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Biomedical subjects

T R Fears

Publications and source records attributed to T R Fears.

At least 19 recordsLinked to original sources
PubMed1992

Control sample size when cases are given in constant ratio stratum-matched case-control studies.

Strata-matched case-control studies based on a given number of cases and k times as many controls are common. We obtain a necessary and sufficient condition for there to exist a numerical solution for k with a desired level of a power. We derive the maximum power of the Cochran test, which may be less than one, when the number of cases is fixed. We provide an approximate formula for the minimum number of cases required for a specified power. There exists a numerical solution (that is, convergence of an iterative method) for k if the number of cases given is greater than this minimum number and no such a solution otherwise. We also show that the incremental gain in relative efficiency of the test with respect to k is diminished as k gets large.

Adult↗
PubMed1992

Optimum sample size determination in stratified case-control studies with cost considerations.

We investigate sample size determination for Cochran's test for stratified case-control studies when samples of cases and controls are allocated to maximize the asymptotic efficiency of Cochran's test subject to fixed total cost with cost per control varying by strata. We consider two situations typical of strata-matched case-control studies: when one samples both cases and controls and when cases are given and one samples controls. In each situation we develop and study an asymptotic method for finding the sample size required for a specific power under the optimum allocation proposed by Nam and Fears. Also, for the second situation, we investigate an asymptotic method for determining the common ratio, k, in one-to-k strata-matched case-control studies without cost consideration for a given power. When cases are given, neither the optimum nor the standard control sample sizes appear in a closed form; we present numerical methods for calculating these sample sizes and illustrate them with examples. We find the reduction in total cost obtained under the optimum allocation compared to standard allocation more pronounced as the differences in stratum-specific costs of sampling controls increase.

Adult↗
PubMed1992

Early menopause in long-term survivors of cancer during adolescence.

OBJECTIVE: We attempted to investigate the risk of early menopause after treatment for cancer during childhood or adolescence. STUDY DESIGN: We interviewed 1067 women in whom cancer was diagnosed before age 20, who were at least 5-year survivors, and who were still menstruating at age 21. Self-reported menopause status in survivors was compared with that in 1599 control women. RESULTS: Cancer survivors, with disease diagnosed between ages 13 and 19, had a risk of menopause four times greater than that of controls during the ages 21 to 25; the risk relative to controls declined thereafter. Significantly increased relative risks of menopause during the early 20s occurred after treatment with either radiotherapy alone (relative risk 3.7) or alkylating agents alone (relative risk 9.2). During ages 21 to 25 the risk of menopause increased 27-fold for women treated with both radiation below the diaphragm and alkylating agent chemotherapy. By age 31, 42% of these women had reached menopause compared with 5% for controls. CONCLUSION: Treatment for cancer during adolescence carries a substantial risk for early menopause among women still menstruating at age 21. Increasing use of radiation and chemotherapy, together with the continued trend toward delayed childbearing, suggests that these women should be made aware of their smaller window of fertility so that they can plan their families accordingly.

Adult↗
PubMed1991

Incidence of nonmelanoma skin cancer in New Hampshire and Vermont.

A survey of skin cancer occurrence between June 1979 and May 1980 among residents of New Hampshire and Vermont identified 277 cases of squamous cell carcinoma and 1761 cases of basal cell carcinoma. The age-adjusted incidence rates for squamous cell carcinoma (32 per 100,000 in men, 8 per 100,000 in women) and for basal cell carcinoma (159 per 100,000 in men, 87 per 100,000 in women) were similar to those reported in other populations in the northern United States. Skin cancer incidence was particularly high among men more than 70 years of age and a large proportion (greater than 30%) of patients 55 years or older had a history of at least one previous skin cancer.

Adolescent↗
PubMed1991

Growth of the great vessels in the normal human fetus and in the fetus with cardiac defects.

BACKGROUND: There is a paucity of quantitative anatomic data regarding human great vessel development that could be useful as a reference for fetal echocardiographers who must distinguish abnormal from normal cardiac development at early stages. METHODS AND RESULTS: To determine normal growth patterns, we plotted the diameters of the aortic and pulmonary valves, ductus arteriosus, aortic isthmus, and descending aorta in 274 autopsy specimens from nonselected spontaneous abortuses of normal karyotype. There was a linear increase in the diameters of these structures within the developmental period studied (10-26 weeks). A relative narrowing of the aorta at the isthmus compared with the aortic valve and descending aorta probably indicates that the majority of fetal left heart output goes to the developing heart and brain. In contrast to previous studies of late gestation and neonatal animals, however, we found that the diameter of the aortic isthmus was larger than that of the ductus arteriosus, suggesting substantial isthmic blood flow in these midtrimester fetuses. Among nineteen other hearts with diverse defects, both of two hearts with a narrow isthmus had an enlarged ductus arteriosus and one heart with pulmonary atresia/intact septum had a narrow ductus and increased aortic valve diameter. CONCLUSIONS: During midgestation, the normal heart may have substantial aortic isthmic blood flow that diminishes due to rerouting in late gestation when increased requirements of the fetal brain and other organs prevail. Although fetal shunts may explain some vessel abnormalities, the majority of cardiac defects in this study were not associated with abnormal growth of the great vessels within this developmental age range.

Aorta↗
PubMed1990

Smoking patterns by occupation and duration of employment.

Lifetime patterns of smoking and occupation based on personal interviews were examined among 3,627 white men and 1,200 white women who were randomly selected from ten areas in the United States during the period 1977-1978. These individuals participated in the control series of the National Bladder Cancer Study. We estimated, based on Axelson's method, the extent to which smoking habits for given occupational groups would confound the estimated relative risk for lung cancer for 62 occupations among men and 18 occupations among women. Among men, confounding by smoking resulted in a 30% or greater increased risk of lung cancer in only three occupational groups--namely, stationary engineers and power station operators (relative risk (RR) = 1.6), printers (RR = 1.3), and fishermen and sailors (RR = 1.3). A decrease in lung cancer risk of 0.8 or less due to smoking habits was observed among the clergy (RR = 0.5) and chemical workers (RR = 0.7). Among women, a 30% increase or greater in the risk of lung cancer based on smoking habits alone was found for food service workers (RR = 1.5), building managers and administrators (RR = 1.3), telephone and telegraph operators (RR = 1.3), and operatives (RR = 1.3). A risk ratio of 0.8 or less was observed for those women employed as farmers (RR = 0.5) and teachers (RR = 0.8). Smoking habits by duration of employment were also examined for 38 occupations among men. The largest increase in the risk of lung cancer based on the smoking habits among long-term workers was only 1.3 and was observed for those men employed 20 or more years as painters and as electricians. These findings suggest that the smoking patterns, in only a few occupational groups that we evaluated, confound estimates of the relative risk by more than 30%, and for most occupational groups under investigation in this study, confounding by smoking alone did not produce trends in relative risks by duration of employment.

Adult↗
PubMed1990

Optimum allocation of samples in strata-matching case-control studies when cost per sample differs from stratum to stratum.

We investigate the allocation of samples over strata in case-control studies with consideration of sampling costs. We consider two situations, typical of strata-matched case-control studies. Subject to a fixed total cost we derived optimum allocations that maximize the asymptotic efficiency of Cochran's test, that is, minimize the variance of the maximum likelihood estimator of the common odds ratio when the common odds ratio is one. Our results show that the standard design with equal numbers of cases and controls in each stratum is inefficient when costs per control differ greatly from stratum to stratum. We show that the optimum design suggested in this paper is robust for values of the odds ratio common in epidemiologic studies.

Case-Control Studies↗
PubMed1989

The statistical analysis of a carcinogen mixture experiment. III. Carcinogens with different target systems, aflatoxin B1, N-butyl-N-(4-hydroxybutyl)nitrosamine, lead acetate, and thiouracil.

This paper describes factorial experiments designed to determine whether two carcinogens that lead to cancers in different organ systems act synergistically to produce cancers in Fischer 344 rats. Four carcinogens, aflatoxin B1 (AFLA), N-butyl-n-(4-hydroxybutyl)nitrosamine (NBBN), lead acetate (LA), and thiouracil (THIO) were studied in pairwise combinations. Each of the six possible pairs were studied by means of a 4 X 4 factorial experiment, each agent being fed at zero and at three non-zero doses. Methods of analysis designed explicitly for this study were derived to study interaction. These methods were supplemented by standard statistical methods appropriate for single agent studies. Neither synergism nor antagonism was demonstrated in these combined exposure studies. Findings for male and female animals were consistent.

Aflatoxin B1↗
PubMed1979

Comparison and evaluation of some experimental designs for use in carcinogen screening.

The development and evaluation of experimental designs for routine in vivo screening of chemicals for potential carcinogenic activity were considered. Such designs have played an important role in the Carcinogenesis Bloassay Program of the National Cancer Institute (NCI). In particular, the current one-stage 50-animal/group screen used by the NCI was considered. A specific two-stage alternative was proposed in which 35 animals/group were used; this alternative allowed for retesting of equivocal compounds. The proposed designs were evaluated in terms of sensitivity, specificity, and throughout. Despite the large number of tests made for each compound, the false-positive rate was found to be less than 0.07 for the current screen and less than 0.05 for the proposed two-stage alternative. The power of the one-stage and two-stage screens was comparable. The two-stage screen was shown to make about 30% more decisions per test period with a savings of around 28% in the expected number of animals needed per compound tested.

Animals↗
PubMed1979

Evaluation of procedures suggested for reducing the pathology workload in a carcinogenesis testing program.

A sampling procedure for reducing the pathology workload in evaluating a carcinogenicity bioassay was utilized for a rodent bioassay. The use of the procedure resulted in 50 percent fewer tissues being examined histologically, in the control groups and 12 percent fewer tissues in the treatment groups. The obvious saving in pathologist's time was negated by an increase in technician time, interference with quality control procedures and loss of nontumor pathology information.

Animals↗
PubMed1978

Skin cancer epidemiology: research needs.

The basis data currently being used to estimate and evaluate the dose-response relationship of UV-B and skin cancer are from a 6-month survey for four areas that participated in the TNCS, 1971-1972. Although most investigators from various fields of interest outside of cancer research, i.e. aviation, environmental ecology, physics, chemistry, and photobiology, etc., may admit an association between nonmelanoma skin cancer and UV-B exists, they point out that 1) the epidemiologic data currently available are too sparse and lack certain detail, such as exposure patterns and skin types, and 2) more data of this type are needed over a broad geographical range to allow for more precise measurements of the effects of stratospheric ozone depletion. They argue that the present relationships could change drastically with the addition even of a few more points (geographical locations) and that location-specific and demographic factors should be evaluated. Therefore, these data need to be updated and expanded to include more locations over a longer study period. The National Cancer Institute and the Environmental Protection Agency undertook a special skin cancer study from June 1, 1977 to May 31, 1978. The objectives of this study were: 1) to determine the incidence of nonmelanoma skin cancer (basal cell and squamous cell carcinomas) in various population groups within the United States, and 2) to ascertain and measure epidemiologic factors that may contribute toward the excess risk of nonmelanoma skin cancer in specific population groups.

Adolescent↗
PubMed1977

Mathematical models of age and ultraviolet effects on the incidence of skin cancer among whites in the United States.

That sunlight leads to skin cancer has been generally accepted for nearly a century. Physical data are, for the first time, available which support this hypothesis. The authors have found that a simple power relationship can be used to describe the data and that the form of this power function suggests that the risk of nonmelanoma skin cancer is related to cumulative lifetime ultraviolet (UV) exposure and that the risk of melanoma skin cancer is related to annual UV exposure. The authors emphasize that skin cancer risk also depends on location-specific demographic variables other than ultraviolet radiation.

Adult↗
PubMed1977

False-positive and false-negative rates for carcinogenicity screens.

The implementation of a number of chemical carcinogen screening programs has been accompanied by the observation that some screens might have high false-positive error rates. With designs presently used at the National Cancer Institute and historical spontaneous tumor rates based upon control animals in previous experiments, we compute upper bounds on the false-positive error rates for several screening strategies. False-positive results are much less likely to occur at tissue sites with low spontaneous tumor rates; hence the site at which a significant tumor increase occurs is important. There is danger in relying solely upon the finding of statistical significance without incorporating biological knowledge and corroborative evidence such as the presence of a dose-response relationship or experimentally consistent results in different species or sexes. A report by the National Cancer Institute Carcinogenesis Program demonstrates these concepts.

Animals↗
PubMed1976

Cancer mortality and asbestos deposits.

Asbestos deposits are found in many parts of the United States. In this paper the question is asked: Is there an increase in risk from cancer associated with naturally-occurring asbestos? In an attempt to control for the urban effect, geographic gradient and socioeconomic class, each county in the United States with asbestos deposits was matched for percent of area that was urban and for median years in school with two nearby counties that did not have known asbestos deposits. The study of cancer mortality rates in these matched counties provides no evidence that naturally-occurring asbestos is a great hazard to the general population of counties with asbestos depostis.

Age Factors↗