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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.

In this commentary we consider the importance of ready access to ecological data, existing resources and approaches for radiological datasets and material, and wider public policy developments in regard to data access and reuse. We describe the development and operation of the STORE database for radiobiology, radioecology and epidemiology as a central data sharing resource, and finally we consider the issues of financial and scientific sustainability of material resource archives and the future of resources like STORE.

Purpose: Projects evaluating the effects of radiation, within the National Institutes of Quantum and Radiological Science and Technology (QST), National Institute of Radiological Sciences (...

Dear Editors:WE READ with interest the paper by Kocher et al. (2018) intended to “develop a probability distribution of a DDREF [dose and dose-rate effectiveness factor] for solid cancers induced by low-LET radiation that is an unbiased representation of the state of knowledge.”The DDREF is a factor

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.

Archival formalin-fixed, paraffin-embedded (FFPE) tissues and their related diagnostic records are an invaluable source of biological information. The archival samples can be used for retrospective investigation of molecular fingerprints and biomarkers of diseases and susceptibility. Radiobiological archives were set up not only following clinical performance such as cancer diagnosis and therapy but also after accidental and occupational radiation exposure events where autopsies or cancer biopsies were sampled. These biobanks provide unique and often irreplaceable materials for the understanding of molecular mechanisms underlying radiation-related biological effects. In recent years, the application of rapidly evolving “omics” platforms, including transcriptomics, genomics, proteomics, metabolomics and sequencing, to FFPE tissues has gained increasing interest as an alternative to fresh/frozen tissue. However, omics profiling of FFPE samples remains a challenge mainly due to the condition and duration of tissue fixation and storage, and the extraction methods of biomolecules. Although biobanking has a long history in radiation research, the application of omics to profile FFPE samples available in radiobiological archives is still young. Application of the advanced omics technologies on archival materials provides a new opportunity to understand and quantify the biological effects of radiation exposure. These newly generated omics data can be well integrated into results obtained from earlier experimental and epidemiological analyses to shape a powerful strategy for modelling and evaluating radiation effects on health outcomes. This review aims to give an overview of the unique properties of radiation biobanks and their potential impact on radiation biology studies. Studies recently performed on FFPE samples from radiobiology archives using advanced omics are summarized. Furthermore, the compatibility of archived FFPE tissues for omics analysis and the major challenges that lie ahead are discussed.

The debate surrounding possible adverse health effects from the civil use of nuclear power under normal operating conditions has been on-going since its introduction. It was particularly intensified by the detection of three leukaemia clusters near nuclear installations, i.e. near the reprocessing plants in Sellafield and Dounreay, UK, and near the Krümmel nuclear power plant, Germany, the last of which commenced between 1990 and 1991 and was first described in 1992; it continued until 2003, and an elevated risk up to 2005 has been reported in the literature. A number of expert commissions and working groups were set up by the governments of the German federal states of Lower Saxony and Schleswig-Holstein to investigate the possible causes of the cluster. An overview of the many risk factors that were investigated as a possible explanation of the Krümmel cluster is given here, focussing on radiation, but also including other risk factors. Further, results from related epidemiological and cytogenetic studies are described. In summary, the cause of the occurrence of the Krümmel cluster has to be considered as unknown. Further research on the causes of childhood leukaemia is needed, focussing on epigenetics and on gene-environment interaction. An update of the leukaemia incidence around the Krümmel site shows that the incidence rates are now comparable to the average rate in Germany.

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.

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.

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.

Direct quantitative assessment of health risks following exposure to ionizing radiation is based on findings from epidemiological studies. Populations affected by nuclear bomb testing are among those that allow such assessment. The population living around the former Soviet Union’s Semipalatinsk nuclear test site is one of the largest human cohorts exposed to radiation from nuclear weapons tests. Following research that started in the 1960s, a registry that contains information on more than 300,000 individuals residing in the areas neighboring to the test site was established. Four nuclear weapons tests, conducted from 1949 to 1956, resulted in non-negligible radiation exposures to the public, corresponding up to approximately 300 mGy external dose. The registry contains relevant information about those who lived at the time of the testing as well as about their offspring, including biological material. An international group of scientists worked together within the research project SEMI-NUC funded by the European Union, and concluded that the registry provides a novel, mostly unexplored, and valuable resource for the assessment of the population risks associated with environmental radiation exposure. Suggestions for future studies and pathways on how to use the best dose assessment strategies have also been described in the project. Moreover, the registry could be used for research on other relevant public health topics.

Summary Background: To follow up populations exposed to several radiation accidents in the Southern Urals, a cause-of-death registry was established at the Urals Center capturing deaths in the Chelyabinsk, Kurgan and Sverdlovsk region since 1950. Objectives: When registering deaths over such a long time period, quality measures need to be in place to maintain quality and reduce the impact of individual coders as well as quality changes in death certificates. Methods: To ensure the uniformity of coding, a method for semi-automatic coding was developed, which is described here. Briefly, the method is based on a dynamic thesaurus, database-supported coding and parallel coding by two different individuals. Results: A comparison of the proposed method for organizing the coding process with the common procedure of coding showed good agreement, with, at the end of the coding process, 70 – 90% agreement for the three-digit ICD -9 rubrics. Conclusions: The semi-automatic method ensures a sufficiently high quality of coding by at the same time providing an opportunity to reduce the labor intensity inherent in the creation of large-volume cause-of-death registries.

MELODI is the European platform dedicated to low-dose radiation risk research. From 7 October through 10 October 2013 the Fifth MELODI Workshop took place in Brussels, Belgium. The workshop offered the opportunity to 221 unique participants originating from 22 countries worldwide to update their knowledge and discuss radiation research issues through 118 oral and 44 poster presentations. In addition, the MELODI 2013 workshop was reaching out to the broader radiation protection community, rather than only the low-dose community, with contributions from the fields of radioecology, emergency and recovery preparedness, and dosimetry. In this review, we summarise the major scientific conclusions of the workshop, which are important to keep the MELODI strategic research agenda up-to-date and which will serve to establish a joint radiation protection research roadmap for the future.

The Wismut cohort is currently the largest single study on the health risks associated with occupational exposures to ionising radiation and dust accrued during activities related to uranium mining. The cohort has ∼59 000 male workers, first employed between 1946 and 1989, at the Wismut Company in Germany. The main effect is a statistically significant increase in mortality from lung cancer with both increasing cumulative radon exposure and silica dust exposure. Risks for cancers of the extrathoracic airways, all extra-pulmonary cancers and cardiovascular diseases associated with radiation exposures have been evaluated. Cohort mortality rates for some other cancer sites, stomach and liver, are statistically significantly increased in relation to the general population, but not statistically significantly related to occupational exposures. No associations between leukaemia mortality and occupational doses of ionising radiation were found.

International audience; Recent findings related to childhood leukaemia incidence near nuclear installations have raised questions which can be answered neither by current knowledge on radiation risk nor by other established risk factors. In 2012, a workshop was organised on this topic with two objectives (a) review of results and discussion of methodological limitations of studies near nuclear installations; (b) identification of directions for future research into the causes and pathogenesis of childhood leukaemia. The workshop gathered 42 participants from different disciplines, extending widely outside of the radiation protection field. Regarding the proximity of nuclear installations, the need for continuous surveillance of childhood leukaemia incidence was highlighted, including a better characterisation of the local population. The creation of collaborative working groups was recommended for consistency in methodologies and the possibility of combining data for future analyses. Regarding the causes of childhood leukaemia, major fields of research were discussed (environmental risk factors, genetics, infections, immunity, stem cells, experimental research). The need for multidisciplinary collaboration in developing research activities was underlined, including the prevalence of potential predisposition markers and investigating further the infectious aetiology hypothesis. Animal studies and genetic/epigenetic approaches appear of great interest. Routes for future research were pointed out. © 2014 IOP Publishing Ltd.

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.

The Fukushima accident was the consequence of a preceding 2-fold natural catastrophe: the earth quake of 11 March 2011 and the subsequent tsunami. Due to favourable winds and to evacuation measures the radiation exposure to the general population in Japan as a whole and with some exceptions in the region outside the evacuation zone, too, was low. In this article the attempt is made to give an estimate of health consequences to the public. This is based upon WHO's dose estimates, knowledge of the consequences of the Chernobyl accident, of the atmospheric nuclear bomb testing in Kazakhstan and on the risk of childhood leukaemia after low dose radiation exposure. For Germany, there was no radiation threat due to the accident. Nonetheless, the events in Japan made clear that the rules and standards that were developed for the case of a reactor accident need to be revised. Language: de

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.

Uranium mining occurred between 1946 and 1990 at the former Wismut mining company in East Germany. 58,987 male former employees form the largest single uranium miners cohort, which has been followed up for causes of mortality occurring from the beginning of 1946 to the end of 2003. The purpose of this paper is to present the radon exposure related cancer mortality risk based on 20,920 deaths, 2 million person-years, and 6,373 cancers. The latter include 3,016 lung cancers and 3,053 extrapulmonary solid cancers. Internal Poisson regression was used to estimate the excess relative risk (ERR) per unit of cumulative radon exposure in Working Level Months (WLM) for all major sites and for the follow-up period from 1946 to 2003. The simple cohort ERR WLM for lung cancer is 0.20% [95% confidence interval (CI): 0.17%; 0.22%]. The ERR model for lung cancer is linear in radon exposure with exponential effect modifiers that depend on age at median exposure, time since median exposure, and radon exposure-rate. In this model the central estimate of ERR WLM is 1.06% (95% CI: 0.69%; 1.42%) for an age at median exposure of 33 y, a time since median exposure of 11 y, and an exposure-rate of 2.7 WL. This central ERR decreases by 5% for each unit exposure-rate increase. The ERR decreases by 32% with each decade increase in age at median exposure and also decreases by 54% with each decade increase in time since median exposure. The ERR WLM for all extrapulmonary solid cancers combined without effect modification is 0.014% (95% CI: 0.006%; 0.023%). The ERR model for extrapulmonary solid cancer is linear in radon exposure with an exponential effect modifier which depends on age-attained. In this model the central estimate of ERR WLM is 0.040% (95% CI: -0.001%; 0.082%) for an age-attained of 44. The ERR decreases by 37% with each decade increase in age-attained. The highest ERR WLM, after lung, is observed for cancers of the pharynx (0.16%), tongue/mouth (0.045%), and liver (0.04%).

Data from the German miners' cohort study were analysed to investigate whether radon in ambient air causes cancers other than lung cancer. The cohort includes 58,987 men who were employed for at least 6 months from 1946 to 1989 at the former Wismut uranium mining company in Eastern Germany. A total of 20,684 deaths were observed in the follow-up period from 1960 to 2003. The death rates for 24 individual cancer sites were compared with the age and calendar year-specific national death rates. Internal Poisson regression was used to estimate the excess relative risk (ERR) per unit of cumulative exposure to radon in working level months (WLM). The number of deaths observed (O) for extrapulmonary cancers combined was close to that expected (E) from national rates (n=3340, O/E=1.02; 95% confidence interval (CI): 0.98-1.05). Statistically significant increases in mortality were recorded for cancers of the stomach (O/E=1.15; 95% CI: 1.06-1.25) and liver (O/E=1.26; 95% CI: 1.07-1.48), whereas significant decreases were found for cancers of the tongue, mouth, salivary gland and pharynx combined (O/E=0.80; 95% CI: 0.65-0.97) and those of the bladder (O/E=0.82; 95% CI: 0.70-0.95). A statistically significant relationship with cumulative radon exposure was observed for all extrapulmonary cancers (ERR/WLM=0.014%; 95% CI: 0.006-0.023%). Most sites showed positive exposure-response relationships, but these were insignificant or became insignificant after adjustment for potential confounders such as arsenic or dust exposure. The present data provide some evidence of increased risk of extrapulmonary cancers associated with radon, but chance and confounding cannot be ruled out.

A German case-control study on leukaemia in children below 5 y of age near nuclear installations showed a trend of increasing risk with decreasing distance of place of residence from the sites. The radiation exposure from the sites is considered as being too low by a factor of at least 1000 to explain the observed effect, but little is known about radiation effects from pre- or postnatal exposures on the leukaemia risk for ages up to 4 y. Within the study, it was shown that the observed trend in risk decreases over time. That could be indicative of some agent being involved for which the prevalence is reduced over time. Previous ecological studies showed increased risks among the youngest age groups in the closest vicinity of the sites, but no elevated risks for children of all ages (0-14). This could implicate a shift towards an earlier onset of the disease.

Purpose: The European Radiobiology Archives (ERA), together with corresponding Japanese and American databases, hold data from nearly all experimental animal radiation biology studies carried out between 1960 and 1998, involving more than 300,000 animals. The Federal Office for Radiation Protection, together with the University of Cambridge have undertaken to transfer the existing ERA archive to a web-based database to maximize its usefulness to the scientific community and bring data coding and structure of this legacy database into congruence with currently accepted semantic standards for anatomy and pathology. Methods: The accuracy of the primary data input was assessed and improved. The original rodent pathology nomenclature was recoded to replace the local ‘DIS-ROD’ (Disease Rodent) formalism with Mouse Pathology (MPATH) and Mouse Anatomy (MA) ontology terms. A pathology panel sampled histopathological slide material and compared the original diagnoses with currently accepted diagnostic criteria. Results: The overall non-systematic error rate varied among the studies between 0.26% and 4.41%, the mean error being 1.71%. The errors found have been corrected and the studies thus controlled have been annotated. The majority of the original pathology terms have been successfully translated into a combination of MPATH and MA ontology terms. Conclusions: ERA has the potential of becoming a world-wide radiobiological research tool for numerous applications, such as the re-analysis of existing data with new approaches in the light of new hypotheses and techniques, and using the database as an information resource for planning future animal studies. When the database is opened for new data it may be possible to offer long-term storage of data from recent and future animal studies.

From 1946 to 1990 extensive uranium mining was conducted in the southern parts of the former German Democratic Republic. The overall workforce included several 100 000 individuals. A cohort of 59 001 former male employees of the Wismut Company was established, forming a large retrospective uranium miners' cohort for the time period 1946–1998. Mean duration of follow-up was 30.5 years with a total of 1 801 630 person-years. Loss to follow-up was low at 5.3%. Of the workers, 16 598 (28.1%) died during the study period. Based on 2388 lung cancer deaths, the radon-related lung cancer risk is evaluated. The excess relative risk (ERR) per working level month (WLM) was estimated as 0.21% (95% CI: 0.18–0.24). It was dependent on time since exposure and on attained age. The highest ERR/WLM was observed 15–24 years after exposure and in the youngest age group (

An increased risk of cardiovascular diseases after exposure to low doses of ionizing radiation has been suggested among the atomic bomb survivors. Few and inconclusive results on this issue are available from miner studies. A positive correlation between coronary heart disease mortality and radon exposure has been reported in the Newfoundland fluorspar miners study, yet low statistical power due to small sample size was of concern. To get further insight into this controversial issue, data from the German uranium miners cohort study were used, which is by far the largest miner study up to date. The cohort includes 59,001 male subjects who were employed for at least six months between 1946 and 1989 at the former Wismut uranium company in Eastern Germany. Exposure to radon, long-lived radionuclides and external gamma radiation was estimated by using a detailed job-exposure matrix. About 16,598 cohort members were deceased until 31 December 1998, including 5,417 deaths from cardiovascular diseases. Linear Poisson regression models were used to estimate the excess relative risk (ERR) per unit of cumulative radiation exposure after adjusting for attained age and calendar period. No trend in risk of circulatory diseases with increasing cumulative exposure to either radon [ERR per 100 working level month: 0.0006; 95% confidence limit (CI): -0.004 to 0.006], external gamma radiation (ERR per Sv: -0.26, 95% CI: -0.6 to 0.05) or long-lived radionuclides (ERR per 100 kBqh/m3: -0.2, 95% CI: -0.5 to 0.06), respectively, was observed. This was also true for the sub-group heart disease and stroke. Our findings do not support an association between cardiovascular disease mortality and exposure to radiation among miners, yet low doses and uncontrolled confounding hamper interpretation.

Since the early 1990s, information on radiation-exposed populations other than those exposed from the Chernobyl accident in 1986 has become increasingly available for international scientific research. It is essential to understand how the cohorts of exposed populations have been defined and what mechanisms can be used to study their health outcomes. Different international scientific research collaborations currently investigate four population groups chronically exposed to ionizing radiation during the late 1940s and early 1950s in the Russian Federation and in Kazakhstan. In this framework, collaborations have been established to develop cause-of-death registers in each of these four areas for future mortality follow-up purposes with the aim of studying the health effects of ionizing radiation. The emphasis of this effort is on assessing the information sources available, the mechanisms of data collection and coding, and the data quality and completeness of the information collected. One of the major challenges is the harmonization of all these aspects between the four different centers to the extent possible, taking into account that much of the actual data has been collected over many decades.

The identification of a local excess of cancer cases, possibly associated with ionizing radiation, always receives substantial media coverage and communication about clusters is difficult. We reviewed studies that examined the risk of leukaemia among young people near nuclear installations. An excess of leukaemia exists near some nuclear installations, at least for the reprocessing plants at Sellafield and Dounreay and the nuclear power plant Krümmel. Nonetheless, the results of multi-site studies invalidate the hypothesis of an increased risk of leukaemia related to nuclear discharge. Up until now, analytic studies have not found an explanation for the leukaemia clusters observed near certain nuclear installations. The hypothesis of an infectious aetiology associated with population mixing has been proposed, but needs to be investigated further. The review illustrates two recent examples in France (La Hague reprocessing plant) and in Germany (Krümmel power plant), where controversies developed after reports of increased leukaemia risks. These examples show the importance of recalling the current epidemiological knowledge and of using systematic recording of cases to replace the alleged excesses in a more general framework. Some elements should also be suggested from the recent French and German experiences to reinforce credibility in the results.

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.

Georg Gerber was born in Stuttgart on 5 May 1926. Both his parents were medical doctors who together ran a GP practice in Stuttgart. Being a single child, he received a perfect classical humanistic education. Even today, former colleagues when asked about their memories of Georg Gerber first mention his amazingly wide knowledge of literature, arts and music. After graduation from the Eberhard–Ludwigs–Gymnasium in Stuttgart in 1944, Georg Gerber was drafted in October 1944 into the German Army, but was spared from fighting in any serious battle. On his 19th birthday, he became an American prisoner of war and soon was transferred to France to help reconstruct roads and to labour in the fields and vineyards. Two years later, he worked as paramedic in French military hospitals in Alsace, France. After altogether nearly 3 years as prisoner of war Georg Gerber was released. While waiting for an admission in medical school, he worked as laboratory assistant in a Stuttgart hospital and studied physics and astronomy. He began his medical study in winter 1948 in Tubingen, following the example of his parents. However, because of his intense interest in science he also studied biology (zoology and biochemistry) in parallel to medicine. Within 5 years he graduated in both subjects, being awarded a MD for research carried out at the Dermatological Clinic dealing with the radiosensitivity of spermatocytes and a PhD in Biochemistry for research carried out at the Max Planck Institute of Biochemistry (Prof. A. Butenandt) dealing with the reproduction of bacterialike organism, both in the same year 1953. This opened his way to enter the ‘‘Max-Planck-Institut fur Biophysik’’ in Frankfurt. Its director Boris Rajewsky, by the way the founding editor of Radiation and Environmental Biophysics, was the leading radiation scientist in Germany, but not an easy boss. Yet entering the field of radiobiology in 1953 was a perfect choice. Radiobiology was popular at the time because of the widespread concern about the dangers from nuclear weapons. Georg Gerber’s background in biochemistry was perfectly suited to be in the forefront of the new direction of radiobiological research, away from pathology towards the biochemistry of radiation effects. In 1957, he moved to the USA, for 5 years working side by side with his wife Gisela in the Department of Experimental Radiology of the University of Rochester, NY. Publications of this time together with K. Altman addressed mainly the use of radionuclides for the investigation of metabolic biochemical processes in experimental animals. In 1962, he returned to Europe to become associated with the EURATOM programme of the European Commission K. Trott University of Pavia, Pavia, Italy

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.

BACKGROUND This study evaluates the histopathology of lung carcinoma in relation to underground radon exposure. METHODS Two hundred forty uranium miners of the former Wismut Company in Eastern Germany with histologically or cytologically confirmed primary lung carcinoma were recruited from 3 study clinics between 1991 and 1995. Information on smoking history was obtained by personal interviews, whereas job histories were derived from original payrolls provided by the Wismut Company. Quantitative estimates of occupational radon exposure were based on a job-exposure matrix. RESULTS Squamous cell carcinoma (SqCC) was the predominant cell type (43%), followed by adenocarcinoma (AC; 26%), small cell lung carcinoma (SCLC; 23%), and other cell types (8%). Nearly all patients were smokers. Time since first occupational exposure was 42 years on average, the mean cumulative radon exposure 506 working level months. Adenocarcinoma appeared to be more likely than both SCLC and SqCC among miners with low cumulative radiation exposure, long time since first exposure, an older age at diagnosis, and among ex- and never-smokers. In current smokers, lung carcinomas developed at a much lower level of radiation exposure than in ex- and never-smokers. The increase in the relative frequency of SCLC and SqCC at the expense of AC with increasing cumulative radiation exposure was more pronounced among ex- and never-smokers and seemed to be masked among current smokers. CONCLUSION The authors' data suggest that all cell types were associated with radon exposure, but high radiation exposure tended to increase the proportion of SCLC and SqCC. Cancer 2000;89:2613–21. © 2000 American Cancer Society.

A registry of the rural population in the Altai region exposed to fallout from nuclear tests at the Semipalatinsk test site (STS) was established more than four decades after the first Soviet nuclear explosion on August 29, 1949. Information about individuals living in an exposed and a control area was collected using all available local sources, such as kolkhoz documentation, school registries, medical treatment records and interviews with residents. As a result, a database comprising an exposed group of 39 179 individuals from 53 Altai region villages, 6769 external and 3303 internal controls was compiled. For several settlements, effective dose estimates reached the level of 1.5 Sv, while the average effective dose estimate in the exposed group was 340 mSv. Dosimetric data, vital status information and health records gathered at rayon and village medical facilities are held in the registry. Cause-of-death information for deceased residents is obtained from death registration forms archived at the Altai region vital statistics office. At present, a follow-up of approximately 40% of the population exposed in 1949 has been done. More will be added by searching for migrants to the larger towns of the Altai region, i.e. Barnaul, Rubtsovsk and Biisk. In order to assess the influence of radiation exposure, analytical studies with a case-control design for stomach and lung cancer are currently being prepared. The number of known cases is sufficient to detect an odds ratio of 1.5 at the 95% confidence level. Epidemiological studies in populations affected by fallout from STS may be equally important to the atomic bomb survivors' study for the direct quantification of radiation effects. The range of exposure rates experienced will extend the acute high-dose-rate findings from Hiroshima/Nagasaki towards acute and protracted lower exposures, which are more relevant for radiation protection issues.

Background Flight crews are exposed to elevated levels of cosmic radiation and to magnetic fields generated by the aircraft's electrical system. The purpose of this study was to quantify these two occupational exposures. Methods Magnetic fields were measured during 37 flights (23 in the cockpit and 14 in the cabin) using an Emdex Lite personal dosimeter. All cockpit measurements were taken on the B737/200. Cabin measurements were taken in several aircraft types, including the B737, B757, DC9, and L1011. Cosmic radiation was computer estimated for 206 flights using the Federal Aviation Administration's program CARI-3C. Results Magnetic field levels in the cockpit had a mean value of approximately 17 milliGauss (mG), while cabin measurements were lower (mean values of approximately 3 or less in economy, 6 in first class, 8 in front serving areas). Cosmic radiation equivalent dose rates to bone marrow and skeletal tissue ranged from 0.3 to 5.7 microsieverts per hour. Conclusions Elevated magnetic field levels in front serving areas and the cockpit suggest the need for further study to evaluate long-term exposure to flight crew members who work in these areas. Cosmic radiation levels are well below occupational limits for adults, but may require some pregnant flight crew members to adjust their flying time or routes. Am. J. Ind. Med. 34:574–580, 1998. © 1998 Wiley-Liss, Inc.

The airline industry may be an occupational setting with specific health risks. Two environmental agents to which flight crews are known to be exposed are cosmic radiation and magnetic fields generated by the aircraft's electrical system. Other factors to be considered are circadian disruption and conditions specific to air travel, such as noise, vibration, mild hypoxia, reduced atmospheric pressure, low humidity, and air quality. This study investigated mortality among US commercial pilots and navigators, using proportional mortality ratios for cancer and noncancer end points. Proportional cancer mortality ratios and mortality odds ratios were also calculated for comparison to the proportional mortality ratios for cancer causes of death. Results indicated that US pilots and navigators have experienced significantly increased mortality due to cancer of the kidney and renal pelvis, motor neuron disease, and external causes. In addition, increased mortality due to prostate cancer, brain cancer, colon cancer, and cancer of the lip, buccal cavity, and pharynx was suggested. Mortality was significantly decreased for 11 causes. To determine if these health outcomes are related to occupational exposures, it will be necessary to quantify each exposure separately, to study the potential synergy of effects, and to couple this information with disease data on an individual basis.

Der Bericht gibt einen Uberblick uber die Geburtspravalenzen von ausgewahlten angeborenen Fehlbildungen bei Lebendgeborenen, die zwischen 1984 und 1991 geboren wurden und ihren Wohnsitz in Bayern hatten. Die Daten wurden retrospektiv in den bayerischen und 2 grenznahen Kinderkliniken erhoben. Die Beschreibung des Datenmaterials ist eine Kombination von kindbezogener (Kind mit mehreren Fehlbildungen geht entsprechend seiner Fehlbildungsklasse nur 1mal in die Analyse ein) und diagnosenbezogener (Kind mit mehreren Fehlbildungen geht mit jeder seiner Fehlbildungsdiagnosen und damit mehrfach in die Analyse ein) Darstellung der Pravalenzen. Ausgewertet wurden 12040 Kinder insgesamt, davon 8527 mit isolierten Defekten eines Organsystems und 3513 mit multiplen Fehlbildungen. Knaben waren insgesamt haufiger betroffen als Madchen (1,4:1 ohne Berucksichtigung der Hypospadie). Wahrend die Zeitreihen der meisten Fehlbildungen keinen zeitlichen Trend erkennen liesen, fiel die Pravalenz der isolierten Spina bifida zwischen 1984 und 1991 leicht ab. Die Pravalenzen von isoliertem Ventrikelseptumdefekt und Verschlusdefekten des Nierenbeckens und Ureters sowie Atresie und Stenose der Harnrohre und des Blasenhalses (ICD9 753,2+ICD9 753,6) zeigten hingegen eine starke Zunahme. Die bayerischen Pravalenzen werden denen des EUROCAT-Registers gegenubergestellt.

The accident which occurred during the night of April 25-26, 1986 in reactor 4 of the Chernobyl nuclear power plant in the Ukraine released considerable amounts of radioactive substances into the environment. Outside the former USSR, the highest levels of contamination were recorded in Bulgaria, Austria, Greece and Romania, followed by other countries of Central, Southeast and Northern Europe. Studies of the health consequences of the accident have been carried out in these countries, as well as in other countries in Europe. This report presents the results of a critical review of cancer studies of the exposed population in Europe, carried out on the occasion of the 10th anniversary of the Chernobyl accident. Overall, three is no evidence to date of a major public health impact of the Chernobyl accident in the field of cancer in countries of Europe outside the former USSR.

The European Radiobiological Archive can be accessed at no cost at https://era.bfs.de. The necessary ID and password can be obtained from the curators at era@bfs.de.

Objectives ‘Dusty occupations’ and exposure to low-dose radiation have been suggested as potential risk factors for stomach cancer. Data from the German uranium miner cohort study are used to further evaluate this topic. Methods The cohort includes 58 677 miners with complete information on occupational exposure to dust, arsenic and radiation dose based on a detailed job-exposure matrix. A total of 592 stomach cancer deaths occurred in the follow-up period from 1946 to 2003. A Poisson regression model stratified by age and calendar year was used to calculate the excess relative risk (ERR) per unit of cumulative exposure to fine dust or from cumulative absorbed dose to stomach from α or low-LET (low linear energy transfer) radiation. For arsenic exposure, a binary quadratic model was applied. Results After adjustment for each of the three other variables, a statistically non-significant linear relationship was observed for absorbed dose from low-LET radiation (ERR/Gy=0.30, 95% CI −1.26 to 1.87), α radiation (ERR/Gy=22.5, 95% CI −26.5 to 71.5) and fine dust (ERR/dust-year=0.0012, 95% CI −0.0020 to 0.0043). The relationship between stomach cancer and arsenic exposure was non-linear with a 2.1-fold higher RR (95% CI 0.9 to 3.3) in the exposure category above 500 compared with 0 dust-years. Conclusion Positive statistically non-significant relationships between stomach cancer and arsenic dust, fine dust and absorbed dose from α and low-LET radiation were found. Overall, low statistical power due to low doses from radiation and dust are of concern.

For financial and ethical reasons, the large-scale radiobiological animal studies conducted over the past 50 years are, to a large extent, unrepeatable experiments. It is therefore important to retain the primary data from these experiments to allow reanalysis, reinterpretation and re-evaluation of results from, for example, carcinogenicity studies, in the light of new knowledge in radiation biology. Consequently, there is an imperative need to keep these data available for the research community. The European Radiobiological Archives (ERA) were developed to fulfill this task. ERA has become a unique archive, including information from almost all European long-term studies carried out between the 1960s and the 1990s. The legacy database was originally developed in a manner that precluded online use. Therefore, strong efforts were made to transform it into a version that is available online through the web. This went together with quality assurance measures, including first the estimation of the rate of non-systematic errors in data entry, which at 2% proved to be very low. Second, every data set was compared against two external sources of information. Standardization of terminology and histopathology is a prerequisite for meaningful comparison of data across studies and analysis of potential carcinogenic effects. Standardization is particularly critical for the construction of a database that includes data from different studies evaluated by pathologists in different laboratories. A harmonized pathology nomenclature with modern standard pathology terms was introduced. As far as possible, references for the various studies were directly linked to the studies themselves. Further, a direct link to the JANUS database was established. ERA is now in a position where it has the potential to become a worldwide radiobiological research tool. ERA can be accessed at no cost at https://era.bfs.de . An ID and password can be obtained from the curators at era@bfs.de .

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.

The possible confounding effect of smoking on radon-associated risk for lung cancer mortality was investigated in a case-control study nested in the cohort of German uranium miners. The study included 704 miners who died of lung cancer and 1,398 controls matched individually for birth year and attained age. Smoking status was reconstructed from questionnaires and records from the mining company's health archives for 421 cases and 620 controls. Data on radon exposure were taken from a job-exposure matrix. Smoking adjusted odds ratios for lung cancer in relation to cumulative radon exposure have been calculated with conditional logistic regression. The increase in risk per Working Level Month (WLM) was assessed with a linear excess relative risk (ERR) model taking smoking into account as a multiplicative factor. In addition, the potential impact of temporal factors on the ERR per WLM was examined. Lung cancer mortality risk increased with increasing radon exposure, yielding a crude ERR per WLM of 0.25% (95% CI: 0.13-0.46%). Adjustment for smoking led only to marginal changes of the radon-associated lung cancer risks. The adjusted ERR per WLM was very similar (0.23%, 95%-CI: 0.11-0.46%) to the crude risk and to the risk found in the Wismut cohort study. This stability of the radon-related lung cancer risks with and without adjustment for smoking suggests that smoking does not act as a major confounder in this study and presumably also not in the cohort study.

Background It is well established that lung cancer is caused by radon, while uncertainty exists as to whether cancers other than lung might be related to exposure from radon. To investigate further the risk of extra-pulmonary cancers, mortality data from the German uranium miners cohort study are analysed. Materials and methods The cohort includes 58,747 men who were employed for at least 6 months between 1946 and 1989 at the former Wismut uranium company in Eastern Germany. Exposure to radon and its progeny, long-lived radionuclides, external gamma radiation as well as exposure to arsenic and dust was estimated by using a detailed job-exposure matrix. A total of 20.680 deaths were observed in the follow-up period 1960 to the end of 2003. The different causes of death were compared with the age- and calendar-year specific national death rates of Eastern Germany, formerly GDR. Standardized mortality ratios (SMR) with 95% confidence limits (CI) were calculated. To investigate the exposure-response relationship an internal poisson regression using a linear model was applied and the excess relative risk (ERR) per unit of cumulative exposure to radon in Working Level Month (WLM) was calculated. Results For 19.598 (94.3%) of the deceased cohort members causes of death had been available, among them 2.999 lung cancer deaths and 3.341 deaths from cancers other than lung. After adjusting for missing causes of deaths, for all cancers other than lung combined mortality in the cohort was close to that expected from national rates (SMR=1.02, 95% CI: 0.98-1.05). Among 23 individual cancer categories, statistically significant increases in mortality for cancers of the stomach (SMR=1.15, 95% CI: 1.06-1.25) and liver (SMR=1.26 , 95% CI: 1.07-1.45) and statistically significant decreases for cancers of the tongue, mouth and pharynx combined and bladder were observed. A statistically significant relation with cumulative exposure was observed for all non-lung cancers combined (ERR/WLM=0.014%) and stomach cancer (ERR/WLM=0.021%). Conclusion Our findings suggest a weak evidence for a relationship between exposure to radon and mortality from cancers other than lung cancer. Chance, confounding by unconsidered risk factors and bias due to missing causes of deaths cannot be ruled out. If at all, the risk for extrapulmonary tumors associated with radon is appreciably lower than that for lung cancer.

Epidemiological evidence of lung cancer risk from radon is known since the early 1960s, when first studies on uranium miners were published. The risk was modeled in terms of relative risk in dependence on cumulated exposure. Since then, follow-up of studies has been extended, which allowed the analysis of modifying factors such as time since exposure (TSE), age at exposure (AE), attained age, and exposure rate. The present analysis was conducted in the frame of the Alpha-Risk European research program and aimed at estimating the lung cancer risk associated to radon exposure among miners with low levels of exposure and good quality of exposure assessment. The large numbers of miners included in the joint study allow a simultaneous analysis of modifying effects using exposure windows, which are appropriate in studies with protracted exposures. The analysis is based on three European cohort studies of uranium miners: Czech, French and German, including 9979, 5086 and 35084 miners, respectively. By the end of follow-up, 921, 159, and 458 lung cancer deaths were observed in these cohorts, respectively. The excess relative risks per working level month (ERR/WLM) for the three studies were 0.0116 (95%CI 0.0076-0.0157), 0.0061 (95%CI 0.0018-0.0105), and 0.0043 (95%CI 0.0028-0.0057), respectively. The different estimates are caused mainly by the so-called inverse effect of exposure rate and by quality of exposure, which both are correlated with time since exposure. We evaluated simultaneously the effects of TSE in 3 windows (5-19 years before, 20-34, 35+) and of AE in 3 windows (-29 years, 30-39, 40+). The analysis showed a strong decrease of the ERR/WLM with TSE (28% in period 20-34 years and 11% after 35 years in comparison to window 5-19). The simultaneous effect of AE was also significant: ERR/WLM for AE more than 40 years was 53% of that for AE below 30). These results will permit to improve our knowledge on the long-term risks associated to radon exposure. The present work was supported by the European Commission (Contract FI6R 516483).

This paper describes the Semipalatinsk historical cohort study and, in particular, examines the association between combined external and internal radiation exposure and esophagus cancer. Esophagus cancer is the most frequent single cancer site in the cause of death follow-up for the Semipalatinsk cohort. Set up in the 1960s, this historical cohort included 10 exposed settlements in the vicinity of the Semipalatinsk nuclear test site in East Kazakhstan as well as 6 comparison settlements in a low exposure area of the same region. The external and internal radiation doses to the population of the settlements under study were mainly due to local fallout from atmospheric nuclear testing (1949-1962). The database includes dosimetry and health information for 19.545 inhabitants of exposed and comparison villages in the Semipalatinsk region, comprising a total of 582.750 person-years of follow-up between 1960 and 1999. Cumulative effective dose estimates in this cohort range from 20 mSv to -4 Sv, with a mean dose of 634 mSv in the exposed group. Relative risks were calculated in terms of rate ratios, using a Poisson regression model for grouped person-time data. Esophagus cancer was found substantially elevated, with a statistically significant increase of the relative risk with dose and an ERR/Sv of 2.37 (1.45; 3.28) for the total cohort. If the data set was restricted to the exposed group only, the ERR/Sv was found considerably lower (0.18 (-0.16; 0.52)), whereas the dose-response remained significant only in women. Overall, our results based on the Semipalatinsk historical cohort indicate an association between fallout exposure and the risk of esophagus cancer that should be further investigated.