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Biomedical subjects

C R Muirhead

Publications and source records attributed to C R Muirhead.

At least 19 recordsLinked to original sources

Modelling lymphocytic leukaemia incidence in England and Wales using generalizations of the two-mutation model of carcinogenesis of Moolgavkar, Venzon and Knudson.

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.

Adolescent

Evidence for curvilinearity in the cancer incidence dose-response in the Japanese atomic bomb survivors.

The recently released data on cancer incidence in the Japanese atomic bomb survivors are analysed using a variety of relative risk models which take account of errors in estimates of dose to assess the dose-response at low doses. For all solid cancers analysed together there is a significant positive dose-response (at the one-sided 2.5% significance level) if all survivors who received < 0.5 Sv are considered, but the significance vanishes if doses of < 0.2 Sv are considered. If a relative risk model with a threshold (the dose-response being assumed linear above the threshold) is fitted to the solid cancer data, a threshold of more than about 0.2 Sv is inconsistent with the data, whereas these data are consistent with there being no threshold. Linear-quadratic models and linear-quadratic models with an exponential cell-sterilization term provide no better fit than the linear model. For the three main radiation-inducible leukaemia subtypes analysed together (acute lymphatic leukaemia, acute myeloid leukaemia and chronic myeloid leukaemia) there is a significant positive dose-response (at the one-sided 2.5% significance level) if all survivors who received < 0.5 Sv are considered, but the significance vanishes if doses of < 0.2 Sv are considered. If a relative risk model with a threshold (the dose-response being assumed linear above the threshold) is fitted to the leukaemia data, a thresh-old of more than about 0.3 Sv is inconsistent with the data. In contrast with the solid cancer data, the best estimate for the threshold level in the leukaemia data is significantly different from zero, even when allowance is made for a possible quadratic term in the dose-response, albeit at borderline levels of statistical significance (p = 0.04). There is little evidence for curvature in the leukaemia dose-response from 0.2 Sv upwards. However, the possible underestimation of the errors in the estimates of the dose threshold as a result of confounding and uncertainties not taken into account in the analysis, together with the lack of biological plausibility of a threshold, makes the interpretation of this finding questionable.

Humans

Comparison of dose histories for U.S. nuclear power plant workers, based on records held by a major dosimetry service company and on the NRC REIRS database.

In order to conduct valid epidemiological studies of nuclear power plant workers, good information on the workers' radiation dose histories is essential. Dose records held by a major dosimetry service company and on the Nuclear Regulatory Commission's Radiation Exposure Information and Recording System have been compared for a sample of 99 workers. About half of the workers in the sample had no records on the Radiation Exposure Information and Recording System, since they had not terminated employment at a Nuclear Regulatory Commission-licensed facility; accordingly, their career doses (as recorded by the service company) were generally higher than those for workers on the Radiation Exposure Information and Recording System. For nearly half of the workers with records on both databases, the total dose recorded for terminated employments at nuclear power plants differed by at least a factor of 5 between the databases. In absolute terms, these differences were of the order of 100 mSv or more. An approach that utilized both the Radiation Exposure Information and Recording System and the dosimetry service company's records might be of value in constructing dose histories for a large epidemiological study. However, the comparisons presented here support the initiatives of the Nuclear Regulatory Commission to request licensees to report voluntarily career doses for current employees. These data are essential if a large and valid epidemiological study of nuclear plant workers is to be conducted in the foreseeable future.

Humans

Childhood leukemia in metropolitan regions in the United States: a possible relation to population density?

Following recent research in Great Britain, the geographic incidence of leukemia and non-Hodgkin's lymphoma among White children in three metropolitan regions of the United States (San Francisco-Oakland, CA; Detroit, MI; and Atlanta, GA) during 1978-82 has been analyzed using census tract-specific data. There was no evidence of a general tendency for cases to cluster geographically, in contrast to results from Britain. Further, rates did not vary with median income or education levels for census tracts. However, there was a statistically significant increasing trend in incidence rates with increasing population density: relative risk for highest relative to lowest category = 1.4 (95% percent confidence interval [CI] = 1.1-2.0) for White population density, and 1.4 (CI = 1.0-2.0) for total population density. The interpretation of these findings is unclear and further investigation is required. It is possible that population density is acting as a surrogate for some virus-related factor.

Adolescent

Radon risks.

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Air Pollutants, Radioactive

Residential radon exposure and lung cancer--an epidemiological study of Norwegian municipalities.

The study is based on a collaboration between the Cancer Registry of Norway, the Norwegian Radiation Protection Authority, and National Radiological Protection Board (NRPB, UK). The association between indoor radon exposure and lung cancer was studied in 427 municipalities. NRPB detectors were sent to 10,000 households, and 7,500 of the detectors were returned. Data from a nation-wide survey of smoking habits in 1964-1965 were available. Data on asbestos exposure were also used in a regression analysis. The reporting to the Cancer Registry of all new cases of cancer is fairly complete, as hospital departments and institutes of pathology are obliged to report all cancer cases. The histologically confirmed lung cancer cases were grouped into squamous-cell carcinoma, small-cell carcinoma, adenocarcinoma and other or non-specified histological types. The age-adjusted rate of lung cancer by histological type was the dependent variable in the regression analysis. A consistent increase in incidence of lung cancer was seen with increasing tobacco consumption, but no positive trend could be shown with increasing radon exposure in the descriptive presentation of the data. In the regression analysis, however, the incidence of small-cell anaplastic lung tumors in females increased significantly with increasing radon exposure. When based on the regression coefficients, the fraction of lung cancers attributable to radon is about 2-4%. However, systematic errors cannot be excluded in an ecological study such as presented here.

Adult

Mortality and occupational exposure to radiation: first analysis of the National Registry for Radiation Workers.

OBJECTIVE: To study cause specific mortality of radiation workers with particular reference to associations between fatal neoplasms and level of exposure to radiation. DESIGN: Cohort study. SETTING: United Kingdom. SUBJECTS: 95,217 radiation workers at major sites of the nuclear industry. MAIN OUTCOME MEASURE: Cause of death. RESULTS: Most standardised mortality ratios were below 100: 83 unlagged, 85 with a 10 year lag for all causes; 84 unlagged, 86 lagged for all cancers; and 80 for all known other causes, indicating a "healthy worker effect." The deficit of lung cancer (75 unlagged, 76 lagged) was significant at the 0.1% level. Standardised mortality ratios were significantly raised (214 unlagged, 303 lagged) for thyroid cancer, but there was no evidence for any trend with external recorded radiation dose. Dose of external radiation and mortality from all cancers were weakly correlated (p = 0.10), and multiple myeloma was more strongly correlated (p = 0.06); for leukaemia, excluding chronic lymphatic, the trend was significant (p = 0.03; all tests one tailed). The central estimates of lifetime risk derived from these data were 10.0% per Sv (90% confidence interval less than 0 to 24%) for all cancers and 0.76% per Sv (0.07 to 2.4%) for leukaemia (excluding chronic lymphatic leukaemia). These are, respectively, 2.5 times and 1.9 times the risk estimates recommended by the International Commission on Radiological Protection, but 90% confidence intervals are large and the commission's risk factors fall well within the range. The positive trend with dose for all cancers, from which the risk estimate was derived, was not significant. The positive association between leukaemia (except chronic lymphatic leukaemia) was significant and robust in subsidiary analyses. This study showed no association between radiation exposure and prostatic cancer. CONCLUSION: There is evidence for an association between radiation exposure and mortality from cancer, in particular leukaemia (excluding chronic lymphatic leukaemia) and multiple myeloma, although mortality from these diseases in the study population overall was below that in the general population. The central estimates of risk from this study lie above the most recent estimates of the International Commission on Radiological Protection for leukaemia (excluding chronic lymphatic leukaemia) and for all malignancies. However, the commission's risk estimates are well within the 90% confidence intervals from this study. Analysis of combined cohorts of radiation workers in the United States indicated lower risk estimates than the commission recommends, and when the American data are combined with our analysis the overall risks are close to those estimated by the commission. This first analysis of the National Registry for Radiation Workers does not provide sufficient evidence to justify a revision in risk estimates for radiological protection purposes.

Adult

Projecting radiation-induced cancer risks across time and populations.

Various methods can be used to project the risks of radiation-induced cancer estimated in cohort studies beyond the period of follow-up and to other populations. The epidemiological evidence for the choice of risk projection model is reviewed based on data from studies such as those of the Japanese atomic bomb survivors and UK ankylosing spondylitis patients given x-ray therapy. The results of risk projections based on various approaches are presented, including those suggested by UNSCEAR and by the BEIR V Committee. It is emphasised that the continued follow-up of populations such as the Japanese atomic bomb survivors is of great importance in estimating lifetime risks, and that further parallel analyses are required to examine how risks vary across populations.

Adolescent

Completeness of follow up in a cohort study of mortality using the United Kingdom National Health Service Central Registers and records held by the Department of Social Security.

STUDY OBJECTIVE: The aim was to evaluate and improve the completeness of follow up in a cohort study of mortality carried out using the UK National Health Service (NHS) Central Registers. SETTING: This was a follow up study of UK servicemen who served abroad in the 1950s and 1960s, including those who participated in the UK atmospheric nuclear weapon tests and experimental programmes. DESIGN: Details of men for whom follow up achieved using the NHS Central Registers was unsatisfactory were submitted to the Department of Social Security (DSS) for tracing, as were details of men born before 1916 and reported by the NHS Central Registers as currently registered with a general practitioner, and a 1% sample of remaining men born in or after 1916. MEASUREMENTS AND MAIN RESULTS: The additional follow up increased the number of deaths fully identified in the cohort by 6.5%. Mortality among those untraced on the NHS Central Registers was substantially greater than in the cohort as a whole (10.2% v 6.9%). Among those reported by the NHS Central Registers as not currently registered with a general practitioner, 2.7% were found to have died, as were 1.1% of men born before 1916 and currently reported to be registered with a general practitioner. As expected there was clear evidence that information about emigrations supplied by both the NHS Central Registers and DSS is far from complete. CONCLUSION: Standardised mortality ratios based on follow up via the NHS Central Registers alone are likely to be somewhat low, and this should be borne in mind when interpreting the data.

Adult

Mortality among United Kingdom servicemen who served abroad in the 1950s and 1960s.

The Registrar General's decennial supplements on occupational mortality provide only limited information on mortality in the armed forces in the United Kingdom. Mortality has therefore been studied among a group of 30,619 United Kingdom servicemen who served abroad in tropical or desert areas in the 1950s and 1960s, and who remained in the services for a total of at least five years. Mortality from all causes of death, all neoplasms, and all other known non-violent causes was lower than that expected from rates for all men in England and Wales, whereas mortality from accidents and violence was raised. These differences remained after adjustment for social class, affected both officers and other ranks, and had not disappeared even after the men had been followed up for at least 20 years. When mortality from 20 specific cancers and 10 other disease groups was examined there were significant excesses for cancers of the oesophagus (standardised mortality ratio (SMR) = 146; p = 0.03) and prostate (SMR = 156; p = 0.03), and significant deficits for cancers of the lung (SMR = 73; p less than 0.001), stomach (SMR = 66; p = 0.002), bladder (SMR = 53; p = 0.02), other specified neoplasms (SMR = 48; p = 0.001), coronary heart disease (SMR = 76; p less than 0.001), bronchitis, emphysema, and chronic obstructive lung disease (SMR = 42; p less than 0.001), and for five further groups of diseases unrelated to smoking or alcohol. Examination of mortality in each of the three services separately identified two specific hazards in the Royal Navy; seven deaths from mesothelioma occurred compared with less than 2.06 expected (p less than 0.005), and there was also an excess of neoplasms and of other diseases associated with alcohol (SMRs of 181 and 229; p = 0.002 and less than 0.001). Mortality from smoking related diseases other than those associated with alcohol was low in all three services, particularly among officers.

Accidents

Relationship between local temperature and heat transfer through the hand and wrist.

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.

Adult

A summary of mortality and incidence of cancer in men from the United Kingdom who participated in the United Kingdom's atmospheric nuclear weapon tests and experimental programmes.

Altogether 22,347 men who participated in the United Kingdom's atmospheric nuclear weapon tests and experimental programmes in Australia and the Pacific Ocean between 1952 and 1967 were identified from the archives of the Ministry of Defence and followed up. Their mortality and incidence of cancer were compared with those in 22,326 matched controls selected from the same archives. The risk of mortality in the participants relative to that in the controls was 1.01 for all causes and 0.96 for all neoplasms. Thirty eight causes of death were examined separately. Significant differences in mortality were found for leukaemia, multiple myeloma, and other injury and poisoning, with higher rates in the participants, and for cancers of the prostate and kidney and chronic bronchitis, with higher rates in the controls. The mortality from leukaemia and multiple myeloma in the participants was slightly greater than would have been expected from national values (standardised mortality ratios of 113 and 111, respectively), but in the controls it was substantially lower (standardised mortality ratios of 32 and 0, respectively). Examination of the rates of leukaemia and multiple myeloma in groups of participants showed very little difference between groups characterised by recorded doses of external radiation or type of test participation and failed to indicate any specific hazard. Evidence obtained from participants who reported themselves voluntarily (or were reported by relatives or friends) suggested that 17% of participants may have been omitted from the main study group but that any resulting bias was small. Most of the differences observed between the participants and controls were interpreted as due to chance, but some may be due to differences in smoking habits. Participation in the test programme did not seem, in itself, to have caused any detectable effect on the participants' expectation of life, apart from possibly causing small risks of developing leukaemia and multiple myeloma.

Environmental Exposure

The risk of leukemia in Seascale from radiation exposure.

An excess of leukemias in children has been observed between 1950 and 1980 in the village of Seascale (population about 3,000) which is situated approximately 3 km to the south of Sellafield nuclear fuel reprocessing plant in West Cumbria, England. Radiation doses from all the main sources of radiation exposure of the population and risks of radiation-induced leukemia have been calculated for children born and living in Seascale during the period of operation of the plant. For the Seascale study population of 1225 children and young persons, followed to age 20 y, or followed until 1980 for those born after 1960, 0.016 radiation-induced leukemias are predicted from the Sellafield discharges. This corresponds to an average risk to children in the population of about one in 75,000. For the four fatal leukemias observed in the study population (0.5 expected from United Kingdom statistics) to be attributed to the operations at Sellafield, the average risk would have to be increased by a factor of about 250, to one in 300. Although there is some uncertainty about the releases from the plant and concentrations of radionuclides in environmental materials in the Sellafield area, particularly for the early years of its operation, the possibility that the doses calculated and the risk coefficients used for radiation-induced leukemia could be so substantially wrong is very unlikely. The number of radiation-induced leukemias from all radiation sources is calculated to be 0.1, which corresponds to a risk of about one in 12,250 for the average child in the study population. About two-thirds of the risk is from natural radiation, 16% from the Sellafield discharges, and nuclear weapons fallout and medical exposure each contribute about 9%. The models used for calculating radiation doses from intakes of radionuclides were based upon those recommended by the International Commission on Radiological Protection (ICRP). This presented a number of difficulties in the assessment, which included the lack of any generally accepted age-related dosimetric models, particularly for bone-seeking radionuclides; limited information on gut transfer factors for radionuclides incorporated in foodstuffs; and no dosimetric models for the fetus. These and other problems identified in the analysis that require more information are discussed.

Air Pollutants, Radioactive