M. Puncher

A Monte Carlo method for calculating Bayesian uncertainties in internal dosimetry.

This paper presents a novel Monte Carlo method (WeLMoS, Weighted Likelihood Monte-Carlo sampling method) that has been developed to perform Bayesian analyses of monitoring data. The WeLMoS method randomly samples parameters from continuous prior probability distributions and then weights each vector by its likelihood (i.e. its goodness of fit to the measurement data). Furthermore, in order to quality assure the method, and assess its strengths and weaknesses, a second method (MCMC, Markov chain Monte Carlo) has also been developed. The MCMC method uses the Metropolis algorithm to sample directly from the posterior distribution of parameters. The methods are evaluated and compared using an artificially generated case involving an exposure to a plutonium nitrate aerosol. In addition to calculating the uncertainty on internal dose, the methods can also calculate the probability distribution of model parameter values given the observed data. In other words, the techniques provide a powerful tool to obtain the estimates of parameter values that best fit the data and the associated uncertainty on these estimates. Current applications of the methodology, including the determination of lung solubility parameters, from volunteer and cohort data, are also discussed.

Uncertainties on Lung Doses from Inhaled Plutonium

In a recent epidemiological study, Bayesian uncertainties on lung doses have been calculated to determine lung cancer risk from occupational exposures to plutonium. These calculations used a revised version of the Human Respiratory Tract Model (HRTM) published by the ICRP. In addition to the Bayesian analyses, which give probability distributions of doses, point estimates of doses (single estimates without uncertainty) were also provided for that study using the existing HRTM as it is described in ICRP Publication 66; these are to be used in a preliminary analysis of risk. To infer the differences between the point estimates and Bayesian uncertainty analyses, this paper applies the methodology to former workers of the United Kingdom Atomic Energy Authority (UKAEA), who constituted a subset of the study cohort. The resulting probability distributions of lung doses are compared with the point estimates obtained for each worker. It is shown that mean posterior lung doses are around two- to fourfold higher than point estimates and that uncertainties on doses vary over a wide range, greater than two orders of magnitude for some lung tissues. In addition, we demonstrate that uncertainties on the parameter values, rather than the model structure, are largely responsible for these effects. Of these it appears to be the parameters describing absorption from the lungs to blood that have the greatest impact on estimates of lung doses from urine bioassay. Therefore, accurate determination of the chemical form of inhaled plutonium and the absorption parameter values for these materials is important for obtaining reliable estimates of lung doses and hence risk from occupational exposures to plutonium.

A Bayesian analysis of uncertainties on lung doses resulting from occupational exposures to uranium

In a recent epidemiological study, Bayesian estimates of lung doses were calculated in order to determine a possible association between lung dose and lung cancer incidence resulting from occupational exposures to uranium. These calculations, which produce probability distributions of doses, used the human respiratory tract model (HRTM) published by the International Commission on Radiological Protection (ICRP) with a revised particle transport clearance model. In addition to the Bayesian analyses, point estimates (PEs) of doses were also provided for that study using the existing HRTM as it is described in ICRP Publication 66. The PEs are to be used in a preliminary analysis of risk. To explain the differences between the PEs and Bayesian analysis, in this paper the methodology was applied to former UK nuclear workers who constituted a subset of the study cohort. The resulting probability distributions of lung doses calculated using the Bayesian methodology were compared with the PEs obtained for each worker. Mean posterior lung doses were on average 8-fold higher than PEs and the uncertainties on doses varied over a wide range, being greater than two orders of magnitude for some lung tissues. It is shown that it is the prior distributions of the parameters describing absorption from the lungs to blood that are responsible for the large difference between posterior mean doses and PEs. Furthermore, it is the large prior uncertainties on these parameters that are mainly responsible for the large uncertainties on lung doses. It is concluded that accurate determination of the chemical form of inhaled uranium, as well as the absorption parameter values for these materials, is important for obtaining unbiased estimates of lung doses from occupational exposures to uranium for epidemiological studies. Finally, it should be noted that the inferences regarding the PEs described here apply only to the assessments of cases provided for the epidemiological study, where central estimates of dose were sought. Approved dosimetry service assessments of exposures are unlikely to yield significant underestimates, as pessimistic assumptions of lung solubility would almost always be used.

Concerted Uranium Research in Europe (CURE): toward a collaborative project integrating dosimetry, epidemiology and radiobiology to study the effects of occupational uranium exposure.

The potential health impacts of chronic exposures to uranium, as they occur in occupational settings, are not well characterized. Most epidemiological studies have been limited by small sample sizes, and a lack of harmonization of methods used to quantify radiation doses resulting from uranium exposure. Experimental studies have shown that uranium has biological effects, but their implications for human health are not clear. New studies that would combine the strengths of large, well-designed epidemiological datasets with those of state-of-the-art biological methods would help improve the characterization of the biological and health effects of occupational uranium exposure. The aim of the European Commission concerted action CURE (Concerted Uranium Research in Europe) was to develop protocols for such a future collaborative research project, in which dosimetry, epidemiology and biology would be integrated to better characterize the effects of occupational uranium exposure. These protocols were developed from existing European cohorts of workers exposed to uranium together with expertise in epidemiology, biology and dosimetry of CURE partner institutions. The preparatory work of CURE should allow a large scale collaborative project to be launched, in order to better characterize the effects of uranium exposure and more generally of alpha particles and low doses of ionizing radiation.

A method for calculating Bayesian uncertainties on internal doses resulting from complex occupational exposures.

Estimating uncertainties on doses from bioassay data is of interest in epidemiology studies that estimate cancer risk from occupational exposures to radionuclides. Bayesian methods provide a logical framework to calculate these uncertainties. However, occupational exposures often consist of many intakes, and this can make the Bayesian calculation computationally intractable. This paper describes a novel strategy for increasing the computational speed of the calculation by simplifying the intake pattern to a single composite intake, termed as complex intake regime (CIR). In order to assess whether this approximation is accurate and fast enough for practical purposes, the method is implemented by the Weighted Likelihood Monte Carlo Sampling (WeLMoS) method and evaluated by comparing its performance with a Markov Chain Monte Carlo (MCMC) method. The MCMC method gives the full solution (all intakes are independent), but is very computationally intensive to apply routinely. Posterior distributions of model parameter values, intakes and doses are calculated for a representative sample of plutonium workers from the United Kingdom Atomic Energy cohort using the WeLMoS method with the CIR and the MCMC method. The distributions are in good agreement: posterior means and Q(0.025) and Q(0.975) quantiles are typically within 20 %. Furthermore, the WeLMoS method using the CIR converges quickly: a typical case history takes around 10-20 min on a fast workstation, whereas the MCMC method took around 12-72 hr. The advantages and disadvantages of the method are discussed.

Risk of Lung Cancer Mortality in Nuclear Workers from Internal Exposure to Alpha Particle-emitting Radionuclides

Background: Carcinogenic risks of internal exposures to alpha-emitters (except radon) are poorly understood. Since exposure to alpha particles—particularly through inhalation—occurs in a range of settings, understanding consequent risks is a public health priority. We aimed to quantify dose–response relationships between lung dose from alpha-emitters and lung cancer in nuclear workers. Methods: We conducted a case–control study, nested within Belgian, French, and UK cohorts of uranium and plutonium workers. Cases were workers who died from lung cancer; one to three controls were matched to each. Lung doses from alpha-emitters were assessed using bioassay data. We estimated excess odds ratio (OR) of lung cancer per gray (Gy) of lung dose. Results: The study comprised 553 cases and 1,333 controls. Median positive total alpha lung dose was 2.42 mGy (mean: 8.13 mGy; maximum: 316 mGy); for plutonium the median was 1.27 mGy and for uranium 2.17 mGy. Excess OR/Gy (90% confidence interval)—adjusted for external radiation, socioeconomic status, and smoking—was 11 (2.6, 24) for total alpha dose, 50 (17, 106) for plutonium, and 5.3 (−1.9, 18) for uranium. Conclusions: We found strong evidence for associations between low doses from alpha-emitters and lung cancer risk. The excess OR/Gy was greater for plutonium than uranium, though confidence intervals overlap. Risk estimates were similar to those estimated previously in plutonium workers, and in uranium miners exposed to radon and its progeny. Expressed as risk/equivalent dose in sieverts (Sv), our estimates are somewhat larger than but consistent with those for atomic bomb survivors. See video abstract at, http://links.lww.com/EDE/B232.

Parameter uncertainty analysis of a biokinetic model of caesium.

Parameter uncertainties for the biokinetic model of caesium (Cs) developed by Leggett et al. were inventoried and evaluated. The methods of parameter uncertainty analysis were used to assess the uncertainties of model predictions with the assumptions of model parameter uncertainties and distributions. Furthermore, the importance of individual model parameters was assessed by means of sensitivity analysis. The calculated uncertainties of model predictions were compared with human data of Cs measured in blood and in the whole body. It was found that propagating the derived uncertainties in model parameter values reproduced the range of bioassay data observed in human subjects at different times after intake. The maximum ranges, expressed as uncertainty factors (UFs) (defined as a square root of ratio between 97.5th and 2.5th percentiles) of blood clearance, whole-body retention and urinary excretion of Cs predicted at earlier time after intake were, respectively: 1.5, 1.0 and 2.5 at the first day; 1.8, 1.1 and 2.4 at Day 10 and 1.8, 2.0 and 1.8 at Day 100; for the late times (1000 d) after intake, the UFs were increased to 43, 24 and 31, respectively. The model parameters of transfer rates between kidneys and blood, muscle and blood and the rate of transfer from kidneys to urinary bladder content are most influential to the blood clearance and to the whole-body retention of Cs. For the urinary excretion, the parameters of transfer rates from urinary bladder content to urine and from kidneys to urinary bladder content impact mostly. The implication and effect on the estimated equivalent and effective doses of the larger uncertainty of 43 in whole-body retention in the later time, say, after Day 500 will be explored in a successive work in the framework of EURADOS.

THE MAYAK WORKER DOSIMETRY SYSTEM (MWDS 2013): A RE-ANALYSIS OF USTUR CASE 0269 TO DETERMINE WHETHER PLUTONIUM BINDS TO THE LUNGS

Radionuclides in ionic form can become chemically bound in the airways of the lungs following dissolution of inhaled particulates in lung fluid. The presence of long-term binding can greatly increase lung doses from inhaled plutonium, particularly if it occurs in the bronchial and bronchiolar regions. However, the only published evidence that plutonium binding occurs in humans comes from an analysis of the autopsy and bioassay data of United States Transuranium and Uranium Registries Case 0269, a plutonium worker who experienced a very high (58 kBq) acute inhalation of plutonium nitrate. This analysis suggested a bound fraction of around 8 %, inferred from an unexpectedly low ratio of estimated total thoracic lymph node activity:total lung activity, at the time of death. However, there are some limitations with this study, the most significant being that measurements of the regional distribution of plutonium activity in the lungs, which provide more direct evidence of binding, were not available when the analysis was performed. The present work describes the analysis of new data, which includes measurements of plutonium activity in the alveolar-interstitial (AI) region, bronchial (BB) and bronchiolar (bb) regions, and extra-thoracic (ET) regions, at the time of death. A Bayesian approach is used that accounts for uncertainties in model parameter values, including particle transport clearance, which were not considered in the original analysis. The results indicate that a long-term bound fraction between 0.4 and 0.7 % is required to explain this data, largely because plutonium activity is present in the extra-thoracic (ET2), bronchial and bronchiolar airways at the time of death.

The Mayak Worker Dosimetry System (MWDS-2013): Plutonium Binding in the Lungs—An Analysis of Mayak Workers

Estimates of plutonium lung doses from urine bioassay are highly dependent on the rate of absorption from the lungs to blood assumed for the inhaled aerosol. Absorption occurs by dissolution of particles in lung fluid followed by uptake to blood. The latter may occur either rapidly or dissolved ions may first become temporarily bound within airway tissue. The presence of long-term binding can greatly increase lung doses, particularly if it occurs in the bronchial and bronchiolar regions. Analyses of autopsy data from Beagle dogs and USTUR Case 0269, obtained following exposure to plutonium nitrate, suggest that a small fraction of 0.2-1.1 and 0.4-0.7%, respectively, of plutonium becomes permanently bound within the lungs. The present work performs a further analysis using autopsy data of former plutonium workers of the Mayak Production Association to determine values of the bound fraction that are supported by these data. The results suggest a bound fraction value of 0-0.3%. The results also indicate that the Mayak worker population median values of the particle transport clearance parameters from the alveolar-interstitial region are largely consistent with expected values, but suggest the rate from the alveolar region to the interstitium may be lower than initially thought.

THE MAYAK WORKER DOSIMETRY SYSTEM-2013 (MWDS-2013): PHASE II—QUALITY ASSURANCE OF ORGAN DOSE CALCULATIONS

In order to check developed software tools, it was necessary to compare estimates of statistical characteristics of annual absorbed plutonium internal doses obtained by PANDORA and IMBA software with the same original data. The results were compared from dose calculations of five cases with different initial data on plutonium inhalation intake, lifetime measurements of plutonium activity in daily urine and post-mortem measurements in lungs, lung lymph nodes, liver and skeleton. Estimates of geometric mean and geometric standard deviation of annual regionally weighted lung dose and bone surface dose were compared. Satisfactory agreements of the estimates of statistical characteristics of annual doses to two critical organs for the selected cases were shown. One hundred individual hyper-realizations (forward model evaluations) are sufficient to calculate MWDS-2013 if only measurements of plutonium activity in daily urine are used, and 2000 individual hyper-realizations if both urine and autopsy measurement results are used.