The State Scientific Automated Medical Registry, Kazakhstan: an important resource for low-dose radiation health research.

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.

Cancer risk from paediatric computed tomography scanning: implications for radiation protection in medicine.

The use of computed tomography (CT) imaging is clearly beneficial for millions of patients. However, the potential adverse health effects, particularly cancer, of ionising radiation exposure from CT early in life are an issue of growing concern in the radiological protection, medical, and public health communities. Although efforts to quantify these effects have been conducted, the precision and accuracy of reported risks needs confirmation. EPI-CT, a European collaborative epidemiological study, was set up to quantify risks from paediatric CT to optimise paediatric diagnostic protocol. The study, coordinated by the International Agency for Research on Cancer, was designed as a multi-national cohort study of children and young adults who underwent CT scanning for long-term follow-up. It combined data from existing and extended cohorts in France, the UK, and Germany, and from new cohorts assembled in Belgium, Denmark, the Netherlands, Norway, Spain, and Sweden using a common protocol. A flexible dose reconstruction approach that can accommodate collection of data from historical sources (prior to 2000) and automatically extract data from the Digital Imaging and Communications in Medicine headers of recorded images available in the Picture Archiving Communication System was developed. Individual organ dose estimates for each child were derived from Monte-Carlo-based radiation transport calculations using hybrid phantoms of different sexes and ages. To account for uncertainties due to missing input data, a simulation method that maintains correlations of doses for persons within subgroups with similar exposure attributes and simulates uncertain dose-model parameter values was used. Simulation studies to evaluate the potential impact of a range of potential confounders (e.g. underlying medical conditions, socio-economic status, missing medical procedures performed outside of participating hospitals) on risk estimates were conducted based on data from some EPI-CT countries and/or reasonable scenarios. In total, 1,170,186 patients (before censorship) were enrolled in the national cohorts. Most patients (75%) had only undergone one CT scan and 29% of all patients were aged <5 years at the time of their first CT examination. The median duration of follow-up was 8 years for the entire cohort, although this varied between countries. Overall, the follow-up accounted for nearly 10 million person-years. This study received partial funding from the European Commission 7th Framework Programme under Grant Agreement No. 269912.

Dose Estimation for a Study of Nuclear Workers in France, the United Kingdom and the United States of America: Methods for the International Nuclear Workers Study (INWORKS).

In the framework of the International Nuclear Workers Study conducted in France, the UK and the U.S. (INWORKS), updated and expanded methods were developed to convert recorded doses of ionizing radiation to estimates of organ doses or individual personal dose equivalent [H(p)(10)] for a total number of 308,297 workers, including 40,035 women. This approach accounts for differences in dosimeter response to predominant workplace energy and geometry of exposure and for the recently published ICRP report on dose coefficients for men and women separately. The overall mean annual individual personal dose equivalent, including zero doses, is 1.73 mSv [median = 0.42; interquartile range (IQR): 0.07, 1.59]. Associated individual organ doses were estimated. INWORKS includes workers who had potential for exposure to neutrons. Therefore, we analyzed neutron dosimetry data to identify workers potentially exposed to neutrons. We created a time-varying indicator for each worker, classifying them according to whether they had a positive recorded neutron dose and if so, whether their neutron dose ever exceeded 10% of their total external penetrating radiation dose. The number of workers flagged as being exposed to neutrons was 13% for the full cohort, with 15% of the cohort in France, 12% of the cohort in the UK and 14% in the U.S. We also used available information on in vivo and bioassay monitoring to identify workers with known depositions or suspected internal contaminations. As a result of this work, information is now available that will allow various types of sensitivity analyses.

A framework for estimating radiation-related cancer risks in Japan from the 2011 Fukushima nuclear accident.

We present here a methodology for health risk assessment adopted by the World Health Organization that provides a framework for estimating risks from the Fukushima nuclear accident after the March 11, 2011 Japanese major earthquake and tsunami. Substantial attention has been given to the possible health risks associated with human exposure to radiation from damaged reactors at the Fukushima Daiichi nuclear power station. Cumulative doses were estimated and applied for each post-accident year of life, based on a reference level of exposure during the first year after the earthquake. A lifetime cumulative dose of twice the first year dose was estimated for the primary radionuclide contaminants ((134)Cs and (137)Cs) and are based on Chernobyl data, relative abundances of cesium isotopes, and cleanup efforts. Risks for particularly radiosensitive cancer sites (leukemia, thyroid and breast cancer), as well as the combined risk for all solid cancers were considered. The male and female cumulative risks of cancer incidence attributed to radiation doses from the accident, for those exposed at various ages, were estimated in terms of the lifetime attributable risk (LAR). Calculations of LAR were based on recent Japanese population statistics for cancer incidence and current radiation risk models from the Life Span Study of Japanese A-bomb survivors. Cancer risks over an initial period of 15 years after first exposure were also considered. LAR results were also given as a percentage of the lifetime baseline risk (i.e., the cancer risk in the absence of radiation exposure from the accident). The LAR results were based on either a reference first year dose (10 mGy) or a reference lifetime dose (20 mGy) so that risk assessment may be applied for relocated and non-relocated members of the public, as well as for adult male emergency workers. The results show that the major contribution to LAR from the reference lifetime dose comes from the first year dose. For a dose of 10 mGy in the first year and continuing exposure, the lifetime radiation-related cancer risks based on lifetime dose (which are highest for children under 5 years of age at initial exposure), are small, and much smaller than the lifetime baseline cancer risks. For example, after initial exposure at age 1 year, the lifetime excess radiation risk and baseline risk of all solid cancers in females were estimated to be 0.7 · 10(-2) and 29.0 · 10(-2), respectively. The 15 year risks based on the lifetime reference dose are very small. However, for initial exposure in childhood, the 15 year risks based on the lifetime reference dose are up to 33 and 88% as large as the 15 year baseline risks for leukemia and thyroid cancer, respectively. The results may be scaled to particular dose estimates after consideration of caveats. One caveat is related to the lack of epidemiological evidence defining risks at low doses, because the predicted risks come from cancer risk models fitted to a wide dose range (0-4 Gy), which assume that the solid cancer and leukemia lifetime risks for doses less than about 0.5 Gy and 0.2 Gy, respectively, are proportional to organ/tissue doses: this is unlikely to seriously underestimate risks, but may overestimate risks. This WHO-HRA framework may be used to update the risk estimates, when new population health statistics data, dosimetry information and radiation risk models become available.

Studies of cancer risk among Chernobyl liquidators: materials and methods.

The current paper presents the methods and design of two case-control studies among Chernobyl liquidators-one of leukaemia and non-Hodgkin lymphoma, the other of thyroid cancer risk-carried out in Belarus, Estonia, Latvia, Lithuania and Russia. The specific objective of these studies is to estimate the radiation induced risk of these diseases among liquidators of the Chernobyl accident, and, in particular, to study the effect of exposure protraction and radiation type on the risk of radiation induced cancer in the low-to-medium- (0-500 mSv) radiation dose range. The study population consists of the approximately 10000 Baltic, 40000 Belarus and 51 000 Russian liquidators who worked in the 30 km zone in 1986-1987, and who were registered in the Chernobyl registry of these countries. The studies included cases diagnosed in 1993-1998 for all countries but Belarus, where the study period was extended until 2000. Four controls were selected in each country from the national cohort for each case, matched on age, gender and region of residence. Information on study subjects was obtained through face-to-face interview using a standardised questionnaire with questions on demographic factors, time, place and conditions of work as a liquidator and potential risk and confounding factors for the tumours of interest. Overall, 136 cases and 595 controls after receiving their consent were included in the studies. A method of analytical dose reconstruction has been developed, validated and applied to the estimation of doses and related uncertainties for all the subjects in the study. Dose-response analyses are underway and results are likely to have important implications to assess the adequacy of existing protection standards, which are based on risk estimates derived from analyses of the mortality of atomic bomb survivors and other high dose studies.

Radiation risk estimates in the beginning of the 21st century.

In the early years of the 21st century, results from a number of epidemiologic studies of populations with specific ionizing radiation exposures will become available. These include populations with accidental exposures in the former Soviet Union and elsewhere and populations with occupational exposures from routine operations of nuclear power plants. The strengths and limitations of these studies are reviewed together with the radiation protection questions they may answer. Many of these studies will provide specific information to complement the atomic-bomb survivor studies, particularly the effects of dose-rate and exposure protraction, modifiers of radiation risks (both environmental and host factors), and different types of radiation. These studies will therefore be important as a test of the adequacy of the current scientific bases for the radiation protection of workers and the general public. An example is thyroid cancer risk in young children following the Chernobyl accident, which has brought attention to a very high sensitivity of very young children that was difficult to assess on the basis of atomic-bomb data alone. Radiation protection will also benefit from formal comparisons and combined analyses of data from populations with different exposure patterns and exposures. Finally, future epidemiological studies will be most valuable if they are well focused, designed specifically to answer outstanding radiation protection questions. An integrated approach based on epidemiology and mechanistic studies, in which epidemiologic studies are designed to test specific mechanistic hypotheses and realistic mechanistic models are used for the analysis of epidemiological data, will probably be the most fruitful for radiation protection.

A unique type II restriction endonuclease FspAI, that recognizes the octanucleotide sequence 5'-RTGC/GCAY-3'.

A new type II restriction endonuclease designated FspAI has been partially purified from a Flexibacter species Tv-m21K. FspAI recognizes the octanucleotide sequence 5'-RTGC/GCAY-3' and cleaves it in the center generating blunt-ended DNA fragments.

High titers of antibodies to two human polyomaviruses, JCV and BKV, correlate with increased frequency of chromosomal damage in human lymphocytes.

Associations of antibody titers to the JC and BK human polyoma viruses and the frequency of chromosome aberrations (CA) in human peripheral blood lymphocytes were studied. Study group consisted of 33 workers occupationally exposed to low doses of ionizing radiation and 11 control persons. There were no statistically significant differences in the JC and BK virus titer values between two groups of donors. It was found that JC and BK virus titers explained approximately 6% of total inter-individual variation in CA frequency. Such factors as alcohol abuse, age and, in this special group, exposure to ionizing radiation explained an additional 53% of the total variation in CA frequency. In six clean-up workers and one control, rogue cell (cells with multiple chromosome-type aberrations) were found. The incidence of rogue cells correlated significantly with JC and BK virus titers as well as a history of recent acute respiratory disease.