Comparison of external dose estimates using different retrospective dosimetry methods in the settlements located near Semipalatinsk Nuclear Test Site, Republic of Kazakhstan.

For correct assessment of health risks after low-dose irradiation, calculation of radiation exposure estimates is crucial. To verify the calculated absorbed doses, instrumental methods of retrospective dosimetry are used. We compared calculated and instrumental-based estimates of external absorbed doses in the residents of Dolon, Mostik and Cheremushki villages, Kazakhstan, affected by the first nuclear weapon test performed at the Semipalatinsk Nuclear Test Site (SNTS) on August 29, 1949. The 'instrumental' doses were retrospectively estimated using the Luminescence Retrospective Dosimetry (LRD) and Electron Spin Resonance (ESR) methods. Correlation between the calculated individual cumulative external absorbed whole-body doses based on typical input data and ESR-based individual doses in the same people was strong (r = 0.782). It was even stronger between the calculated doses based on individual questionnaires' input data and the ESR-based doses (r = 0.940). Application of the LRD method is useful for validation of the calculated settlement-average cumulated external absorbed dose to air. Reconstruction of external exposure can be supplemented with the data from later measurements of soil contamination with long-lived radionuclides, such as, 137Cs. Our results show the reliability of the calculational method used for the retrospective assessment of individual external doses.

Response to Tsuda et al. "demonstrating the undermining of science and health policy after the Fukushima nuclear accident by applying the toolkit for detecting misused epidemiological methods".

BACKGROUND: The SHAMISEN (Nuclear Emergency Situations - Improvement of Medical And Health Surveillance) European project was conducted in 2015-2017 to review the lessons learned from the experience of past nuclear accidents and develop recommendations for preparedness and health surveillance of populations affected by a nuclear accident. Using a toolkit approach, Tsuda et al. recently published a critical review of the article by Cléro et al. derived from the SHAMISEN project on thyroid cancer screening after nuclear accident. MAIN BODY: We address the main points of criticism of our publication on the SHAMISEN European project. CONCLUSION: We disagree with some of the arguments and criticisms mentioned by Tsuda et al. We continue to support the conclusions and recommendations of the SHAMISEN consortium, including the recommendation not to launch a mass thyroid cancer screening after a nuclear accident, but rather to make it available (with appropriate information counselling) to those who request it.

Lessons learned from Chernobyl and Fukushima on thyroid cancer screening and recommendations in case of a future nuclear accident.

Exposure of the thyroid gland to ionizing radiation at a young age is the main recognized risk factor for differentiated thyroid cancer. After the Chernobyl and Fukushima nuclear accidents, thyroid cancer screening was implemented mainly for children, leading to case over-diagnosis as seen in South Korea after the implementation of opportunistic screening (where subjects are recruited at healthcare sites). The aim of cancer screening is to reduce morbidity and mortality, but screening can also cause negative effects on health (with unnecessary treatment if over-diagnosis) and on quality of life. This paper from the SHAMISEN special issue (Nuclear Emergency Situations - Improvement of Medical And Health Surveillance) presents the principles of cancer screening, the lessons learned from thyroid cancer screening, as well as the knowledge on thyroid cancer incidence after exposure to iodine-131. The SHAMISEN Consortium recommends to envisage systematic health screening after a nuclear accident, only when appropriately justified, i.e. ensuring that screening will do more good than harm. Based on the experience of the Fukushima screening, the consortium does not recommend mass or population-based thyroid cancer screening, as the negative psychological and physical effects are likely to outweigh any possible benefit in affected populations; thyroid health monitoring should however be made available to persons who request it (regardless of whether they are at increased risk or not), accompanied with appropriate information and support.

Establishing the Japan-Store house of animal radiobiology experiments (J-SHARE), a large-scale necropsy and histopathology archive providing international access to important radiobiology data.

Purpose: Projects evaluating the effects of radiation, within the National Institutes of Quantum and Radiological Science and Technology (QST), National Institute of Radiological Sciences (NIRS), have focused on risk analyses for life shortening and cancer prevalence using laboratory animals. Genetic and epigenetic alterations in radiation-induced tumors have been also analyzed with the aim of better understanding mechanisms of radiation carcinogenesis. As well as the economic and practical limitations of repeating such large-scale experiments, ethical considerations make it vital that we store and share the pathological data and samples of the animal experiments for future use. We are now constructing such an archive called the Japan-Storehouse of Animal Radiobiology Experiments (J-SHARE). Methods: J-SHARE records include information such as detailed experimental protocols, necropsy records and photographs of organs at necropsy. For each animal organs and tumor tissues are dissected, and parts are stored as frozen samples at -80 °C. Samples fixed with formalin are also embedded in paraffin blocks for histopathological analyses. Digital copies of stained tissues are being systematically saved using a virtual slide system linked to original records by barcodes. Embedded and frozen tissues are available for molecular analysis. Conclusion: Similar archive systems for radiation biology have also been under construction in the USA and Europe, the Northwestern University Radiation Archive (NURA), and STORE at the BfS, respectively. The J-SHARE will be linked with the sister-archives and made available for collaborative research to institutions and universities all over the world.

Big data in radiation biology and epidemiology; an overview of the historical and contemporary landscape of data and biomaterial archives.

Over the past 60 years a great number of very large datasets have been generated from the experimental exposure of animals to external radiation and internal contamination. This accumulation of 'big data' has been matched by increasingly large epidemiological studies from accidental and occupational radiation exposure, and from plants, humans and other animals affected by environmental contamination. We review the creation, sustainability and reuse of this legacy data, and discuss the importance of Open data and biomaterial archives for contemporary radiobiological sciences, radioecology and epidemiology. We find evidence for the ongoing utility of legacy datasets and biological materials, but that the availability of these resources depends on uncoordinated, often institutional, initiatives to curate and archive them. The importance of open data from contemporary experiments and studies is also very clear, and yet there are few stable platforms for their preservation, sharing, and reuse. We discuss the development of the ERA and STORE data sharing platforms for the scientific community, and their contribution to FAIR sharing of data. The contribution of funding agency and journal policies to the support of data sharing is critical for the maximum utilisation and reproducibility of publicly funded research, but this needs to be matched by training in data management and cultural changes in the attitudes of investigators to ensure the sustainability of the data and biomaterial commons.

Typical doses and dose rates in studies pertinent to radiation risk inference at low doses and low dose rates.

In order to quantify radiation risks at exposure scenarios relevant for radiation protection, often extrapolation of data obtained at high doses and high dose rates down to low doses and low dose rates is needed. Task Group TG91 on 'Radiation Risk Inference at Low-dose and Low-dose Rate Exposure for Radiological Protection Purposes' of the International Commission on Radiological Protection is currently reviewing the relevant cellular, animal and human studies that could be used for that purpose. This paper provides an overview of dose rates and doses typically used or present in those studies, and compares them with doses and dose rates typical of those received by the A-bomb survivors in Japan.

Background gamma radiation and childhood cancer in Germany: an ecological study.

The relationship of low-dose background gamma radiation and childhood leukaemia was investigated in a number of studies. Results from these studies are inconclusive. Therefore, in the present study 25 years of German childhood cancer data were analyzed using interpolated background annual gamma dose rate per community in an ecological study. The main question was leukaemia; as exploratory questions we investigate central nervous system (CNS) tumours, thyroid carcinomas and diagnoses less likely to be related to radiation. A Poisson regression model was applied and a fractional polynomial model building procedure. As the main sensitivity analysis a community deprivation index was included as a potential confounder. It was found that outdoor background gamma annual dose rates in Germany range roughly from 0.5-1.5 mSv/a with an average of 0.817 mSv/a. No association of annual ambient gamma dose rates with leukaemia incidence was found. Amongst the exploratory analyses, a strong association was found with CNS tumour incidence [rate ratio for 1.5 vs 0.5 mSv/a: 1.35; 95% confidence interval (1.17, 1.57)]. The community level deprivation index was not a confounder. It is concluded that the present study did not confirm an association of annual outdoor ambient gamma dose rate and childhood leukaemia, corresponding to some studies and contrasting others. An association with CNS incidence was found in the exploratory analyses. As this is an ecological study no causal interpretation is possible.

Modeling Lung Carcinogenesis in Radon-Exposed Miner Cohorts: Accounting for Missing Information on Smoking.

Epidemiological miner cohort data used to estimate lung cancer risks related to occupational radon exposure often lack cohort-wide information on exposure to tobacco smoke, a potential confounder and important effect modifier. We have developed a method to project data on smoking habits from a case-control study onto an entire cohort by means of a Monte Carlo resampling technique. As a proof of principle, this method is tested on a subcohort of 35,084 former uranium miners employed at the WISMUT company (Germany), with 461 lung cancer deaths in the follow-up period 1955-1998. After applying the proposed imputation technique, a biologically-based carcinogenesis model is employed to analyze the cohort's lung cancer mortality data. A sensitivity analysis based on a set of 200 independent projections with subsequent model analyses yields narrow distributions of the free model parameters, indicating that parameter values are relatively stable and independent of individual projections. This technique thus offers a possibility to account for unknown smoking habits, enabling us to unravel risks related to radon, to smoking, and to the combination of both.

Dose and dose-rate effects of ionizing radiation: a discussion in the light of radiological protection.

The biological effects on humans of low-dose and low-dose-rate exposures to ionizing radiation have always been of major interest. The most recent concept as suggested by the International Commission on Radiological Protection (ICRP) is to extrapolate existing epidemiological data at high doses and dose rates down to low doses and low dose rates relevant to radiological protection, using the so-called dose and dose-rate effectiveness factor (DDREF). The present paper summarizes what was presented and discussed by experts from ICRP and Japan at a dedicated workshop on this topic held in May 2015 in Kyoto, Japan. This paper describes the historical development of the DDREF concept in light of emerging scientific evidence on dose and dose-rate effects, summarizes the conclusions recently drawn by a number of international organizations (e.g., BEIR VII, ICRP, SSK, UNSCEAR, and WHO), mentions current scientific efforts to obtain more data on low-dose and low-dose-rate effects at molecular, cellular, animal and human levels, and discusses future options that could be useful to improve and optimize the DDREF concept for the purpose of radiological protection.

Studies of Health Effects from Nuclear Testing near the Semipalatinsk Nuclear Test Site, Kazakhstan.

The nuclear bomb testing conducted at the Semipalatinsk nuclear test site in Kazakhstan is of great importance for today's radiation protection research, particularly in the area of low dose exposures. This type of radiation is of particular interest due to the lack of research in this field and how it impacts population health. In order to understand the possible health effects of nuclear bomb testing, it is important to determine what studies have been conducted on the effects of low dose exposure and dosimetry, and evaluate new epidemiologic data and biological material collected from populations living in proximity to the test site. With time, new epidemiological data has been made available, and it is possible that these data may be linked to biological samples. Next to linking existing and newly available data to examine health effects, the existing dosimetry system needs to be expanded and further developed to include residential areas, which have not yet been taken into account. The aim of this paper is to provide an overview of previous studies evaluating the health effects of nuclear testing, including some information on dosimetry efforts, and pointing out directions for future epidemiologic studies.

State of the art in research into the risk of low dose radiation exposure--findings of the fourth MELODI workshop.

The fourth workshop of the Multidisciplinary European Low Dose Initiative (MELODI) was organised by STUK-Radiation and Nuclear Safety Authority of Finland. It took place from 12 to 14 September 2012 in Helsinki, Finland. The meeting was attended by 179 scientists and professionals engaged in radiation research and radiation protection. We summarise the major scientific findings of the workshop and the recommendations for updating the MELODI Strategic Research Agenda and Road Map for future low dose research activities.

Joint analysis of three European nested case-control studies of lung cancer among radon exposed miners: exposure restricted to below 300 WLM.

Analyses of lung cancer risk were carried out using restrictions to nested case-control data on uranium miners in the Czech Republic, France, and Germany. With the data restricted to cumulative exposures below 300 working-level-months (WLM) and adjustment for smoking status, the excess relative risk (ERR) per WLM was 0.0174 (95% CI: 0.009-0.035), compared to the estimate of 0.008 (95% CI: 0.004-0.014) using the unrestricted data. Analysis of both the restricted and unrestricted data showed that time since exposure windows had a major effect; the ERR/WLM was six times higher for more recent exposures (5-24 y) than for more distant exposures (25 y or more). Based on a linear model fitted to data on exposures <300 WLM, the ERR WLM of lung cancer at 30 y after exposure was estimated to be 0.021 (95% CI: 0.011-0.040), and the risks decreased by 47% per decade increase in time since exposure. The results from analyzing the joint effects of radon and smoking were consistent with a sub-multiplicative interaction; the ERR WLM was greater for non-smokers compared with current or ex-smokers, although there was no statistically significant variation in the ERR WLM by smoking status. The patterns of risk with radon exposure from the combined European nested case-control miner analysis were generally consistent with those based on the BEIR VI Exposure-Age-Concentration model. Based on conversions from WLM to time weighted averaged radon concentration (expressed per 100 Bq m), the results from this analysis of miner data were in agreement with those from the joint analysis of the European residential radon studies.

Childhood leukemia--risk factors and the need for an interdisciplinary research agenda.

The International Agency for Research on Cancer (IARC) has classified high as well as low-frequency fields as "possibly carcinogenic to humans" (Group 2B). For high frequency fields the recent assessment is based mainly on weak positive associations described in some epidemiological studies between glioma and acoustic neuroma and the use of mobile and other wireless phones. Also for lowfrequency fields the evidence is based on epidemiological findings revealing a statistic association between childhood leukemia (CL) and low-level magnetic fields. The basic findings are already 10 years old. They have since been supported by further epidemiological studies. However, the knowledge on the main/crucial question of causality has not improved. This fact and in addition the small, but statistically significant increased incidence of CL in the surrounding of German nuclear power plants have motivated the German Office for Radiation Protection (BfS) to work toward a better understanding of the main causes of CL. A long-term strategic research agenda has been developed which builds on an interdisciplinary, international network and aims at clarifying the aetiology of childhood acute lymphoblastic leukemia.

Radon, smoking and lung cancer risk: results of a joint analysis of three European case-control studies among uranium miners.

A combined analysis of three case-control studies nested in three European uranium miner cohorts was performed to study the joint effects of radon exposure and smoking on lung cancer death risk. Occupational history and exposure data were available from the cohorts. Smoking information was reconstructed using self-administered questionnaires and occupational medical archives. Linear excess relative risk models adjusted for smoking were used to estimate the lung cancer risk associated with radon exposure. The study includes 1046 lung cancer cases and 2492 controls with detailed radon exposure data and smoking status. The ERR/WLM adjusted for smoking is equal to 0.008 (95% CI: 0.004-0.014). Time since exposure is shown to be a major modifier of the relationship between radon exposure and lung cancer risk. Fitting geometric mixture models yielded arguments in favor of a sub-multiplicative interaction between radon and smoking. This combined study is the largest case-control study to investigate the joint effects of radon and smoking on lung cancer risk among miners. The results confirm that the lung carcinogenic effect of radon persists even when smoking is adjusted for, with arguments in favor of a sub-multiplicative interaction between radon and smoking.

Mortality from cardiovascular diseases in the Semipalatinsk historical cohort, 1960-1999, and its relationship to radiation exposure.

The data on risk of mortality from cardiovascular disease due to radiation exposure at low or medium doses are inconsistent. This paper reports an analysis of the Semipalatinsk historical cohort exposed to radioactive fallout from nuclear testing in the vicinity of the Semipalatinsk Nuclear Test Site, Kazakhstan. The cohort study, which includes 19,545 persons of exposed and comparison villages in the Semipalatinsk region, had been set up in the 1960s and comprises 582,656 person-years of follow-up between 1960 and 1999. A dosimetric approach developed by the U.S. National Cancer Institute (NCI) has been used. Radiation dose estimates in this cohort range from 0 to 630 mGy (whole-body external). Overall, the exposed population showed a high mortality from cardiovascular disease. Rates of mortality from cardiovascular disease in the exposed group substantially exceeded those of the comparison group. Dose-response analyses were conducted for both the entire cohort and the exposed group only. A dose-response relationship that was found when analyzing the entire cohort could be explained completely by differences between the baseline rates in exposed and unexposed groups. When taking this difference into account, no statistically significant dose-response relationship for all cardiovascular disease, for heart disease, or for stroke was found. Our results suggest that within this population and at the level of doses estimated, there is no detectable risk of radiation-related mortality from cardiovascular disease.

Lung cancer from radon: a two-stage model analysis of the WISMUT Cohort, 1955-1998.

A biologically based two-stage carcinogenesis model is applied to epidemiological data for lung cancer mortality in a large uranium miner cohort of the WISMUT company (Germany). To date, this is the largest uranium miner cohort analyzed by a mechanistic model, comprising 35,084 workers among whom 461 died from lung cancer in the follow-up period 1955-1998. It comprises only workers who were first employed between 1955 and 1989 and contains information on annual exposures to radon progeny. We fitted the model's free parameters, including the average growth time of one malignant cell into a lethal tumor. This lag time has an extraordinary value of 13 to 14 years, larger than that previously used or found in miner studies. Even though cohort-wide information on smoking habits is limited and the calendar-year dependence of tobacco smoke exposure was only implicitly accounted for by a birth cohort effect, we find good agreement between the modeled (expected) and empirical (observed) lung cancer mortality. Model calculations of excess relative lung cancer death risk agree well with those from the descriptive, BEIR VI-type exposure-age-concentration model for WISMUT miners. The large variety of exposure profiles in the cohort leads to a well-determined mechanistic model that in principle allows for an extrapolation from occupational to indoor radon exposure.