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This article reports the study design, methodological issues and early results of a pilot study testing methods for collecting nutrition, physical activity, and ultraviolet (UV) radiation exposure data in a groundbreaking study in China. Epidemiological studies suggest that exposures across the entire life course, including in utero, early childhood, and adolescence, may be important in the etiology of adult cancers and other chronic diseases. The Chinese Children and Families Cohort Study intends to follow-up subjects from the 1993 to 1995 Community Intervention Program of folic acid supplementation for the prevention of neural tube defects. This cohort is unique in that only folic acid exposure during pregnancy varies between groups as other supplements were not available, and there were nutrient deficiencies in the populations. Prior to launching a large-scale follow-up effort, a pilot study was conducted to assess the feasibility of recontacting original study participants to collect extensive diet, physical activity, and UV radiation exposure data in this population. The pilot study included 92 mothers and 184 adolescent children aged 14 to 17 years from 1 urban and 1 rural Community Intervention Program site. Subjects completed a Food Frequency Questionnaire, a 3-day food record, a physical activity questionnaire, a 3-day sun exposure diary together with 3 days of personal UV dosimetry, and 7 days of pedometry measurements and provided blood, saliva, and toenail samples. Grip strength and body composition measurements were taken, and ambient solar UV radiation was monitored in both study sites. While most of the assessments were successful, future studies would likely require different dietary intake instruments. The purpose of this report is to describe the study design and methodological issues emerging from this pilot work relevant for the follow-up of this large birth cohort.

This study summarizes and compares estimates of radiation absorbed dose to the thyroid gland for typical patients who underwent diagnostic radiology examinations in the years from 1930 to 2010. The authors estimated the thyroid dose for common examinations, including radiography, mammography, dental radiography, fluoroscopy, nuclear medicine, and computed tomography (CT). For the most part, a clear downward trend in thyroid dose over time for each procedure was observed. Historically, the highest thyroid doses came from the nuclear medicine thyroid scans in the 1960s (630 mGy), full-mouth series dental radiography (390 mGy) in the early years of the use of x rays in dentistry (1930s), and the barium swallow (esophagram) fluoroscopic exam also in the 1930s (140 mGy). Thyroid uptake nuclear medicine examinations and pancreatic scans also gave relatively high doses to the thyroid (64 mGy and 21 mGy, respectively, in the 1960s). In the 21st century, the highest thyroid doses still result from nuclear medicine thyroid scans (130 mGy), but high thyroid doses are also associated with chest/abdomen/pelvis CT scans (18 and 19 mGy for males and females, respectively). Thyroid doses from CT scans did not exhibit the same downward trend as observed for other examinations. The largest thyroid doses from conventional radiography came from cervical spine and skull examinations. Thyroid doses from mammography (which began in the 1960s) were generally a fraction of 1 mGy. The highest average doses to the thyroid from mammography were about 0.42 mGy, with modestly larger doses associated with imaging of breasts with large compressed thicknesses. Thyroid doses from dental radiographic procedures have decreased markedly throughout the decades, from an average of 390 mGy for a full-mouth series in the 1930s to an average of 0.31 mGy today. Upper GI series fluoroscopy examinations resulted in up to two orders of magnitude lower thyroid doses than the barium swallow. There are considerable uncertainties associated with the presented doses, particularly for characterizing exposures of individual identified patients. Nonetheless, the tabulations provide the only comprehensive report on the estimation of typical radiation doses to the thyroid gland from medical diagnostic procedures over eight decades (1930-2010). These data can serve as a resource for epidemiologic studies that evaluate the late health effects of radiation exposure associated with diagnostic radiologic examinations.

Ionizing radiation exposure to the general U.S. population nearly doubled between 1980 and 2006, due almost entirely to the significant increase in the number of radiologic and nuclear medicine procedures performed. Significant changes in the types of procedures and radionuclides used in nuclear medicine, as well as in detection technology, have led to notable changes over time in absorbed doses to specific organs. This study is the first to estimate per-procedure organ doses to nuclear medicine patients and trends in doses over five decades. Weighted average organ doses per examination to 14 organs of interest were calculated for 17 examination types over 10 5-y time periods (1960-2010) as the product of the percentage of use of each radiopharmaceutical in those diagnostic procedures based on comprehensive literature review, the administered activity, and ICRP dose coefficients; doses per radiopharmaceutical were also provided for each organ, procedure, and time period. The weighted doses to adult nuclear medicine patients from cardiac procedures increased to all organs of interest between 1960 and 2010 except for the urinary bladder wall. From high radiation doses for most other procedures in the 1960s, with up to 0.7 Gy in the specific case of radioiodinated thyroid scans, organ-absorbed doses generally decreased from 1960 to 1990. In contrast, during the 1990s and 2000s, the weighted doses were gradually increased for some procedures, such as brain and skeleton scans. The increasing number of nuclear medicine procedures, specifically cardiac scans and changes in weighted doses, underscore the need to monitor exposure levels and radiation-related disease risks in nuclear medicine patients.

This study provides a retrospective assessment of doses to 13 organs for the most common radiographic examinations conducted between the 1930s and 2010, taking into account typical technical parameters used for radiography during those years. This study is intended to be a resource on changes in medical diagnostic radiation exposure over time with a specific purpose of supporting retrospective epidemiological studies of radiation health risks. The authors derived organ doses to the brain, esophagus, thyroid, red bone marrow, lungs, breast, heart, stomach, liver, colon, urinary bladder, ovaries, and testes based on 14 common radiographic procedures and compared, when possible, with doses reported in the literature. These dose estimates were based on radiographic exposure parameters described in textbooks widely used by radiologic technologists in training from 1939 to 2010. The derived estimated doses presented here are believed to be representative of typical organs for an average-size adult who might be considered to be similar to the reference person. There were large variations in organ doses noted among the different types of radiographic examinations. Doses were highest in organs within the area imaged and next highest in organs in close proximity to the area imaged. Estimated organ doses have declined substantially [overall 22-fold (±38)] over time as a consequence of changes in technology, imaging protocols and protective measures. For some examinations, only slight differences were observed in doses for the decades of the 1960s, 1970s, and 1980s due to minor changes in technical parameters. Substantial dose reductions were observed in the 1990s and 2000s.

To reconstruct reliable nuclear medicine-related occupational radiation doses or doses received as patients from radiopharmaceuticals over the last five decades, the authors assessed which radiopharmaceuticals were used in different time periods, their relative frequency of use, and typical values of the administered activity. This paper presents data on the changing patterns of clinical use of radiopharmaceuticals and documents the range of activity administered to adult patients undergoing diagnostic nuclear medicine procedures in the U.S. between 1960 and 2010. Data are presented for 15 diagnostic imaging procedures that include thyroid scan and thyroid uptake; brain scan; brain blood flow; lung perfusion and ventilation; bone, liver, hepatobiliary, bone marrow, pancreas, and kidney scans; cardiac imaging procedures; tumor localization studies; localization of gastrointestinal bleeding; and non-imaging studies of blood volume and iron metabolism. Data on the relative use of radiopharmaceuticals were collected using key informant interviews and comprehensive literature reviews of typical administered activities of these diagnostic nuclear medicine studies. Responses of key informants on relative use of radiopharmaceuticals are in agreement with published literature. Results of this study will be used for retrospective reconstruction of occupational and personal medical radiation doses from diagnostic radiopharmaceuticals to members of the U.S. radiologic technologists' cohort and in reconstructing radiation doses from occupational or patient radiation exposures to other U.S. workers or patient populations.

Recent studies demonstrated an excess of winter births in children with brain tumors and in adults with various neurologic or psychiatric diseases relative to the general population.To investigate a possible association between month of birth and risk of brain tumors in adults using data from a large, hospital-based case-control study.Cases were patients with incident glioma (n = 489) or meningioma (n = 197) diagnosed at hospitals in Boston, MA, Phoenix, AZ, and Pittsburgh, PA. Controls (n = 799) were patients hospitalized for a variety of nonmalignant conditions and frequency matched to cases by hospital, age, sex, race/ethnicity, and distance of residence from hospital. Odds ratios (ORs) were calculated using multivariate unconditional logistic regression allowing for cyclic variation in risk with month of birth.A relationship between month of birth and risk of adult glioma and meningioma was found, best described by a 12-month periodic function with peaks in February and January and troughs in August and July. The association between month of birth and risk of glioma differed significantly by handedness, with left-handed and ambidextrous subjects born during late fall through early spring being at particularly high risk of adult glioma as compared with those born at other times of the year.These findings suggest the importance of seasonally varying exposures during the pre- or postnatal period in the development of brain tumors in adults.

Cancer risk in patients with cirrhosis could be modified by factors such as changes in hormonal levels, impaired metabolism of carcinogens, or alteration of immunological status. We investigated the risk of liver and various forms of cancer in patients with cirrhosis in a follow-up study. We identified 11,605 1-year survivors of cirrhosis from the files of the Danish National Registry of Patients (NRP) from 1977 to 1989. Occurrence of cancer through 1993 was determined by linkage to the Danish Cancer Registry. For comparison, the expected number of cancer cases was estimated from national age-, sex-, and site-specific incidence rates. Overall, 1,447 cancers were diagnosed among the study subjects, as compared with 708.1 expected, to yield a standardized incidence ratio (SIR) of 2.0 (95% CI: 1.9 to 2.2). In all diagnostic subgroups of cirrhosis, the risk of primary liver cancer, mainly hepatocellular carcinoma, was markedly elevated, with 245 observed cases and an overall 36-fold elevated risk (59.9-fold elevated for hepatocellular carcinoma and 10-fold for cholangiocarcinoma). Substantial and persistent excesses during follow-up were seen for all types of cancer associated with tobacco and alcohol habits (cancer of the lung, larynx, buccal cavity, pharynx, pancreas, urinary bladder, and kidney), while moderate excesses were seen for cancers of the colon and breast. The latter, however, were not complemented by any decrease in the risk of prostate cancer (SIR: 1.0; 95% CI: 0.7 to 1. 3). A slightly increased risk was seen for testis cancer, but disappeared after 10 years. We found evidence of an increased risk for liver and several extrahepatic cancers in patients with cirrhosis. Although part of this increase is likely attributable to alcohol and tobacco consumption, our study opens up the possibility that cirrhosis plays a role in the carcinogenesis of types of cancer other than liver cancer.

As part of a comprehensive study of residential magnetic field exposure in nine midwestern and mid-Atlantic states, we evaluated the use of appliances by 640 patients with acute lymphoblastic leukemia, 0–14 years of age, diagnosed between 1989 and 1993, and 640 matched control children. Mothers were

We utilized data from two Kaiser Permanente medical care programs to evaluate risks of hematopoietic and lymphoproliferative (HLP) malignancies after use of 14 common medications. The subjects were adult cases of non-Hodgkin's lymphoma (NHL) (N = 94), multiple myeloma (N = 159), and leukemia (N = 257) and individually matched controls (N = 695). Abstractors reviewed medical records and recorded medication notations. Using a minimum 5-year exposure lag between first notation and malignancy diagnosis, the risk of NHL was greater among plan members who were prescribed amphetamines [odds ratio (OR) = 2.2; 95% confidence interval (CI) = 1.1-4.8], lidocaine (OR = 2.6; 95% CI = 1.2-5.5), and meprobamate (OR = 2.1; 95% CI = 1.03-4.3). The risk of NHL rose with increasing number of medical record notations for amphetamines; however, there was no association with number of notations for lidocaine or meprobamate. The odds ratio for total leukemia was decreased among patients who took chloramphenicol (OR = 0.4; 95% CI = 0.2-0.97).

We examined the relation between area measurements of residential magnetic fields and personal dosimetry measurements among 64 control children age 2-14 years from the National Cancer Institute-Children's Cancer Group's nine-state case-control study of childhood leukemia. During a typical weekday, an activity diary was completed, and a 24-hour measurement was obtained in each child's bedroom. According to the activity diaries, children spent more than 40% of the 24 hours in their bedrooms, and 68% of their time at home. We found that at-home personal dosimetry levels were highly correlated with total personal dosimetry levels in children under 9 years (Spearman correlation coefficient, R = 0.94), whereas the correlation was lower in older children (R = 0.59). For all children combined, bedroom 24-hour measurements correlated well with at-home personal dosimetry levels (R = 0.76). The 24-hour bedroom measurement was a useful predictor of both at-home and total personal dosimetry measurements. Particularly for younger children, our data suggest that in-home area measurements predict both current residential and current total magnetic field exposures. This information will be valuable for assessing the validity of exposure assessment in previous and ongoing studies and for developing measurement protocols for future studies.

Objective: Liver cirrhosis is associated with increased levels of estrogens, which may be causally related to breast cancer. Because background estrogen levels are lower in men than in women, an estrogen-mediated link between liver cirrhosis and breast cancer would be easier to detect in men. Methods: Men hospitalized with liver cirrhosis in Denmark from January 1, 1977, to December 31, 1989, were followed up, through record linkage, until the end of December 1993 for the possible occurrence of breast cancer. Results: A total of 11,642 men with liver cirrhosis were identified and were followed for a mean period of 4.3 yr, for a total of 49,687 person-years. Three cases of male breast cancer were observed whereas 0.75 was expected, for a standardized incidence ratio of 4.0 (95% confidence interval, 0.81.7). Conclusions: Cirrhosis, possibly via high levels of endogenous estrogens, increases the risk of breast cancer in men.

The report by Divan et al linking early exposures to cell phones with behavioral problems in young children, published in this issue of Epidemiology, provides an opportunity to consider pursuit of high-risk hypotheses that could open new areas of understanding in contrast with the more common assessment of lower-risk leads. Other key considerations for epidemiologists are the requirements for selecting plausible risk factors while remaining alert to serendipitous discovery, for validating proxy measures of complex disease outcomes and exposures, and for pursuing replication of unexpected results in independent settings. In the face of unexpected findings, research consortia provide opportunities for pursuing exploratory and follow-up studies of high-risk hypotheses. Reviewers and editors also play major roles.

Gilbert Beebe died on March 3, 2003, 1 month short of his 91st birthday and 2 days after working a full Saturday at the office. Gil was renowned as a radiation epidemiologist. He conducted ground-breaking studies of mortality and morbidity among persons exposed to the atomic bombings in Japan and to the Chernobyl reactor accident in Ukraine. His 70 years as a statistician/epidemiologist spanned several careers. Gil first worked at the National Committee on Maternal Health, where he conducted an important study of contraceptive services in economically depressed areas. From there he went to the office ofthe Surgeon General ofthe Army, and then to the National Academy of Sciences (NAS). Gil and others (including Michael DeBakey) had been advocating an ongoing follow-up system based on military and medical records, and it was at the NAS that Gil created the Medical Follow-up Agency (MFUA) to accomplish that. While at NAS, Gil worked with Seymour Jablon to organize the Atomic Bomb Casualty Commission (ABCC) research program to study the late health effects of radiation exposure in Japanese A-bomb survivors. Later known as the Life Span Study, this remains the most important source of information on radiation-related risk of cancer and other long-term health effects in humans.

pelvidureter cancer (SIR = 2.5; 95% GI = 1.8-3.3) and bladder cancer (SIR = 1.4; 95% CI = 1.3-1.6) were observed, but the SIRS for women were more than twice those for men. Risks varied little by age or duration of follow-up. Risks of renal pelvidureter cancer and bladder cancer among patients with an associated diagnosis of urinary tract infection were more than double those among patients without such infection, although the risks were significantly elevated in both groups. Conclusions: Individuals hospitalized for kidney or ureter stones are at increased risk of developing renal pelvidureter or bladder cancer, even beyond 10 years of follow-up. Chronic irritation and infection may play a role, since kidney or ureter stones were located on the same side of the body as the tumors in most patients with renal pelvidureter cancer evaluated in our study. Editorial Comment: First, it was vasectomy and its possible association with subsequent coronary artery disease, and now it is urolithiasis leading to urothelial cancer. While the former raised a furor later calmed by additional studies, this most recent finding remains unchallenged. Although squamous cell cancer of the renal pelvis has been related to a history of urolithiasis, this study is possibly the first to link stone disease and transitional cell cancer. The data hold up even if one were to eliminate all patients with tumors discovered during the first year after a stone episode, that is concurrent disease states, or patients with tumors found only at autopsy, that is clinically silent tumors. Notably, there was no increase in renal cell or lung cancer in this patient group, suggesting that the findings cannot be attributed to a generalized renal problem or other confounding problems, such as smoking or job related risks. Also of interest, in 75% of the patients the tumor and stone were located on the same side, again invoking the argument that tumor formation was possibly due to local irritation from the stone. Lastly, the risk of urothelial tumor formation remained as long as 10 years after the initial stone event. The bottom line question is whether radiographic or cystoscopidcytology surveillance is indicated in all patients with stones to detect renal pelvidureteral or bladder tumors in 0.14 and 0.62%, respectively. This article has made me more aware but I am not planning to expand my followup of urolithiasis beyond that of urinalysis and a plain radiograph of the abdomen at routine intervals. Ralph V. Clayman, M.D.