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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.

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 40–50 years 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 0.5 Gy is proposed herein for practical purposes, irrespective of the rate of dose delivery, and future studies may elucidate this judgement further.

In its 1990 recommendations, ICRP published information on the fatal cancer risk of chronic exposure to radiation. Calculations of the same form were repeated in a report by the first author using health effects information specific to a UK population. For constant annual doses over a complete lifetime, the UK estimates are broadly consistent with those given by ICRP and BEIR. However, because differences exist in the methodologies used, this may not be true of more realistic exposure situations. For the purpose of individual risk assessments, this paper gives some additional information on age- and sex-related organ risks for various tissue groups. Furthermore, a simple approach is presented for calculating fatal cancer risks for protracted exposure at different ages, and over different lengths of time.

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.

The results of epidemiological studies of populations exposed to electromagnetic fields are summarised in respect of general health, cataracts, suicide, and birth outcome. It is concluded that the bulk of the evidence suggests that there are no effects at exposures below the limits advised by NRPB and INIRC. Some studies have indicated minor changes in components of the cerebrospinal fluid and in blood cell concentrations and function after exposures at or close to the advised limits. Although they appear to have no effect on health or performance, these need to be confirmed by further studies. For the average female user of visual display units there is no evidence of any influence on birth outcome.

The results of epidemiological studies of possible associations between exposure to electromagnetic fields and cancer are summarised. A risk has been identified to workers in electrical and electronic occupations of leukaemia and brain tumours. The estimated level of this risk is likely to have been overestimated due to the confounding factor of occupational class. The highest risk appears to be to those who may be exposed to other carcinogenic agents. Apart from an isolated Swedish study, the only studies indicating a cancer risk due to living in proximity to power supply lines have been in the Denver area of the United States. These indicate that the risk, if real, is probably confined to children. There may be confounding factors of maternal smoking, degree of access to medical care, and traffic density. The risk estimates based on measured magnetic fields, as distinct from those based on distance from the lines, yield lower and more uncertain values.

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.

To compare quantitative estimates of lifetime cancer risk in humans for exposures to internally deposited radionuclides and external radiation. To assess the possibility that risks from radionuclide exposures may be underestimated.Risk estimates following internal exposures can be made for a small number of alpha-particle-emitting nuclides. (1) Lung cancer in underground miners exposed by inhalation to radon-222 gas and its short-lived progeny. Studies of residential (222)Rn exposure are generally consistent with predictions from the miner studies. (2) Liver cancer and leukaemia in patients given intravascular injections of Thorotrast, a thorium-232 oxide preparation that concentrates in liver, spleen and bone marrow. (3) Bone cancer in patients given injections of radium-224, and in workers exposed occupationally to (226)Ra and (228)Ra, mainly by ingestion. (4) Lung cancer in Mayak workers exposed to plutonium-239, mainly by inhalation. Liver and bone cancers were also seen, but the dosimetry is not yet sufficiently good enough to provide quantitative estimates of risks. Comparisons can be made between risk estimates for radiation-induced cancer derived for radionuclide exposure and those derived for the A-bomb survivors, exposed mainly to low-LET (linear energy transfer) external radiation. Data from animal studies, using dogs and rodents, allow comparisons of cancer induction by a range of alpha- and beta-/gamma-emitting radionuclides. They provide information on relative biological effectiveness (RBE), dose-response relationships, dose-rate effects and the location of target cells for different malignancies.For lung and liver cancer, the estimated values of risk per Sv for internal exposure, assuming an RBE for alpha-particles of 20, are reasonably consistent with estimates for external exposure to low-LET radiation. This also applies to bone cancer when risk is calculated on the basis of average bone dose, but consideration of dose to target cells on bone surfaces suggests a low RBE for alpha-particles. Similarly, for leukaemia, the comparison of risks from alpha-irradiation ((232)Th and progeny) and external radiation suggest a low alpha RBE; this conclusion is supported by animal data. Risk estimates for internal exposure are dependent on the assumptions made in calculating dose. Account is taken of the distribution of radionuclides within tissues and the distribution of target cells for cancer induction. For the lungs and liver, the available human and animal data provide support for current assumptions. However, for bone cancer and leukaemia, it may be that changes are required. Bone cancer risk may be best assessed by calculating dose to a 50 micro m layer of marrow adjacent to endosteal (inner) bone surfaces rather than to a single 10 micro m cell layer as currently assumed. Target cells for leukaemia may be concentrated towards the centre of marrow cavities so that the risk of leukaemia from bone-seeking radionuclides, particularly alpha emitters, may be overestimated by the current assumption of uniform distribution of target cells throughout red bone marrow.The lifetime risk estimates considered here for exposure to internally deposited radionuclides and to external radiation are subject to uncertainties, arising from the dosimetric assumptions made, from the quality of cancer incidence and mortality data and from aspects of risk modelling; including variations in baseline rates between populations for some cancer types. Bearing in mind such uncertainties, comparisons of risk estimates for internal emitters and external radiation show good agreement for lung and liver cancers. For leukaemia, the available data suggest that the assumption of an alpha-particle RBE of 20 can result in overestimates of risk. For bone cancer, it also appears that current assumptions will overestimate risks from alpha-particle-emitting nuclides, particularly at low doses.

Six statistics are compared in a simulation study for their ability to identify geographical areas with a known excess incidence of a rare disease. The statistics are the standardized incidence ratio, the empirical Bayes method of Clayton and Kaldor, Poisson probability, a statistic based on the 'Breslow T' test (BT) and two statistics based on the 'Potthoff-Whittinghill' test (PW) for extra-Poisson variance. Two alternative processes of clustering are simulated in which high-risk locations could be caused by environmental sources or could be sites of microepidemics of an infectious agent contributing to a rare disease such as childhood leukaemia. The simulation processes use two parameters (proportion of cases found in clusters and mean cluster size) which are varied to embrace a variety of situations. Real and artificial data sets of small area populations are considered. The most extreme of the artificial sets has all areas of equal population size. The other data sets use the small census areas (municipalities) in Finland since these have extremely heterogeneous population size distribution. Subset selection allows examination of this variability. Receiver operator curve methodology is used to compare the efficacy of the statistics in identifying the cluster areas; statistics are compared for the proportion of true high-risk areas identified in the top 1 per cent and 10 per cent of ranked areas. One of the PW statistics performed consistently well under all circumstances, although the results for the BT statistic were marginally better when only the top 1 per cent of ranked areas was considered. The standardized incidence ratio performed consistently worst.

A cohort of 4,400 persons treated for various cancers of childhood in France and the UK was followed up over an extended period to assess risks of subsequent brain tumour in relation to the radiotherapy and chemotherapy that the children received for their first cancer. Elevated risks of subsequent brain tumours were associated with first central nervous system (CNS) tumour (two-sided p = 0.0002) and neurofibromatosis (two-sided p = 0.001). There was also elevated brain tumour risk (two-sided p = 0.003) associated with ionising radiation exposure, the risk being concentrated among benign and unspecified brain tumours. The radiation-related risk of benign and unspecified brain tumours was significantly higher than that of malignant brain tumours (two-sided por =0.05); there was no significant change of malignant brain tumour risk with ionising radiation dose (two-sided p0.2). In general, there were no strong associations between alkylating agent dose and brain tumour risk. The only significant association between brain tumour risk and alkylating agent dose was in relation to compounds used (bleomycin, chloraminophen) that are thought not to deliver substantial doses to the brain; the statistical significance of the trend with dose depended on a single case, and thus must be considered a weak result.

OBJECTIVES: To test the "Gardner hypothesis" that childhood leukaemia and non-Hodgkin lymphoma can be caused by fathers' exposure to ionising radiation before the conception of the child, and, more generally, to investigate whether such radiation exposure of either parent is a cause of childhood cancer. DESIGN: Case-control study. SETTING: Great Britain. SUBJECTS: 35,949 children diagnosed as having cancer, together with matched controls. MAIN OUTCOME MEASURES: Parental employment as radiation worker as defined by inclusion in the National Registry for Radiation Workers and being monitored for external radiation before conception of child; cumulative dose of external ionising radiation for various periods of employment before conception; dose during pregnancy. RESULTS: After cases studied by Gardner and colleagues were excluded, fathers of children with leukaemia or non-Hodgkin lymphoma were significantly more likely than fathers of controls to have been radiation workers (relative risk 1.77, 95% confidence interval 1.05 to 3.03) but there was no dose-response relation for any of the exposure periods studied; indeed, the association was greatest for those with doses below the level of detection. No increased risk was found for fathers with a lifetime preconception dose of 100 mSv or more, or with a dose in the 6 months before conception of 10 mSv or more. There was no increased risk for the group of other childhood cancers. Mothers' radiation work was associated with a significant increase of childhood cancer (relative risk 5.00, 1.42 to 26.94; based on 15 cases and 3 controls). Only four of the case mothers and no controls were radiation workers during pregnancy. CONCLUSIONS: These results do not support the hypothesis that paternal preconception irradiation is a cause of childhood leukaemia and non-Hodgkin lymphoma; the observed associations may be chance findings or results from exposure to infective or other agents. If there is any increased risk for the children of fathers who are radiation workers, it is small in absolute terms: in Britain the average risk by age 15 years is 6.5 per 10,000; our best estimate, using all available data, is that the increase is 5.4 per 10,000. For mothers, the numbers are too small for reliable estimates of the risk, if any, to be made.

Generalizations of the two-mutation carcinogenesis model of Moolgavkar, Venzon and Knudson (MVK) are fitted to England and Wales lymphocytic leukaemia incidence data covering the period 1971-1988. Both acute lymphocytic leukaemia (ALL) and chronic lymphocytic leukaemia (CLL) can be fitted by a model with two mutations. These two-mutation models are such that the first (but not the second) mutation rate and the susceptible stem cell population vary rapidly with age. CLL is also adequately fitted by a model with three mutations, and the mutation rates and the variation in the stem cell population numbers implied by the three-mutation model are more plausible than those of the two-mutation model. For CLL there are no significant differences between the sexes in either of the optimal models fitted, but this is not the case for ALL. Thus the original MVK model adequately describes population rates of lymphocytic leukaemia in England and Wales.

A shortened 23 amino acid analog (dextronatrin) of rat ANP(1–28) in which, in position 6 next to Cys, there is a D-Tyr residue, has been compared to rat ANP(1–28) for its diuretic and electrolyte-excreting properties in male normotensive rats. Both compounds elicited an equally large but short-lasting diuresis. The natriuresis was also short-lasting as were the changes in Cl− and K+ excretion. In a rabbit aortic strip preparation dextronatrin antagonized the vasoconstricting effects of noradrenaline but to a lesser extent than rat ANP(1–28).

The heat uptake that resulted from immersing the hand and wrist into a water-filled calorimeter maintained at temperatures between 37-40 degrees C was measured under standard conditions in a group of eight subjects of either sex. The rate of heat transfer (W) increased exponentially with temperature and was a function of hand or body size and age, but not sex. The heat transfer rate normalized to hand mass (W.kg-1) was determined by temperature and age: best-fit mean values (and 95% confidence limits of the population) were 6.0 W.kg-1 (3.2-11.2 W.kg-1) at an immersion temperature of 37 degrees C and 25.4 W.kg-1 (13.7-47.0 W.kg-1) at 40 degrees C. The application of these results to limits on specific energy absorption rate induced in the hands and wrists by radiofrequency dielectric heat sealer welders is discussed.

Distinguishing an outlier in a time series arising through measurement error from one arising through a perturbation of the underlying system can be of use in data validation. In this paper a method of testing for the presence of an outlier of unknown type is proposed. Then the properties of a rule based on the likelihood ratio which attempts to distinguish the two types of outlier are examined and compared with those of the corresponding Bayes rules. An example involving data from an industrial production process is studied.