M. A. Lopez

Spontaneous mutation for a quantitative trait in Drosophila melanogaster. I: Response to artificial selection

Divergent selection for abdominal bristle number was carried out for 47 generations, starting from a completely homozygous population of Drosophila melanogaster. All lines were selected with the same proportion (20%) but at two different numbers of selected parents of each sex (5 or 25). A significant response to selection was obtained in 25 lines (out of 40). In most cases, it could be wholly attributed to a single mutation of relatively large effect (> 0.3 phenotypic standard deviations). A total number of 30 mutations were detected. In agreement with theory, larger responses in each direction were achieved by those lines selected at greater effective population sizes. A large fraction of mutations were lethals (10/30). Thus, the observed divergence between lines of the same effective size selected in opposite directions was smaller than expected under neutrality. The ratio of new mutational variance to environmental variance was estimated to be (0.52 +/- 0.09) x 10(-3).

EURADOS-IDEAS GUIDELINES (VERSION 2) FOR THE ESTIMATION OF COMMITTED DOSES FROM INCORPORATION MONITORING DATA.

Dose assessment after intakes of radionuclides requires application of biokinetic and dosimetric models and assumptions about factors influencing the final result. In 2006, a document giving guidance for such assessment was published, commonly referred to as the IDEAS Guidelines. Following its publication, a working group within the European networks CONRAD and EURADOS was established to improve and update the IDEAS Guidelines. This work resulted in Version 2 of the IDEAS Guidelines, which was published in 2013 in the form of a EURADOS report. The general structure of the original document was maintained; however, new procedures were included, e.g. the direct dose assessment method for (3)H or special procedure for wound cases applying the NCRP wound model. In addition, information was updated and expanded, e.g. data on dietary excretion of U, Th, Ra and Po for urine and faeces or typical and achievable values for detection limits for different bioassay measurement techniques.

Biokinetic modelling of DTPA decorporation therapy: the CONRAD approach

Administration of diethylene triamine pentaacetic acid (DTPA) can enhance the urinary excretion rate of plutonium (Pu) for several days, but most of this Pu decorporation occurs on the first day after treatment. The development of a biokinetic model describing the mechanisms of decorporation of actinides by administration of DTPA was initiated as a task of the coordinated network for radiation dosimetry project. The modelling process was started by using the systemic biokinetic model for Pu from Leggett et al. and the biokinetic model for DTPA compounds of International Commission on Radiation Protection Publication 53. The chelation of Pu and DTPA to Pu-DTPA was treated explicitly and is assumed to follow a second-order process. It was assumed that the chelation takes place in the blood and in the rapid turnover soft tissues compartments of the Pu model, and that Pu-DTPA behaves in the same way as administered DTPA. First applications of this draft model showed that the height of the peak of urinary excretion after administration of DTPA was determined by the chelation rate. However, repetitions of DTPA administration shortly after the first one showed no effect in the application of the draft model in contrast to data from real cases. The present draft model is thus not yet realistic. Therefore several questions still have to be answered, notably about where the Pu-DTPA complexes are formed, which biological ligands of Pu are dissociated, if Pu-DTPA is stable and if the biokinetics of Pu-DTPA excretion is similar to that of DTPA. Further detailed studies of human contamination cases and experimental data about Pu-DTPA kinetics will be needed in order to address these issues. The work will now be continued within a working group of EURADOS.

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.

EURADOS intercomparison on measurements and Monte Carlo modelling for the assessment of americium in a USTUR leg phantom

A collaboration of the EURADOS working group on Internal Dosimetry and the United States Transuranium and Uranium Registries (USTUR) has taken place to carry out an intercomparison on measurements and Monte Carlo modelling determining americium deposited in the bone of a USTUR leg phantom. Preliminary results and conclusions of this intercomparison exercise are presented here.

THE CONRAD APPROACH TO BIOKINETIC MODELING OF DTPA DECORPORATION THERAPY

Diethylene Triamine Pentaacetic Acid (DTPA) is used for decorporation of plutonium because it is known to be able to enhance its urinary excretion for several days after treatment by forming stable Pu-DTPA complexes. The decorporation prevents accumulation in organs and results in a dosimetric benefit, which is difficult to quantify from bioassay data using existing models. The development of a biokinetic model describing the mechanisms of actinide decorporation by administration of DTPA was initiated as a task in the European COordinated Network on RAdiation Dosimetry (CONRAD). The systemic biokinetic model from Leggett et al. and the biokinetic model for DTPA compounds of International Commission on Radiological Protection Publication 53 were the starting points. A new model for biokinetics of administered DTPA based on physiological interpretation of 14C-labeled DTPA studies from literature was proposed by the group. Plutonium and DTPA biokinetics were modeled separately. The systems were connected by means of a second order kinetics process describing the chelation process of plutonium atoms and DTPA molecules to Pu-DTPA complexes. It was assumed that chelation only occurs in the blood and in systemic compartment ST0 (representing rapid turnover soft tissues), and that Pu-DTPA complexes and administered forms of DTPA share the same biokinetic behavior. First applications of the CONRAD approach showed that the enhancement of plutonium urinary excretion after administration of DTPA was strongly influenced by the chelation rate constant. Setting it to a high value resulted in a good fit to the observed data. However, the model was not yet satisfactory since the effects of repeated DTPA administration in a short time period cannot be predicted in a realistic way. In order to introduce more physiological knowledge into the model several questions still have to be answered. Further detailed studies of human contamination cases and experimental data will be needed in order to address these issues. The work is now continued within the European Radiation Dosimetry Group, EURADOS.

EURADOS strategic research agenda: vision for dosimetry of ionising radiation

Since autumn 2012, the European Radiation Dosimetry Group (EURADOS) has been developing its Strategic Research Agenda (SRA), which is intended to contribute to the identification of future research needs in radiation dosimetry in Europe. The present article summarises-based on input from EURADOS Working Groups (WGs) and Voting Members-five visions in dosimetry and defines key issues in dosimetry research that are considered important for the next decades. The five visions include scientific developments required towards (a) updated fundamental dose concepts and quantities, (b) improved radiation risk estimates deduced from epidemiological cohorts, (c) efficient dose assessment for radiological emergencies, (d) integrated personalised dosimetry in medical applications and (e) improved radiation protection of workers and the public. The SRA of EURADOS will be used as a guideline for future activities of the EURADOS WGs. A detailed version of the SRA can be downloaded as a EURADOS report from the EURADOS website (www.eurados.org).

EURADOS coordinated action on research, quality assurance and training of internal dose assessments

EURADOS working group on Internal Dosimetry (WG7) represents a frame to develop activities in the field of internal exposures as coordinated actions on quality assurance (QA), research and training. The main tasks to carry out are the update of the IDEAS Guidelines as a reference document for the internal dosimetry community, the implementation and QA of new ICRP biokinetic models, the assessment of uncertainties related to internal dosimetry models and their application, the development of physiology-based models for biokinetics of radionuclides, stable isotope studies, biokinetic modelling of diethylene triamine pentaacetic acid decorporation therapy and Monte-Carlo applications to in vivo assessment of intakes. The working group is entirely supported by EURADOS; links are established with institutions such as IAEA, US Transuranium and Uranium Registries (USA) and CEA (France) for joint collaboration actions.

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.

EURADOS intercomparison on emergency radiobioassay

Nine laboratories participated in an intercomparison exercise organised by the European Radiation Dosimetry Group (EURADOS) for emergency radiobioassay involving four high-risk radionuclides ((239)Pu, (241)Am, (90)Sr and (226)Ra). Diverse methods of analysis were used by the participating laboratories for the in vitro determination of each of the four radionuclides in urine samples. Almost all the methods used are sensitive enough to meet the requirements for emergency radiobioassay derived for this project in reference to the Clinical Decision Guide introduced by the NCRP. Results from most of the methods meet the requirements of ISO 28218 on accuracy in terms of relative bias and relative precision. However, some technical gaps have been identified. For example, some laboratories do not have the ability to assay samples containing (226)Ra, and sample turnaround time would be expected to be much shorter than that reported by many laboratories, as timely results for internal contamination and early decisions on medical intervention are highly desired. Participating laboratories are expected to learn from each other on the methods used to improve the interoperability among these laboratories.