurrence of 21 selected surgical complications within 30 days postoperatively: wound complications (3 types), respiratory complications (4), urinary tract complications (3), nervous system complications (3), cardiac complications (3), and other complications (5). MEASUREMENTS: Mortality and the occurrence of 21 surgical complications within 30 days of surgery. RESULTS: Thirty-day all-cause mortality rates varied widely across operations and were higher for patients aged 80 and older than for younger patients (8% vs 3%, P<.001). Mortality rates for those aged 80 and older were less than 2% for many commonly performed operations (e.g., transurethral prostatectomy, hernia repair, knee replacement, carotid endarterectomy). Of patients aged 80 and older, 20% had one or more postoperative complications, and patients who suffered complications had higher 30-day mortality than those who did not (26% vs 4%, P<.001). For 11 of the 21 complications, mortality for patients aged 80 and older was greater than 33%. The risk factors for poor outcomes were the same for older and younger patients, and the NSQIP Mortality Risk model performed well on patients aged 80 and older (C statistic=0.83). CONCLUSION: A substantial minority of patients aged 80 and older died or suffered a complication within 30 days of surgery, but for many operations mortality rates were extremely low. Postoperative complications were associated with high 30-day mortality in patients aged 80 and older.

Age Distribution↗

PubMed2004

Vocal production mechanisms in a non-human primate: morphological data and a model.

Human beings are thought to be unique amongst the primates in their capacity to produce rapid changes in the shape of their vocal tracts during speech production. Acoustically, vocal tracts act as resonance chambers, whose geometry determines the position and bandwidth of the formants. Formants provide the acoustic basis for vowels, which enable speakers to refer to external events and to produce other kinds of meaningful communication. Formant-based referential communication is also present in non-human primates, most prominently in Diana monkey alarm calls. Previous work has suggested that the acoustic structure of these calls is the product of a non-uniform vocal tract capable of some degree of articulation. In this study we test this hypothesis by providing morphological measurements of the vocal tract of three adult Diana monkeys, using both radiography and dissection. We use these data to generate a vocal tract computational model capable of simulating the formant structures produced by wild individuals. The model performed best when it combined a non-uniform vocal tract consisting of three different tubes with a number of articulatory manoeuvres. We discuss the implications of these findings for evolutionary theories of human and non-human vocal production.

Animals↗

PubMed2001

Development and validation of a clinical prediction rule for major adverse outcomes in coronary bypass grafting.

In this study, we develop and internally validate a clinical prediction rule for in-hospital major adverse outcomes, defined as death, renal failure, reinfarction, cardiac arrest, cerebrovascular accident, or coma, in patients who underwent coronary artery bypass grafting (CABG). All adult patients (n = 9,498) who underwent a CABG and no other concomitant surgery at 12 academic medical centers from August 1993 to October 1995 were included in the study. We assessed in-hospital major adverse outcomes and their predictors using information on admission, coronary angiography, and postoperative hospital course. Predictor variables were limited to information available before the procedure, and outcome variables were represented only by events that occurred postoperatively. We developed and internally validated a clinical prediction rule for any major adverse outcome after CABG. The rule's ability to discriminate outcomes and its calibration were assessed using receiver-operating characteristic analysis and the Hosmer-Lemeshow goodness-of-fit statistic, respectively. A major adverse outcome occurred in 6.5% of patients in the derivation set and 7.2% in the validation set. Death occurred in 2.5% of patients in the derivation set and 2.2% in the validation set. Sixteen variables were independently correlated with major adverse outcomes, with the risk score value attributed to each risk factor ranging from 2 to 12 points. The rule stratified patients into 6 levels of risk based on the total risk score. The spread in probability between the lowest and highest risk groups of having a major adverse outcome was 1.7% to 32.3% in the derivation set and 2.2% to 22.3% in the validation set. The prediction model performed well in both outcome discrimination and calibration. Thus, this clinical prediction rule allows accurate stratification of potential CABG candidates before surgery according to the risk of experiencing a major adverse outcome postoperatively.

Aged↗