Resilience after a nuclear accident: readiness in using mobile phone applications to measure radiation and health indicators in various groups (SHAMISEN SINGS project).

An anonymous web-based survey was developed to check different aspects (SHAMISEN SINGS project): stakeholder awareness and perceptions of available mobile applications (apps) for measuring ionising radiation doses and health/well-being indicators; whether they would be ready to use them in the post-accidental recovery; and what are their preferred methodologies to acquire information etc. The results show that participation of the citizens would be most beneficial during post-accident recovery, providing individual measurements of external ionizing dose and health/well-being parameters, with possible follow-up. Also, participants indicated different preferences for sources to gain knowledge on ionising radiation and for the functions that an ideal app should have. The level of awareness and readiness to use apps to measure ionising radiation dose depended on two main aspects: individual differences (age & gender) and whether people were from countries affected by the previous major accidents. We concluded that stakeholders could have benefits from the data management plan: (1) it potentiates resilience at individual and community level; (2) citizens' measurements contribute to environmental monitoring and public health screening; (3) linkages between different types of data (environmental exposure, individual behavioural diaries, and measurements of health indicators) allow to perform more rigorous epidemiological studies.

International Comparison Exercise for Biological Dosimetry after Exposures with Neutrons Performed at Two Irradiation Facilities as Part of the BALANCE Project.

In the case of a radiological or nuclear event, biological dosimetry can be an important tool to support clinical decision-making. During a nuclear event, individuals might be exposed to a mixed field of neutrons and photons. The composition of the field and the neutron energy spectrum influence the degree of damage to the chromosomes. During the transatlantic BALANCE project, an exposure similar to a Hiroshima-like device at a distance of 1.5 km from the epicenter was simulated, and biological dosimetry based on dicentric chromosomes was performed to evaluate the participants ability to discover unknown doses and to test the influence of differences in neutron spectra. In a first step, calibration curves were established by irradiating blood samples with 5 doses in the range of 0-4 Gy at two different facilities in Germany (Physikalisch-Technische Bundesanstalt [PTB]) and the USA (the Columbia IND Neutron Facility [CINF]). The samples were sent to eight participating laboratories from the RENEB network and dicentric chromosomes were scored by each participant. Next, blood samples were irradiated with 4 blind doses in each of the two facilities and sent to the participants to provide dose estimates based on the established calibration curves. Manual and semiautomatic scoring of dicentric chromosomes were evaluated for their applicability to neutron exposures. Moreover, the biological effectiveness of the neutrons from the two irradiation facilities was compared. The calibration curves from samples irradiated at CINF showed a 1.4 times higher biological effectiveness compared to samples irradiated at PTB. For manual scoring of dicentric chromosomes, the doses of the test samples were mostly successfully resolved based on the calibration curves established during the project. For semiautomatic scoring, the dose estimation for the test samples was less successful. Doses >2 Gy in the calibration curves revealed nonlinear associations between dose and dispersion index of the dicentric counts, especially for manual scoring. The differences in the biological effectiveness between the irradiation facilities suggested that the neutron energy spectrum can have a strong impact on the dicentric counts.

Evaluation of γ-H2AX foci distribution among different peripheral blood mononucleated cell subtypes.

INTRODUCTION: The detection of γ-H2AX foci in peripheral blood mononucleated cells (PBMCs) has been incorporated as an early assay for biological dosimetry. However, overdispersion in the γ-H2AX foci distribution is generally reported. In a previous study from our group, it was suggested that overdispersion could be caused by the fact that when evaluating PBMCs, different cell subtypes are analyzed, and that these could differ in their radiosensitivity. This would cause a mixture of different frequencies that would result in the overdispersion observed. OBJECTIVES: The objective of this study was to evaluate both the possible differences in the radiosensitivities of the different cell subtypes present in the PBMCs and to evaluate the distribution of γ-H2AX foci in each cell subtype. MATERIALS AND METHODS: Peripheral blood samples from three healthy donors were obtained and total PBMCs, and CD3+, CD4+, CD8+, CD19+, and CD56+ cells were separated. Cells were irradiated with 1 and 2 Gy and incubated at 37 °C for 1, 2, 4, and 24 h. Sham-irradiated cells were also analyzed. γ-H2AX foci were detected after immunofluorescence staining and analyzed automatically using a Metafer Scanning System. For each condition, 250 nuclei were considered. RESULTS: When the results from each donor were compared, no observable significant differences between donors were observed. When the different cell subtypes were compared, CD8+ cells showed the highest mean of γ-H2AX foci in all post-irradiation time points. The cell type that showed the lowest γ-H2AX foci frequency was CD56+. The frequencies observed in CD4+ and CD19+ cells fluctuated between CD8+ and CD56+ without any clear pattern. For all cell types evaluated, and at all post-irradiation times, overdispersion in γ-H2AX foci distribution was significant. Independent of the cell type evaluated the value of the variance was four times greater than that of the mean. CONCLUSION: Although different PBMC subsets studied showed different radiation sensitivity, these differences did not explain the overdispersion observed in the γ-H2AX foci distribution after exposure to IR.

Biodose Tools: an R shiny application for biological dosimetry.

INTRODUCTION: In the event of a radiological accident or incident, the aim of biological dosimetry is to convert the yield of a specific biomarker of exposure to ionizing radiation into an absorbed dose. Since the 1980s, various tools have been used to deal with the statistical procedures needed for biological dosimetry, and in general those who made several calculations for different biomarkers were based on closed source software. Here we present a new open source program, Biodose Tools, that has been developed under the umbrella of RENEB (Running the European Network of Biological and retrospective Physical dosimetry). MATERIALS AND METHODS: The application has been developed using the R programming language and the shiny package as a framework to create a user-friendly online solution. Since no unique method exists for the different mathematical processes, several meetings and periodic correspondence were held in order to reach a consensus on the solutions to be implemented. RESULTS: The current version 3.6.1 supports dose-effect fitting for dicentric and translocation assay. For dose estimation Biodose Tools implements those methods indicated in international guidelines and a specific method to assess heterogeneous exposures. The app can include information on the irradiation conditions to generate the calibration curve. Also, in the dose estimate, information about the accident can be included as well as the explanation of the results obtained. Because the app allows generating a report in various formats, it allows traceability of each biological dosimetry study carried out. The app has been used globally in different exercises and training, which has made it possible to find errors and improve the app itself. There are some features that still need consensus, such as curve fitting and dose estimation using micronucleus analysis. It is also planned to include a package dedicated to interlaboratory comparisons and the incorporation of Bayesian methods for dose estimation. CONCLUSION: Biodose Tools provides an open-source solution for biological dosimetry laboratories. The consensus reached helps to harmonize the way in which uncertainties are calculated. In addition, because each laboratory can download and customize the app's source code, it offers a platform to integrate new features.

Assessment methods for inter-laboratory comparisons of the dicentric assay.

PURPOSE: To test the performance of different algorithms that can be used in inter-laboratory comparisons based on dicentric chromosome analysis, and to evaluate the impact of considering a priori values different to calculate individual laboratory performance based on the ionizing radiation dose estimation. METHODS: Mean and standard deviation estimations in inter-laboratory comparisons are tested on simulated data and data from previously published inter-laboratory comparisons using three robust algorithms, Algorithm A, Algorithm B and Q/Hampel, all programmed in R-project language and implemented in a Shiny application. The simulated data were generated assuming three different probabilities to contaminate inter-laboratory comparisons samples with atypical dose values. Comparison between different algorithms was also done using published exercises where blood samples were irradiated at 0 and 0.7 Gy that represent a challenge for the assessment of an inter-laboratory comparison. RESULTS: The best performance was obtained with the Q/Hampel algorithm for the estimation of the dose mean and with the Algorithm B for the estimation of the dose standard deviation under the conditions tested in the simulations. The Q/Hampel algorithm showed the best performance when non-irradiated samples were evaluated and there was a high proportion of identical values. The presence identical values cause the Algorithm B to fail. Real examples illustrating the need to consider standard deviation priors, and the need to use algorithms resistant to a high proportion of identical values are presented. CONCLUSIONS: Q/Hampel algorithm is a serious candidate to estimate the dose mean in the inter-laboratory comparisons, and to estimate both parameters when the proportion of identical values equals or higher than the half of the results. When the proportion of identical values is less than the half of the results, the Algorithm B should be considered as a candidate to estimate the standard deviation in the inter-laboratory comparisons with small number of laboratories. We remark that special attention is needed to establish prior definitions of standard deviation in the assessment of inter-laboratory dicentric assay comparisons.

Differential Radiosensitizing Effect of 50 nm Gold Nanoparticles in Two Cancer Cell Lines.

Radiation therapy is widely used as an anti-neoplastic treatment despite the adverse effects it can cause in non-tumoral tissues. Radiosensitizing agents, which can increase the effect of radiation in tumor cells, such as gold nanoparticles (GNPs), have been described. To evaluate the radiosensitizing effect of 50 nm GNPs, we carried out a series of studies in two neoplastic cell lines, Caco2 (colon adenocarcinoma) and SKBR3 (breast adenocarcinoma), qualitatively evaluating the internalization of the particles, determining with immunofluorescence the number of γ-H2AX foci after irradiation with ionizing radiation (3 Gy) and evaluating the viability rate of both cell lines after treatment by means of an MTT assay. Nanoparticle internalization varied between cell lines, though they both showed higher internalization degrees for functionalized GNPs. The γ-H2AX foci counts for the different times analyzed showed remarkable differences between cell lines, although they were always significantly higher for functionalized GNPs in both lines. Regarding cell viability, in most cases a statistically significant decreasing tendency was observed when treated with GNPs, especially those that were functionalized. Our results led us to conclude that, while 50 nm GNPs induce a clear radiosensitizing effect, it is highly difficult to describe the magnitude of this effect as universal because of the heterogeneity found between cell lines.

RENEB/EURADOS field exercise 2019: robust dose estimation under outdoor conditions based on the dicentric chromosome assay.

PURPOSE: Biological and/or physical assays for retrospective dosimetry are valuable tools to recover the exposure situation and to aid medical decision making. To further validate and improve such biological and physical assays, in 2019, EURADOS Working Group 10 and RENEB performed a field exercise in Lund, Sweden, to simulate various real-life exposure scenarios. MATERIALS AND METHODS: For the dicentric chromosome assay (DCA), blood tubes were located at anthropomorphic phantoms positioned in different geometries and were irradiated with a 1.36 TBq 192Ir-source. For each exposure condition, dose estimates were provided by at least one laboratory and for four conditions by 17 participating RENEB laboratories. Three radio-photoluminescence glass dosimeters were placed at each tube to assess reference doses. RESULTS: The DCA results were homogeneous between participants and matched well with the reference doses (≥95% of estimates within ±0.5 Gy of the reference). For samples close to the source systematic underestimation could be corrected by accounting for exposure time. Heterogeneity within and between tubes was detected for reference doses as well as for DCA doses estimates. CONCLUSIONS: The participants were able to successfully estimate the doses and to provide important information on the exposure scenarios under conditions closely resembling a real-life situation.

RENEB Inter-Laboratory comparison 2017: limits and pitfalls of ILCs.

PURPOSE: In case of a mass-casualty radiological event, there would be a need for networking to overcome surge limitations and to quickly obtain homogeneous results (reported aberration frequencies or estimated doses) among biodosimetry laboratories. These results must be consistent within such network. Inter-laboratory comparisons (ILCs) are widely accepted to achieve this homogeneity. At the European level, a great effort has been made to harmonize biological dosimetry laboratories, notably during the MULTIBIODOSE and RENEB projects. In order to continue the harmonization efforts, the RENEB consortium launched this intercomparison which is larger than the RENEB network, as it involves 38 laboratories from 21 countries. In this ILC all steps of the process were monitored, from blood shipment to dose estimation. This exercise also aimed to evaluate the statistical tools used to compare laboratory performance. MATERIALS AND METHODS: Blood samples were irradiated at three different doses, 1.8, 0.4 and 0 Gy (samples A, C and B) with 4-MV X-rays at 0.5 Gy min-1, and sent to the participant laboratories. Each laboratory was requested to blindly analyze 500 cells per sample and to report the observed frequency of dicentric chromosomes per metaphase and the corresponding estimated dose. RESULTS: This ILC demonstrates that blood samples can be successfully distributed among laboratories worldwide to perform biological dosimetry in case of a mass casualty event. Having achieved a substantial harmonization in multiple areas among the RENEB laboratories issues were identified with the available statistical tools, which are not capable to advantageously exploit the richness of results of a large ILCs. Even though Z- and U-tests are accepted methods for biodosimetry ILCs, setting the number of analyzed metaphases to 500 and establishing a tests' common threshold for all studied doses is inappropriate for evaluating laboratory performance. Another problem highlighted by this ILC is the issue of the dose-effect curve diversity. It clearly appears that, despite the initial advantage of including the scoring specificities of each laboratory, the lack of defined criteria for assessing the robustness of each laboratory's curve is a disadvantage for the 'one curve per laboratory' model. CONCLUSIONS: Based on our study, it seems relevant to develop tools better adapted to the collection and processing of results produced by the participant laboratories. We are confident that, after an initial harmonization phase reached by the RENEB laboratories, a new step toward a better optimization of the laboratory networks in biological dosimetry and associated ILC is on the way.

Lessons from past radiation accidents: Critical review of methods addressed to individual dose assessment of potentially exposed people and integration with medical assessment.

The experiences of the Chernobyl and Fukushima nuclear accidents showed that dosimetry was the essential tool in the emergency situation for decision making processes, such as evacuation and application of protective measures. However, at the consequent post-accidental phases, it was crucial also for medical health surveillance and in further adaptation to changed conditions with regards to radiation protection of the affected populations. This review provides an analysis of the experiences related to the role of dosimetry (dose measurements, assessment and reconstruction) regarding health preventive measures in the post-accidental periods on the examples of the major past nuclear accidents such as Chernobyl and Fukushima. Recommendations derived from the review are called to improve individual dose assessment in case of a radiological accident/incident and should be considered in advance as guidelines to follow for having better information. They are given as conclusions.

Redox Status, Dose and Antioxidant Intake in Healthcare Workers Occupationally Exposed to Ionizing Radiation.

The purpose of this study was to evaluate the relationship between blood redox status, dose and antioxidant dietary intake of different hospital staff groups exposed to low doses of ionizing radiation (LDIR) (Interventional Radiology and Cardiology, Radiation Oncology, and Nuclear Medicine) and non-exposed. Personal dose equivalent (from last year and cumulative), plasma antioxidant markers (total antioxidant capacity, extracellular superoxide dismutase activity, and glutathione/oxidized glutathione ratio), oxidative stress markers (nitrites and nitrates, and lipid peroxidation) and dietary intake (antioxidant capacity using ORAC values) were collected and analyzed from 28 non-exposed healthcare workers and 42 healthcare workers exposed to LDIR. Hospital staff exposed to LDIR presented a redox imbalance in blood that seems to correlate with dose. Workers from the Nuclear Medicine Unit were the most affected group with the lowest value of plasma antioxidant response and the highest value of plasma thiobarbituric acid reactive substances, TBARS (indicator of lipid peroxidation) of all four groups. Cumulative personal dose equivalent positively correlated with nitrites and negatively correlated with total antioxidant capacity in blood. The diet of healthcare workers from Nuclear Medicine Unit had higher ORAC values than the diet of non-exposed. Therefore, occupational exposure to LDIR, especially for the Nuclear Medicine Unit, seems to produce an imbalanced redox status in blood that would correlate with cumulative personal dose equivalent.

Chromosomal aberration dynamics through the cell cycle.

DNA double-strand breaks are the crucial lesions underlying the formation of chromosomal aberrations, their formation and kinetics have been extensively studied, although dynamics of the repair process has not been fully understood. By using a combination of different cytogenetic techniques to analyze cells in G0, G2 and M phase, in the present study we perform a follow up study of the dynamics of different radiation induced chromosomal aberrations. Data here presented show that in G0 phase chromosome fragments lacking telomere signals (incomplete chromosome elements, ICE) show a slow repair, but when repair occurs tend to reconstitute the original chromosomes, and those that do not repair seem to be selected by interphase cell death and cell cycle checkpoints. In contrast, complete chromosome aberrations, as dicentrics, show a very fast formation kinetics. Similar frequencies of dicentrics were observed in G0, G2 and M cells, indicating that this chromosome-type of aberration can progress through the cell cycle without negative selection. Our study reinforce the hypothesis that ICE are strongly negatively selected from G2 to M phase. However, the G2/M checkpoint seems to be not involved in this selection. The ICE frequencies observed after G2/M abrogation by caffeine are similar to the ones without abrogation, and clearly lower to the ones observed in G2.

From Energy Deposition of Ionizing Radiation to Cell Damage Signaling: Benchmarking Simulations by Measured Yields of Initial DNA Damage after Ion Microbeam Irradiation.

Advances in accelerator technology, which have enabled conforming radiotherapy with charged hadronic species, have brought benefits as well as potential new risks to patients. To better understand the effects of ionizing radiation on tumor and surrounding tissue, it is important to investigate and quantify the relationship between energy deposition at the nanometric scale and the initial biological events. Monte Carlo track structure simulation codes provide a powerful tool for investigating this relationship; however, their success and reliability are dependent on their improvement and development accordingly to the dedicated biological data to which they are challenged. For this aim, a microbeam facility that allows for fluence control, down to one ion per cell nucleus, was used to evaluate relative frequencies of DNA damage after interaction between the incoming ion and DNA according to radiation quality. Primary human cells were exposed to alpha particles of three different energies with respective linear energy transfers (LETs) of approximately 36, 85 or 170 keV·µm-1 at the cells' center position, or to protons (19 keV·µm-1). Statistical evaluation of nuclear foci formation (53BP1/γ-H2AX), observed using immunofluorescence and related to a particle traversal, was undertaken in a large population of cell nuclei. The biological results were adjusted to consider the factors that drive the experimental uncertainties, then challenged with results using Geant4-DNA code modeling of the ionizing particle interactions on a virtual phantom of the cell nucleus with the same mean geometry and DNA density as the cells used in our experiments. Both results showed an increase of relative frequencies of foci (or simulated DNA damage) in cell nuclei as a function of increasing LET of the traversing particles, reaching a quasi-plateau when the LET exceeded 80-90 keV·µm-1. For the LET of an alpha particle ranging from 80-90 to 170 keV·µm-1, 10-30% of the particle hits did not lead to DNA damage inducing 53BP1 or γ-H2AX foci formation.

Polymorphisms in MDM2 and TP53 Genes and Risk of Developing Therapy-Related Myeloid Neoplasms.

One of the most severe complications after successful cancer therapy is the development of therapy-related myeloid neoplasms (t-MN). Constitutional genetic variation is likely to impact on t-MN risk. We aimed to evaluate if polymorphisms in the p53 pathway can be useful for predicting t-MN susceptibility. First, an association study revealed that the Pro variant of the TP53 Arg72Pro polymorphism and the G allele of the MDM2 SNP309 were associated with t-MN risk. The Arg variant of TP53 is more efficient at inducing apoptosis, whereas the Pro variant is a more potent inductor of cell cycle arrest and DNA repair. As regards MDM2 SNP309, the G allele is associated with attenuation of the p53 apoptotic response. Second, to evaluate the biological effect of the TP53 polymorphism, we established Jurkat isogenic cell lines expressing p53Arg or p53Pro. Jurkat p53Arg cells presented higher DNA damage and higher apoptotic potential than p53Pro cells, after treatment with chemotherapy agents. Only p53Pro cells presented t(15;17) translocation and del(5q). We suggest that failure to repair DNA lesions in p53Arg cells would lead them to apoptosis, whereas some p53Pro cells, prone to cell cycle arrest and DNA repair, could undergo misrepair, generating chromosomal abnormalities typical of t-MN.

Cytogenetic damage analysis in mice chronically exposed to low-dose internal tritium beta-particle radiation.

The aim of this study was to carry out a comprehensive examination of potential genotoxic effects of low doses of tritium delivered chronically to mice and to compare these effects to the ones resulting from equivalent doses of gamma-irradiation. Mice were chronically exposed for one or eight months to either tritiated water (HTO) or organically bound tritium (OBT) in drinking water at concentrations of 10 kBq/L, 1 MBq/L or 20 MBq/L. Dose rates of internal ß-particle resulting from such tritium treatments were calculated and matching external gamma-exposures were carried out. We measured cytogenetic damage in bone marrow and in peripheral blood lymphocytes (PBLs) and the cumulative tritium doses (0.009 - 181 mGy) were used to evaluate the dose-response of OBT in PBLs, as well as its relative biological effectiveness (RBE). Neither tritium, nor gamma exposures produced genotoxic effects in bone marrow. However, significant increases in chromosome damage rates in PBLs were found as a result of chronic OBT exposures at 1 and 20 M Bq/L, but not at 10 kBq/L. When compared to an external acute gamma-exposure ex vivo, the RBE of OBT for chromosome aberrations induction was evaluated to be significantly higher than 1 at cumulative tritium doses below 10 mGy. Although found non-existent at 10 kBq/L (the WHO limit), the genotoxic potential of low doses of tritium (>10 kBq/L), mainly OBT, may be higher than currently assumed.

Twenty years of FISH-based translocation analysis for retrospective ionizing radiation biodosimetry.

PURPOSE: The fluorescent in situ hybridization (FISH) technique, which easily detects reciprocal translocations, is currently used to estimate doses in retrospective biological dosimetry, after suspected accidental overexposure to ionizing radiation (IR). This study of 42 cases aimed to verify the appropriateness of this assay for radiation dose reconstruction, compared to the dicentric assay, and to evaluate other limitations. MATERIAL AND METHODS: We labeled chromosomes 2, 4, and 12 by 3-color FISH painting to detect translocations on lymphocytes of patients with suspected past IR overexposure. RESULT: Translocation dose estimation showed doses significantly different from 0 Gy in 25 of the 42 cases. The lowest positive dose measured was 0.3 Gy. Several months after IR exposure, the doses measured by translocation and dicentric assays are quite similar. For a year, dose estimation by translocation assay becomes more relevant as dicentric frequency starts to decrease, coming close to 0 for more than a year after the exposure. The persistence of translocations enabled us to corroborate an overexposure 44 years earlier. Interpretation of the observed translocation yield requires the knowledge of the patient's other radiation exposures. A dose assessment by this biomarker is relevant only if the radiation exposure is confirmed. CONCLUSIONS: This technique is appropriate for corroborating a former IR exposure of individuals. When the radiation dose is greater than 1 Gy, the translocations in complex exchanges must be considered. Another relevant point is the use of an appropriate background yield of translocations. The dose assessment, however, also depends on exposure to various genotoxic agents besides IR. If no evidence about the existence of radiation exposure is available, dose assessment is not useful. For this reason, report only the translocation frequency and its comparison with the background yield by age class is preferable.

Transmission of persistent ionizing radiation-induced foci through cell division in human primary cells.

Unrepaired DNA double-strand breaks (DSBs) induced by ionizing radiation are associated with lethal effects and genomic instability. After the initial breaks and chromatin destabilization, a set of post-translational modifications of histones occurs, including phosphorylation of serine 139 of histone H2AX (γH2AX), which leads to the formation of ionizing radiation-induced foci (IRIF). DSB repair results in the disappearance of most IRIF within hours after exposure, although some remain 24h after irradiation. Their relation to unrepaired DSBs is generally accepted but still controversial. This study evaluates the frequency and kinetics of persistent IRIF and analyzes their impact on cell proliferation. We observed persistent IRIF up to 7 days postirradiation, and more than 70% of cells exposed to 5Gy had at least one of these persistent IRIF 24h after exposure. Moreover we demonstrated that persistent IRIF did not block cell proliferation definitively. The frequency of IRIF was lower in daughter cells, due to asymmetric distribution of IRIF between some of them. We report a positive association between the presence of IRIF and the likelihood of DNA missegregation. Hence, the structure formed after the passage of a persistent IRI focus across the S and G2 phases may impede the correct segregation of the affected chromosome's sister chromatids. The ensuing abnormal resolution of anaphase might therefore cause the nature of IRIF in daughter-cell nuclei to differ before and after the first cell division. The resulting atypical chromosomal assembly may be lethal or result in a gene dosage imbalance and possibly enhanced genomic instability, in particular in the daughter cells.

RENEB - Running the European Network of biological dosimetry and physical retrospective dosimetry.

PURPOSE: A European network was initiated in 2012 by 23 partners from 16 European countries with the aim to significantly increase individualized dose reconstruction in case of large-scale radiological emergency scenarios. RESULTS: The network was built on three complementary pillars: (1) an operational basis with seven biological and physical dosimetric assays in ready-to-use mode, (2) a basis for education, training and quality assurance, and (3) a basis for further network development regarding new techniques and members. Techniques for individual dose estimation based on biological samples and/or inert personalized devices as mobile phones or smart phones were optimized to support rapid categorization of many potential victims according to the received dose to the blood or personal devices. Communication and cross-border collaboration were also standardized. To assure long-term sustainability of the network, cooperation with national and international emergency preparedness organizations was initiated and links to radiation protection and research platforms have been developed. A legal framework, based on a Memorandum of Understanding, was established and signed by 27 organizations by the end of 2015. CONCLUSIONS: RENEB is a European Network of biological and physical-retrospective dosimetry, with the capacity and capability to perform large-scale rapid individualized dose estimation. Specialized to handle large numbers of samples, RENEB is able to contribute to radiological emergency preparedness and wider large-scale research projects.

Investigation of the influence of calibration practices on cytogenetic laboratory performance for dose estimation.

PURPOSE: In the frame of the QA program of RENEB, an inter-laboratory comparison (ILC) of calibration sources used in biological dosimetry was achieved to investigate the influence of calibration practices and protocols on the results of the dose estimation performance as a first step to harmonization and standardization of dosimetry and irradiation practices in the European biological dosimetry network. MATERIALS AND METHODS: Delivered doses by irradiation facilities used by RENEB partners were determined with EPR/alanine dosimetry system. Dosimeters were irradiated in the same conditions as blood samples. A short survey was also performed to collect the information needed for the data analysis and evaluate the diversity of practices. RESULTS: For most of partners the deviation of delivered dose from the targeted dose remains below 10%. Deviations larger than 10% were observed for five facilities out of 21. Origins of the largest discrepancies were identified. Correction actions were evaluated as satisfactory. The re-evaluation of some ILC results for the fluorescence in situ hybridization (FISH) and premature chromosome condensation (PCC) assays has been performed leading to an improvement of the overall performances. CONCLUSIONS: This work has shown the importance of dosimetry in radiobiology studies and the needs of harmonization, standardization in irradiation and dosimetry practices and educational training for biologists using ionizing radiation.

Web based scoring is useful for validation and harmonisation of scoring criteria within RENEB.

PURPOSE: To establish a training data set of digital images and to investigate the scoring criteria and dose assessment of the dicentric assay within the European network of biodosimetry (RENEB), a web based scoring inter-comparison was undertaken by 17 RENEB partners. MATERIALS AND METHODS: Two sets of 50 high resolution images were uploaded onto the RENEB website. One set included metaphases after a moderate exposure (1.3 Gy) and the other set consisted of metaphases after a high dose exposure (3.5 Gy). The laboratories used their own calibration curves for estimating doses based on observed aberration frequencies. RESULTS: The dose estimations and 95% confidence limits were compared to the actual doses and the corresponding z-values were satisfactory for the majority; only the dose estimations from two laboratories were too low or too high. The coefficients of variation were 17.6% for the moderate and 11.2% for the high dose. Metaphases with controversial results could be identified for training purposes. CONCLUSIONS: Overall, the web based scoring of the two galleries by the 17 laboratories produced very good results. Application of web based scoring for the dicentric assay may therefore be a relevant strategy for an operational biodosimetry assistance network.

Uncertainty of fast biological radiation dose assessment for emergency response scenarios.

PURPOSE: Reliable dose estimation is an important factor in appropriate dosimetric triage categorization of exposed individuals to support radiation emergency response. MATERIALS AND METHODS: Following work done under the EU FP7 MULTIBIODOSE and RENEB projects, formal methods for defining uncertainties on biological dose estimates are compared using simulated and real data from recent exercises. RESULTS: The results demonstrate that a Bayesian method of uncertainty assessment is the most appropriate, even in the absence of detailed prior information. The relative accuracy and relevance of techniques for calculating uncertainty and combining assay results to produce single dose and uncertainty estimates is further discussed. CONCLUSIONS: Finally, it is demonstrated that whatever uncertainty estimation method is employed, ignoring the uncertainty on fast dose assessments can have an important impact on rapid biodosimetric categorization.