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An analysis of the uncertainties in estimates of radon-induced lung cancer.

A recent report by the National Academy of Sciences estimates that the radiation dose to the bronchial epithelium, per working level month (WLM) of radon daughter exposure, is about 30% lower for residential exposures than for exposures received in underground mines. Adjusting the previously published BEIR IV radon risk model accordingly, the unit risk for indoor exposures of the general population is about 2.2 x 10(-4) lung cancer deaths (lcd)/WLM. Using results from EPA's National Residential Radon Survey, the average radon level is estimated to be about 1.25 pCi/L, and the annual average exposure about 0.242 WLM. Based on these estimates, 13,600 radon-induced lcd/yr are projected for the United States. A quantitative uncertainty analysis was performed, which considers: statistical uncertainties in the epidemiological studies of radon-exposed miners; the dependence of risk on age at, and time since, exposure; the extrapolation of risk estimates from mines to homes based on comparative dosimetry; and uncertainties in the radon daughter levels in homes and in the average residential occupancy. Based on this assessment of the uncertainties in the unit risk and exposure estimates, an uncertainty range of 7000-30000 lcd/yr is derived.

Adult↗

Uncertainty and variation in indirect exposure assessments: an analysis of exposure to tetrachlorodibenzo-p-dioxin from a beef consumption pathway.

Indirect exposures to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other toxic materials released in incinerator emissions have been identified as a significant concern for human health. As a result, regulatory agencies and researchers have developed specific approaches for evaluating exposures from indirect pathways. This paper presents a quantitative assessment of the effect of uncertainty and variation in exposure parameters on the resulting estimates of TCDD dose rates received by individuals indirectly exposed to incinerator emissions through the consumption of home-grown beef. The assessment uses a nested Monte Carlo model that separately characterizes uncertainty and variation in dose rate estimates. Uncertainty resulting from limited data on the fate and transport of TCDD are evaluated, and variations in estimated dose rates in the exposed population that result from location-specific parameters and individuals' behaviors are characterized. The analysis indicates that lifetime average daily dose rates for individuals living within 10 km of a hypothetical incinerator range over three orders of magnitude. In contrast, the uncertainty in the dose rate distribution appears to vary by less than one order of magnitude, based on the sources of uncertainty included in this analysis. Current guidance for predicting exposures from indirect exposure pathways was found to overestimate the intakes for typical and high-end individuals.

Air Pollutants↗

Assessment and intervention for certainty and uncertainty.

Research suggests that high degrees of uncertainty and absolute certainty can be very stressful for nursing's clients. Yet, research also suggests that a moderate degree of unexpectedness, unpredictability, and uncertainty may actually produce positive effects--pleasure, hope, information pattern search, and a sense of well-being. The author discusses the research related to psychological certainty and uncertainty, provides suggestions for assessing clients' degree of certainty and uncertainty, and delineates interventions for dealing with detrimental levels of certainty and uncertainty. Precautions for instituting interventions are also stressed.

Adaptation, Psychological↗

Uncertainty in the relation between exposure to magnetic fields and brain cancer due to assessment and assignment of exposure and analytical methods in dose-response modeling.

Incomplete scientific knowledge ensures that, in every study, uncertainty will enter the processes of exposure estimation and exposure-response modeling. In the light of the heated debate about the health effects of magnetic fields resulting from power production and usage, we undertook a sensitivity analysis to evaluate uncertainty related to key decisions in a previous study of brain cancer and occupational exposure to magnetic fields. The findings appeared to be relatively insensitive to most variations in the methods of exposure assessment, exposure assignment, and data analysis. The results can be visualized by defining bands of uncertainty about a best-bet estimate of the association based on our original study. These bands of methodological uncertainties were similar in magnitude to the conventional 95% confidence interval, but they provide a measure of the potential range of systematic bias in the results, rather than reflecting statistical variability alone. The methodology employed here can be applied to other studies, and other researchers are encouraged to conduct sensitivity analysis in order to estimate methodological uncertainty as an alternative to statistical confidence intervals.

Adult↗

Sources of uncertainty in dose-response modeling of epidemiological data for cancer risk assessment.

Epidemiologic data is increasingly being used for dose-response analysis in risk assessment. The Environmental Protection Agency (EPA) and other U.S. agencies have expressed a preference for using epidemiologic data rather than toxicologic data when possible. However, there are a number of important sources of uncertainty in using epidemiologic data for this purpose that need to be clearly recognized and, when possible, quantified. This paper presents a critical review of the major sources of uncertainty in the use of epidemiologic data for cancer risk assessment. These may include: (1) study design issues such as potential confounding and other biases, inadequate sample size, and followup, (2) the choice of the data set, (3) specification of the dose-response model, (4) estimation of exposure and dose, and (5) unrecognized variability in susceptibility. Examples from risk assessments for cadmium, asbestos, and diesel exhaust are used to illustrate the potential magnitude of some of these sources of uncertainty. It is shown that the overall uncertainty from these various sources combined may often result in highly uncertain risk estimates from dose-response modeling of epidemiologic data. For this reason, we believe it is best to present a range of possible risk estimates, which, to the extent possible, reflects the variability and uncertainty inherent in the dose-response evaluation of epidemiologic data.

Asbestos↗

Evaluation of mechanical precision and alignment uncertainties for an integrated CT/LINAC system.

A new integrated CT/LINAC combination, in which the CT scanner is inside the radiation therapy treatment room and the same patient couch is used for CT scanning and treatment (after a 180-degree couch rotation), should allow for accurate correction of interfractional setup errors. The purpose of this study was to evaluate the sources of uncertainties, and to measure the overall precision of this system. The following sources of uncertainty were identified: (1) the patient couch position on the LINAC side after a rotation, (2) the patient couch position on the CT side after a rotation, (3) the patient couch position as indicated by its digital readout, (4) the difference in couch sag between the CT and LINAC positions, (5) the precision of the CT coordinates, (6) the identification of fiducial markers from CT images, (7) the alignment of contours with structures in the CT images, and (8) the alignment with setup lasers. The largest single uncertainties (one standard deviation or 1 SD) were found in couch position on the CT side after a rotation (0.5 mm in the RL direction) and the alignment of contours with the CT images (0.4 mm in the SI direction). All other sources of uncertainty are less than 0.3 mm (1 SD). The overall precision of two setup protocols was investigated in a controlled phantom study. A protocol that relies heavily on the mechanical integrity of the system, and assumes a fixed relationship between the LINAC isocenter and the CT images, gave a predicted precision (1 SD) of 0.6, 0.7, and 0.6 mm in the SI, RL and AP directions, respectively. The second protocol reduces reliance on the mechanical precision of the total system, particularly the patient couch, by using radio-opaque fiducial markers to transfer the isocenter information from the LINAC side to the CT images. This protocol gave a slightly improved predicted precision of 0.5, 0.4, and 0.4 mm in the SI, RL and AP directions, respectively. The distribution of phantom position after CT-based correction confirmed these results. Knowledge of the individual sources of uncertainty will allow alternative setup protocols to be evaluated in the future without the need for significant additional measurements.

Artifacts↗

EUD-based margin selection in the presence of set-up uncertainties.

To assess the impact of geometric uncertainties on treatment plan design, we have performed a numerical simulation in which both systematic and random errors were included. A clinical target volume (CTV) with an abutting organ at risk (OAR), both of 50 mm diameter, in a cubic phantom was modeled. A four-field conformal treatment plan was designed in which one pair of parallel-opposed beams traversed the OAR and CTV while the other pair intersected the CTV only. Field size, prescribed (isocenter) dose and systematic set-up uncertainty were varied in two orthogonal directions to examine their impact on the outcome as predicted by the dose volume histogram (DVH) and the phenomenological form of equivalent uniform dose (EUD). Of the systematic uncertainty levels considered (0, 2, 4, and 6 mm standard deviations of a Gaussian distribution), 10 mm margin (CTV-PTV) was adequate to maintain the integrity of the dose distribution within the CTV. However, reducing the margin (and hence field size) without reducing set-up errors required an increase in the isocenter dose to compensate for the loss in EUD. It was found that, in the direction containing both the CTV and OAR, with random and systematic uncertainties of 2 and 4 mm respectively, increasing the isocenter dose by about 3.5 Gy on a 6 mm-margin plan resulted in the statistically equivalent EUD value to that with a 10 mm-margin for the CTV, while the OAR EUD is dropped by 1 Gy. In general, though, the directional sensitivity to geometric uncertainties, and hence the required margin size in different directions, was dependent on beam geometries and the relative positions of the structures under consideration relative to the beam directions. Based on the validity of the EUD concept, our general conclusion is that modest dose escalation may result in plans that better achieve clinical objectives. Also, a simple single number plan quality index such as EUD5%, discussed in the paper, facilitates meaningful statistical comparisons between competing treatment strategies.

Computer Simulation↗

Inverse plan optimization accounting for random geometric uncertainties with a multiple instance geometry approximation (MIGA).

Radiotherapy treatment plans that are optimized to be highly conformal based on a static patient geometry can be degraded by setup errors and/or intratreatment motion, particularly for IMRT plans. To achieve improved plans in the face of geometrical uncertainties, direct simulation of multiple instances of the patient anatomy (to account for setup and/or motion uncertainties) is used within the inverse planning process. This multiple instance geometry approximation (MIGA) method uses two or more instances of the patient anatomy and optimizes a single beam arrangement for all instances concurrently. Each anatomical instance can represent expected extremes or a weighted distribution of geometries. The current implementation supports mapping between instances that include distortions, but this report is limited to the use of rigid body translations/ rotations. For inverse planning, the method uses beamlet dose calculations for each instance, with the resulting doses combined using a weighted sum of the results for the multiple instances. Beamlet intensities are then optimized using the inverse planning system based on the cost for the composite dose distribution. MIGA can simulate various types of geometrical uncertainties, including random setup error and intratreatment motion. A limited number of instances are necessary to simulate Gaussian-distributed errors. IMRT plans optimized using MIGA show significantly less degradation in the face of geometrical errors, and are robust to the expected (simulated) motions. Results for a complex head/neck plan involving multiple target volumes and numerous normal structures are significantly improved when the MIGA method of inverse planning is used. Inverse planning using MIGA can lead to significant improvements over the use of simple PTV volume expansions for inclusion of geometrical uncertainties into inverse planning, since it can account for the correlated motions of the entire anatomical representation. The optimized plan results reflect the differing patient geometry situations which can be important near the surface or heterogeneities. For certain clinical situations, the MIGA optimization approach can correct for a significant part of the degradation of the plan caused by the setup uncertainties.

Artifacts↗

Uncertainty analysis of absorbed dose calculations from thermoluminescence dosimeters.

Thermoluminescence dosimeters (TLD) are widely used to verify absorbed doses delivered from radiation therapy beams. Specifically, they are used by the Radiological Physics Center for mailed dosimetry for verification of therapy machine output. The effects of the random experimental uncertainties of various factors on dose calculations from TLD signals are examined, including: fading, dose response nonlinearity, and energy response corrections; reproducibility of TL signal measurements and TLD reader calibration. Individual uncertainties are combined to estimate the total uncertainty due to random fluctuations. The Radiological Physics Center's (RPC) mail out TLD system, utilizing throwaway LiF powder to monitor high-energy photon and electron beam outputs, is analyzed in detail. The technique may also be applicable to other TLD systems. It is shown that statements of +/- 2% dose uncertainty and +/- 5% action criterion for TLD dosimetry are reasonable when related to uncertainties in the dose calculations, provided the standard deviation (s.d.) of TL readings is 1.5% or better.

Humans↗

Effects of environmental uncertainties on sonar detection performance prediction.

The development of effective passive sonar systems depends upon the ability to accurately predict the performance of sonar detection algorithms in realistic ocean environments. Such environments are typically characterized by a high degree of uncertainty, thus limiting the usefulness of performance prediction approaches that assume a deterministic environment. Here we derive closed-form receiver operating characteristic (ROC) expressions for an optimal Bayesian detector and for several typical suboptimal detectors, based on a statistical model of environmental uncertainty. Various scenarios extended from an NRL benchmark shallow-water model were used to check the analytical ROC expressions and to illustrate the effect of environmental uncertainty on detection performance. The results showed that (1) optimal detection performance in an uncertain environment in diffuse noise depends primarily on the signal-to-noise ratio at the receivers and the rank of the signal matrix, where the rank is an effective representation of the scale of environmental uncertainty; (2) the ROC expression for the optimal Bayesian detector provides a more realistic performance upper bound than that obtained from conventional sonar equations that do not incorporate environmental uncertainty; and (3) detection performance predictions can be performed much faster than with commonly used numerical methods such as Monte Carlo performance evaluations.

Journal Article↗

Signal and masker uncertainty in intensity discrimination.

Intensity discrimination thresholds were assessed in a series of experiments. Signals were in-phase increments in the level of one component of a multitone masker. The main parameters of interest were the effects of signal uncertainty (which frequency is tested on a given trial) and masker uncertainty (which components were selected as the multitone masker on a given trial). Thresholds were measured as a function of signal frequency, number of components, and amount of overall changes in masker level. The results suggest a form of profile processing, in which the signal is detected by comparing levels in adjacent critical bands. Such a mechanism will account for the relatively small effects generally observed with signal uncertainty, for masker uncertainty showing larger effects on thresholds than signal uncertainty, and for the near constancy of signal threshold despite large (60 dB) fluctuations in overall level of the stimulus in the two intervals of the forced-choice trial.

Acoustic Stimulation↗

Statistical uncertainty in estimates of an effective scatterer number density for ultrasound.

In a previous paper [J. Acoust. Soc. Am. 95, 77-85 (1994)], a method for determining an effective scatterer number density in ultrasonography was presented. This is the actual number density multiplied by a frequency-dependent factor that depends on the differential scattering cross sections of all scatterers. This method involves evaluating the ratio of the fourth moment to the square of the second moment of echo signals scattered from the sample. The random processes involved in forming these echo signals give rise to an uncertainty in the estimated effective scatterer number density. This uncertainty is evaluated here using error propagation. The statistical uncertainty depends on the effective number of scatterers contributing to the segmented echo signal; it increases when the effective number of scatterers increases. Tests of the statistical uncertainty estimator were in good agreement with uncertainties computed from experimental data.

Models, Theoretical↗

Climate change. Uncertainty and climate change assessments.

Clear and quantitative discussion of uncertainties is critical for public policy making on climate change. The recently completed report of the Intergovernmental Panel on Climate Change assessed the uncertainty in its findings and forecasts. The uncertainty assessment process of the IPCC should be improved in the future by using a consistent approach to quantifying uncertainty, focusing the quantification on the few key results most important for policy making. The uncertainty quantification procedure should be fully documented, and if expert judgment is used, a specific list of the experts consulted should be included.

Journal Article↗

Sensitivity analysis of respiratory parameter uncertainties: impact of criterion function form and constraints.

A sensitivity analysis based on weighted least-squares regression is presented to evaluate alternative methods for fitting lumped-parameter models to respiratory impedance data. The goal is to maintain parameter accuracy simultaneously with practical experiment design. The analysis focuses on predicting parameter uncertainties using a linearized approximation for joint confidence regions. Applications are with four-element parallel and viscoelastic models for 0.125- to 4-Hz data and a six-element model with separate tissue and airway properties for input and transfer impedance data from 2-64 Hz. The criterion function form was evaluated by comparing parameter uncertainties when data are fit as magnitude and phase, dynamic resistance and compliance, or real and imaginary parts of input impedance. The proper choice of weighting can make all three criterion variables comparable. For the six-element model, parameter uncertainties were predicted when both input impedance and transfer impedance are acquired and fit simultaneously. A fit to both data sets from 4 to 64 Hz could reduce parameter estimate uncertainties considerably from those achievable by fitting either alone. For the four-element models, use of an independent, but noisy, measure of static compliance was assessed as a constraint on model parameters. This may allow acceptable parameter uncertainties for a minimum frequency of 0.275-0.375 Hz rather than 0.125 Hz. This reduces data acquisition requirements from a 16- to a 5.33- to 8-s breath holding period. These results are approximations, and the impact of using the linearized approximation for the confidence regions is discussed.

Airway Resistance↗

A measure of perceived environmental uncertainty in hospitals.

The purpose of this study is to evaluate the preliminary psychometric properties of the Perceived Environmental Uncertainty Questionnaire (PEUQ). Environmental uncertainty (EU) refers to times when within the organization unanticipated events and problems occur with frequency and cannot be predicted by members of the organization due to a lack of critical information. The PEUQ was designed as a measure of EU and was tested with 375 patient-care and nonpatient-care hospital employees. Internal consistency as measured by Cronbach's alpha was .81. Confirmatory factor analysis supported two of the PEUQ's hypothesized three factors: state and effect EU. These two factors accounted for 61.1% of the variance in subjects' level of uncertainty. Factor analysis failed to confirm response uncertainty as a subconstruct of EU. Contrasted group analysis found expected differences in the level of perceived EU between workers on different hospital units (t = -5.02, p < .001). This study provides evidence of the PEUQ's beginning reliability and validity as a measure of EU. Failure to identify response uncertainty as a salient subconstruct of EU warrants further exploration. The design of nursing care delivery structures (NCDS) to minimize EU first requires a means to measure hospital units' EU. The establishment of the PEUQ's psychometric soundness is antecedent to measuring EU and improving the efficacy of our NCDS.

Attitude of Health Personnel↗

An international comparison of physicians' judgments of outcome rates of cardiac procedures and attitudes toward risk, uncertainty, justifiability, and regret.

OBJECTIVE: Compare U.K. and U.S. physicians' judgments of population probabilities of important outcomes of invasive cardiac procedures; and values held by them about risk, uncertainty, regret, and justifiability relevant to utilization of cardiac treatments. DESIGN: Cross-sectional study. SETTING: University hospital and VA medical center in the United States; two teaching hospitals in the United Kingdom. PARTICIPANTS: 171 housestaff and attendings at U.S. teaching hospitals; 51 physician trainees and consultants at U.K. hospitals. MEASURES: Judgments of probabilities of severe complications and deaths due to Swan-Ganz catheterization, cardiac catheterization, percutaneous transluminal coronary angioplasty (PTCA), and coronary artery bypass grafting (CABG); judgments of malpractice risks for case vignettes; Nightingale's risk-aversion instrument; Gerrity's reaction-to-uncertainty instrument; questions about need to justify decisions; responses to case vignettes regarding regret. RESULTS: The U.S. physicians judged rates of two bad outcomes of cardiac procedures (complications due to cardiac catheterization; death due to CABG) to be significantly higher (p < or = 0.01) than did the U.K. physicians (U.S. medians, 5 and 3.5, respectively; U.K. medians 3 and 2). The median ratio of (risk of malpractice suit I error of omission)/(risk of suit I error of commission) judged by U.K. physicians, 3, was significantly (p=0.0006) higher than that judged by U.S. physicians, 1.5. The U.K. physicians were less often risk-seeking in the context of possible losses than the U.S. physicians (odds ratio for practicing in the U.K. as a predictor of risk seeking 0.3, p=0.003). The U.K. physicians had significantly more discomfort with uncertainty than did the U.S. physicians, as reflected by higher scores on the stress scale (U.K. median 48, U.S. 42, p=0.0001) and the reluctance-to-disclose-uncertainty scale (U.K. 40, U.S. 37, p < 0.0001) of the Gerrity instrument. There was no clear international difference in perceived need to justify decisions, or in regret. CONCLUSIONS: The results were not clearly consistent with the uncertainty hypothesis that international practice variation is due to differences in judged rates of outcomes of therapy or with the imperfect-agency hypothesis that practice variation is due to differences in physicians' personal values. The causes and implications of practice variations remain unclear.

Angioplasty, Balloon, Coronary↗

Depression during exacerbations in multiple sclerosis: the importance of uncertainty.

The following correlates of depression were examined in a sample of 166 patients with clinically definite relapsing-remitting (n=140) or secondary progressive (n=26) multiple sclerosis: (a) the present state of the patients' illness (i.e., whether or not they were currently experiencing an exacerbation of their symptoms); (b) their level of uncertainty concerning their illness; and (c) their strategies for coping with their illness. A current exacerbation in symptoms, greater uncertainty of illness, and greater use of emotion-centered forms of coping were all related to depression. Multivariate analyses revealed that uncertainty of illness played a pivotal role as a mediating variable. Exacerbations in illness appeared to heighten patients' levels of uncertainty, and it was largely through this heightened uncertainty that the increases in depression came about.

Adaptation, Psychological↗

The many meanings of uncertainty in illness: toward a systematic accounting.

Uncertainty is widely believed to be a central feature in illness experiences. Moreover, communication is thought to be essential to the construction, management, and resolution of uncertainty. Not surprisingly, however, there are substantial variations in conceptions and analyses of this focal construct and its relation to communication. In this article, we first argue that understandings of the role of communication in health and illness can be improved substantially--thereby enhancing both theory development and practical applications of health communication theory--by recognizing and reconciling sources of variation in conceptions of uncertainty and by synthesizing various specific conceptions. We then review individual-psychological models. linguistic and discourse analyses, and sociocultural and historical perspectives on uncertainty in illness Following the review, we present a framework that synthesizes many conceptions of uncertainty We close with a discussion of 5 challenges and opportunities for research and application.

Journal Article↗