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In this article we review the history of key epidemiological studies of populations exposed to ionizing radiation. We highlight historical and recent findings regarding radiation-associated risks for incidence and mortality of cancer and non-cancer outcomes with emphasis on study design and methods of exposure assessment and dose estimation along with brief consideration of sources of bias for a few of the more important studies. We examine the findings from the epidemiological studies of the Japanese atomic bomb survivors, persons exposed to radiation for diagnostic or therapeutic purposes, those exposed to environmental sources including Chornobyl and other reactor accidents, and occupationally exposed cohorts. We also summarize results of pooled studies. These summaries are necessarily brief, but we provide references to more detailed information. We discuss possible future directions of study, to include assessment of susceptible populations, and possible new populations, data sources, study designs and methods of analysis., (© 2024 by Radiation Research Society. All rights of reproduction in any form reserved.)

Background: The aetiology of neuroblastic tumours is likely to involve both genetic and environmental factors. A number of possible environmental risk factors have been suggested, including infection. If an irregular temporal pattern in incidence is found, this might suggest that a transient agent, such as an infection, is implicated. Previous work has found evidence for temporal clustering in children and young adults living in northern England., Methods: We examined data from a second population-based registry from Ontario, Canada to determine whether there was evidence of temporal clustering of neuroblastic tumours. Cases diagnosed in children and young adults aged 0-19 years between 1985 and 2016 were extracted from the population-based Pediatric Oncology Group of Ontario Networked Information System (POGONIS). A modified version of the Potthoff-Whittinghill method was used to test for temporal clustering. Estimates of extra-Poisson variation (EPV) and standard errors (SE) were obtained., Results: Eight hundred seventy-six cases of neuroblastic tumours were diagnosed during the study period. Overall, no evidence of temporal clustering was found between fortnights, between months or between quarters within years. However, significant EPV was found between years within the full study period (EPV = 1.05, SE = 0.25; P = 0.005)., Conclusions: The findings are consistent with the possibility that a transient agent, such as an infection that is characterised by 'peaks and troughs' in its occurrence, might be implicated in the aetiology of neuroblastic tumours. However, this pattern may also reflect a long-term increase in the numbers of cases, rather than peaks and troughs., (© 2022. The Author(s).)

Aims: An updated Cochrane systematic review assessed effectiveness of screening and brief intervention to reduce hazardous or harmful alcohol consumption in general practice or emergency care settings. This paper summarises the implications of the review for clinicians., Methods: Cochrane methods were followed. Reporting accords with PRISMA guidance. We searched multiple resources to September 2017, seeking randomised controlled trials of brief interventions to reduce hazardous or harmful alcohol consumption in people attending general practice, emergency care or other primary care settings for reasons other than alcohol treatment. Brief intervention was defined as a conversation comprising five or fewer sessions of brief advice or brief lifestyle counselling and a total duration of less than 60 min. Our primary outcome was alcohol consumption, measured as or convertible to grams per week. We conducted meta-analyses to assess change in consumption, and subgroup analyses to explore the impact of participant and intervention characteristics., Results: We included 69 studies, of which 42 were added for this update. Most studies (88%) compared brief intervention to control. The primary meta-analysis included 34 studies and provided moderate-quality evidence that brief intervention reduced consumption compared to control after one year (mean difference -20 g/wk, 95% confidence interval -28 to -12). Subgroup analysis showed a similar effect for men and women., Conclusions: Brief interventions can reduce harmful and hazardous alcohol consumption in men and women. Short, advice-based interventions may be as effective as extended, counselling-based interventions for patients with harmful levels of alcohol use who are presenting for the first time in a primary care setting., (© The Author(s) 2019. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Background: Digital behavior change interventions (DBCIs) appear to reduce alcohol consumption, but greater understanding is needed of their mechanisms of action., Purpose: To describe the behavior change techniques (BCTs) used in DBCIs and examine whether individual BCTs, the inclusion of more BCTs or more Control Theory congruent BCTs is associated with increased effectiveness., Methods: Forty-one randomized control trials were extracted from a Cochrane review of alcohol reduction DBCIs and coded for up to 93 BCTs using an established and reliable method. Random effects unadjusted and adjusted meta-regression models were performed to assess associations between BCTs and intervention effectiveness., Results: Interventions used a mean of 9.1 BCTs (range 1-22), 23 different BCTs were used in four or more trials. Trials that used "Behavior substitution" (-95.112 grams per week [gpw], 95% CI: -162.90, -27.34), "Problem solving" (-45.92 gpw, 95% CI: -90.97, -0.87) and "Credible source" (-32.09 gpw, 95% CI: -60.64, -3.55) were significantly associated with greater alcohol reduction than trials without these BCTs. The "Behavior substitution" result should be treated as preliminary because it was reported in only four trials, three of which were conducted by the same research group. "Feedback" was used in 98% of trials (n = 41); other Control Theory congruent BCTs were used less frequently: for example, "Goal setting" 43% (n = 18) and "Self-monitoring" 29%, (n = 12)., Conclusions: "Behavior substitution," "Problem solving," and "Credible source" were associated with greater alcohol reduction. Many BCTs were used infrequently in DBCIs, including BCTs with evidence of effectiveness in other domains, such as "Self-monitoring" and "Goal setting."

Exposure to ionizing radiation is ubiquitous, and it is well established that moderate and high doses cause ill-health and can be lethal. The health effects of low doses or low dose-rates of ionizing radiation are not so clear. This paper describes a project which sets out to summarize, as a restatement, the natural science evidence base concerning the human health effects of exposure to low-level ionizing radiation. A novel feature, compared to other reviews, is that a series of statements are listed and categorized according to the nature and strength of the evidence that underpins them. The purpose of this restatement is to provide a concise entrée into this vibrant field, pointing the interested reader deeper into the literature when more detail is needed. It is not our purpose to reach conclusions on whether the legal limits on radiation exposures are too high, too low or just right. Our aim is to provide an introduction so that non-specialist individuals in this area (be they policy-makers, disputers of policy, health professionals or students) have a straightforward place to start. The summary restatement of the evidence and an extensively annotated bibliography are provided as appendices in the electronic supplementary material., (© 2017 The Authors.)

Background: There is a known association between psoriasis and heavy alcohol consumption. The association between heavy alcohol consumption and other inflammatory skin diseases remains to be defined., Objectives: To examine the prevalence of heavy drinking using the Alcohol Use Disorders Identification Test (AUDIT) in patients with inflammatory skin disease., Methods: We conducted an observational cross-sectional study in a single hospital outpatient department. We recruited 609 patients with either psoriasis, eczema, cutaneous lupus or other inflammatory disorders, and a reference population with skin lesions. Primary outcome was the proportion of patients in each group with an alcohol use disorder (AUD)., Results: The observed prevalence of AUD was 30·6% in patients with psoriasis, 33·3% in those with eczema, 12·3% in those with cutaneous lupus, 21·8% in those with other inflammatory disease and 14·3% in those with non-inflammatory disease. Odds ratios (OR) for AUD in patients in the inflammatory groups compared with those in the noninflammatory groups, adjusted for age and sex, were as follows: psoriasis 1·65 [95% confidence interval (CI) 0·86-3·17], eczema 2·00 (95% CI 1·03-3·85), lupus 1·03 (95% CI 0·39-2·71), other inflammatory disease 1·32 (95% CI 0·68-2·56). ORs were reduced if also adjusted for Dermatology Life Quality Index (DLQI). The prevalence of DLQI ≥ 11 was 31·1% for psoriasis, 43·7% for eczema, 17·5% for cutaneous lupus, 17·2% for other inflammatory disease and 2·8% for noninflammatory disease., Conclusions: Patients with eczema attending a hospital clinic have been shown to have high levels of AUD of a similar level to patients with psoriasis and higher than patients with noninflammatory skin diseases., (© 2017 British Association of Dermatologists.)

Objective: to investigate barriers and facilitators to physical activity (PA) guideline implementation for midwives when advising obese pregnant women., Design: a cross-sectional, self-completion, anonymous questionnaire was designed using the Theoretical Domains Framework. this framework was developed to evaluate the implementation of guidelines by health care professionals. A total of 40 questions were included. These were informed by previous research on pregnant women's and midwives views, knowledge and attitudes to PA, and supported by national evidence based guidelines. Demographic information and free text comments were also collected., Setting: three diverse NHS Trusts in the North East of England., Participants: all midwives employed by two hospital Trusts and the community midwives from the third Trust (n=375) were invited to participate., Measurements: mean domain scores were calculated. Factor and regression analysis were performed to describe which theoretical domains may be influencing practice. Free text comments were analysed thematically., Findings: 192 (53%) questionnaires were returned. Mean domain scores were highest for social professional role and knowledge, and lowest for skills, beliefs about capabilities and behaviour regulation. Regression analysis indicated that skills and memory/attention/decision domains had a statistically significant influence on midwives discussing PA with obese pregnant women and advising them accordingly. Midwives comments indicated that they felt it was part of their role to discuss PA with all pregnant women but felt they lacked the skills and resources to do so effectively., Key Conclusions: midwives seem to have the necessary knowledge about the need/importance of PA advice for obese women and believe it is part of their role, but perceive they lack necessary skills and resources, and do not plan or prioritise the discussion regarding PA with obese pregnant woman., Implications for Practice: designing interventions that improve skills, promote routine enquiry regarding PA and provide resources (eg. information, referral pathways) may help improve midwives' PA advice., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Importance: Nausea and vomiting affects approximately 85% of pregnant women. The most severe form, hyperemesis gravidarum, affects up to 3% of women and can have significant adverse physical and psychological sequelae., Objective: To summarize current evidence on effective treatments for nausea and vomiting in pregnancy and hyperemesis gravidarum., Evidence Review: Databases were searched to June 8, 2016. Relevant websites and bibliographies were also searched. Titles and abstracts were assessed independently by 2 reviewers. Results were narratively synthesized; planned meta-analysis was not possible because of heterogeneity and incomplete reporting of findings., Findings: Seventy-eight studies (n  = 8930 participants) were included: 67 randomized clinical trials (RCTs) and 11 nonrandomized studies. Evidence from 35 RCTs at low risk of bias indicated that ginger, vitamin B6, antihistamines, metoclopramide (for mild symptoms), pyridoxine-doxylamine, and ondansetron (for moderate symptoms) were associated with improved symptoms compared with placebo. One RCT (n = 86) reported greater improvements in moderate symptoms following psychotherapy (change in Rhodes score [range, 0 {no symptoms} to 40 {worst possible symptoms}], 18.76 [SD, 5.48] to 7.06 [SD, 5.79] for intervention vs 19.18 [SD, 5.63] to 12.81 [SD, 6.88] for comparator [P < .001]). For moderate-severe symptoms, 1 RCT (n = 60) suggested that pyridoxine-doxylamine combination taken preemptively reduced risk of recurrence of moderate-severe symptoms compared with treatment once symptoms begin (15.4% vs 39.1% [P < .04]). One RCT (n = 83) found that ondansetron was associated with lower nausea scores on day 4 than metoclopramide (mean visual analog scale [VAS] score, 4.1 [SD, 2.9] for ondansetron vs 5.7 [SD, 2.3] for metoclopramide [P = .023]) but not episodes of emesis (5.0 [SD, 3.1] vs 3.3 [SD, 3], respectively [P = .013]). Although there was no difference in trend in nausea scores over the 14-day study period, trend in vomiting scores was better in the ondansetron group (P = .042). One RCT (n = 159) found no difference between metoclopramide and promethazine after 24 hours (episodes of vomiting, 1 [IQR, 0-5] for metoclopramide vs 2 [IQR, 0-3] for promethazine [P = .81], VAS [0-10 scale] for nausea, 2 [IQR, 1-5] vs 2 [IQR, 1-4], respectively [P = .99]). Three RCTs compared corticosteroids with placebo or promethazine or metoclopramide in women with severe symptoms. Improvements were seen in all corticosteroid groups, but only a significant difference between corticosteroids vs metoclopramide was reported (emesis reduction, 40.9% vs 16.5% at day 2; 71.6% vs 51.2% at day 3; 95.8% vs 76.6% at day 7 [n = 40, P < .001]). For other interventions, evidence was limited., Conclusions and Relevance: For mild symptoms of nausea and emesis of pregnancy, ginger, pyridoxine, antihistamines, and metoclopramide were associated with greater benefit than placebo. For moderate symptoms, pyridoxine-doxylamine, promethazine, and metoclopramide were associated with greater benefit than placebo. Ondansetron was associated with improvement for a range of symptom severity. Corticosteroids may be associated with benefit in severe cases. Overall the quality of evidence was low.

Background: There are limited data on admission trends and outcomes of individuals with bronchiectasis admitted to intensive care (ICU). Using national critical care data, we analysed admissions to ICU and estimated outcomes in terms of mortality in individuals with bronchiectasis and chronic obstructive pulmonary disease (COPD) admitted to ICU., Methods: Using data from the Intensive Care National Audit and Research Centre, admissions from bronchiectasis and COPD from 1 January 2009 to 31 December 2013 were extracted. Crude admission rates for bronchiectasis and COPD were calculated and Poisson regression was used to estimate unadjusted annual admission rate ratios. We investigated changes to length of stay on ICU, ICU mortality and in-hospital mortality during the study period. We also compared mortality rates in people with bronchiectasis and COPD aged 70 or above., Results: We found an annual increase of 8% (95% Confidence Interval [CI] 2-15) in the number of ICU admissions from bronchiectasis, whilst the yearly increase in ICU admissions from COPD was 1% (95% CI 0.3-2). ICU and in-hospital mortality was higher in individuals with bronchiectasis compared with those with COPD, especially in people aged 70 years or above., Conclusion: Admission to ICU in people with bronchiectasis are uncommon, but are increasing in frequency over time, and carries a substantial mortality rate. This needs to be considered allocating health care resources and planning respiratory services., (© The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The aetiology of neuroblastic tumours is unclear with both genetic and environmental factors implicated. The possibility that an infectious agent may be involved has been suggested. 'Temporal clustering' occurs if cases display an irregular temporal distribution and may indicate the involvement of an agent that exhibits epidemicity. We tested for the presence and nature of temporal clustering using population-based data from northern England., Methods: We extracted all cases of neuroblastic tumours diagnosed in children and young adults aged 0-24 years during 1968-2011 from the Northern Region Young Persons' Malignant Disease Registry. This is a population-based registry, covering a population of approximately 900,000 young persons, and includes all cases resident in northern England at the time of diagnosis. Tests for temporal clustering were applied using a modified version of the Potthoff-Whittinghill method. Estimates of extra-Poisson variation (β) and standard errors (SEs) were obtained., Results: 227 cases of neuroblastic tumours were diagnosed during the study period. All the analyses between fortnights and between months found significant extra-Poisson variation, with β = 0.846 (SE = 0.310, P = 0.004) for the analysis between fortnights within months. Restricting the analyses to the 76 cases diagnosed at ages less than 18 months showed significant extra-Poisson variation between fortnights within months (β = 1.532, SE = 0.866, P = 0.038), but not between months. In contrast, analyses of cases aged 18 months to 24 years showed significant extra-Poisson variation between quarters within years, as well as over shorter timescales., Conclusions: Transient environmental agents may be involved in the aetiology of neuroblastic tumours. The initiating factor might be a geographically-widespread agent that occurs in 'mini-epidemics'.

The risk of lung cancer mortality up to 75 years of age due to radon exposure has been estimated for both male and female continuing, ex- and never-smokers, based on various radon risk models and exposure scenarios. We used risk models derived from (i) the BEIR VI analysis of cohorts of radon-exposed miners, (ii) cohort and nested case-control analyses of a European cohort of uranium miners and (iii) the joint analysis of European residential radon case-control studies. Estimates of the lifetime lung cancer risk due to radon varied between these models by just over a factor of 2 and risk estimates based on models from analyses of European uranium miners exposed at comparatively low rates and of people exposed to radon in homes were broadly compatible. For a given smoking category, there was not much difference in lifetime lung cancer risk between males and females. The estimated lifetime risk of radon-induced lung cancer for exposure to a concentration of 200 Bq m(-3) was in the range 2.98-6.55% for male continuing smokers and 0.19-0.42% for male never-smokers, depending on the model used and assuming a multiplicative relationship for the joint effect of radon and smoking. Stopping smoking at age 50 years decreases the lifetime risk due to radon by around a half relative to continuing smoking, but the risk for ex-smokers remains about a factor of 5-7 higher than that for never-smokers. Under a sub-multiplicative model for the joint effect of radon and smoking, the lifetime risk of radon-induced lung cancer was still estimated to be substantially higher for continuing smokers than for never smokers. Radon mitigation-used to reduce radon concentrations at homes-can also have a substantial impact on lung cancer risk, even for persons in their 50 s; for each of continuing smokers, ex-smokers and never-smokers, radon mitigation at age 50 would lower the lifetime risk of radon-induced lung cancer by about one-third. To maximise risk reductions, smokers in high-radon homes should both stop smoking and remediate their homes.

This study investigated the cross-sectional association between an anti-inflammatory and anti-oxidant dietary pattern and diabetes in the national diet and nutrition survey (NDNS) rolling programme years 1-4. A total of 1531 survey members provided dietary data. Reduced Rank Regression (RRR) was used to derive an anti-inflammatory and anti-oxidant dietary pattern. Serum C-reactive protein (CRP) and plasma carotenoids were selected as response variables and markers of inflammation and antioxidant status, respectively. Overall, 52 survey members had diabetes. The derived anti-inflammatory and anti-oxidant dietary pattern was inversely related to CRP and positively to carotenoids. It was associated with lower odds of diabetes (multivariate adjusted OR for highest compared with lowest quintile: 0.17; 95%CI: 0.04-0.73; p for linear trend = 0.013). In conclusion, an anti-inflammatory and anti-oxidant dietary pattern is inversely related to diabetes. Further research is required to understand the overall framework within which foods and nutrients interact to affect metabolic pathways related to diabetes risk.

The aetiology of primary biliary cirrhosis (PBC) is not well established. Previously we found evidence of space-time clustering and seasonal variation in the date of diagnosis, suggesting a possible role for a transient or seasonally varying environmental factor. We examined whether a temporally varying environmental agent may be involved by analysing population-based PBC data from northeast England over 1987-2003. Using an adaptation of a method proposed by Potthoff and Whittinghill, we found significant temporal variation by date of diagnosis at the level of aggregation of one year. However, there was no evidence for general irregular (non-seasonal) temporal clustering within periods less than a year. These results provide little support for the involvement of agents occurring in geographically widespread mini-epidemics, but--taken together with studies of spatial and spatio-temporal clustering--do not preclude the role of more localised sporadic mini-epidemics. Future research should seek to elicit putative environmental agents., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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

Background: Previous studies have indicated that type 1 diabetes may have an infectious origin. The presence of temporal clustering-an irregular temporal distribution of cases--would provide additional evidence that occurrence may be linked with an agent that displays epidemicity. We tested for the presence and form of temporal clustering using population- based data from northeast England., Materials and Methods: The study analysed data on children aged 0-14 years diagnosed with type 1 diabetes during the period 1990-2007 and resident in a defined geographical region of northeast England (Northumberland, Newcastle upon Tyne, and North Tyneside). Tests for temporal clustering by time of diagnosis were applied using a modified version of the Potthoff-Whittinghill method., Results: The study analysed 468 cases of children diagnosed with type 1 diabetes. There was highly statistically significant evidence of temporal clustering over periods of a few months and over longer time intervals (p<0.001). The clustering within years did not show a consistent seasonal pattern., Conclusions: The study adds to the growing body of literature that supports the involvement of infectious agents in the aetiology of type 1 diabetes in children. Specifically it suggests that the precipitating agent or agents involved might be an infection that occurs in "mini-epidemics".

Introduction: Health registers have been established in the United Kingdom (UK) and elsewhere following mass exposure to novel agents or known agents, but there is no consensus on the criteria for establishing such registers., Objective: This study aimed to develop a decision framework to assess the need for establishing a health register for major chemical, biological, radiological, and nuclear (CBRN) incidents., Methods: The study comprised three stages. In the first stage, the study team prepared a list of potential criteria that may be used to assess the need for setting up a health register based on literature review and personal experiences in previous incidents. In the second stage, the potential criteria were evaluated in two Delphi rounds involving experts and key decision makers from the UK Health Protection Agency (HPA) and academic organizations. In the final stage, the criteria were converted into a decision framework, and its utility was tested using four fictional scenarios., Results: A total of 11 statements were proposed by the study group. These criteria were revised following feedback from 16 experts in the first Delphi round. All 11 statements achieved consensus at the end of the second Delphi round. Pilot testing of the agreed criteria on four fictional scenarios confirmed validity and reliability for use in the decision process., Conclusions: A decision framework to assess the need for setting up a health register after a major incident was agreed upon and tested using fictional scenarios. Further areas of work for practical implementation of the criteria and related planning for systems and protocols have been identified.

Following an earlier study of incidence and mortality of ischemic heart disease (IHD) published in 2010, a second analysis has been conducted based on an extended cohort and five additional years of follow-up. The cohort includes 18,763 workers, of whom 25% were females, first employed at the Mayak PA in 1948-1972 and followed up to the end of 2005. Some of these workers were exposed to external gamma rays only, and others were exposed to a mixture of external gamma-rays and internal alpha-particle radiation. A total of 6,134 cases and 2,629 deaths from IHD were identified in the study cohort. A statistically significant increasing trend was found with total external gamma-ray dose in IHD incidence (ERR/Gy 0.099; 95% CI: 0.045-0.153) after adjusting for non-radiation factors. This value reduced slightly when adjusting for internal liver dose. There was no statistically significant increase trend for internal liver dose in IHD incidence. These findings were consistent with an earlier study. New findings in IHD incidence revealed a statistically significant decrease in IHD incidence among workers exposed to external gamma-rays doses of 0.2-0.5 Gy in relation to the external doses below 0.2 Gy. This decreased risk is heavily influenced by female workers. This finding has never been reported in other studies, and the results should be treated with caution. The findings for IHD mortality are similar to those results in the earlier analysis; there was no statistically significant trend with external gamma-ray dose or for internal liver dose after adjustment for external dose. The risk estimates obtained from these analyses of IHD incidence and mortality in relation to external gamma-rays in the cohort of Mayak workers are generally compatible with those from other large occupational radiation worker studies and the Japanese atomic bomb survivors.

This report provides a review of early and late effects of radiation in normal tissues and organs with respect to radiation protection. It was instigated following a recommendation in Publication 103 (ICRP, 2007), and it provides updated estimates of 'practical' threshold doses for tissue injury defined at the level of 1% incidence. Estimates are given for morbidity and mortality endpoints in all organ systems following acute, fractionated, or chronic exposure. The organ systems comprise the haematopoietic, immune, reproductive, circulatory, respiratory, musculoskeletal, endocrine, and nervous systems; the digestive and urinary tracts; the skin; and the eye. Particular attention is paid to circulatory disease and cataracts because of recent evidence of higher incidences of injury than expected after lower doses; hence, threshold doses appear to be lower than previously considered. This is largely because of the increasing incidences with increasing times after exposure. In the context of protection, it is the threshold doses for very long follow-up times that are the most relevant for workers and the public; for example, the atomic bomb survivors with 40-50years of follow-up. Radiotherapy data generally apply for shorter follow-up times because of competing causes of death in cancer patients, and hence the risks of radiation-induced circulatory disease at those earlier times are lower. A variety of biological response modifiers have been used to help reduce late reactions in many tissues. These include antioxidants, radical scavengers, inhibitors of apoptosis, anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, growth factors, and cytokines. In many cases, these give dose modification factors of 1.1-1.2, and in a few cases 1.5-2, indicating the potential for increasing threshold doses in known exposure cases. In contrast, there are agents that enhance radiation responses, notably other cytotoxic agents such as antimetabolites, alkylating agents, anti-angiogenic drugs, and antibiotics, as well as genetic and comorbidity factors. Most tissues show a sparing effect of dose fractionation, so that total doses for a given endpoint are higher if the dose is fractionated rather than when given as a single dose. However, for reactions manifesting very late after low total doses, particularly for cataracts and circulatory disease, it appears that the rate of dose delivery does not modify the low incidence. This implies that the injury in these cases and at these low dose levels is caused by single-hit irreparable-type events. For these two tissues, a threshold dose of 0.5Gy is proposed herein for practical purposes, irrespective of the rate of dose delivery, and future studies may elucidate this judgement further., (Copyright © 2012. Published by Elsevier Ltd.)

Incidence and mortality from cerebrovascular diseases (CVD) (430-438 ICD-9 codes) have been studied in a cohort of 18,763 workers first employed at the Mayak Production Association (Mayak PA) in 1948-1972 and followed up to the end of 2005. Some of the workers were exposed to external gamma-rays only while others were exposed to a mixture of external gamma-rays and internal alpha-particle radiation due to incorporated (239)Pu. After adjusting for non-radiation factors, there were significantly increasing trends in CVD incidence with total absorbed dose from external gamma-rays and total absorbed dose to liver from internal alpha radiation. The CVD incidence was statistically significantly higher among workers with total absorbed external gamma-ray doses greater than 0.20 Gy compared to those exposed to lower doses; the data were consistent with a linear trend in risk with external dose. The CVD incidence was statistically significantly higher among workers with total absorbed internal alpha-radiation doses to liver from incorporated (239)Pu greater than 0.025 Gy compared to those exposed to lower doses. There was no statistically significant trend in CVD mortality risk with either external gamma-ray dose or internal alpha-radiation dose to liver. The risk estimates obtained are generally compatible with those from other large occupational studies, although the incidence data point to higher risk estimates compared to those from the Japanese A-bomb survivors. Further studies of the unique cohort of Mayak workers chronically exposed to external and internal radiation will allow improving the reliability and validating the radiation safety standards for occupational and public exposure.

Safegrounds is a forum for developing and disseminating good practice guidance on the management of radioactively contaminated land on nuclear and defence sites in the UK. This review has been provided to Safegrounds as a summary of the basis for current radiation risk estimates and the International Commission on Radiological Protection (ICRP) protection system, in a form that will be accessible to a wide range of stakeholders. Safegrounds has also received viewpoint papers from other members who contend that the ICRP methodology results in substantial underestimates of risk, particularly for internal emitters. There is an extensive literature on the risks of radiation exposure, regularly reviewed by the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) and other expert groups. These data provide a sound basis for the system of protection recommended by ICRP. The available epidemiological and experimental evidence supports the application of cancer risk estimates derived for acute, high dose, external exposures to low dose exposures to external and internal sources. In the context of radioactively contaminated land on nuclear and defence sites, the national standards for the cleaning up of land and for waste disposal correspond to very low doses, two orders of magnitude less than average annual doses in the UK from natural background radiation (10-20  µSv compared with 2-3 mSv). Risks at such very low doses can only be estimated on the basis of observations after exposure of population groups at much higher doses. The estimated risks at these very low doses, while uncertain, are as likely to be overestimates as underestimates.

In this paper, a simple model for analysing variability in radon concentrations in homes is tested. The approach used here involves two error components, representing additive and multiplicative errors, together with variation between-houses. We use a Bayesian approach for our analysis and apply this model to two datasets of repeat radon measurements in homes; one based on 3-month long measurements for which the original measurements were close to the current UK Radon Action Level (200 Bq m(-3)), and the other based on 6-month measurement data (from regional and national surveys), for which the original measurements cover a wide range of radon concentrations, down to very low levels. The model with two error components provides a better fit to these datasets than does a model based on solely multiplicative errors., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Introduction: Patients diagnosed with breast cancer are often treated with surgery followed by radiation therapy. In this paper, we evaluate the effect that radiotherapy may have had on the subsequent risk of second malignancies, including the possible influences of age at treatment and menopausal status., Methods: In order to evaluate the long-term consequences of radiotherapy, a cohort study was conducted based on clinical records for 5,248 women treated for breast cancer in Florence (Italy), with continuous follow-up from 1965 to 1994. The Cox proportional hazards model for ungrouped survival data was used to estimate the relative risk for second cancer after radiotherapy., Results: This study indicated an increased relative risk of all second cancers combined following radiotherapy (1.22, 95% CI: 0.88 to 1.69). The increased relative risk appeared five or more years after radiotherapy and appeared to be highest amongst women treated after the menopause (1.61, 95% CI: 1.13 to 2.29). Increased relative risks were observed specifically for leukaemia (8.13, 95% CI: 0.96 to 69.1) and other solid cancers (1.84, 95% CI: 1.06 to 3.16), excluding contralateral breast cancer. For contralateral breast cancer, no raised relative risk was observed during the period more than five years after radiotherapy., Conclusions: The study indicated a raised risk of second malignancies associated with radiotherapy for breast cancer, particularly for women treated after the menopause.

The incidence of and mortality from cerebrovascular diseases (CVD) have been studied in a cohort of 12,210 workers first employed at one of the main plants of the Mayak nuclear facility during 1948-1958 and followed up to 31 December 2000. Information on external γ-ray doses is available for virtually all of these workers (99.9%); the mean total γ-ray dose (± SD) was 0.91 ± 0.95 Gy (99th percentile 3.9 Gy) for men and 0.65 ± 0.75 Gy (99th percentile 2.99 Gy) for women. In contrast, plutonium body burden was measured only for 30.0% of workers; among those monitored, the mean cumulative liver dose from plutonium α-particle exposure (± SD) was 0.40 ± 1.15 Gy (99th percentile 5.88 Gy) for men and 0.81 ± 4.60 Gy (99th percentile 15.95 Gy) for women. A total of 4418 cases of CVD, including 665 cases of stroke, and 753 deaths from CVD, including 404 deaths from stroke, were identified in the study cohort. Having adjusted for non-radiation factors, there were statistically significant increasing trends in CVD incidence but not mortality with both total external γ-ray dose and internal liver dose. Much of the evidence for increased incidence in relation to external dose arose for workers with cumulative doses above 1 Gy. Although the dose response is consistent with linearity, the statistical power to detect non-linearity at external doses below 1 Gy was low. CVD incidence was statistically significantly higher among workers with a plutonium liver dose above 0.1 Gy. There was a statistically significant increasing trend in incidence with increasing internal dose, even after adjusting for external dose, although the trend estimates differed between workers at different plants. The risk estimates for external radiation are generally compatible with those from other large occupational studies, although the incidence data point to higher risk estimates compared to those from the Japanese A-bomb survivors.

Data collected as a part of a survey on radon concentrations from about 40 000 dwellings in England for six contrasting geological units were analysed to evaluate the impact of house-specific factors (building characteristics and construction dates) and of proximity to geological boundaries. After adjusting for temperature and outdoor radon, geological unit, house type, double glazing and date of building were found to have a statistically significant influence on indoor radon concentrations and explained about 29 % of the total variation between dwellings in logarithmically transformed radon values. In addition, there were statistically significant differences in radon concentrations according to proximity to geological boundaries categories for most of the geological units, but no consistent pattern could be detected.

The lens of the eye is recognized as one of the most radiosensitive tissues in the human body, and it is known that cataracts can be induced by acute doses of less than 2 Gy of low-LET ionizing radiation and less than 5 Gy of protracted radiation. Although much work has been carried out in this area, the exact mechanisms of radiation cataractogenesis are still not fully understood. In particular, the question of the threshold dose for cataract development is not resolved. Cataracts have been classified as a deterministic effect of radiation exposure with a threshold of approximately 2 Gy. Here we review the combined results of recent mechanistic and human studies regarding induction of cataracts by ionizing radiation. These studies indicate that the threshold for cataract development is certainly less than was previously estimated, of the order of 0.5 Gy, or that radiation cataractogenesis may in fact be more accurately described by a linear, no-threshold model.

Information on Japanese A-bomb survivors exposed to gamma radiation has been used to estimate cancer risks for the whole range of photon (x-rays) and electron energies which are commonly encountered by radiation workers in the work place or by patients and workers in diagnostic radiology. However, there is some uncertainty regarding the radiation effectiveness of various low-linear energy transfer (low-LET) radiations (x-rays, gamma radiation and electrons). In this paper we review information on the effectiveness of low-LET radiations on the basis of epidemiological and in vitro radiobiological studies. Data from various experimental studies for chromosome aberrations and cell transformation in human lymphocytes and from epidemiological studies of the Japanese A-bomb survivors, patients medically exposed to radiation for diagnostic and therapeutic procedures, and occupational exposures of nuclear workers are considered. On the basis of in vitro cellular radiobiology, there is considerable evidence that the relative biological effectiveness (RBE) of high-energy low-LET radiation (gamma radiation, electrons) is less than that of low-energy low-LET radiation (x-rays, betas). This is a factor of about 3 to 4 for 29 kVp x-rays (e.g. as in diagnostic radiation exposures of the female breast) and for tritium beta-rays (encountered in parts of the nuclear industry) relative to Co-60 gamma radiation and 2-5 MeV gamma-rays (as received by the Japanese A-bomb survivors). In epidemiological studies, although for thyroid and breast cancer there appears to be a small tendency for the excess relative risks to decrease as the radiation energy increases for low-LET radiations, it is not statistically feasible to draw any conclusion regarding an underlying dependence of cancer risk on LET for the nominally low-LET radiations.

Mortality and cancer incidence were studied in the National Registry for Radiation Workers in, relative to earlier analyses, an enlarged cohort of 174 541 persons, with longer follow-up (to 2001) and, for the first time, cancer registration data. SMRs for all causes and all malignant neoplasms were 81 and 84 respectively, demonstrating a 'healthy worker effect'. Within the cohort, mortality and incidence from both leukaemia excluding CLL and the grouping of all malignant neoplasms excluding leukaemia increased to a statistically significant extent with increasing radiation dose. Estimates of the trend in risk with dose were similar to those for the Japanese A-bomb survivors, with 90% confidence intervals that excluded both risks more than 2-3 times greater than the A-bomb values and no raised risk. Some evidence of an increasing trend with dose in mortality from all circulatory diseases may, at least partly, be due to confounding by smoking. This analysis provides the most precise estimates to date of mortality and cancer risks following occupational radiation exposure and strengthens the evidence for raised risks from these exposures. The cancer risk estimates are consistent with values used to set radiation protection standards.

This study uses record linkage between the National Registry of Childhood Tumours (NRCT) and the National Registry for Radiation Workers to re-assess our earlier finding that the offspring of women radiation workers exposed to ionising radiation before the child's conception may be at an increased risk of childhood cancer. An additional 16,964 childhood cancer patients taken from the NRCT, together with the same number of matched controls, are included. Pooled analyses, based on the new and original datasets, include 52,612 cases and their matched controls. Relative risks (RRs) for maternal employment as a radiation worker, maternal exposure or not during the relevant pregnancy and pattern of employment relative to conception and diagnosis dates were calculated.The new data provide no evidence of an increased risk of childhood cancer associated with maternal preconception radiation work and thus do not support our earlier finding of a raised risk in the offspring of female radiation workers. Considering the pooled data, a weak association was found between maternal radiation work during pregnancy and childhood cancer in offspring although the evidence is limited by the small numbers of linked cases and controls.

In contrast to other types of leukemia, chronic lymphocytic leukemia (CLL) has long been regarded as non-radiogenic, i.e. not caused by ionizing radiation. However, the justification for this view has been challenged. We therefore report on the relationship between CLL mortality and external ionizing radiation dose within the 15-country nuclear workers cohort study. The analyses included, in seven countries with CLL deaths, a total of 295,963 workers with more than 4.5 million person-years of follow-up and an average cumulative bone marrow dose of 15 mSv; there were 65 CLL deaths in this cohort. The relative risk (RR) at an occupational dose of 100 mSv compared to 0 mSv was 0.84 (95% CI 0.39, 1.48) under the assumption of a 10-year exposure lag. Analyses of longer lag periods showed little variation in the RR, but they included very small numbers of cases with relatively high doses. In conclusion, the largest nuclear workers cohort study to date finds little evidence for an association between low doses of external ionizing radiation and CLL mortality. This study had little power due to low doses, short follow-up periods, and uncertainties in CLL ascertainment from death certificates; an extended follow-up of the cohorts is merited and would ideally include incident cancer cases.

Generalized relative and absolute risk models are fitted to the latest Japanese atomic bomb survivor solid cancer and leukemia mortality data (through 2000), with the latest (DS02) dosimetry, by classical (regression calibration) and Bayesian techniques, taking account of errors in dose estimates and other uncertainties. Linear-quadratic and linear-quadratic-exponential models are fitted and used to assess risks for contemporary populations of China, Japan, Puerto Rico, the U.S. and the UK. Many of these models are the same as or very similar to models used in the UNSCEAR 2006 report. For a test dose of 0.1 Sv, the solid cancer mortality for a UK population using the generalized linear-quadratic relative risk model is estimated as 5.4% Sv(-1) [90% Bayesian credible interval (BCI) 3.1, 8.0]. At 0.1 Sv, leukemia mortality for a UK population using the generalized linear-quadratic relative risk model is estimated as 0.50% Sv(-1) (90% BCI 0.11, 0.97). Risk estimates varied little between populations; at 0.1 Sv the central estimates ranged from 3.7 to 5.4% Sv(-1) for solid cancers and from 0.4 to 0.6% Sv(-1) for leukemia. Analyses using regression calibration techniques yield central estimates of risk very similar to those for the Bayesian approach. The central estimates of population risk were similar for the generalized absolute risk model and the relative risk model. Linear-quadratic-exponential models predict lower risks (at least at low test doses) and appear to fit as well, although for other (theoretical) reasons we favor the simpler linear-quadratic models.

To study early (deterministic) and long-term effects of radiation exposure, the "Clinic" medical-dosimetric database for the Mayak Production Association worker cohort has been established at the Southern Urals Biophysics Institute (SUBI). This paper describes the principles of organization, structure and prospects of future utilization of this database.

Studies of persons exposed to radiation in the course of their work are directly relevant to the task of estimating the health risks of protracted radiation exposures. However, such investigations are not always easy to undertake, and not all studies are equally informative. Considerable care is required, therefore, in order to be able to draw reliable inferences from studies of radiation workers. This paper highlights some important aspects concerning the design, conduct and interpretation of such investigations, with reference to experience gained from a large long-term study of radiation workers in the United Kingdom (the National Registry for Radiation Workers, NRRW). Key findings from the NRRW are summarised, together with a brief description of a recent international study and of work in progress.

Quantitative estimates of ionizing radiation exposure are often available for use in epidemiological studies. However, depending on the context, the quality of the exposure estimates can vary. For example, the estimates may be specific to individuals in the study or generic values averaged over populations; unavailable for some of the potential study subjects or vary in their form between individuals; based on contemporary measurements or assessed retrospectively; based on measurements alone, on surrogate measures of exposure, or on an exposure assessment model; or, as is often the case, cover one source of radiation exposure rather than all of them. Various ways in which ionizing radiation exposures have been assessed are illustrated through reference to some studies of childhood leukaemia, concerning environmental, medical, natural and parental occupational exposures. Based on this, implications for the interpretation of radiation epidemiological studies are discussed.

Radiation protection standards are based mainly on risk estimates from studies of atomic bomb survivors in Japan. The validity of extrapolations from the relatively high-dose acute exposures in this population to the low-dose, protracted or fractionated environmental and occupational exposures of primary public health concern has long been the subject of controversy. A collaborative retrospective cohort study was conducted to provide direct estimates of cancer risk after low-dose protracted exposures. The study included nearly 600,000 workers employed in 154 facilities in 15 countries. This paper describes the design, methods and results of descriptive analyses of the study. The main analyses included 407,391 nuclear industry workers employed for at least 1 year in a participating facility who were monitored individually for external radiation exposure and whose doses resulted predominantly from exposure to higher-energy photon radiation. The total duration of follow-up was 5,192,710 person-years. There were 24,158 deaths from all causes, including 6,734 deaths from cancer. The total collective dose was 7,892 Sv. The overall average cumulative recorded dose was 19.4 mSv. A strong healthy worker effect was observed in most countries. This study provides the largest body of direct evidence to date on the effects of low-dose protracted exposures to external photon radiation.

A 15-Country collaborative cohort study was conducted to provide direct estimates of cancer risk following protracted low doses of ionizing radiation. Analyses included 407,391 nuclear industry workers monitored individually for external radiation and 5.2 million person-years of follow-up. A significant association was seen between radiation dose and all-cause mortality [excess relative risk (ERR) 0.42 per Sv, 90% CI 0.07, 0.79; 18,993 deaths]. This was mainly attributable to a dose-related increase in all cancer mortality (ERR/Sv 0.97, 90% CI 0.28, 1.77; 5233 deaths). Among 31 specific types of malignancies studied, a significant association was found for lung cancer (ERR/Sv 1.86, 90% CI 0.49, 3.63; 1457 deaths) and a borderline significant (P = 0.06) association for multiple myeloma (ERR/Sv 6.15, 90% CI <0, 20.6; 83 deaths) and ill-defined and secondary cancers (ERR/Sv 1.96, 90% CI -0.26, 5.90; 328 deaths). Stratification on duration of employment had a large effect on the ERR/Sv, reflecting a strong healthy worker survivor effect in these cohorts. This is the largest analytical epidemiological study of the effects of low-dose protracted exposures to ionizing radiation to date. Further studies will be important to better assess the role of tobacco and other occupational exposures in our risk estimates.

In trying to interpret reports of disease clusters in specific localities, it is valuable to know whether the disease in question has a general tendency to cluster spatially. Methods for investigating localized disease clustering were the subject of a comparative study organized by the International Agency for Research on Cancer some years ago. This paper addresses some further aspects of one of the methods used in this exercise, namely the Potthoff-Whittinghill (P-W) test. Particular consideration is given to methodology for estimating the magnitude of overdispersion and for detecting whether one area, in particular, has an undue influence on the evidence for overdispersion using the P-W test, the extent to which is possible to detect clustering over regions of differing sizes using a components-of-variance approach and how adjustment for overdispersion might affect tests for raised disease rates in specific locations. These points are illustrated using data on childhood leukaemia incidence and reference is made to other analyses of the geographical distribution of childhood leukaemia that are based on this approach.