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Since early April 2020, there has been intense debate over proposed clinical use of ionizing radiation to treat life-threatening pneumonia in Coronavirus Disease 2019 (COVID-19) patients. At least twelve relevant papers appeared by 20 May 2020. The radiation dose proposed for clinical trials are a single dose (0.1-1 Gy) or two doses (a few mGy followed by 0.1-0.25 Gy involving a putative adaptive response, or 1-1.5 Gy in two fractions 2-3 days apart). The scientific rationale for such proposed so-called low dose radiotherapy (LDRT) is twofold (note that only doses below 0.1 Gy are considered as low doses in the field of radiation protection, but here we follow the term as conventionally used in the field of radiation oncology). Firstly, the potentially positive observations in human case series and biological studies in rodent models on viral or bacterial pneumonia that were conducted in the pre-antibiotic era. Secondly, the potential anti-inflammatory properties of LDRT, which have been seen when LDRT is applied locally to subacute degenerative joint diseases, mainly in Germany. However, the human and animal studies cited as supportive evidence have significant limitations, and whether LDRT produces anti-inflammatory effects in the inflamed lung or exacerbates ongoing COVID-19 damage remains unclear. Therefore, we conclude that the available scientific evidence does not justify clinical trials of LDRT for COVID-19 pneumonia, with unknown benefit and known mortality risks from radiogenic cancer and circulatory disease. Despite the significant uncertainties in these proposals, some clinical trials are ongoing and planned. This paper gives an overview of current situations surrounding LDRT for COVID-19 pneumonia.

This letter addresses our concerns regarding a paper by Salomaa et al. entitled ‘Low dose radiation therapy for COVID-19 pneumonia: is there any supportive evidence?’ published in International Jou...

Glaucoma is a major cause of visual impairment, and secondary glaucoma manifested as neovascular glaucoma has long been known to occur following high-dose fractionated radiation therapy. In contrast, little is known as to whether ionizing radiation exposure causes primary glaucoma, except that a single study in Japanese atomic bomb survivors has reported a significantly increase risk. Therefore, the effect of lower dose and lower dose rate remains unclear. Here we report that in Russian Mayak Production Association workers occupationally exposed to chronic radiation for prolonged periods, incidence of total primary glaucoma and primary open-angle glaucoma is significantly associated with various non-radiation factors (sex, attained age, and cataract diagnosed prior to glaucoma), but neither with cumulative dose from external γ-rays nor with cumulative neutron dose nor with the unweighted sum of cumulative γ and neutron doses. The present results suggest for the first time that chronic radiation exposure does not cause primary glaucoma, although the analyses need to be made in other cohorts exposed at various dose and dose rate.

Purpose: In 2011, the International Commission on Radiological Protection (ICRP) recommended an equivalent dose limit for the lens of the eye of 20 mSv/year, averaged over defined periods o...

Dr. William Francis Morgan, known as Bill by many of his friends and colleagues, was a leading figure in the field of radiation research. He passed away on 13 November 2015, at the age of 62 years ...

Risks to health are the prime consideration in all human situations of ionizing radiation exposure and therefore of relevance to radiation protection in all occupational, medical, and public exposure situations. Over the past few decades, advances in therapeutic strategies have led to significant improvements in cancer survival rates. However, a wide range of long-term complications have been reported in cancer survivors, in particular circulatory diseases and their major risk factors, metabolic diseases. However, at lower levels of exposure, the evidence is less clear. Under real-life exposure scenarios, including radiotherapy, radiation effects in the whole organism will be determined mainly by the response of normal tissues receiving relatively low doses, and will be mediated and moderated by systemic effects. Therefore, there is an urgent need for further research on the impact of low-dose radiation. In this article, we review radiation-associated risks of circulatory and metabolic diseases in clinical, occupational or environmental exposure situations, addressing epidemiological, biological, risk modelling, and systems biology aspects, highlight the gaps in knowledge and discuss future directions to address these gaps.

Dr. William Francis Morgan, known as Bill to many of his friends and colleagues, passed away on 13 November 2015, at the age of 62 years (Hamada et al. 2016, 2017). To commemorate the first anniver...

Currently, there are 14 ongoing clinical studies on low dose radiotherapy (LDRT) for COVID-19 pneumonia. An underlying assumption is that irradiation of about 1 Gy is effective at ameliorating viral pneumonia. Its rationale, however, relies on early human case series or animal studies mostly obtained in the pre-antibiotic era, where rigorous statistical analyses were not performed. It therefore remains unclear whether those early data support such assumptions. With standard statistical survival models, and based on a systematic literature review, we re-analyzed 14 radiobiological animal datasets in which animals received mostly fractionated doses of radiation before or after bacterial/viral inoculation, and assessing various health endpoints (mortality, pneumonia morbidity). In most datasets absorbed doses did not exceed 7 Gy. Various different model systems and types of challenging infection are considered. For 7 studies that evaluated post-inoculation radiation exposure (more relevant to LDRT for COVID-19 pneumonia) the results are heterogeneous, with 2 studies showing a significant increase (p, 2 tables, 7 figures, 15 Appendix Tables, 36 references, 49 double spaced pages

Dosimetric measurement error is known to potentially bias the magnitude of the dose response, and can also affect the shape of dose response. In this report, generalized relative and absolute rate models are fitted to the latest Japanese atomic bomb survivor solid cancer, leukemia and circulatory disease mortality data (followed from 1950 through 2003), with the latest (DS02R1) dosimetry, using Bayesian techniques to adjust for errors in dose estimates and assessing other model uncertainties. Linear-quadratic models are fitted and used to assess lifetime mortality risks for contemporary UK, USA, French, Russian, Japanese and Chinese populations. For a test dose of 0.1 Gy absorbed dose weighted by neutron relative biological effectiveness, solid cancer, leukemia and circulatory disease mortality risks for a UK population using a generalized linear-quadratic relative rate model were estimated to be 3.88% Gy(−1) [95% Bayesian credible interval (BCI): 1.17, 6.97], 0.35% Gy(−1) (95% BCI: −0.03, 0.78) and 2.24% Gy(−1) (95% BCI: −0.17, 13.76), respectively. Using a generalized absolute rate linear-quadratic model at 0.1 Gy, the lifetime risks for these three end points were estimated to be 3.56% Gy(−1) (95% BCI: 0.54, 6.78), 0.41% Gy(−1) (95% BCI: 0.01, 0.86) and 1.56% Gy(−1) (95% BCI: −1.10, 7.21), respectively. There was substantial evidence of curvature for solid cancer (in particular, the group of solid cancers excluding lung, breast and stomach cancers) and leukemia, so that for solid cancer and leukemia, estimates of excess risk per unit dose were nearly doubled by increasing the dose from 0.01 to 1.0 Gy, with most of the increase occurring in the interval from 0.1 to 1.0 Gy. For circulatory disease, the dose-response curvature was inverse, so that risk per unit dose was nearly halved by going from 0.01 to 1.0 Gy weighted absorbed dose, although there were substantial uncertainties. In general, there were higher radiation risks for females compared to males. This was true for solid cancer and circulatory disease overall, as well as for lung, breast, stomach and the group of other solid cancers, and was the case whether relative or absolute rate projection models were employed; however, for leukemia this pattern was reversed. Risk estimates varied somewhat between populations, with lower cancer risks in aggregate for China and Russia, but higher circulatory disease risks for Russia, particularly using the relative rate model. There was more pronounced variation for certain cancer sites and certain types of projection models, so that breast cancer risk was markedly lower in China and Japan using a relative rate model, but the opposite was the case for stomach cancer. There was less variation between countries using the absolute rate models for stomach cancer and breast cancer, but this was not the case for lung cancer and the group of other solid cancers, or for circulatory disease.

Use of computed tomography (CT) scanning has increased worldwide over the decades, and Japan is one of the leading countries in annual frequency of diagnostic CT. While benefits of CT scan are undisputable, concerns have been raised about potential health effects of ionizing radiation exposure from CT, particularly among children who are likely more susceptible to radiation than adults. This study aims to evaluate the cumulated lifetime risk of the brain/central nervous system (CNS) cancer due to head CT examinations performed on Japanese children at age 0-10 years in 2012, 2015, and 2018. The frequency and dose distribution of head CT examinations were estimated based on information from recent national statistics and nationwide surveys. The lifetime risk attributable to exposure was calculated by applying risk models based on the study of Japanese atomic-bomb survivors. In contrast to the overall increasing trend, the frequency of childhood CT, especially at age

Purpose: To estimate incidence risk for senile cataracts in a cohort of workers employed at nuclear production facility, that were occupationally exposed to radiation taking into account non-radiation risk factors. Material and methods: Senile cataract incidence (cataracts) is studied in the cohort of Mayak PA workers first employed at one of the main facilities (reactors, radiochemical or plutonium production plants) during 1948–1982 (22,377 individuals). All members of the study cohort were occupationally exposed to gamma-rays or neutrons over a prolonged period. Absorbed doses from external and/or neutron exposure used in the study were provided by MWDS-2008. Relative risk (RR) and excess relative risk per unit dose (ERR/Gy) were estimated based on maximum likelihood using AMFIT module of EPICURE software. Results: 4159 cataract diagnoses were verified in the study cohort of workers during 482217 person-years of follow-up. The majority of cataracts were diagnosed in cohort members included in the age group 61–70 years old in both males and females. The mean age at cataract diagnosis was 63.1 ± 0.2 years in males and 64.8 ± 0.2 years in females, respectively. RR of cataract incidence was statistically significant in all dose categories when compared to a reference category (0–0.25 Gy) and increased with increasing dose from external gamma-rays and was the highest in workers exposed to external gamma-rays at doses exceeding 2.0 Gy (1.61 95 % CI: 1,41–1,83). Significant linear association of cataracts with dose from external gamma-rays was observed with ERR/Gy = 0.28 (95 % CI: 0.20, 0.37). The risk estimate varied slightly with inclusion of additional adjustments for different non-radiation factors (smoking status and alcohol consumption, smoking index, hypertension, body mass index, severe myopia diagnosed). After adjusting for dose from neutrons ERR/Gy of external gamma-rays for cataracts increased considerably (0.31; 95 % CI: 0.22, 0.40). Significant ERR/Gy of external gamma-rays for senile cataract was revealed in both male and female workers of the study cohort, however the variations between the sexes were insignificant (p = 0.09). ERR/Gy of external gamma-rays for senile cataract was significant in all age groups except for workers under 40 years, but the differences among the age groups were insignificant (p > 0.5). Conclusion: Risk of senile cataract incidence in the cohort of Mayak PA workers, occupationally exposed to radiation over prolonged periods, was significantly associated with dose from external gamma-rays.

There are well-documented associations of glaucoma with high-dose radiation exposure, but only a single study suggesting risk of glaucoma, and less conclusively macular degeneration, associated with moderate-dose exposure. We assessed risk of glaucoma and macular degeneration associated with occupational eye-lens radiation dose, using participants from the US Radiologic Technologists Study, followed from the date of surveys in 1994–1998, 2003–2005 to the earliest of diagnosis of glaucoma or macular degeneration, cancer other than non-melanoma skin cancer, or date of last survey (2012–2014). We excluded those with baseline disease or previous radiotherapy history. Cox proportional hazards models with age as timescale were used. There were 1631 cases of newly self-reported doctor-diagnosed cases of glaucoma and 1331 of macular degeneration among 69,568 and 69,969 eligible subjects, respectively. Estimated mean cumulative eye-lens absorbed dose from occupational radiation exposures was 0.058 Gy. The excess relative risk/Gy for glaucoma was −0.57 (95% CI −1.46, 0.60, p = 0.304) and for macular degeneration was 0.32 (95% CI −0.32, 1.27, p = 0.381), suggesting that there is no appreciable risk for either endpoint associated with low-dose and low dose-rate radiation exposure. Since this is the first examination of glaucoma and macular degeneration associated with low-dose radiation exposure, this result needs to be replicated in other low-dose studies.

Objective In 2010, candid advice concerning the low rate of typhoid vaccination among Japanese travelers was received from Nepal. Recently, progressive Japanese travel clinics have encouraged Japanese travelers to be vaccinated against typhoid fever in conjunction with officially approved vaccines, such as hepatitis A vaccine. We herein report the status of typhoid vaccinations for Japanese travelers to the most endemic area (South Asia) and describe the factors associated with compliance. Methods In the travel clinic at Kurume University Hospital, we used the following criteria to retrospectively extract the records of new pre-travel Japanese clients between January 2011 and March 2015: hepatitis A vaccine administered, traveling to South Asian countries, and ≥2 years of age. We first summarized the participants and then divided them into typhoid-vaccinated and typhoid non-vaccinated groups for a comparative analysis. Results This study included 160 clients. A majority (70.0%) of these clients traveled for business. The duration of trips was long (≥1 month) (75.0%), and India was a popular destination (90.6%). A comparative study between the vaccinated group (n=122) and the non-vaccinated group (n=38) revealed that the two factors most positively associated with typhoid vaccination were business trips [adjusted odds ratio (aOR) 3.59, 95% confidence interval (CI) 1.42-9.06] and coverage by a company/organization payment plan (aOR 7.14, 95% CI 2.67-20.3). Conclusion The trend toward typhoid vaccination among Japanese travelers to South Asia with pre-travel consultation is correlated with business trips and coverage by a company/organization payment plan. If problems concerning the cost of vaccines were resolved, more travelers would request typhoid vaccination.

Since the International Commission on Radiological Protection recommended reducing the occupational equivalent dose limit for the lens of the eye in 2011, there have been extensive discussions in various countries. This paper reviews the current situation in radiation protection of the ocular lens and the discussions on the potential impact of the new lens dose limit in Japan. Topics include historical changes to the lens dose limit, the current situation with occupational lens exposures (e.g., in medical workers, nuclear workers, and Fukushima nuclear power plant workers) and measurements, and the current status of biological studies and epidemiological studies on radiation cataracts. Our focus is on the situation in Japan, but we believe such information sharing will be useful in many other countries.

Metastasis represents the leading cause of breast cancer deaths, necessitating strategies for its treatment. Although radiotherapy is employed for both primary and metastatic breast cancers, the difference in their ionizing radiation response remains incompletely understood. This study is the first to compare the radioresponse of a breast cancer cell line with its metastatic variants and report that such metastatic variants are more radioresistant. A luciferase expressing cell line was established from human basal-like breast adenocarcinoma MDA-MB-231 and underwent in vivo selections, whereby a cycle of inoculations into the left cardiac ventricle or the mammary fat pad of athymic nude mice, isolation of metastases to the bone, lung and lymph nodes visualized with bioluminescence imaging, and expansion of obtained cells was repeated twice or three times. The established metastatic cell lines were assessed for cell proliferation, wound healing, invasion, clonogenic survival, and apoptosis. The established metastatic cell lines possessed an increased proliferative potential in vivo and were more chemotactic, invasive, and resistant to X‑ray-induced clonogenic inactivation and apoptosis in vitro. Breast cancer metastasis to the bone, lung, and lymph nodes promotes radioresistance.

International audience; Purpose: Radiation detriment is a concept used by the International Commission on Radiological Protection (ICRP) to quantify the harmful health effects of radiation exposure in humans. The current approach of radiation detriment calculation has been defined in ICRP Publication 103 in 2007. It is determined from lifetime risk of cancer and heritable effects for a composite reference population, taking into account the severity of the disease in terms of lethality, quality of life and years of life lost. Many parameters are used in the calculations and the variation of these parameterscan have effects on the cancer detriment, which needs to be investigated.Materials and methods: In this paper, we conducted a sensitivity analysis for examining the impact of 12 different parameters or methodological choices on the calculation of solid cancer detriment, such as the lifetime risk calculation method, survival curve, dose and dose-rate effectiveness factor (DDREF), age-at-exposure, sex, reference population, risk transfer model, latency, attained age, lethality, minimum quality of life factor and relative cancer-free life lost. Sensitivity calculations have been performed systematically for each of 10 solid cancer sites, by changingeach one of the parameters in turn.Results: This sensitivity analysis demonstrated a large impact on estimated detriment from DDREF, age-at-exposure, sex and lethality, a noticeable impact of risk transfer model associated to variation of baseline rates, and a limited impact of risk calculation method, survival curve, latency, attained age, quality of life and relative years of life lost.Conclusion: These results could have implications for radiation protection standards, and they should help define priorities for future research in the field of low radiation dose and dose rate research. The present sensitivity analysis is part of a global effort of ICRP to review the bases of radiation detriment calculation and assess potential evolutions to improve the radiation protection system.

Background Patients receiving radiotherapy demonstrate cognitive deficits, impairment of neurogenesis and neurovascular damage developing as late side effects of radiation exposure to the head. In light of the increasing use of diagnostic radiological procedures, epidemiological data raise concerns about possible harmful effects of low-level radiation on the human brain. A series of studies of chronically exposed Russian nuclear workers have provided information on risks of cancer and non-cancer diseases. Methods This study aimed to assess the risk of Parkinson’s-disease (PD) incidence in a cohort of workers occupationally exposed to chronic radiation. The cohort comprised workers of a Russian nuclear production facility who were first employed in 1948–1982 and followed up until the end of 2013 (22 377 individuals; 25% female). Using the AMFIT module of EPICURE software, relative risk and excess relative risk per unit dose (ERR/Gy) were calculated based on maximum likelihood. Results A linear association was found between PD incidence and cumulative γ-dose after adjusting for sex and attained age [ERR/Gy = 1.02 (95% confidence interval, 0.59 to 1.63, p = 5.44 × 10–5)]. The ERR/Gy of external radiation for PD incidence was stable after adjusting for neutron dose (ERR/Gy = 1.03; 95% confidence interval: 0.59 to 1.67, p = 6.86 × 10–5). The risk increased with increasing lag period and decreased notably after adjusting for body mass index, smoking and alcohol consumption. Additional adjustments for hypertension, gout, gastric ulcer, head injuries with loss of awareness and diabetes mellitus did not affect the risk estimate. Conclusions This study is the first to suggest that PD is associated with prolonged occupational external γ-ray exposure.

Cataracts have long been known, but a biomathematical model is still unavailable for cataratogenesis. There has been a renewed interest in ionizing radiation cataracts because the recent international recommendation of the reduced lens dose limit stimulated the discussion toward its regulatory implementation in various countries. Nevertheless, a relationship between radiation (dose and dose rate) and response (e.g., incidence, onset and progression) remains incompletely understood, raising the need for a risk-predictive mathematical model. We here report for the first time an in silico model for cataractogenesis. First, a simplified cell proliferation model was developed for human lens growth based on stem and progenitor cell proliferation as well as epithelial-fiber cell differentiation. Then, a model for spontaneous cataractogenesis was developed to reproduce the human data on a relationship between age and cataract incidence. Finally, a model for radiation cataractogenesis was developed that can reproduce the human data on a relationship between dose and cataract onset at various ages, which was further applied to estimate cataract incidence following chronic lifetime exposure. The model can serve as the foundation for further development of the risk-predictive model for cataractogenesis along with additional considerations of various biological mechanisms and epidemiological datasets.

International audience; In 2011, the International Commission on Radiological Protection (ICRP) recommended reducing the occupational equivalent dose limit for the lens of the eye from 150 mSv/year to 20 mSv/year, averaged over five years, with no single year exceeding 50 mSv. With this recommendation, several important assumptions were made, such as lack of dose rate effect, classification of cataracts as a tissue reaction with a dose threshold at 0.5 Gy, and progression of minor opacities into vision-impairing cataracts.However, although new dose thresholds and occupational dose limits have been set for radiation-induced cataract, ICRP clearly states that the recommendations are chiefly based on epidemiological evidence because there are a very small number of studies that provide explicit biological and mechanistic evidence at doses under 2 Gy.Since the release of the 2011 ICRP statement, the Multidisciplinary European Low Dose Initiative (MELODI) supported in April 2019 a scientific workshop that aimed to review epidemiological, clinical and biological evidence for radiation-induced cataracts.The purpose of this article is to present and discuss recent related epidemiological and clinical studies, ophthalmic examination techniques, biological and mechanistic knowledge, and to identify research gaps, towards the implementation of a research strategy for future studies on radiation-induced lens opacities.The authors recommend particularly to study the effect of ionizing radiation on the lens in the context of the wider, systemic effects, including in the retina, brain and other organs, and as such cataract is recommended to be studied as part of larger scale programs focused on multiple radiation health effects.

The International Commission on Radiological Protection (ICRP) has considered for over 60 years that the lens of the eye is among the most radiosensitive tissues, and has recommended dose limits for the lens to prevent occurrence of vision impairing cataracts (VICs). Epidemiological evidence that doses much lower than previously thought produce cataracts led ICRP to recommend reducing dose threshold for VICs and reducing an occupational equivalent dose limit for the lens in 2011, when only a single threshold of 0.5 Gy was recommended. On the basis of epidemiological evidence, ICRP assumed progression of minor opacities into VICs and no dose rate effect. This contrasts with previously recommended separate thresholds for minor opacities and VICs, and for different exposure scenarios. Progression was assumed based on similar risks of cataracts and cataract surgery in Japanese atomic bomb survivors. The absence of dose rate effect derived from the observed similar thresholds for protracted exposures in Chernobyl cleanup workers and in atomic bomb survivors. Since 2011, there has been an increasing body of epidemiological evidence relating to cataracts and other ocular diseases (i.e. glaucoma and macular degeneration), particularly at low doses and low dose rates. This review paper gives an overview of the scientific basis of the 2011 ICRP recommendation, discusses the plausibility of these two assumptions in the light of emerging scientific evidence, and considers the radiosensitivity of the lens among ocular structures.

There has been a recent upsurge of interest in the effects of ionizing radiation exposure on the circulatory system, because a mounting body of epidemiological evidence suggests that irradiation induces cardio- and cerebrovascular disease at a much lower dose and lower dose rate than previously considered. The goal of our project is to determine whether dose protraction alters radiation effects on the circulatory system in a mouse model. To this end, the use of wild-type mice is pivotal albeit without manifestation of vascular diseases, because disease models (e.g., apolipoprotein E-deficient mice) are prone to hormetic responses following protracted exposures. As such, here, we first set out to analyze prelesional changes in the descending thoracic aorta of wild-type mice up to six months after a single acute exposure to 0 or 5 Gy of 137Cs &gamma, rays. Scanning electron microscopy demonstrated that irradiation facilitated structural disorganizations and detachment of the aortic endothelium. The Miles assay with an albumin-binding dye Evans Blue revealed that irradiation enhanced vascular permeability. Immunofluorescence staining showed that irradiation led to partial loss of the aortic endothelium (evidenced by a lack of adhesion molecule CD31 and 4&prime, 6-diamidino-2-phenylindole (DAPI) signals), a decrease in endothelial nitric oxide synthase and adherens junction protein (vascular endothelial (VE)-cadherin) in the aortic endothelium, along with an increase in inflammation (tumor necrosis factor (TNF)-&alpha, ) and macrophage (F4/80) markers in the aorta. These findings suggest that irradiation produces vascular damage manifested as endothelial cell loss and increased vascular permeability, and that the decreased adherens junction and the increased inflammation lead to macrophage recruitment implicated in the early stage of atherosclerosis.

Cataract is one of the major morbidities in the U.S. population and it has long been appreciated that high and acutely delivered radiation doses of 1 Gy or more can induce cataract. Some more recent studies, in particular those of the U.S. Radiologic Technologists, have suggested that cataract may be induced by much lower, chronically delivered doses of ionizing radiation. It is well recognized that dosimetric measurement error can substantially alter the shape of the radiation dose-response relationship and thus, the derived study risk estimates, and can also inflate the variance of the estimates. In the current study, we evaluate the impact of uncertainties in eye-lens absorbed doses on the estimated risk of cataract in the U.S. Radiologic Technologists' Monte Carlo Dosimetry System, using both absolute and relative risk models. Among 11,345 cases we show that the inflation in the standard error for the excess relative risk (ERR) is generally modest, at most approximately 20% of the unadjusted standard error, depending on the model used for the baseline risk. The largest adjustment results from use of relative risk models, so that the ERR/Gy and its 95% confidence intervals change from 1.085 (0.645, 1.525) to 1.085 (0.558, 1.612) after adjustment. However, the inflation in the standard error of the excess absolute risk (EAR) coefficient is generally minimal, at most approximately 0.04% of the standard error.

Glaucoma is a group of optic neuropathies causing optic nerve damage and visual field defects, and is one of the leading causes of blindness. Nearly a century has passed since the first report of glaucoma manifested following ionizing radiation therapy of cancers. Nevertheless, associations between glaucoma and radiation exposures, a dose response relationship, and the mechanistic underpinnings remain incompletely understood. Here we review the current knowledge on manifestations and mechanisms of radiogenic glaucoma. There is some evidence that neovascular glaucoma is manifest relatively quickly, within a few years after high-dose and high dose-rate radiotherapeutic exposure, but little evidence of excess risks of glaucoma after exposure to much lower doses or dose rates. As such, glaucoma appears to have some of the characteristics of a tissue reaction effect, with a threshold of at least 5 Gy but possibly much higher.

In this study, the risk of cataract removal surgery was assessed in a cohort of workers occupationally exposed to ionizing radiation over a prolonged period. The study cohort includes 22,377 workers of the Mayak Production Association (about 25% of whom are females) first employed at one of the main facilities in 1948–1982, who were followed up to the end of 2008. Dose estimates used in the study are provided by the Mayak Worker Dosimetry System 2008. The mean cumulative dose from external γ-rays [personal dose equivalent Hp(10)] is 0.54 ± 0.76 Sv for males and 0.44 ± 0.65 Sv for females. The mean cumulative doses from neutrons (personal dose equivalent Hp(10)n) were 0.034 ± 0.080 Sv for males and 0.033 ± 0.092 Sv for females. Relative risks and excess relative risks per unit dose were calculated based on maximum likelihood. Among 4,177 workers diagnosed with a verified diagnosis of senile cataract, 701 lens removal surgeries (16.7%) were performed by the end of the follow-up period. The risk of cataract removal surgery was shown to be significantly associated with non-radiation factors such as sex, attained age, smoking, an ocular comorbidity (e.g., glaucoma), and a somatic comorbidity (e.g., diabetes mellitus). There was no significant association of cataract removal surgery with external γ-dose regardless of inclusion of the neutron dose adjustment with either linear or non-linear models. It is concluded that cataract removal surgery rate may not be a highly sensitive and specific indicator that could serve as a surrogate for radiation-related cataracts.

International audience; It has long been known that relatively high-dose ionising radiation exposure (> 1 Gy) can induce cataract, but there has been no evidence that this occurs at low doses (< 100 mGy). To assess low-dose risk, participants from the US Radiologic Technologists Study, a large, prospective cohort, were followed from date of mailed questionnaire survey completed during 1994-1998 to the earliest of self-reported diagnosis of cataract/cataract surgery, cancer other than non-melanoma skin, or date of last survey (up to end 2014). Cox proportional hazards models with age as timescale were used, adjusted for a priori selected cataract risk factors (diabetes, body mass index, smoking history, race, sex, birth year, cumulative UVB radiant exposure). 12,336 out of 67,246 eligible technologists reported a history of diagnosis of cataract during 832,479 person years of follow-up, and 5509 from 67,709 eligible technologists reported undergoing cataract surgery with 888,420 person years of follow-up. The mean cumulative estimated 5-year lagged eye-lens absorbed dose from occupational radiation exposures was 55.7 mGy (interquartile range 23.6-69.0 mGy). Five-year lagged occupational radiation exposure was strongly associated with self-reported cataract, with an excess hazard ratio/mGy of 0.69 é— 10ˆ’3 (95% CI 0.27 é— 10ˆ’3 to 1.16 é— 10ˆ’3, p < 0.001). Cataract risk remained statistically significant (p = 0.030) when analysis was restricted to < 100 mGy cumulative occupational radiation exposure to the eye lens. A non-significantly increased excess hazard ratio/mGy of 0.34 é— 10ˆ’3 (95% CI ˆ’ 0.19 é— 10ˆ’3 to 0.97 é— 10ˆ’3, p = 0.221) was observed for cataract surgery. Our results suggest that there is excess risk for cataract associated with radiation exposure from low-dose and low dose-rate occupational exposures. © 2018, This is a U.S. government work and its text is not subject to copyright protection in the United States; however, its text may be subject to foreign copyright 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.

Purpose: To assess cataract type specific risks in a cohort of workers occupationally exposed to ionizing radiation over prolonged periods. Material and methods: The present retrospective cohort study included 22,377 workers first employed at a nuclear production facility in 1948–1982 and followed up till the end of 2008. By the end of the follow-up period in the study worker cohort 3123 cases of cortical cataract, 1239 cases of posterior subcapsular cataract (PSC) and 2033 cases of nuclear cataracts were registered over 486,245, 489,162, 492,004 person-years of follow-up, respectively. Results: The incidence of PSC, cortical and nuclear cataracts was significantly linearly associated with the cumulative radiation dose. The excess relative risk per unit dose of external gamma-ray exposure (ERR/Sv) was 0.91 (95 % CI: 0.67–1.20) for PSC, 0.63 (95 % CI: 0.49–0.76) for cortical cataracts and 0.47 (95 % CI: 0.35–0.60) for nuclear cataracts. Exclusion of an adjustment for neutron dose and inclusion of additional adjustments for body mass index and smoking index reduced ERRs/Sv for all types of cataracts. However, an additional adjustment for glaucoma increased the incidence risks of cortical and nuclear cataracts just modestly (but not for PSC). Inclusion of an adjustment for diabetes mellitus reduced the ERR/Sv of external gamma-ray exposure only for PSC incidence. Increased incidence risks of all cataract types were observed in both males and females of the study cohort, but ERR/Sv was significantly higher in females (p

An adult Japanese man who had just returned from Thailand developed dengue hemorrhagic fever (DHF). A primary infection of dengue virus (DENV) was confirmed, specifically DENV serotype 2 (DENV-2), on the basis of the detection of the virus genome, a significant increase in the neutralizing antibody and the isolation of DENV-2. DHF is often observed following a secondary infection from another serotype of dengue virus, particularly in children, but this case was a primary infection of DENV. Japan is a non-endemic country for dengue disease. In fact, only Japanese encephalitis (JE) is known to be a member of the endemic flavivirus family. In this study, IgG antibody against Japanese encephalitis virus (JEV) was detected. JEV belongs to the family of dengue virus and prevails in Japan, particularly Kyushu. Among many risk factors for the occurrence of DHF, a plausible candidate could be a cross-reactive antibody-dependent enhancement (ADE) mechanism caused by JEV antibody. This indicates that most Japanese travelers who living in dengue non-endemic areas, particularly Kyushu, should be aware of the occurrence of DHF.

In 2011, the International Commission on Radiological Protection issued a statement on tissue reactions (formerly termed non-stochastic or deterministic effects) to recommend lowering the threshold for cataracts and the occupational equivalent dose limit for the crystalline lens of the eye. Furthermore, this statement was the first to list circulatory disease (cardiovascular and cerebrovascular disease) as a health hazard of radiation exposure and to assign its threshold for the heart and brain. These changes have stimulated various discussions and may have impacts on some radiation workers, such as those in the medical sector. This paper considers emerging issues associated with cataracts and cardiovascular disease. For cataracts, topics dealt with herein include (i) the progressive nature, stochastic nature, target cells and trigger events of lens opacification, (ii) roles of lens protein denaturation, oxidative stress, calcium ions, tumor suppressors and DNA repair factors in cataractogenesis, (iii) dose rate effect, radiation weighting factor, and classification systems for cataracts, and (iv) estimation of the lens dose in clinical settings. Topics for cardiovascular disease include experimental animal models, relevant surrogate markers, latency period, target tissues, and roles of inflammation and cellular senescence. Future research needs are also discussed.

Radiation exposure causes cancer and non-cancer health effects, each of which differs greatly in the shape of the dose–response curve, latency, persistency, recurrence, curability, fatality and impact on quality of life. In recent decades, for dose limitation purposes, the International Commission on Radiological Protection has divided such diverse effects into tissue reactions (formerly termed non-stochastic and deterministic effects) and stochastic effects. On the one hand, effective dose limits aim to reduce the risks of stochastic effects (cancer/heritable effects) and are based on the detriment-adjusted nominal risk coefficients, assuming a linear-non-threshold dose response and a dose and dose rate effectiveness factor of 2. On the other hand, equivalent dose limits aim to avoid tissue reactions (vision-impairing cataracts and cosmetically unacceptable non-cancer skin changes) and are based on a threshold dose. However, the boundary between these two categories is becoming vague. Thus, we review the changes in radiation effect classification, dose limitation concepts, and the definition of detriment and threshold. Then, the current situation is overviewed focusing on (i) stochastic effects with a threshold, (ii) tissue reactions without a threshold, (iii) target organs/tissues for circulatory disease, (iv) dose levels for limitation of cancer risks vs prevention of non-life-threatening tissue reactions vs prevention of life-threatening tissue reactions, (v) mortality or incidence of thyroid cancer, and (vi) the detriment for tissue reactions. For future discussion, one approach is suggested that classifies radiation effects according to whether effects are life threatening, and radiobiological research needs are also briefly discussed.

Exactly a century after Röntgen's discovery of X rays, I entered a university to major in radiological sciences. At that time, I felt that, despite extensive use and indispensable roles of ionizing radiation in medicine and industry, many fascinating questions have yet to be answered concerning its biological mechanisms of action, and thus I decided to get into the field of radiation research. Fifteen years have passed since I started radiobiological studies in 1998, during which time various basic tenets I initially learned in my late teens and early twenties have been challenged by recent observations. Of these, this brief overview particularly focuses on the following five different albeit non mutually exclusive questions: (i) "Is nuclear DNA the only intracellular target for radiation effects?"; (ii) "What is the significance of delayed cell death in clonogenic survival?"; (iii) "Does an irradiated cell become a cancer cell?"; (iv) "Are cataracts tissue reactions?"; and (v) "Why is high-LET radiation biologically effective?".

SUMMARYUsing a newly developed rapid test, an outbreak of human metapneumovirus (HMPV) infection in a long-term care facility was detected within only 2 days after the onset of symptoms in a putative index case. The outbreak was almost under control within 8 days mainly by zoning patients, with the exception of two cases of HMPV that were diagnosed 16 and 17 days after the onset of the outbreak. According to an immunological diagnosis as well as the rapid test, it was eventually proven that 18 patients had HMPV infections. We suspected that even asymptomatic residents, who had not been completely separated from the facility population, were a source of infection. That suggested that all asymptomatic residents should be tested and that the separation of the infected patients should be absolute, if an outbreak of HMPV infection is suspected in such a facility.

This review summarizes the conclusions and recommendations of the new National Council on Radiation Protection and Measurements (NCRP) Commentary No. 26 guidance on radiation dose limits for the lens of the eye. The NCRP addressed radiation protection principles in respect to the lens of the eye, discussed the current understanding of eye biology and lens effects, reviewed and evaluated epidemiology, and assessed exposed populations with the potential for significant radiation exposures to the lens while suggesting monitoring and protection practices.Radiation-induced damage to the lens of the eye can include the loss of clarity resulting in opacification or clouding several years after exposure. The impact is highly dependent on the type of radiation, how the exposure of the lens was delivered, the genetic susceptibilities of the individual exposed, and the location of the opacity relative to the visual axis of the individual. The preponderance of epidemiological evidence suggests that lens damage could occur at lower doses than previously considered and the NCRP has determined that it is prudent to reduce the recommended annual lens of the eye occupational dose limit from an equivalent dose of 150 mSv to an absorbed dose of 50 mGy. Significant additional research is still needed in the following areas: comprehensive evaluation of the overall effects of ionizing radiation on the eye, dosimetry methodology and dose-sparing optimization techniques, additional high quality epidemiology studies, and a basic understanding of the mechanisms of cataract development.

This study clarified the characteristics of travelers who received hepatitis B vaccinations. Subjects were 233 Japanese travelers who visited our clinic prior to travel. We summarized the characteristics of the clients and performed two comparative studies: first, we compared a hepatitis B-vaccinated group with an unvaccinated group; second, we compared a group that had completed the hepatitis B vaccine series with a group that did not complete the series. The hepatitis B vaccine was administered to 152 clients. Factors positively associated with the hepatitis B vaccination (after adjusting for age and sex) included the following: travel for business or travel as an accompanying family member; travel to Asia; travel for a duration of a month or more; and, inclusion of the vaccine in a company or organization's payment plan. Meanwhile, factors negatively associated with the vaccination were travel for leisure or education, and travel to North America or Africa. Among 89 record-confirmed cases, only 53 completed 3 doses. The completion rate was negatively associated with the scheduled duration of travel if it was from a month to less than a year (after adjusting for age and sex). The present study provides a basis for promoting vaccination compliance more vigorously among Japanese adults.

The Japanese government ordered the analysis of thousands of foods after the Fukushima nuclear accident to ascertain compliance with regulatory limits for anthropogenic radionuclides in food. Four hundred and forty-five samples obtained until 31 December 2011 from 11 prefectures exceeded the regulatory limits that were in force until 31 March 2012. The possibility of these 445 samples representing localized areas of high radiocesium concentration was investigated. The objective of this study was to determine the radiocesium activity ratio ((134)Cs/(137)Cs) in foods from each geographic area to possibly identify the radioactive signature of the four different reactors (i.e., four independent sources) in the distinct regions. The average (134)Cs/(137)Cs activity ratio was 0.98 ± 0.01 for all samples. However, no statistically significant deviations from this value could be confirmed in the various regions. Therefore, we conclude that the releases from reactor No. 4 (carrying a significantly smaller activity ratio) are assumed to be small when compared with the other three reactor releases. The individual radioisotopic signatures of reactors No. 1, 2, and 3 could not be identified in various Japanese regions using the food samples, indicating integral radiocesium contamination from these sources. Subsequent releases of fission products from the reactors (e.g., after possible criticalities reported in October 2011) proved to have no impact on the radiocesium activity ratio. A discussion of the development of the regulatory limits in Japan and Europe with regard to the current limits and radiological food safety are also included.