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.

The Mayak Worker Dosimetry System-2013: Treatment of Organ Masses in the Calculation of Organ Doses.

Previous Mayak worker epidemiological studies designed to quantify the risk of cancer following exposure to airborne plutonium have calculated organ doses by dividing the organ-absorbed energy by the individual's estimated organ mass. For living workers, this was done by using a relationship between organ mass and total mass and height. For autopsy cases, this was measured directly. In the Mayak Worker Dosimetry System-2013 study, organ doses are calculated by dividing this energy by a population average organ mass. The reasons for departing from previous methodologies are described in this note. The average organ masses that were used in the final analysis are tabulated for males and females.

Mayak Worker Dosimetry System (MWDS-2013): Phase I-Quality Assurance of Organ Doses and Excretion Rates From Internal Exposures of Plutonium-239 for the Mayak Worker Cohort.

The calculation of reliable and realistic doses for use in epidemiological studies for the quantification of risk from internal exposure to radioactive material is fundamental to the development of advice, guidance and regulations for the control and use of radioactive material. Thus, any programme of work carried out which requires the calculation of doses for use by epidemiologists ideally should contain a rigorous program of quality assurance (QA). This paper describes the initial QA (Phase I) implemented by Public Health England (PHE) and the Southern Urals Biophysics Institute (SUBI) as part of the work programme on internal dosimetry in the Joint Coordinating Committee for Radiation Effects Research Project 2.4 for the 2013 Mayak Worker Dosimetry System. SUBI designed and implemented new software (PANDORA) to include the latest Mayak Worker Dosimetry System and to calculate organ burdens, urinary excretion rates, intakes and absorbed doses, while PHE modified their commercially available IMBA Professional Plus software package. Comparisons of output from the two codes for the Mayak Worker Dosimetry System 2013 showed calculated values of absorbed doses, intakes, organ burdens and urinary excretion agreed to within 1%. The 1% discrepancy can be explained by the approximation used in IMBA to speed up dose calculations.

The Mayak Worker Dosimetry System (MWDS 2013): Soluble Plutonium Retention in the Lungs of An Occupationally Exposed USTUR Case.

For the first time, plutonium retention in human upper airways was investigated based on the dosimetric structure of the human respiratory tract proposed by the International Commission on Radiological Protection (ICRP). This paper describes analytical work methodology, case selection criteria, and summarizes findings on soluble (ICRP 68 Type M material) plutonium distribution in the lungs of a former nuclear worker occupationally exposed to plutonium nitrate [239Pu(NO3)4]. Thirty-eight years post-intake, plutonium was found to be uniformly distributed between bronchial (BB), bronchiolar (bb) and alveolar-interstitial (AI) dosimetric compartments as well as between the left and right lungs. 239+240Pu and 238Pu total body activity was estimated to be 2333 ± 23 and 42.1 ± 0.7 Bq, respectively. The results of this work provide key information on the extent of plutonium binding in the upper airways of the human respiratory tract.

THE MAYAK WORKER DOSIMETRY SYSTEM (MWDS-2013) FOR INTERNALLY DEPOSITED PLUTONIUM: AN OVERVIEW.

The Mayak Worker Dosimetry System (MWDS-2013) is a system for interpreting measurement data from Mayak workers from both internal and external sources. This paper is concerned with the calculation of annual organ doses for Mayak workers exposed to plutonium aerosols, where the measurement data consists mainly of activity of plutonium in urine samples. The system utilises the latest biokinetic and dosimetric models, and unlike its predecessors, takes explicit account of uncertainties in both the measurement data and model parameters. The aim of this paper is to describe the complete MWDS-2013 system (including model parameter values and their uncertainties) and the methodology used (including all the relevant equations) and the assumptions made. Where necessary, Supplementary papers which justify specific assumptions are cited.

The Mayak Worker Dosimetry System (MWDS-2013): How to Weight the Absorbed Dose to Different Lung Regions in the Calculation of Lung Dose.

In the Mayak Worker Dosimetry System-2013, lung dose is calculated as an average of the three absorbed doses to the bronchial, the bronchiolar and the alveolar regions. Previous epidemiological studies involving Mayak Workers have used a lung dose calculated as the total energy deposited in the lungs divided by the mass. These two definitions lead to very different estimates of lung dose, especially for radon dosimetry. This paper uses the results of recent epidemiological studies to justify the use of a regionally weighted lung dose (wi = 1/3, I = 1, 3) over the use of an 'average lung' dose.

The Mayak Worker Dosimetry System (Mwds-2013): Plutonium Dissolution in The Lungs-An Analysis of Mayak Workers.

Lung doses resulting from inhalation of plutonium aerosols are highly dependent on the assumed rate of particle clearance, which occurs by two competing processes: (1) particle transport clearance to the alimentary tract and to the thoracic lymph nodes and (2) clearance to systemic tissues, which occurs by dissolution of particles in lung fluid followed by uptake to blood, which is a process collectively known as absorption. Unbiased and accurate estimates of the values of lung absorption parameters are required to obtain reliable estimates of lung dose, particularly those inferred from urine bioassay. Parameter values governing the rate of absorption are best estimated from data, such as autopsy measurements of plutonium in the lungs and systemic tissues, which directly relate to the exposed workers of interest. However, because the mathematical models that determine clearance from the lungs and systemic tissues are complex and consist of many parameters, estimates of model parameter values are subject to significant uncertainties. With this in mind, this paper uses a Bayesian approach to estimate one of the most important dissolution parameters: the slow rate of dissolution. This is estimated for both plutonium nitrate and plutonium oxide bearing aerosols in the lungs of former workers of the Mayak Production Association. A value of 2.6 × 10-4 d-1 is estimated for plutonium nitrates, and 4.7 × 10-5 d-1 for plutonium oxides.

The Mayak Worker Dosimetry System (MWDS-2013): A Bayesian Analysis to Quantify Pulmonary Binding of Plutonium in Lungs Using Historic Beagle Dog Data.

The revised human respiratory tract model, published in Part 1 of the International Commission on Radiological Protection's (ICRP) report on Occupational Intakes of Radionuclides (OIR), includes a bound fraction, fb, to represent radionuclides that have become chemically bound in the lungs following dissolution of particulates in lung fluid. Bound radionuclides are not subject to particle transport clearance but can be absorbed to blood at a rate, sb. The occurrence of long-term binding of plutonium can greatly increase lung doses, particularly if it occurs in the bronchial and bronchiolar regions. However, there has been little evidence that currently supports the existence of a long-term bound state for plutonium. The present work describes the analysis of measurements of lung data obtained from a life span study of Beagle dogs that were exposed by inhalation to different concentrations of plutonium-239 (239Pu) nitrate aerosol at Pacific Northwest Laboratories, USA. The data have been analysed to assess whether a bound state was required to explain the data. A Bayesian approach was adopted for the analysis that accounts for uncertainties in model parameter values, including uncertainties in the rates of particle transport clearance. Furthermore, it performs the analysis using two different modelling hypotheses: a model based on the current ICRP human respiratory tract model and its treatment of alveolar particle transport clearance; and a model of particle transport clearance that is based on the updated model developed by ICRP to calculate dose coefficients for the OIR. The current model better represents clearance in dogs at early times (up to 1 year following intake) and the latter better represents retention at greater times (>5 years following intake). The results indicate that a long-term bound fraction of between 0.16 and 1.1%, with a mean value of between 0.24 and 0.8% (depending on the model) is required to explain the data.

The Mayak Worker Dosimetry System (MWDS-2013): How to Reduce Hyper-Realisations to Realisations.

Two important aspects in which the MWDS-2013 output (absorbed dose to organs calculated in each calendar year) differs from previous data bases (MWDS-2008 and DOSES-2005) are that they have been designed to (a) deal explicitly with uncertainties in model parameters, and (b) differentiate parameters that are considered to be shared (unknown, but having the same value for all workers) and unshared (unknown, but having different values between workers). A multiple-realisation approach is used to preserve information on the effects of shared and unshared parameters both for internal and external doses. Previously, a single realisation (a set of organ doses: one for each worker in the cohort) was calculated using the best estimates of parameter values only. In MWDS-2013, a set of 1000 realisations is produced, to reflect the uncertainty in assumed model parameters: each realisation using a different set of parameter values. Within each realisation, shared parameter values are fixed throughout the cohort, while unshared parameters are allowed to vary between workers. One problem is that because the calculation of organ dose is Bayesian, the estimate for each organ dose is not just a single value, but is itself a distribution (hyper-dose). Technically, it is the probability density of dose given the sampled set of parameter values and given the data for that worker. Thus, in our case, the realisations consist not of single doses, but distributions of doses. The term hyper-realisation is used to differentiate this from the more conventional realisation. Although the multiple hyper-realisation in principle contains all of the necessary information on parameter uncertainty, including shared and unshared parameters, in order to make preliminary epidemiological analyses tractable, and also for consistency with the external doses, it was required to convert the hyper-realisations to realisations. The aim of this paper is to discuss the different approaches that were considered to do this, and to define the method that was eventually chosen. Single spot (point) estimates of dose (for each worker) were also calculated to support the epidemiological analysis. The different methods for obtaining these and the implications are also discussed.

The Mayak Worker Dosimetry System (MWDS-2013): A Comparison of Intakes Based on Urine Versus Autopsy Data From Mayak Workers Using the Leggett Systemic Model for Plutonium.

The Mayak Worker Dosimetry System-2013 (MWDS-2013) uses a model developed by Leggett and colleagues to represent the biokinetic behaviour of plutonium after uptake to blood. Of particular importance, with regard to estimating intakes (and doses), is the distribution of activity between urine and body organs (particularly liver and skeleton). In this study, measurement data (urine and autopsy) from around 500 Mayak workers have been used to validate use of this model. A robust method has been developed and used to estimate intakes from both urine and autopsy data separately, and the ratio of these estimates has been calculated for each worker. The geometric mean ratio has been shown to lie within a range of 0.92-1.14, depending on assumptions made. Since this range includes 1, the hypothesis that the model is unbiased with regard to estimating intakes either with urine or autopsy data cannot be rejected on the basis of these data. This lends weight to the argument for increasing the MWDS-2013 cohort to include an additional 500 workers for whom only autopsy data are available, and who have previously been excluded from the cohort. Future directions in which this work could be extended are also suggested.

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): Implementation of the Dose Calculations.

The calculation of internal doses for the Mayak Worker Dosimetry System (MWDS-2013) involved extensive computational resources due to the complexity and sheer number of calculations required. The required output consisted of a set of 1000 hyper-realizations: each hyper-realization consists of a set (1 for each worker) of probability distributions of organ doses. This report describes the hardware components and computational approaches required to make the calculation tractable. Together with the software, this system is referred to here as the 'PANDORA system'. It is based on a commercial SQL server database in a series of six work stations. A complete run of the entire Mayak worker cohort entailed a huge amount of calculations in PANDORA and due to the relatively slow speed of writing the data into the SQL server, each run took about 47 days. Quality control was monitored by comparing doses calculated in PANDORA with those in a specially modified version of the commercial software 'IMBA Professional Plus'. Suggestions are also made for increasing calculation and storage efficiency for future dosimetry calculations using PANDORA.

A multicentre study of the precision and accuracy of the TruSlice and TruSlice Digital histological dissection devices.

BACKGROUND: Five key factors enabling a good surgical grossing technique include a flat uniformly perpendicular specimen cutting face, appropriate immobilisation of the tissue specimen during grossing, good visualisation of the cutting tissue face, sharp cutting knives and the grossing knife action. TruSlice and TruSlice Digital are new innovative tools based on a guillotine configuration. The TruSlice has plastic inserts whilst the TruSlice Digital has an electronic micrometre attached: both features enable these dissection factors to be controlled. The devices were assessed in five hospitals in the UK. MATERIAL AND METHODS: A total of 267 fixed tissue samples from 23 tissue types were analysed, principally the breast (n = 32) skin (30), rectum (28), colon (27) and cervix (17). Precision and accuracy were evaluated by measuring the defined thickness, and the consistency of achieving the defined thickness of tissue samples taken respectively. Both parameters were expressed as a total percentage of compliance for the cohort of samples accessed. RESULTS: Overall, the mean (standard deviation) score for precision was 81 (11) % whilst the accuracy score was 82 (11) % (both p < 0.05, chi-squared test), although this varied with type of tissue. Accuracy and precision were strongly correlated (rp = 0.83, p < 0.001). CONCLUSION: The TruSlice Digital devices offer an assured precision and accuracy performance which is reproducible across an assortment of tissue types. The use of a micrometre to set tissue slice thickness is innovative and should comply with laboratory accreditation requirements, alleviating concerns of how to tackle issues such as the 'measurement of uncertainty' at the grossing bench.

An intake prior for the Bayesian analysis of plutonium and uranium exposures in an epidemiology study.

In Bayesian inference, the initial knowledge regarding the value of a parameter, before additional data are considered, is represented as a prior probability distribution. This paper describes the derivation of a prior distribution of intake that was used for the Bayesian analysis of plutonium and uranium worker doses in a recent epidemiology study. The chosen distribution is log-normal with a geometric standard deviation of 6 and a median value that is derived for each worker based on the duration of the work history and the number of reported acute intakes. The median value is a function of the work history and a constant related to activity in air concentration, M, which is derived separately for uranium and plutonium. The value of M is based primarily on measurements of plutonium and uranium in air derived from historical personal air sampler (PAS) data. However, there is significant uncertainty on the value of M that results from paucity of PAS data and from extrapolating these measurements to actual intakes. This paper compares posterior and prior distributions of intake and investigates the sensitivity of the Bayesian analyses to the assumed value of M. It is found that varying M by a factor of 10 results in a much smaller factor of 2 variation in mean intake and lung dose for both plutonium and uranium. It is concluded that if a log-normal distribution is considered to adequately represent worker intakes, then the Bayesian posterior distribution of dose is relatively insensitive to the value assumed of M.

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.

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.

Internal dosimetry: towards harmonisation and coordination of research.

The CONRAD Project is a Coordinated Network for Radiation Dosimetry funded by the European Commission 6th Framework Programme. The activities developed within CONRAD Work Package 5 ('Coordination of Research on Internal Dosimetry') have contributed to improve the harmonisation and reliability in the assessment of internal doses. The tasks carried out included a study of uncertainties and the refinement of the IDEAS Guidelines associated with the evaluation of doses after intakes of radionuclides. The implementation and quality assurance of new biokinetic models for dose assessment and the first attempt to develop a generic dosimetric model for DTPA therapy are important WP5 achievements. Applications of voxel phantoms and Monte Carlo simulations for the assessment of intakes from in vivo measurements were also considered. A Nuclear Emergency Monitoring Network (EUREMON) has been established for the interpretation of monitoring data after accidental or deliberate releases of radionuclides. Finally, WP5 group has worked on the update of the existing IDEAS bibliographic, internal contamination and case evaluation databases. A summary of CONRAD WP5 objectives and results is presented here.

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.

Internal dose assessments: uncertainty studies and update of ideas guidelines and databases within CONRAD project.

The work of Task Group 5.1 (uncertainty studies and revision of IDEAS guidelines) and Task Group 5.5 (update of IDEAS databases) of the CONRAD project is described. Scattering factor (SF) values (i.e. measurement uncertainties) have been calculated for different radionuclides and types of monitoring data using real data contained in the IDEAS Internal Contamination Database. Based upon this work and other published values, default SF values are suggested. Uncertainty studies have been carried out using both a Bayesian approach as well as a frequentist (classical) approach. The IDEAS guidelines have been revised in areas relating to the evaluation of an effective AMAD, guidance is given on evaluating wound cases with the NCRP wound model and suggestions made on the number and type of measurements required for dose assessment.