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BACKGROUND: The case-cohort study design has received significant methodological attention in the statistical and epidemiological literature but has not been used as widely as other cohort-based sampling designs, such as the nested case-control design. Despite its efficiency and practicality for a wide range of epidemiological study purposes, researchers may not yet be aware of the fact that the design can be analysed using standard software with only minor adjustments. Furthermore, although the large number of options for design and analysis of case-cohort studies may be daunting, they can be reduced to a few simple recommendations.
METHODS: We review conventional methods for the design and analysis of case-cohort studies and describe empirical comparisons based on a study of radiation, gene polymorphisms and cancer in the Japanese atomic bomb survivor cohort.
RESULTS: Stratified, as opposed to simple, random subcohort selection is recommended, especially for studies of gene-environment interaction, which are notorious for lacking statistical power. Methods based on the score-unbiased exact pseudo-likelihood (or its analogue with stratified case-cohort data) are recommended for use in conjunction with the asymptotic variance estimator.
CONCLUSIONS: We present an example of how to implement case-cohort analysis methods using SPSS, a popular statistical package that lacks some of the features necessary to directly adapt and implement published methods based on other software platforms. We also illustrate case-control analysis using Epicure, which provides greater risk-modelling flexibility than other software. Our conclusions and recommendations should help investigators to better understand and apply the case-cohort design in epidemiological research.

Forty-one atmospheric nuclear weapons tests (plus five safety tests) were conducted in French Polynesia between 1966 and 1974. To evaluate the potential role of atmospheric nuclear weapons testing on a high incidence of thyroid cancer observed since 1985 in French Polynesia, a population-based case-control study was performed. The study included 602 subjects, either cases or controls, all aged less than 40 y at the end of nuclear weapons testing in 1974. Radiation doses to the thyroids of the study subjects were assessed based on the available historical results of radiation measurements. These were mainly found in the annual reports on the radiological situation in French Polynesia that had been sent to the UNSCEAR Secretariat. For each atmospheric nuclear weapons test that contributed substantially to the local deposition of radionuclides, the radiation dose to the thyroid from I intake was estimated. In addition, thyroid doses from the intake of short-lived radioiodines (132I, 133I, 135I) and 132Te, external exposure from gamma-emitted radionuclides deposited on the ground, and ingestion of long-lived Cs were reconstructed. The mean thyroid dose among the study subjects was found to be around 3 mGy while the highest dose was estimated to be around 40 mGy. Doses from short-lived iodine and tellurium isotopes ranged up to 10 mGy. Thyroid doses from external exposure ranged up to 3 mGy, while those from internal exposure due to cesium ingestion did not exceed 1 mGy. The dose estimates that have been obtained are based on a rather limited number of radiation measurements performed on a limited number of islands and are highly uncertain. A thorough compilation of the results of all radiation monitoring that was performed in French Polynesia in 1966-1974 would be likely to greatly improve the reliability and the precision of the dose estimates.

World War II and the Cold War have left the Unites States, and other Nations, with massive cleanup and remediation tasks for radioactive and other legacy hazardous wastes. While some sites can be cleaned up to acceptable residential risk levels, others will continue to hold hazardous wastes, which must be contained and monitored to protect human health and the environment. While media (soil, sediment, groundwater) monitoring is the usual norm at many radiological waste sites, for some situations (both biological and societal), biomonitoring may provide the necessary information to assure greater peace of mind for local and regional residents, and to protect ecologically valuable buffer lands or waters. In most cases, indicators are selected using scientific expertise and a literature review, but not all selected indicators will seem relevant to stakeholders. In this paper, I provide a model for the inclusion of stakeholders in the development of bioindicators for assessing radionuclide levels of biota in the marine environment around Amchitka Island, in the Aleutian Chain of Alaska. Amchitka was the site of three underground nuclear tests from 1965 to 1971. The process was stakeholder-initiated, stakeholder-driven, and included stakeholders during each phase. Phases included conceptualization, initial selection of biota and radionuclides, refinement of biota and radionuclide target lists, collection of biota, selection of biota and radionuclides for analysis, and selection of biota, tissues, and radionuclides for bioindicators. The process produced site-specific information on biota availability and on radionuclide levels that led to selection of site-appropriate bioindicators. I suggest that the lengthy, iterative, stakeholder-driven process described in this paper results in selection of bioindicators that are accepted by biologists, public health personnel, public-policy makers, resource agencies, regulatory agencies, subsistence hunters/fishers, and a wide range of other stakeholders. The process is applicable to other sites with ecologically important buffer lands or waters, or where contamination issues are contentious.

Managers of contaminated sites are faced with options ranging from monitoring natural attenuation to complete removal of contaminants to meet residential health standards. Conceptual site models (CSMs) are one tool used by the U.S. Department of Energy (DOE) and other environmental managers to understand, track, help with decisions, and communicate with the public about the risk from contamination. CSMs are simplified graphical representations of the sources, releases, transport and exposure pathways, and receptors, along with possible barriers to interdict pathways and reduce exposure. In this article, three CSMs are created using Amchitka Island, where the remaining contamination is from underground nuclear test shot cavities containing large quantities of numerous radionuclides in various physical and chemical forms: (1) a typical underground nuclear test shot CSM (modeled after other sites), (2) an expanded CSM with more complex receptors, and (3) a regional CSM that takes into account contaminant pathways from sources other than Amchitka. The objective was to expand the CSM used by DOE to be more responsive to different types of receptors. Amchitka Island differs from other DOE test shot sites because it is surrounded by a marine environment that is highly productive and has a high biodiversity, and the source of contamination is underground, not on the surface. The surrounding waters of the Bering Sea and North Pacific Ocean are heavily exploited by commercial fisheries and provide the United States and other countries with a significant proportion of its seafood. It is proposed that the CSMs on Amchitka Island should focus more on the pathways of exposure and critical receptors, rather than sources and blocks. Further, CSMs should be incorporated within a larger regional model because of the potentially rapid transport within ocean ecosystems. The large number of migratory or highly mobile species that pass by Amchitka provide the potential for a direct pathway to the local human population, known as Aleut, and commercial fisheries, which are remote from the island itself. The exposure matrix for receptors requires expansion for the Amchitka Island ecosystem because of the valuable marine and seafood resources in the region. CSMs with an expanded exposure/receptor matrix can be used effectively to clarify the conceptualization of the problem for scientists, regulators, and the general public.

The present article describes the series of incident primary ovarian tumors in the Life Span Study (LSS) cohort of the Radiation Effects Research Foundation, with particular emphasis on case ascertainment and characterization of histological features of the tumors. We identified 723 ovarian tumors (260 malignant, 463 benign) in 648 individuals of about 70,000 female LSS subjects; 71 cases had more than one ovarian tumor. We histologically confirmed 601 tumors (182 malignant, 419 benign tumors). The most frequent histological type was common epithelial tumor (90.7% for malignant and 59.7% for benign tumors). The distributions of ovarian tumors by histological type were similar to those from other studies. Among malignancies, the frequency of common epithelial types relative to other tumor types increased with radiation dose (p = 0.02). Among benign tumors, the relative frequency of sex-cord stromal tumors increased with radiation dose (p = 0.04). The women with mucinous cancer had better survival than those with serous cancers (p = 0.03). Within tumor types, there was no consistent pattern of survival by radiation dose. Variations in histological types of ovarian tumors in response to radiation dose, suggested by the case series data need to be followed up by population-based incidence analysis.

The objectives of the present work were to study isotope ratios and the inventory of plutonium and uranium isotope compositions in sediments from Lake Obuchi, which is in the vicinity of several nuclear fuel facilities in Rokkasho, Japan. Pu and its isotopes were determined using sector-field ICP-MS and U and its isotopes were determined with ICP-QMS after separation and purification with a combination of ion-exchange and extraction chromatography. The observed (240)Pu/(239)Pu atom ratio (0.186 +/- 0.016) was similar to that of global fallout, indicating that the possible early tropospheric fallout Pu did not deliver Pu from the Pacific Proving Ground to areas above 40 degrees N. The previously reported higher Pu inventory in the deep water area of Lake Obuchi could be attributed to the lateral transportation of Pu deposited in the shallow area which resulted from the migration of deposited global fallout Pu from the land into the lake by river runoff and from the Pacific Ocean by tide movement and sea water scavenging, as well as from direct soil input by winds. The (235)U/(238)U atom ratios ranged from 0.00723 to 0.00732, indicating the natural origin of U in the sediments. The average (234)U/(238)U activity ratio of 1.11 in a sediment core indicated a significant sea water U contribution. No evidence was found for the release of U containing wastes from the nearby nuclear facilities. These results will serve as a reference baseline on the levels of Pu and U in the studied site so that any further contamination from the spent nuclear fuel reprocessing plants, the radioactive waste disposal and storage facilities, and the uranium enrichment plant can be identified, and the impact of future release can be rapidly assessed.

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The concept of health transitions assumes that health status improves with the introduction of western medicine. In this paper I demonstrate that the health of the people of Rongelap, Marshall Islands, has undergone serious damage as a result of nuclear testing, and that women in particular have suffered unduly. Exposure to nuclear radiation over a period of almost fifty years has been recognised by US authorities as a major contributory cause to the high rates of cancers and birth defects suffered by the Rongelap people. Women\'s reproduction has been severely affected, as evidenced by the many stillbirths and small stature of children born alive. Two generations have been exposed to both background radiation and to radiation ingested with the local foods on which they rely in the absence of other food sources. Clean up has commenced only after this and other communities sought compensation from the United States. The Rongelap people will live with the effects of radiation for generations to come. This transition to ongoing health problems is thus a negative outcome of modern health transition.

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