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Precaution, uncertainty and causation in environmental decisions.

What measures of uncertainty and what causal analysis can improve the management of potentially severe, irreversible or dreaded environmental outcomes? Environmental choices show that policies intended to be precautionary (such as adding MTBE to petrol) can cause unanticipated harm (by mobilizing benzene, a known leukemogen, in the ground water). Many environmental law principles set the boundaries of what should be done but do not provide an operational construct to answer this question. Those principles, ranging from the precautionary principle to protecting human health from a significant risk of material health impairment, do not explain how to make environmental management choices when incomplete, inconsistent and complex scientific evidence characterizes potentially adverse environmental outcomes. Rather, they pass the task to lower jurisdictions such as agencies or authorities. To achieve the goals of the principle, those who draft it must deal with scientific casual conjectures, partial knowledge and variable data. In this paper we specifically deal with the qualitative and quantitative aspects of the European Union's (EU) explanation of consistency and on the examination of scientific developments relevant to variability and uncertain data and causation. Managing hazards under the precautionary principle requires inductive, empirical methods of assessment. However, acting on a scientific conjecture can also be socially unfair, costly, and detrimental when applied to complex environmental choices. We describe a constructive framework rationally to meet the command of the precautionary principle using alternative measures of uncertainty and recent statistical methods of causal analysis. These measures and methods can bridge the gap between conjectured future irreversible or severe harm and scant scientific evidence, thus leading to more confident and resilient social choices. We review two sets of measures and computational systems to deal with uncertainty and link them to causation through inductive empirical methods such as Bayesian Networks. We conclude that primary legislation concerned with large uncertainties and potential severe or dreaded environmental outcomes can produce accurate and efficient choices. To do so, primary legislation should specifically indicate what measures can represent uncertainty and how to deal with uncertain causation thus providing guidance to an agency's rulemaking or to an authority's writing secondary legislation. A corollary conclusion with legal, scientific and probabilistic implications concerns how to update past information when the state of information increases because a failure to update can result in regretting past choices. Elected legislators have the democratic mandate to formulate precautionary principles and are accountable. To preserve that mandate, imbedding formal methods to represent uncertainty in the statutory language of the precautionary principle enhances subsequent judicial review of legislative actions. The framework that we propose also reduces the Balkanized views and interpretations of probabilities, possibilities, likelihood and uncertainty that exists in environmental decision-making.

Bayes Theorem↗

Uncertainties in model-based outcome predictions for treatment planning.

PURPOSE: Model-based treatment-plan-specific outcome predictions (such as normal tissue complication probability [NTCP] or the relative reduction in salivary function) are typically presented without reference to underlying uncertainties. We provide a method to assess the reliability of treatment-plan-specific dose-volume outcome model predictions. METHODS AND MATERIALS: A practical method is proposed for evaluating model prediction based on the original input data together with bootstrap-based estimates of parameter uncertainties. The general framework is applicable to continuous variable predictions (e.g., prediction of long-term salivary function) and dichotomous variable predictions (e.g., tumor control probability [TCP] or NTCP). Using bootstrap resampling, a histogram of the likelihood of alternative parameter values is generated. For a given patient and treatment plan we generate a histogram of alternative model results by computing the model predicted outcome for each parameter set in the bootstrap list. Residual uncertainty ("noise") is accounted for by adding a random component to the computed outcome values. The residual noise distribution is estimated from the original fit between model predictions and patient data. RESULTS: The method is demonstrated using a continuous-endpoint model to predict long-term salivary function for head-and-neck cancer patients. Histograms represent the probabilities for the level of posttreatment salivary function based on the input clinical data, the salivary function model, and the three-dimensional dose distribution. For some patients there is significant uncertainty in the prediction of xerostomia, whereas for other patients the predictions are expected to be more reliable. In contrast, TCP and NTCP endpoints are dichotomous, and parameter uncertainties should be folded directly into the estimated probabilities, thereby improving the accuracy of the estimates. Using bootstrap parameter estimates, competing treatment plans can be ranked based on the probability that one plan is superior to another. Thus, reliability of plan ranking could also be assessed. CONCLUSIONS: A comprehensive framework for incorporating uncertainties into treatment-plan-specific outcome predictions is described. Uncertainty histograms for continuous variable endpoint models provide a straightforward method for visual review of the reliability of outcome predictions for each treatment plan.

Humans↗

User introduced uncertainties in the measurement of field misalignment by a computer aided technique.

While images acquired using an electronic portal imager may be visually compared to other portal or simulator images to assess patient alignment, a more quantitative comparison is desirable. Computer aided alignment tools are available which are based on user placed landmarks. The purpose of this study was to estimate uncertainties introduced by the user to the final measurement of field misalignment using such a tool. Both intra- and inter-user reproducibility were assessed. To complete this task, a number of image pairs including both phantom and patient images were compared by multiple observers. Results of the comparisons (x- and y- translation and rotation) were tabulated for each image pair and their reproducibility assessed by calculating a mean and standard deviation. User introduced uncertainty was found to be independent of the magnitude of rotation or x- or y- translation. In all cases, there was no difference between intra-observer and inter-observer uncertainty. For clinical cases, there is a significant difference between uncertainty in x- and y-translation due to both image quality and patient anatomy. In addition, the magnitude of uncertainty tracks qualitatively with image quality and number of available anatomical landmarks. The decision to make a correction in field alignment must be made considering these uncertainty estimates. Image comparison must be fully automated to eliminate uncertainties introduced by the user.

Humans↗

Assessment of uncertainty of NO2 measurements by the chemiluminescence method and discussion of the quality objective of the NO2 European Directive.

Hereafter, an assessment of the ability of the chemiluminescence method to measure ambient NO2 with an accuracy within 15%, as requested by the data quality objective of European directive 1999/30/CE, is presented. In general, uncertainty is evaluated using the response to reference materials or by means of inter-comparisons used to determine some statistics like repeatability, reproducibility and calibration bias. These are incomplete approaches and the method of the Guide to the Expression of Uncertainty in Measurement, advised by the Directive, should be preferred. In fact, even if it requires a large data set, it allows the relative influence of all possible sources of uncertainty to be studied. The extent of NO2 uncertainty is mainly dependent on the level of NO. It is decreased by NOx and the correlation between NOx and NO. Furthermore, the uncertainty budget reveals that the contribution of accuracy of calibration standard, linearity, converter efficiency and drift of the analyser between calibration checks to the overall uncertainty is less important than the contribution of interference, mainly humidity and PAN in rural areas. The relative expanded uncertainty of the NO2 hourly average exceeds 30% for NO2 concentrations lower than 40 microg m(-3). Nevertheless, the data quality objective of 15% is reached for 200 microg m(-3), the hourly limit value of the European directive. On the contrary, at the limit value on the annual average, 40 microg m(-3), the data quality objective is not met if NO is higher than 100 microg m(-3). However, the data quality objective could be reached by correcting the measurements with the bias due to interference.

Air Pollutants↗

Pre-analytical factors and measurement uncertainty.

Pre-analytical factors are an important source of variation or errors in clinical laboratory measurements. Based on the new accreditation standards, medical and laboratory professions now seek to develop tools to deal systematically with these diverse factors. Several obvious pre-analytical uncertainty components were estimated in pragmatic experiments and combined with data on analytical variation and literature knowledge on biological variation, to estimate the measurement uncertainty of most common chemical and haematological examinations in clinical laboratories. The main aim was to assess quality specifications for regional laboratory services. The expanded measurement uncertainties (level of confidence 95%) of serum cholesterol, albumin and potassium remained within 13-16%. The major uncertainty component for cholesterol was biological variation, whereas those for albumin and potassium were sample collection and pretreatment. The measurement uncertainties for serum free thyroxin, thyrotropin and C-reactive protein, 20%, 42% and 125% respectively, were largely due to their biological variation. The measurement uncertainties of basic erythrocyte parameters (erythrocyte count and mean corpuscular volume, blood haemoglobin concentration) were less than 10%. Larger measurement uncertainties were obtained for thrombocyte and leukocyte counts, 24 and 31%, respectively, and for the reticulocyte fraction, 41%.

Adult↗

Evaluation of a TG-43 compliant analytical dosimetry model in clinical 192Ir HDR brachytherapy treatment planning and assessment of the significance of source position and catheter reconstruction uncertainties.

A simple, time efficient, analytical model incorporating heterogeneities and body dimensions around a point 192Ir source is generalized for accurate dosimetry around commercially available 192Ir brachytherapy sources. The generalized model was verified in dosimetry of a clinical 192Ir high dose rate prostate monotherapy application, involving 16 catheters and 83 source dwell positions, through comparison with corresponding treatment planning system data. The computational time efficiency and accuracy of the proposed model allowed the assessment of the impact that uncertainties in source dwell positions and catheter reconstruction may have on dose distributions, and how these could potentially affect the clinical outcome. Results revealed that a 0.1 cm catheter reconstruction uncertainty and a 0.15 cm source position uncertainty along the catheter lead to a dose uncertainty of less than 2% for doses lower than 200% of the prescribed dose, reaching up to 5% for points lying in close proximity to the catheters. These uncertainties were found to have no impact (less than 1%) on dose volume histogram results of both the planning target volume and the urethra. A catheter reconstruction uncertainty as high as 0.2 cm results in a dose uncertainty greater than 2%, reaching up to 9%, only for points inside the 150% contour. However, even in this case, the impact on dose volume histogram calculations is less than 3%.

Brachytherapy↗

The effect of Monte Carlo statistical uncertainties on the evaluation of dose distributions in radiation treatment planning.

This paper discusses the effect of statistical uncertainties present in Monte Carlo (MC) calculated dose distributions on the evaluation of a 'cost function' that expresses the suitability of a treatment plan for the intended treatment. The mathematical derivations given are valid for any 'well-behaved' cost function. The validity of the general expressions is demonstrated using numerical examples. It is shown that random dose uncertainties lead to statistical and systematic uncertainties on the cost function. The balance between the two types of uncertainty and the desired accuracy on the cost function presents a clear criterion for the maximum acceptable MC dose uncertainties. It is demonstrated that it is possible to remove the systematic cost function uncertainty. Finally, it is shown that when the dose distribution is close to a true optimum, MC calculations of the cost function converge to the true result as one over the number of particles simulated, i.e. much faster than the individual dose uncertainties.

Humans↗

Intensity modulated radiation therapy for oropharyngeal cancer: the sensitivity of plan objectives and constraints to set-up uncertainty.

The goal of this study was to assess the impact of set-up uncertainty on compliance with the objectives and constraints of an intensity modulated radiation therapy protocol for early stage cancer of the oropharynx. As the convolution approach to the quantitative study of set-up uncertainties cannot accommodate either surface contours or internal inhomogeneities, both of which are highly relevant to sites in the head and neck, we have employed the more resource intensive direct simulation method. The impact of both systematic (variable from 0 to 6 mm) and random (fixed at 2 mm) set-up uncertainties on compliance with the criteria of the RTOG H-0022 protocol has been examined for eight geometrically complex structures: CTV66 (gross tumour volume and palpable lymph nodes suspicious for metastases), CTV54 (lymph node groups or surgical neck levels at risk of subclinical metastases), glottic larynx, spinal cord, brainstem, mandible and left and right parotids. In a probability-based approach, both dose-volume histograms and equivalent uniform doses were used to describe the dose distributions achieved by plans for two patients, in the presence of set-up uncertainty. The equivalent uniform dose is defined to be that dose which, when delivered uniformly to the organ of interest, will lead to the same response as the non-uniform dose under consideration. For systematic set-up uncertainties greater than 2 mm and 5 mm respectively, coverage of the CTV66 and CTV54 could be significantly compromised. Directional sensitivity was observed in both cases. Most organs at risk (except the glottic larynx which did not comply under static conditions) continued to meet the dose constraints up to 4 mm systematic uncertainty for both plans. The exception was the contra lateral parotid gland, which this protocol is specifically designed to protect. Sensitivity to systematic set-up uncertainty of 2 mm was observed for this organ at risk in both clinical plans.

Algorithms↗

The effect of covariance between the K alpha and the K beta lead peak concentrations on the uncertainty in the result of in vivo (109)Cd KXRF bone lead measurement.

The effect of covariance between the K alpha and K beta lead peak concentrations on the uncertainty in the (109)Cd K x-ray fluorescence measurement of lead in bone is addressed here. It is commonly believed that this covariance arises as a result of the mutual dependence of the ratios of x-ray to coherent amplitudes on the same coherent peak amplitude. Previous work assumes statistical independence between spectral quantities of interest, crudely estimates the uncertainties in the lead peak concentrations, and suggests that the effect of covariance on the measurement uncertainty is small and can be ignored. Consequently, the current method followed by most laboratories reports the measurement uncertainty as if the fluctuations in the measured peak concentrations were independent. The robustness of such assumption, however, is undermined by existing epidemiological data. This paper assesses the magnitude of the covariance effect, using a method based on the observed significant correlations between the ratios of x-ray to coherent peak amplitudes in series of repeat phantom measurements. The revised uncertainties following this approach can exceed the uncertainties estimated by the accepted method by as much as 40%, which suggests a much stronger effect of covariance on the measurement uncertainty than previously reported.

Analysis of Variance↗

Measurement uncertainty of liquid chromatographic analyses visualized by Ishikawa diagrams.

Ishikawa, or cause-and-effect diagrams, help to visualize the parameters that influence a chromatographic analysis. Therefore, they facilitate the set up of the uncertainty budget of the analysis, which can then be expressed in mathematical form. If the uncertainty is calculated as the Gaussian sum of all uncertainty parameters, it is necessary to quantitate them all, a task that is usually not practical. The other possible approach is to use the intermediate precision as a base for the uncertainty calculation. In this case, it is at least necessary to consider the uncertainty of the purity of the reference material in addition to the precision data. The Ishikawa diagram is then very simple, and so is the uncertainty calculation. This advantage is given by the loss of information about the parameters that influence the measurement uncertainty.

Journal Article↗

Uncertainties in dose coefficients for intakes of tritiated water and organically bound forms of tritium by members of the public.

The International Commission on Radiological Protection (ICRP) provides models for the calculation of doses from intakes of radionuclides, including intakes of tritium as tritiated water (HTO) or organically bound tritium (OBT). The ICRP models for HTO and OBT are explained and the assumptions made are examined. The reliability of dose estimates is assessed in terms of uncertainties in central estimates for population groups. The models consider intakes of HTO and OBT by ingestion and inhalation by adults and children and doses to the fetus following intakes by the mother. The analysis includes uncertainties in the absorption of OBT to blood, incorporation of tritium into OBT in body tissues, retention times in tissues, transfer to the fetus and the relative biological effectiveness (RBE) of tritium beta emissions compared with gamma rays. Heterogeneity of dose within tissues and cells is also considered. For intakes as HTO, dose is predominantly due to distribution and retention of HTO in body water and it was concluded that adult doses are reliable to within a factor of 2. For intakes of OBT, the extent of incorporation into OBT in body tissues results in greater uncertainties with estimates relying on animal data for selected compounds. The analysis indicated that adult doses from OBT can be considered to be known to within a factor of 3. Greater uncertainties in estimated doses for children and for in utero exposures were considered. Central values from the uncertainty analyses of doses for HTO and OBT were greater than the corresponding ICRP dose coefficients by about a factor of 2, mainly due to the inclusion of uncertainties in RBE for tritium. A detailed assessment of doses using appropriate parameters and considering uncertainties would be of particular importance in situations where the dose may approach dose limits or constraints. For exposures to known forms of OBT, specific dose assessments may be required.

Adult↗

The importance of preparing medical students to manage different types of uncertainty.

Price competition and other aspects of the changing health care environment are threatening many academic health centers (AHCs) and causing them to reassess their education and research missions. In order to design effective AHCs for the next century, medical leaders must define the unique competencies needed by tomorrow's physicians and describe the educational enterprises required to produce physicians with these competencies. Two of the most important of these competencies are the ability to manage the uncertainty associated with creating clinical paradigms and the ability to manage the uncertainty associated with managing care delivery. Creating clinical paradigms involves (1) developing knowledge about disease categories and (2) developing knowledge about the most appropriate therapy for a disease in a particular category. Both these tasks involve uncertainty. The second type of uncertainty is associated with managing care delivery and is largely a matter of optimizing current clinical paradigms. The challenges are (1) to correctly assign patients' diseases to existing disease categories, and (2) to correctly choose and manage the delivery of the most appropriate therapies to these patients. Currently, AHCs are more competent in managing--and educating students to manage--the uncertainty involved in creating clinical paradigms. But there is an increasing demand for physicians who manage the second type of uncertainty associated with care delivery. The authors conclude that in order to remain viable, AHCs, and particularly their medical schools, must broaden their educational goals so that students can learn to manage both forms of uncertainty.

Academic Medical Centers↗

Uncertainty, symptom distress, and information needs after surgery for cancer of the colon.

The purpose of this study was to determine the relationships between uncertainty, symptom distress, and discharge information needs in individuals after a colon resection for cancer. The theoretical framework for the study was derived from Lazarus and Folkman's stress, appraisal, and coping model, and Mishel's theory of uncertainty in illness. Uncertainty was measured by the Mishel Uncertainty Illness Scale (MUIS); symptom distress of pain, fatigue, constipation, diarrhea and loss of appetite by visual analogue scales; and discharge information needs by the Patient Learning Need Scale (PLNS). Forty individuals with a first diagnosis of cancer were interviewed after surgical resection of colon cancer. The study results indicated that they had moderate levels of uncertainty, low levels of symptom distress, and a moderate number of discharge information needs. Information related to treatment, complications, and activities of living were identified as highly important. An increase in uncertainty was significantly associated with an increase in discharge information needs. Increased attention to information needs at discharge may decrease an individual's level of uncertainty and facilitate the transition from hospital to home.

Adaptation, Psychological↗

The limitations of atmospheric dispersion data and their contribution to uncertainties in dose assessment.

The calculation of atmospheric dispersion patterns is often an important component of radiation dose estimates. These dispersion calculations are a possible source of error and such errors or uncertainties need to be quantified. An important source of uncertainty is the meteorological data used in the calculations. Such data may be less than ideal because of constraints imposed by both availability and by the variances associated with population from which the data are obtained. We have studied a simple and much used model of atmospheric dispersion--the Gaussian plume. We discuss the uncertainties on the meteorological data which are input to the model and how these uncertainties could be used to estimate uncertainties for the modeling results. In doing this we have addressed both the uncertainty associated with a recorded climatology and the added uncertainty arising from the year-to-year variability at any given location.

Air Pollution, Radioactive↗

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↗

Uncertainties in doses due to the number of aerosol particles: study on 239PuO2 using default parameters for workers.

The behavior of individual particles has been taken into account to estimate, after inhalation, uncertainties in deposition fractions and doses due to the number of 239PuO2 aerosol particles. Using ICRP models and default parameters recommended for workers, similar results were obtained after calculation and after simulations of exposures to 500 to 3 x 10(6) particles (from about 1 Bq to 6 kBq). Uncertainties obtained from simulations increase as the number of particles decreases. The maximal uncertainties in the deposition fraction were observed for the sequestered regions in which no deposit often occurs for exposures of less than 1 x 10(5) particles. Similar large uncertainties in the number of nuclear disintegrations over 50 years were observed in the sequestered regions as well as in lymph nodes. For a given number of particles, uncertainties in committed equivalent doses gradually decrease from the extra-thoracic region to lymph nodes, bronchi, bronchioles, and alveolar interstitium. For 1 x 10(4) particles, similar uncertainties were observed for the committed equivalent doses delivered to lung, liver, bone surfaces, red marrow and gonads, and for dose per unit intake (DPUI), whereas for 1 x 10(5) particles and more, uncertainties in DPUI were higher than those in equivalent doses. The explanation is that in some simulations the maximal committed equivalent dose was delivered to the extra-thoracic respiratory tract region (in which case the DPUI calculation mode must be changed).

Air Pollutants, Radioactive↗

Physicians' reactions to uncertainty in patient care. A new measure and new insights.

Although variations in physicians' practice patterns and use of resources are well documented, the reasons for these variations are less well understood. The uncertainty inherent in patient care may be one explanation. Existing measures of intolerance to uncertainty, developed in contexts outside of patient care, fail to explain these variations. To address this limitation, the Physicians' Reactions to Uncertainty scale was developed. A questionnaire containing an initial pool of 61 items was mailed to a random sample of 700 physicians in North Carolina and Oregon, stratified by specialty. The items covered nine areas of physicians' reactions to uncertainty derived from interviews with physicians and a definition of the concept affective reactions to uncertainity in patient care. Factor analysis of the 428 responses received yielded two primary factors that accounted for 58% of the common variance among the 61 items. Items with unambiguous loadings on these factors defined two reliable and readily interpretable subscales: Stress from Uncertainty (Cronbach's alpha = 0.90, 13 items) and Reluctance to Disclose Uncertainty to Others (alpha = 0.75, 9 items). By virtue of its clarity and good psychometric properties, this new measure promises insights into the role that uncertainty plays in physicians' resource utilization and practice patterns.

Adaptation, Psychological↗

Uncertainties analysis of doses resulting from chronic inhalation of plutonium at the Mayak production association.

A method is presented to determine the uncertainties in the reported dose due to incorporated plutonium for the Mayak Worker Cohort. The methodology includes errors generated by both detection methods and modeling methods. To accomplish the task, the method includes classical statistics, Monte Carlo, perturbation, and reliability groupings. Uncertainties are reported in percent of reported dose as a function of total body burden. The cohort was initially sorted into six reliability groups, with "A" being the data set that the investigators are most confident is correct and "G" being the data set with the most ambiguous data. Categories were adjusted based on preliminary calculation of uncertainties using the sorting criteria. Specifically, the impact of transportability (the parameter used to describe the transport of plutonium from the lung to systemic organs) was underestimated, and the structure of the sort was reorganized to reflect the impact of transportability. The finalized categories are designated with Roman numerals I through V, with "I" being the most reliable. Excluding Category V (neither bioassay nor autopsy), the highest uncertainty in lung doses is for individuals from Category IV-which ranged from 90-375% for total body burdens greater than 10 Bq, along with work histories that indicated exposure to more than one transportability class. The smallest estimated uncertainties for lung doses were determined by autopsy. Category I has a 32-38% uncertainty in the lung dose for total body burdens greater than 1 Bq. First, these results provide a further definition and characterization of the cohort and, second, they provide uncertainty estimates for these plutonium exposure categories.

Administration, Inhalation↗