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Results for “Uncertainty modelling”

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PubMed1994

Phylogenetic relationships among eutherian orders estimated from inferred sequences of mitochondrial proteins: instability of a tree based on a single gene.

The phylogenetic relationships among Primates (human), Artiodactyla (cow), Cetacea (whale), Carnivora (seal), and Rodentia (mouse and rat) were estimated from the inferred amino acid sequences of the mitochondrial genomes using Marsupialia (opossum), Aves (chicken), and Amphibia (Xenopus) as an outgroup. The overall evidence of the maximum likelihood analysis suggests that Rodentia is an outgroup to the other four eutherian orders and that Cetacea and Artiodactyla form a clade with Carnivora as a sister taxon irrespective of the assumed model for amino acid substitutions. Although there remains an uncertainty concerning the relation among Artiodactyla, Cetacea, and Carnivora, the existence of a clade formed by these three orders and the outgroup status of Rodentia to the other eutherian orders seems to be firmly established. However, analyses of individual genes do not necessarily conform to this conclusion, and some of the genes reject the putatively correct tree with nearly 5% significance. Although this discrepancy can be due to convergent or parallel evolution in the specific genes, it was pointed out that, even without a particular reason, such a discrepancy can occur in 5% of the cases if the branching among the orders in question occurred within a short period. Due to uncertainty about the assumed model underlying the phylogenetic inference, this can occur even more frequently. This demonstrates the importance of analyzing enough sequences to avoid the danger of concluding an erroneous tree.

Animals↗

PubMed2006

Nonlinear regression approach to evaluate nutrient delivery coefficient.

Implementation of the Korean Total Maximum Daily Load Act calls for new tools to quantify nutrient losses from diffuse sources at a river basin district scale. In this study, it was elucidated that the nonlinear regression model (NRM) reduces the uncertainty of the boundary conditions of the water quality model. The NRM was proposed to analyse the delivery coefficients of surface waters and retention coefficients of pollutants. Delivery coefficient of pollution load was considered as a function of two variables: the watershed form ratio, S(f), which is a measurable geomorphologic variable and the retention coefficient, phi, which is an empirical constant representing the basin-wide retarding capacity of pollutant wash-off. This model was applied on the Geum River, one of the major basins in South Korea. The QUAL2E was used to simulate stream water quality using NRM. In this paper, we elucidate the possibility to use a nonlinear regression model for delivery and retention of nutrients in a drainage basin characterized as both data-rich and data-poor, and the magnitude of the nutrient loads and sources has been uncertain for a long time.

Environmental Monitoring↗

PubMed2004

Radiation-induced statistical uncertainty in the threshold voltage measurement of MOSFET dosimeters.

The results of a recent study on the limiting uncertainties in the measurement of photon radiation dose with MOSFET dosimeters are reported. The statistical uncertainty in dose measurement from a single device has been measured before and after irradiation. The resulting increase in 1/f noise with radiation dose has been investigated via various analytical models. The limit of uncertainty in the ubiquitous linear trend of threshold voltage with dose has been measured and compared to two nonlinear models. Inter-device uncertainty has been investigated in a group of 40 devices, and preliminary evidence for kurtosis and skewness in the distributions for devices without external bias has been observed.

Algorithms↗

PubMed2001

Chronic and temporarily activated causal uncertainty beliefs and stereotype usage.

In 3 studies, we examined the hypothesis that the effects of stereotype usage on target judgments are moderated by causal uncertainty beliefs and related accuracy goal structures. In Study 1, we focused on the role of chronically accessible causal uncertainty beliefs as predictors of a target's level of guilt for an alleged academic misconduct offense. In Study 2, we examined the role of chronic causal uncertainty reduction goals and a manipulated accuracy goal; in Study 3, we investigated the role of primed causal uncertainty beliefs on guilt judgments. In all 3 studies, we found that activation of causal uncertainty beliefs and accuracy concerns was related to a reduced usage of stereotypes. Moreover, this reduction was not associated with participants' levels of perceived control, depression, state affect, need for cognition, or personal need for structure. Results are discussed in terms of their implications for the model of causal uncertainty and, more generally, in terms of the motivational processes underlying stereotype usage.

Adult↗

PubMed2006

Inlet conditions for image-based CFD models of the carotid bifurcation: is it reasonable to assume fully developed flow?

BACKGROUND: Computational fluid dynamics tools are useful for their ability to model patient specific data relevant to the genesis and progression of atherosclerosis, but unavailable to measurement tools. The sensitivity of the physiologically relevant parameters of wall shear stress (WSS) and the oscillatory shear index (OSI) to secondary flow in the inlet velocity profiles was investigated in three realistic models of the carotid bifurcation. METHOD OF APPROACH: Secondary flow profiles were generated using sufficiently long entrance lengths, to which curvature and helical pitch were added. The differences observed were contextualized with respect to effect of the uncertainty of the models' geometry on the same parameters. RESULTS: The effects of secondary velocities in the inlet profile on WSS and OSI break down within a few diameters of the inlet. Overall, the effect of secondary inlet flow on these models was on average more than 3.5 times smaller than the effect of geometric variability, with 13% and 48% WSS variability induced by inlet secondary flow and geometric differences, respectively. CONCLUSIONS: The degree of variation is demonstrated to be within the range of the other computational assumptions, and we conclude that given a sufficient entrance length of realistic geometry, simplification to fully developed axial (i.e., Womersley) flow may be made without penalty. Thus, given a choice between measuring three components of inlet velocity or a greater geometric extent, we recommend effort be given to more accurate and detailed geometric reconstructions, as being of primary influence on physiologically significant indicators.

Blood Flow Velocity↗

PubMed2004

The US EPA reference dose for methylmercury: sources of uncertainty.

The US Environmental Protection Agency (EPA) derived a reference dose for methylmercury in 2001, based on an extensive analysis by the National Research Council (NRC) of the National Academy of Sciences. The NRC performed benchmark dose analysis on a number of endpoints from three longitudinal prospective studies: the Seychelles Islands, the Faroe Islands, and the New Zealand studies. Adverse effects were reported in the latter two studies, but not in the Seychelles study. The NRC also performed an integrative analysis of all three studies. Dose conversion from cord blood or maternal hair mercury concentration was performed by EPA using a one-compartment pharmacokinetic model. A total uncertainty factor of 10 was applied for intrahuman pharmacokinetic and pharmacodynamic variability. There are numerous decisions made by the NRC/EPA that could greatly affect the value of the reference dose (RfD). Some of these include the choice of a linear model for the relationship between mercury body burden and neuropsychological performance, the choice of values of P0 and the benchmark response, the use of the "critical study/critical endpoint" approach in the interpretation of the maternal body burden that corresponds to the RfD, the use of central tendencies in a one-compartment pharmacokinetic model rather than the inclusion of the distributions of variables for the population of reproductive-age women, the assumption of unity for the ratio of fetal cord blood to maternal blood methylmercury concentrations, the choice of a total of 10 as an uncertainty factor, and the lack of dose-response analysis for other health effects such as cardiovascular disease. In addition, it may be argued that derivation of a RfD for methylmercury is inappropriate, given that there does not appear to be a threshold for adverse neuropsychological effects based on available data.

Adult↗

PubMed2002

A Bayesian analysis of a proportion under non-ignorable non-response.

The National Health Interview Survey (NHIS) is one of the surveys used to assess one aspect of the health status of the U.S. population. One indicator of the nation's health is the total number of doctor visits made by the household members in the past year. We study the binary variable of at least one doctor visit versus no doctor visit by all household members to each of the 50 states and the District of Columbia. The proportion of households with at least one doctor visit is an indicator of the status of health of the U.S. population. There is a substantial number of non-respondents among the sampled households. The main issue we address here is that the non-response mechanism should not be ignored because respondents and non-respondents differ. The purpose of this work is to estimate the proportion of households with at least one doctor visit, and to investigate what adjustment needs to be made for non-ignorable non-response. We consider a non-ignorable non-response model that expresses uncertainty about ignorability through the ratio of odds of a household doctor visit among respondents to the odds of doctor visit among all households, and this ratio varies from state to state. We use a hierarchical Bayesian selection model to accommodate this non-response mechanism. Because of the weak identifiability of the parameters, it is necessary to 'borrow strength' across states as in small area estimation. We also perform a simulation study to compare the expansion model with an alternative expansion model, an ignorable model and a non-ignorable model. Inference for the probability of a doctor visit is generally similar across the models. Our main result is that for some of the states the non-response mechanism can be considered non-ignorable, and that 95 per cent credible intervals of the probability for a household doctor visit and the probability that a household responds shed important light on the NHIS data.

Bayes Theorem↗

PubMed1994

Propagation of variance uncertainty calculation for an autopsy tissue analysis.

An assay value is almost useless unless it is accompanied by a measure of the uncertainty associated with that value. The uncertainty value should reflect all the major sources of variation and bias affecting the assay and should provide a specified level of confidence (for example, 95%). An approach to uncertainty calculation that includes the uncertainty due to instrument calibration, values of the standards, and intermediate measurements as well as counting statistics is presented and applied to the analysis of an autopsy tissue. This approach, usually called propagation of variance, attempts to clearly distinguish between errors that have systematic (bias) effects and those that have random effects on the assays. The effects of these different types of errors are then propagated to the assay using formal statistical techniques. The result is an uncertainty on the assay that has a defensible level of confidence and which can be traced to individual major contributors. However, since only measurement steps are readily quantified and since all models are approximations, it is emphasized that without empirical verification, a propagation of uncertainty model may be just a fancy model with no connection to reality.

Autopsy↗

PubMed2002

Decision analytical economic modelling within a Bayesian framework: application to prophylactic antibiotics use for caesarean section.

Economic evaluation of health care interventions based on decision analytic modelling can generate valuable information for health policy decision makers. However, the usefulness of the results obtained depends on the quality of the data input into the model; that is, the accuracy of the estimates for the costs, effectiveness, and transition probabilities between the different health states of the model. The aim of this paper is to review the use of Bayesian decision models in economic evaluation and to demonstrate how the individual components required for decision analytical modelling (i.e., systematic review incorporating meta-analyses, estimation of transition probabilities, evaluation of the model, and sensitivity analysis) may be addressed simultaneously in one coherent Bayesian model evaluated using Markov Chain Monte Carlo simulation implemented in the specialist Bayesian statistics software WinBUGS. To illustrate the method described, a simple probabilistic decision model is developed to evaluate the cost implications of using prophylactic antibiotics in caesarean section to reduce the incidence of wound infection. The advantages of using the Bayesian statistical approach outlined compared to the conventional classical approaches to decision analysis include the ability to: (i) perform all necessary analyses, including all intermediate analyses (e.g., meta-analyses) required to derive model parameters, in a single coherent model; (ii) incorporate expert opinion either directly or regarding the relative credibility of different data sources; (iii) use the actual posterior distributions for parameters of interest (opposed to making distributional assumptions necessary for the classical formulation); and (iv) incorporate uncertainty for all model parameters.

Antibiotic Prophylaxis↗

PubMed2003

A basin-specific aquatic food web biomagnification model for estimation of mercury target levels.

In the Willamette River Basin (WRB, Oregon, USA), health advisories currently limit consumption of fish that have accumulated methylmercury (MeHg) to levels posing a potential health risk for humans. Under the Clean Water Act, these advisories create the requirement for a total maximum daily load (TMDL) for mercury in the WRB. A TMDL is a calculation of the maximum amount of a pollutant that a body of water can receive and still meet water-quality standards. Because MeHg is known to biomagnify in aquatic food webs, a basin-specific biomagnification factor can be used, given a protective fish tissue criterion, to estimate total mercury concentrations in surface waters required to lower advisory mercury concentrations currently in fish in the WRB. This paper presents an aquatic food web biomagnification model that simulates inorganic mercury (Hg(II)) and MeHg accumulation in fish tissue and estimates WRB-specific biomagnification factors for resident fish species of concern to stakeholders. Probabilistic (two-dimensional Monte Carlo) techniques propagate parameter variability and uncertainty throughout the model, providing decision makers with credible range information and increased flexibility in establishing a specific mercury target level. The model predicts the probability of tissue mercury concentrations in eight fish species within the range of concentrations measured in these species over 20 years of water-quality monitoring. Estimated mean biomagnification factor values range from 1.12 x 10(6) to 7.66 x 10(6) and are within the range of U.S. Environmental Protection Agency national values. Several WRB-specific mercury target levels are generated, which very by their probability of affording human health protection relative to the federal MeHg tissue criterion of 0.30 mg/kg. Establishing a specific numeric target level is, however, a public policy decision, and one that will require further discussions among WRB stakeholders.

Animals↗

PubMed2002

Modeling assessment of air emission flux of mercury from soils in terrestrial landscape components: model tests and sensitivities.

The abilities of a screening-level model to predict variations in elemental mercury (Hg0) air emissions from soils in terrestrial landscapes are examined by comparing simulation results to published observational data and by performing sensitivity analyses. Despite uncertainties and simplifications, the model results obtained offer some degree of confidence in the model's joint ability to relate readily available environmental parameters to airborne emissions of Hg predicted by coupling simple atmospheric and soil parameters with Hg cycling and transport algorithms. The model reasonably predicted the observational data in the considered data sets except for one site for which significant uncertainty was associated with model input data. Predictions are consistent with many trends observed in the field studies; better predictions were obtained for nonvegetated systems (relative errors between 0.4 and 9.7%) than for shaded-soil landscapes (relative errors between 2.3 and 27%). The model reflected field data showing that daily average emission rates of Hg0, formed by the reduction of Hg(II), are primarily controlled by changes in solar radiation, soil moisture, temperature, and, to a lesser extent, wind conditions. The model may have potential use in several preliminary studies to characterize trends of airborne Hg emitted from terrestrial sources to the atmosphere.

Air Pollutants↗

PubMed2001

Uncertainty in particulate deposition for 1 microm AMAD particles in an adult lung model.

The ICRP 66 lung model may be used to determine dose estimates for members of the public via the inhalation pathway. A significant source of uncertainty in internal dosimetric modelling is due to particulate deposition in regions of the respiratory tract. Uncertainties in estimates of particulate deposition are present because model input parameters have their own inherent variability. These sources of uncertainty need to be examined in an effort to understand better model processes and to estimate better the doses received by individuals exposed through the inhalation pathway. An improved understanding of the uncertainty in particulate deposition will further guide research efforts and improve our ability to quantify internal dose estimates. The ICRP 66 lung deposition model is most sensitive to breathing rate when 1 microm AMAD particles are inhaled by members of the public. Uncertainties in deposition fractions are shown to span an order of magnitude with their distributions varying by gender for a particular lung region. The largest fractional deposition occurs in the deep lung alveolar and extrathoracic regions.

Administration, Inhalation↗

PubMed2006

A probabilistic framework for non-cancer risk assessment.

Risk assessment involves an analysis of the relationship between exposure and health related outcomes to derive an allowable exposure level or to estimate a low-dose risk. Acceptable levels of human exposure for non-cancer effects generally are derived by dividing an experimental no-observed-adverse-effect-level or a lower confidence limit benchmark dose by a product of several uncertainty factors. This paper presents a hierarchical modeling framework for a probabilistic approach to non-cancer risk assessment. The hierarchical model integrates the distributions of uncertainty factors and the distribution of the actual exposure level to construct the dose-response model for the proportion of population at risk and the dose-response model for the expected proportion of population at risk for a given exposure distribution. The proposed approach is based on the use of the BMDL (lower confidence limit on the benchmark dose) as a POD (point of departure) for risk assessment of non-cancer effects.

Animals↗

PubMed2005

Human exposure and health risk of alpha-, beta-, gamma- and delta-hexachlorocyclohexane (HCHs) in Tianjin, China.

The dynamic exposures to HCHs of individuals born between the years 1913 and 1993 in Tianjin have been simulated by connecting a fugacity model (IV) with a multimedia exposure model. Ingestion is the most important pathway for human beings to take up HCHs, and concentrations in the human body correlate with body weight changes. Accumulations of HCHs were derived assuming that the degradation in human body behaved linearly. The health risk of exposure to HCHs was measured using cancer risk and loss of life expectancy (LLE), and LLE was modified from its original definition to incorporate a dynamic calculation that takes variances in exposure into account. Monte-Carlo simulations were run to analyze the uncertainties of the model.

Age Factors↗

PubMed2001

Uncertainty, variability and sensitivity analysis applied to the RAGENA model of radon generation, entry and accumulation indoors.

The application of a radon model is useful to understand the processes that drive the radon gas behaviour from its sources to its accumulation indoors. Since in a given inhabited house the detailed knowledge of the values of all the parameters that affect indoor radon levels is not available, the response of the model has to be explored in a reference site in which all the parameters are supposed to be known. We call this site the reference configuration. In this paper we report on the procedure followed to carry out uncertainty, sensitivity and variability analysis of the model response for a reference configuration that corresponds to a single family multi-zone house. We have obtained from the uncertainty analysis that, assuming a normal distribution of all the input parameters with a 10% relative standard deviation (R.S.D.), the model outputs present a R.S.D. in the range 17-22%. The sensitivity analysis reflects, in general, a good behaviour of the model, in the sense that its response describes a realistic behaviour of the system. The variability analysis has shown that the model is applicable to a wide range of situations, and that the most relevant parameters for the reference configuration are: the soil gas-permeability (obtained from the mean soil grain diameter); the ventilation rate of the rooms; the air-exchange rate between the basement and room 2; the soil-indoor pressure difference; the open area; and the concrete radium content.

Journal Article↗

PubMed2003

Risk coefficients for childhood cancer after intrauterine irradiation: a review.

PURPOSE: To review the estimates of the risk of childhood cancer per unit dose of radiation received in utero derived from the largest case-control study of obstetric X-ray examinations and to compare them with the childhood cancer risk coefficients obtained from the cohorts of Japanese atomic bomb survivors irradiated either in utero or as young children. MATERIALS AND METHODS: Data from the Oxford Survey of Childhood Cancers (OSCC) case-control study of foetal exposure to diagnostic X-rays and from the cohort studies of the Japanese survivors of the atomic bombings of Hiroshima and Nagasaki were used, together with associated dose estimates. Excess relative risk and excess absolute risk coefficients were compared, fully taking into consideration the various sources of uncertainty. RESULTS: The excess relative risk coefficient for childhood (< 15 years of age) cancer obtained from the OSCC was around 50 Gy(-1), leading to an excess absolute risk coefficient for incident cases of about 8% Gy(-1). However, the statistical, dosimetry, modelling and other uncertainties associated with these risk estimates are appreciable, and there is reason to believe that these coefficients could be systematic overestimates. When these uncertainties and those associated with the equivalent risk coefficients derived from the Japanese cohort exposed in utero are taken into account, the risk estimates for childhood cancer obtained from these two sources are compatible. These coefficients are consistent with the high relative risk of childhood leukaemia among the Japanese survivors exposed as children. The absence of cases of childhood solid tumours among the Japanese children irradiated after birth in contrast to the significant excesses found in both intrauterine exposure studies might be explained by the cells from which these cancers originate being predominantly sensitive only to exposure in utero. CONCLUSIONS: The consistency of the childhood cancer risk coefficients derived from the Oxford Survey and from the Japanese cohort irradiated in utero supports a causal explanation of the association between childhood cancer and an antenatal X-ray examination found in case-control studies. This implies that doses to the foetus in utero of the order of 10 mSv discernibly increase the risk of childhood cancer. However, uncertainties in risk estimates are such that it is difficult to conclude reliably from these epidemiological data what the level of risk at these low doses might be, beyond the inference that the risk is not zero or has been grossly underestimated.

Adolescent↗

PubMed1998

Cost-effectiveness of tissue plasminogen activator for acute ischemic stroke. NINDS rt-PA Stroke Study Group.

Tissue plasminogen activator (tPA) has been shown to improve 3-month outcome in stroke patients treated within 3 hours of symptom onset. The costs associated with this new treatment will be a factor in determining the extent of its utilization. Data from the NINDS rt-PA Stroke Trial and the medical literature were used to estimate the health and economic outcomes associated with using tPA in acute stroke patients. A Markov model was developed to estimate the costs per 1,000 patients eligible for treatment with tPA compared with the costs per 1,000 untreated patients. One-way and multiway sensitivity analyses (using Monte Carlo simulation) were performed to estimate the overall uncertainty of the model results. In the NINDS rt-PA Stroke Trial, the average length of stay was significantly shorter in tPA-treated patients than in placebo-treated patients (10.9 versus 12.4 days; p = 0.02) and more tPA patients were discharged to home than to inpatient rehabilitation or a nursing home (48% versus 36%; p = 0.002). The Markov model estimated an increase in hospitalization costs of $1.7 million and a decrease in rehabilitation costs of $1.4 million and nursing home cost of $4.8 million per 1,000 eligible treated patients for a health care system that includes acute through long-term care facilities. Multiway sensitivity analysis revealed a greater than 90% probability of cost savings. The estimated impact on long-term health outcomes was 564 (3 to 850) quality-adjusted life-years saved over 30 years of the model per 1,000 patients. Treating acute ischemic stroke patients with tPA within 3 hours of symptom onset improves functional outcome at 3 months and is likely to result in a net cost savings to the health care system.

Acute Disease↗

PubMed2000

Active control of lateral balance in human walking.

We measured variability of foot placement during gait to test whether lateral balance must be actively controlled against dynamic instability. The hypothesis was developed using a simple dynamical model that can walk down a slight incline with a periodic gait resembling that of humans. This gait is entirely passive except that it requires active control for a single unstable mode, confined mainly to lateral motion. An especially efficient means of controlling this instability is to adjust lateral foot placement. We hypothesized that similar active feedback control is performed by humans, with fore-aft dynamics stabilized either passively or by very low-level control. The model predicts that uncertainty within the active feedback loop should result in variability in foot placement that is larger laterally than fore-aft. In addition, loss of sensory information such as by closing the eyes should result in larger increases in lateral variability. The control model also predicts a slight coupling between step width and length. We tested 15 young normal human subjects and found that lateral variability was 79% larger than fore-aft variability with eyes open, and a larger increase in lateral variability (53% vs. 21%) with eyes closed, consistent with the model's predictions. We also found that the coupling between lateral and fore-aft foot placements was consistent with a value of 0.13 predicted by the control model. Our results imply that humans may harness passive dynamic properties of the limbs in the sagittal plane, but must provide significant active control in order to stabilize lateral motion.

Biomechanical Phenomena↗