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PubMedDate not supplied

MODFLOW 2000 head uncertainty, a first-order second moment method.

A computationally efficient method to estimate the variance and covariance in piezometric head results computed through MODFLOW 2000 using a first-order second moment (FOSM) approach is presented. This methodology employs a first-order Taylor series expansion to combine model sensitivity with uncertainty in geologic data. MODFLOW 2000 is used to calculate both the ground water head and the sensitivity of head to changes in input data. From a limited number of samples, geologic data are extrapolated and their associated uncertainties are computed through a conditional probability calculation. Combining the spatially related sensitivity and input uncertainty produces the variance-covariance matrix, the diagonal of which is used to yield the standard deviation in MODFLOW 2000 head. The variance in piezometric head can be used for calibrating the model, estimating confidence intervals, directing exploration, and evaluating the reliability of a design. A case study illustrates the approach, where aquifer transmissivity is the spatially related uncertain geologic input data. The FOSM methodology is shown to be applicable for calculating output uncertainty for (1) spatially related input and output data, and (2) multiple input parameters (transmissivity and recharge).

Calibration↗

PubMed2003

Scientific basis and development of internal dosimetry models (BIODOS).

Assessments of doses and risks to workers and members of the public exposed to radionuclides require biokinetic and dosimetric models which describe the behaviour of the radionuclides and provide tools for dose calculations. The overall objective of BIODOS is to improve the scientific basis of existing models and to provide new or improved models. One part aims to provide models targeting specific uncertainties, including estimates of doses and risks from radionuclides ingested by adults and children; estimates of the transfer of radionuclides to breast milk and doses to infants; development of systemic models to improve the interpretation of bioassays; and studies of the importance of heterogeneous distribution of dose within tissues and cells. The other part forms a comprehensive research programme on the inhalation of radionuclides and addresses four areas of uncertainty, namely ultrafine particles, inter-subject variation, absorption into blood and clearance mechanisms.

Adult↗

PubMed2003

Pulsatile machine perfusion vs. cold storage of kidneys for transplantation: a rapid and systematic review.

OBJECTIVE: To identify and prioritize key areas for further research in kidney preservation systems. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of the effectiveness of machine perfusion and cold storage techniques in reducing delayed graft function (DGF) and improving graft survival in recipients of kidneys from beating and non-heart-beating donors. Literature quantifying the link between DGF and graft survival was used to evaluate the potential long-term impact of machine perfusion and cold storage systems. Cox proportional hazards modelling was used to predict graft survival and graft years gained over 10 yr. Monte Carlo sensitivity analysis was conducted to evaluate stochastic uncertainties within the model. RESULTS: Machine perfusion leads to a relative risk of DGF of approximately 80% (67%, 96%) compared with cold storage, although the evidence base is limited in quality and study size. Direct evidence on graft survival at 1 yr demonstrates no statistically significant difference between machine perfusion and cold storage. Predictions based upon quantifying the link between DGF and graft survival suggest potential improvements of between 0 and 6% at 10 yr. DISCUSSION: Studies of high methodological quality and sufficient size are required to determine whether machine preservation leads to reduce rates of DGF. Predicted impact on graft survival implies that direct evidence would require a large population followed up over a long period of time. Registry database analysis supported by validation of the link between DGF and graft survival may be preferable and more feasible than randomized controlled trials.

Cryopreservation↗

PubMed1997

An approach for modeling noncancer dose responses with an emphasis on uncertainty.

This paper presents an approach for characterizing the probability of adverse effects occurring in a population exposed to dose rates in excess of the Reference Dose (RfD). The approach uses a linear threshold (hockey stick) model of response and is based on the current system of uncertainty factors used in setting RfDs. The approach requires generally available toxicological estimates such as No-Observed-Adverse-Effect Levels (NOAELs) or Benchmark Doses and doses at which adverse effects are observed in 50% of the test animals (ED50s). In this approach, Monte Carlo analysis is used to characterize the uncertainty in the dose response slope based on the range and magnitude of the key sources of uncertainty in setting protective doses. The method does not require information on the shape of the dose response curve for specific chemicals, but is amenable to the inclusion of such data. The approach is applied to four compounds to produce estimates of response rates for dose rates greater than the RfD.

Acetamides↗

PubMed2005

A multi-group model of Schistosoma japonicum transmission dynamics and control: model calibration and control prediction.

Previously we formulated a quantitative model to characterize site-specific schistosomiasis transmission. In this paper, we present a procedure to calibrate the model to data collected in endemic villages of south-western Sichuan, China, with the objective of reducing parametric uncertainty to allow the model to describe local transmission with relative confidence. A Bayesian approach using local epidemiological data and expert opinion is employed to calibrate the model. Results indicate that, after calibration, the output uncertainty is reduced substantially. The calibrated model is then used for prediction of the effects of different intervention options. Simulations reflect a bimodal transmission in both human (early summer and early fall) and snail (late summer and late fall) infections in this area, for which there is some field evidence. Also shown in the simulations are relatively high reinfection rates following chemotherapy in these endemic villages. These results suggest that a sustainable control strategy is essential in reducing transmission, and that transmission can be reduced by chemotherapy, focal snail (e.g. snail clusters) control, and egg control. Our work demonstrates the feasibility of characterizing site-specific schistosomiasis transmission using a mathematical model and a calibration approach that integrates diverse field data, and the use of the calibrated model to design control strategies.

Animals↗

PubMed1980

Detection of temporally uncertain signals.

The effects of signal uncertainty on detection performance were measured using a new procedure that allows precise specification of the initial temporal uncertainty. Five different models of the detection process, two assuming a continous representation of the sensory input and three assuming a discrete representation, were compared with the obtained data. The effects of varying signal uncertainty (the number of potential signal intervals was one, five, or ten) had little effect on detection performance. The one-parameter form of the choice model can be rejected without hesitation. The continuous Gaussian model and the symmetric two-state model are significantly different from the data. The high threshold and sophisticated two-state models provide accurate descriptions of the data that cannot be rejected on statistical grounds.

Acoustic Stimulation↗

PubMed2003

MEAD (part II)-Predictions of radioactivity concentrations in the Irish Sea.

The predictions from MEAD, a model that simulates the transport of radionuclides in the marine environment, are presented for the Irish Sea. MEAD predictions for (137)Cs and Pu(alpha) are presented following discharges from BNFL Sellafield and the predictions compared to measured data from near the discharge location and further a field in the Irish Sea. The model performs well in most circumstances given the uncertainties involved in both modelling and data collection although some inconsistencies in the predictions are found. MEAD is also compared to other models of radionuclide transport in the Irish Sea.

Cesium Radioisotopes↗

PubMedDate not supplied

Using absolute and relative reasoning in the prediction of the potential metabolism of xenobiotics.

To be useful, a system which predicts the metabolic fate of a chemical should predict the more likely metabolites rather than every possibility. Reasoning can be used to prioritize biotransformations, but a real biochemical domain is complex and cannot be fully defined in terms of the likelihood of events. This paper describes the combined use of two models for reasoning under uncertainty in a working system, METEOR-one model deals with absolute reasoning and the second with relative reasoning.

Cyclohexanols↗

PubMed2002

The role of the thermohaline circulation in abrupt climate change.

The possibility of a reduced Atlantic thermohaline circulation in response to increases in greenhouse-gas concentrations has been demonstrated in a number of simulations with general circulation models of the coupled ocean-atmosphere system. But it remains difficult to assess the likelihood of future changes in the thermohaline circulation, mainly owing to poorly constrained model parameterizations and uncertainties in the response of the climate system to greenhouse warming. Analyses of past abrupt climate changes help to solve these problems. Data and models both suggest that abrupt climate change during the last glaciation originated through changes in the Atlantic thermohaline circulation in response to small changes in the hydrological cycle. Atmospheric and oceanic responses to these changes were then transmitted globally through a number of feedbacks. The palaeoclimate data and the model results also indicate that the stability of the thermohaline circulation depends on the mean climate state.

Journal Article↗

PubMed2003

Critical evaluation of the role of scientific analysis in UK local authority AQMA decision-making: method development and preliminary results.

Over the past 4 years, local government in the UK has undertaken a process of scientific review and assessment of air quality, which has culminated in a suite of designated air quality management areas (AQMAs) in over 120 of the 403 local authorities in England (including London), Scotland and Wales. Methods to identify specific pollution hot-spots have involved the use of advanced and complex air-quality dispersion modelling and monitoring techniques, and the UK government has provided guidance on both the general and technical methods for undertaking local air quality review and assessments. Approaches to implementing UK air quality policy, through the local air quality management (LAQM) process (Air Quality Strategy 2000) has not been uniform across the UK, as an inevitable consequence of non-prescriptive guidelines. This has led to a variety of outcomes with respect to how different tools and techniques have been applied, the interpretation of scientific uncertainty and the application of caution. A technique to appraise the scientific approaches undertaken by local government and to survey local government officers involved in the LAQM process have been devised, and a conceptual model proposed to identify the main influences in the process of determining AQMAs. Modelling tools used and the consideration of modelling uncertainty, error and model inputs have played a significant role in AQMA decision-making in the majority of local authorities declaring AQMAs in the UK.

Air Pollutants↗

PubMed2003

Measured and modeled radiometric quantities in coastal waters: toward a closure.

Accurate radiative transfer modeling in the coupled atmosphere-sea system is increasing in importance for the development of advanced remote-sensing applications. Aiming to quantify the uncertainties in the modeling of coastal water radiometric quantities, we performed a closure experiment to intercompare theoretical and experimental data as a function of wavelength lambda and water depth z. Specifically, the study focused on above-water downward irradiance E(d)(lambda, 0+) and in-water spectral profiles of upward nadir radiance L(u)(lambda, z), upward irradiance E(u)(lambda, z), downward irradiance E(d)(lambda, z), the E(u)(lambda, z)/L(u)(lambda, z) ratio (the nadir Q factor), and the E(u)(lambda, z)/E(d)(lambda, z) ratio (the irradiance reflectance). The theoretical data were produced with the finite-element method radiative transfer code ingesting in situ atmospheric and marine inherent optical properties. The experimental data were taken from a comprehensive coastal shallow-water data set collected in the northern Adriatic Sea. Under various measurement conditions, differences between theoretical and experimental data for the above-water E(d)(lambda, 0+) and subsurface E(d)(lambda, 0-) as well as for the in-water profiles of the nadir Q factor were generally less than 15%. In contrast, the in-water profiles of L(u)(lambda, z), E(d)(lambda, z), E(u)(lambda, z) and of the irradiance reflectance exhibited larger differences [to approximately 60% for L(u)(lambda, z) and E(u)(lambda, z), 30% for E(d)(lambda, z), and 50% for the irradiance reflectance]. These differences showed a high sensitivity to experimental uncertainties in a few input quantities used for the simulations: the seawater absorption coefficient; the hydrosol phase function backscattering probability; and, mainly for clear water, the bottom reflectance.

Journal Article↗

PubMed2002

Effect of uncertainty in transfer rates for the ICPR publication 67 biokinetic model on dose estimation for 239Pu from results of individual monitoring. International Commission on Radiological Protection.

The radiation dose due to internal exposures from 239Pu is mainly estimated by measuring actual urinary or faecal excretion of activity and comparing those values with the standard excretion rates calculated from the models of the International Commission on Radiological Protection (ICRP). Recently, on the other hand, uncertainties in the ICRP's models and parameters are under consideration because of the paucity of human data. In addition, there is a possibility of variation between individuals. A code has been developed to reproduce the ICRP's dose coefficients and excretion rates for 239Pu, which is one of the most important elements for occupational exposure. By using this code, the respective transfer rates for the ICRP Publication 67 biokinetic model were modified, and the effect owing to these changes on present hazard assessment was investigated. As a result, it was shown that dose estimates for workers exposed to 239Pu were not very sensitive to changes in these transfer rates.

Evaluation Studies as Topic↗

PubMed2006

How accurately can the parameters from a model of anisotropic 3He gas diffusion in lung acinar airways be estimated? Bayesian view.

In the framework of a recently proposed method for in vivo lung morphometry, acinar lung airways are considered as a set of randomly oriented cylinders covered by alveolar sleeves. Diffusion of (3)He in each airway is anisotropic and can be described by distinct longitudinal and transverse diffusion coefficients. This macroscopically isotropic but microscopically anisotropic model allows estimation of these diffusion coefficients from multi b-value MR experiments despite the airways being too small to be resolved by direct imaging. Herein a Bayesian approach is used for analyzing the uncertainties in the model parameter estimates. The approach allows evaluation of relative errors of the parameter estimates as functions of the "true" values of the parameters, the signal-to-noise ratio, the maximum b-value and the total number of b-values used in the experiment. For a given set of the "true" diffusion parameters, the uncertainty in the estimated diffusion coefficients has a minimum as a function of maximum b-value and total number of data points. Choosing the MR pulse sequence parameters corresponding to this minimum optimizes the diffusion MR experiment and gives the best possible estimates of the diffusion coefficients. The mathematical approach presented can be generalized for models containing arbitrary numbers of estimated parameters.

Anisotropy↗

PubMed2001

Reconstruction of doses from radionuclide inhalation for nuclear power plant workers using air concentration measurements and associated uncertainties.

This paper presents a case study to illustrate the influence of parameter uncertainties on calculating an internal radiation dose of one actual nuclear plant worker, alias Mr. X, as well as the utility of air sampling for internal dose reconstruction. Input probability distributions for air concentrations of radionuclides were derived from empirical air measurements taken by fixed area air samplers. The total internal dose was calculated by multiplying radionuclide intake by dose conversion factors in Monte-Carlo simulations. There is significant variability in dose conversion factors and uncertainty in the estimated concentrations of radionuclides in the air to which Mr. X was exposed. The high variability and uncertainty of the model parameters contributed to large ranges of predicted internal doses for Mr. X. Two-dimensional Monte-Carlo simulations were conducted to separate contributions of the uncertainty and variability. Sensitivity analysis was conducted to determine which of the input parameters contributed most to uncertainty in internal dose estimates. Our analysis suggests that the uncertainty resulting from use of general air surveys contributes more to the internal dose ranges than the variability from DCFs and other population-derived parameters. Reduction of the uncertainty in reconstructed internal dose can be achieved by using personal air sampling and/or individual bioassays and regular whole-body counting.

Air Pollutants, Radioactive↗

PubMed2004

The burden of major depression avoidable by longer-term treatment strategies.

BACKGROUND: Major depression is the largest single cause of nonfatal disease burden in Australia. Effective drug and psychological treatments exist, yet are underused. OBJECTIVE: To quantify the burden of disease currently averted in people seeking care for major depression and the amount of disease burden that could be averted in these people under optimal episodic and maintenance treatment strategies. DESIGN: Modeling impact of current and optimal treatment strategies based on secondary analysis of mental health survey data, studies of the natural history of major depression, and meta-analyses of effectiveness data. Monte Carlo simulation of uncertainty in the model. SETTING: The cohort of Australian adults experiencing an episode of major depression in 2000 are modeled through "what if" scenarios of no treatment, current treatment, and optimal treatment strategies with cognitive behavioral therapy or antidepressant drug treatment. MAIN OUTCOME MEASURE: Disability-Adjusted Life Year. RESULTS: Current episodic treatment averts 9% (95% uncertainty interval, 6%-12%) of the disease burden of major depression in Australian adults. Optimal episodic treatment with cognitive behavioral therapy could avert 28% (95% uncertainty interval, 19%-39%) of this disease burden, and with drugs 24% (95% uncertainty interval, 19%-30%) could be averted. During the 5 years after an episode of major depression, current episodic treatment patterns would avert 13% (95% uncertainty interval, 10%-17%) of Disability-Adjusted Life Years, whereas maintenance drug treatment could avert 50% (95% uncertainty interval, 40%-60%) and maintenance cognitive behavioral therapy could avert 52% (95% uncertainty interval, 42%-64%), even if adherence of around 60% is taken into account. CONCLUSIONS: Longer-term maintenance drug or psychological treatment strategies are required to make significant inroads into the large disease burden associated with major depression in the Australian population.

Adult↗

PubMed1997

Ecosystem Manipulation Experimentation as a Means of Testing a Biogeochemical Model

/ Numerical simulation models have found increased usage in the past decade for projecting the environmental effects of ecosystem perturbations such as atmospheric deposition of sulfur and nitrogen, increased atmospheric CO2 concentration, and global or regional temperature change. Such model projections are frequently used as the basis or justification for public policy decisions and legislation. A substantial need has therefore arisen to test and substantiate the veracity of mathematical model projections. Unfortunately, environmental models can never be truly validated because natural systems are never closed and model solutions are always nonunique. Partial model confirmation is possible, however, and entails demonstration of agreement between prediction and observation. Experimental ecosystem manipulation provides one of the best, and in many cases only, available basis for model confirmation. The use and potential misuse of data from experimental ecosystem manipulations for model testing is explored using examples drawn from the application of an acid-base chemistry model, MAGIC. As model projections provide an increasingly important basis for public policy decisions, and as both the scientific questions and the models become increasingly complex, it will become critical to provide data from a suite of well-designed ecosystem manipulation experiments in order to evaluate the quality and uncertainty of those model projections and the models upon which they are based.KEY WORDS: Modeling; Model testing; Acidification; Ecosystem manipulation

Journal Article↗

PubMed2001

Bayesian methods in meta-analysis and evidence synthesis.

This paper reviews the use of Bayesian methods in meta-analysis. Whilst there has been an explosion in the use of meta-analysis over the last few years, driven mainly by the move towards evidence-based healthcare, so too Bayesian methods are being used increasingly within medical statistics. Whilst in many meta-analysis settings the Bayesian models used mirror those previously adopted in a frequentist formulation, there are a number of specific advantages conferred by the Bayesian approach. These include: full allowance for all parameter uncertainty in the model, the ability to include other pertinent information that would otherwise be excluded, and the ability to extend the models to accommodate more complex, but frequently occurring, scenarios. The Bayesian methods discussed are illustrated by means of a meta-analysis examining the evidence relating to electronic fetal heart rate monitoring and perinatal mortality in which evidence is available from a variety of sources.

Bayes Theorem↗

PubMed1996

Modeling therapeutic benefit in the midst of uncertainty: therapy for hepatitis C.

Randomized, double-blind, controlled clinical trials are the gold standard for medical therapy. When a disease is rare or slowly progressive over many years, such a trial may not be feasible. Decision analysis provides a bridge between current studies with short-term surrogate markers and a large, longitudinal clinical trial. With decision analysis, results of current studies can be summarized and the outcome of a long-term study projected under explicit assumptions. Chronic hepatitis C is a disease that is slowly progressive, and the requirements of a longitudinal clinical study could be prohibitive. Therefore, we review the basic steps of decision analysis, apply these steps to two recent decision analyses evaluating the use of interferon-alpha2b (IFN) in the treatment of chronic hepatitis C, and discuss possible implications of decision modeling for this disease. The estimated marginal cost per year of life gained from IFN therapy ranged from approximately $3000 to $55,000 in these two studies. The wide range is based on different estimates of treatment costs and disease progression. This analysis has identified gaps in the current knowledge regarding the natural progression of hepatitis C and has established criteria to evaluate new developments and their impact on chronic hepatitis C.

Chronic Disease↗