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.

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.

Development, implementation and quality assurance of biokinetic models within CONRAD.

The work of the Task Group 5.2 'Research Studies on Biokinetic Models' of the CONRAD project is presented. New biokinetic models have been implemented by several European institutions. Quality assurance procedures included intercomparison of the results as well as quality assurance of model formulation. Additionally, the use of the models was examined leading to proposals of tuning parameters. Stable isotope studies were evaluated with respect to their implications to the new models, and new biokinetic models were proposed on the basis of their results. Furthermore, the development of a biokinetic model describing the effects of decorporation of actinides by diethylenetriaminepentaacetic acid treatment was initiated.

Dosimetric models used in the Alpha-Risk project to quantify exposure of uranium miners to radon gas and its progeny.

The European project Alpha-Risk aims to quantify the cancer and non-cancer risks associated with multiple chronic radiation exposures by epidemiological studies, organ dose calculation and risk assessment. In the framework of this project, mathematical models have been applied to the organ dosimetry of uranium miners who are internally exposed to radon and its progeny as well as to long-lived radionuclides present in the uranium ore. This paper describes the methodology and the dosimetric models used to calculate the absorbed doses to specific organs arising from exposure to radon and its progeny in the uranium mines. The results of dose calculations are also presented.

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.

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.

Estimating uncertainty on internal dose assessments.

The estimation of uncertainty on doses broadly falls into three categories. (1) Estimating the uncertainty on prospective doses. Here, the intake is known and the uncertainties in individual parameter values must be propagated through the calculated dose. (2) Estimating the error or uncertainty on dose assessments made from single measurements. Here, intake, model parameter and measurement uncertainties are propagated into the measurement, but default ICRP parameter values are used to estimate the intake and dose from the measurement. (3)Estimating the probability distribution of an individual's dose from a set of monitoring data. Here, Bayesian inference methods must be used to estimate the uncertainty on the estimated dose. A computer code is being developed that performs all three types of uncertainty analysis using Monte Carlo simulation. The software samples biokinetic parameters from probability density functions and then calculates doses from these parameters by calling the dosimetry code IMBA Professional Plus. A description of the methodology, together with an example application of the software, is included in this paper.

Avoiding biased estimates of dose when nothing is known about the time of intake.

A common problem in internal dosimetry occurs in routine monitoring, when it is required to estimate an intake from a measurement made at the end of a monitoring interval, and the time of intake is unknown. ICRP suggests that it should be assumed that the intake occurred in the middle of the monitoring period. However, it has been shown that this will, in the long-term, lead to biased estimates of a worker's intake and dose. In order to overcome this biasing, the United States Department of Energy (USDOE) recommends a different method based on calculating the intakes for all possible intake times in the interval and then taking an arithmetic average. In a recent paper, it has been shown that both the ICRP and USDOE methods were biased and that the only unbiased estimator of the true intake was obtained by assuming a constant chronic intake throughout the monitoring interval. In all of the analyses carried out to date on this 'Constant Chronic' method, it was assumed that the measurements were exact. In this paper, the effects of assuming either normally or log-normally distributed measurement errors are explored, and the effect on the bias of the intake estimate is investigated.

The autocorrelation coefficient as a tool for assessing goodness of fit between bioassay predictions and measurement data.

Project IDEAS has produced guidelines for internal dose assessment. An integral part of this process is assessing the goodness of fit of biokinetic models to bioassay data. It is recommended that a fit should only be accepted if (a) it is close enough to the data not to be rejected by a chi2 test and (b) if it looks acceptable to 'the eye'. The latter criterion was added to enable the assessor to reject fits which seemed to display some sort of systematic bias. However, there are problems with both of these tests: (a) the chi2 test is dependent on the assumed uncertainties which are often unknown, (b) 'by eye' assessment is subjective. In this paper, another statistic, the autocorrelation coefficient of the residuals, rho, is investigated. The main advantages of the rho statistic are that it is objective, very sensitive to biasing and independent of the assumed errors.

IMBA Professional Plus: a flexible approach to internal dosimetry.

IMBA (Integrated Modules for Bioassay Analysis) is a suite of software modules that implement the current ICRP biokinetic and dosimetric models for estimation of intakes and doses. The IMBA modules have gone through extensive quality assurance, and are now used for routine formal dose assessment by Approved Dosimetry Services throughout the UK. HPA has continued to develop the IMBA modules. In addition, several projects, sponsored by organisations both in the USA and in Canada, have resulted in the development of customised user-friendly interfaces (IMBA Expert 'editions'). These enable users not only to use the standard ICRP models, but also to change many of the parameter values from ICRP defaults, and to apply sophisticated data handling techniques to internal dose calculations. These include: fitting measurement data with the maximum likelihood method; using multiple chronic and acute intakes; and dealing with different data types, such as urine, faces and whole body simultaneously. These interfaces were improved further as a result of user-feedback, and a general 'off-the-shelf' product, IMBA Professional, was developed and made available in January 2004. A new version, IMBA Professional Plus, was released in April 2005, which is both faster and more powerful than previous software. The aim of this paper is to describe the capabilities of IMBA Professional Plus, and the mathematical methods used.

The work of the CONRAD task group 5.2: research studies on biokinetic models.

The objective of this Task Group is the coordination of research studies on biokinetic models and the evaluation of the implications of new biokinetic models on dose assessment and safety standards. For this the new ICRP models, which will be used for a revision of ICRP Publications 30, 54, 68 and 78, are implemented into six different computer codes in five European countries and quality assured by intercomparison procedures. The work has started with the implementation of the new ICRP Alimentary Tract Model. New systemic models and the new NCRP wound model will follow. The work also includes the evaluation of experimental results in terms of formulation by the new model structures and a quality assurance of model formulation.

Application of IDEAS guidelines: the IDEAS/IAEA intercomparison exercise on internal dose assessment.

As part of the EU Fifth Framework Programme IDEAS project 'General Guidelines for the Evaluation of Incorporation Monitoring Data', and in collaboration with the International Atomic Energy Agency, a new intercomparison exercise for the assessment of doses from intakes of radionuclides was organised. Several cases were selected, to cover a wide range of practices in the nuclear fuel cycle and medical applications. The cases were: (1) acute intake of HTO, (2) acute inhalation of the fission products 137Cs and 90Sr, (3) acute inhalation of 60Co, (4) repeated intakes of 131I, (5) intake of enriched uranium and (6) single intake of Pu isotopes and 241Am. This intercomparison exercise especially focused on the effect of the Guidelines proposed by the IDEAS project for harmonisation of internal dosimetry.

Comparison of dose estimation from occupational exposure to 239Pu using different modelling approaches.

Several approaches are available for bioassay interpretation when assigning Pu doses to Mayak workers. First, a conventional approach is to apply ICRP models per se. An alternative method involves individualised fitting of bioassay data using Bayesian statistical methods. A third approach is to develop an independent dosimetry system for Mayak workers by adapting ICRP models using a dataset of available bioassay measurements for this population. Thus, a dataset of 42 former Mayak workers, who died of non-radiation effects, with both urine bioassay and post-mortem tissue data was used to test these three approaches. All three approaches proved to be adequate for bioassay and tissue interpretation, and thus for Pu dose reconstruction purposes. However, large discrepancies are observed in the resulting quantitative dose estimates. These discrepancies can, in large part, be explained by differences in the interpretation of Pu behaviour in the lungs in the context of ICRP lung model. Thus, a careful validation of Pu lung dosimetry model is needed in Mayak worker dosimetry systems.

Evaluation of scattering factor values for internal dose assessment following the IDEAS guidelines: preliminary results.

The IDEAS Guidelines for the assessment of internal doses from monitoring data suggest default measurement uncertainties (i.e. scattering factors, SFs) to be used for different types of monitoring data. However, these default values were mainly based upon expert judgement. In this paper, SF values have been calculated for different radionuclides and types of monitoring data using real data contained in the IDEAS Internal Contamination Database. Results are presented.

Coordination of research on internal dosimetry in Europe: the CONRAD project.

The EUropean RAdiation DOSimetry Group (EURADOS) initiated in 2005 the CONRAD Project, a Coordinated Network for Radiation Dosimetry funded by the European Commission (EC), within the 6th Framework Programme (FP). The main purpose of CONRAD is to generate a European Network in the field of Radiation Dosimetry and to promote both research activities and dissemination of knowledge. The objective of CONRAD Work Package 5 (WP5) is the coordination of research on assessment and evaluation of internal exposures. Nineteen institutes from 14 countries participate in this action. Some of the activities to be developed are continuations of former European projects supported by the EC in the 5th FP (OMINEX and IDEAS). Other tasks are linked with ICRP activities, and there are new actions never considered before. A collaboration is established with CONRAD Work Package 4, dealing with Computational Dosimetry, to organise an intercomparison on Monte Carlo modelling for in vivo measurements of (241)Am deposited in a knee phantom. Preliminary results associated with CONRAD WP5 tasks are presented here.

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.

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): 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): 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-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.