Biomedical subjects

Lawrence L Kupper

Publications and source records attributed to Lawrence L Kupper.

16 recordsLinked to original sources

PubMed2006

Inference for case-control studies when exposure status is both informatively missing and misclassified.

In case-control studies, it is common for a categorical exposure variable to be misclassified. It is also common for exposure status to be informatively missing for some individuals, in that the probability of missingness may be related to exposure. Procedures for addressing the bias due to misclassification via validation data have been extensively studied, and related methods have been proposed for dealing with informative missingness based on supplemental sampling of some of those with missing data. In this paper, we introduce study designs and analytic procedures for dealing with both problems simultaneously in a 2x2 analysis. Results based on convergence in probability illustrate that the combined effects of missingness and misclassification, even when the latter is non-differential, can lead to naïve exposure odds ratio estimates that are inflated or on the wrong side of the null. The motivating example comes from a case-control study of the association between low birth weight and the diagnosis of breast cancer later in life, where self-reported birth weight for some women is supplemented by accurate information from birth certificates.

Adult↗

PubMed2006

Selenium, apoptosis, and colorectal adenomas.

BACKGROUND: Selenium is an essential trace element found in cereals, wheat, dairy products, meat, and fish. This micronutrient may prevent carcinogenesis through several biochemical pathways; one suggested pathway is enhanced apoptosis. OBJECTIVES: The relation between selenium and colorectal adenomas was evaluated because the colorectal adenoma is the established precursor lesion of most colorectal cancers. Apoptosis was a pathway of interest because decreased apoptosis has been associated with an increased prevalence of adenomas. Our objectives were as follows: to investigate the association between (a) selenium and colorectal adenomas and (b) selenium and apoptosis. METHODS: The study population was assembled for the Diet and Health Study III (n = 803), a cross-sectional study conducted at the University of North Carolina Hospital (Chapel Hill, NC). There were 451 participants in the analysis of selenium and adenoma prevalence and 351 participants in the analysis of selenium and apoptosis. Selenium was measured from serum collected at the time of colonoscopy. Apoptosis was measured in biopsies from normal rectal epithelium obtained during the colonoscopy procedure. RESULTS: Participants in the highest fifth of serum selenium were less likely to have adenomas in comparison with those in the lowest fifth (prevalence ratio, 0.6; 95% confidence interval, 0.4-1.1). Selenium and apoptosis (>2.76 cells per crypt) were not strongly related, but results collectively suggested a roughly inverse association. CONCLUSIONS: High selenium was associated with a reduced prevalence of colorectal adenomas. Apoptosis, however, did not seem to be the mechanism by which selenium was related to adenoma prevalence in our data.

Adenoma↗

PubMed2006

Intimate partner violence and women's depression before and during pregnancy.

Depressive symptoms of 95 prenatal care patients were examined relative to the women's experiences of intimate partner violence. Women who were victims of psychological aggression during the year before pregnancy were not at elevated risk for depression except when the psychological aggression was very frequent. However, during pregnancy, psychological aggression was more closely tied to women's depression levels, regardless of its frequency. In addition, women who experienced any level of physical assault or sexual coercion by their intimate partners (before or during pregnancy) had higher levels of depressive symptoms compared to nonvictims.

Adult↗

PubMed2006

Physical and sexual assault of women with disabilities.

North Carolina women were surveyed to examine whether women's disability status was associated with their risk of being assaulted within the past year. Women's violence experiences were classified into three groups: no violence, physical assault only (without sexual assault), and sexual assault (with or without physical assault). Multivariable analysis revealed that women with disabilities were not significantly more likely than women without disabilities to have experienced physical assault alone within the past year (odds ratio [OR] = 1.18, 95% Confidence Interval [CI] = 0.62 to 2.27); however, women with disabilities had more than 4 times the odds of experiencing sexual assault in the past year compared to women without disabilities (OR = 4.89, 95% CI = 2.21 to 10.83).

Adult↗

PubMed2006

Dermal exposure to jet fuel JP-8 significantly contributes to the production of urinary naphthols in fuel-cell maintenance workers.

Jet propulsion fuel 8 (JP-8) is the major jet fuel used worldwide and has been recognized as a major source of chemical exposure, both inhalation and dermal, for fuel-cell maintenance workers. We investigated the contributions of dermal and inhalation exposure to JP-8 to the total body dose of U.S. Air Force fuel-cell maintenance workers using naphthalene as a surrogate for JP-8 exposure. Dermal, breathing zone, and exhaled breath measurements of naphthalene were obtained using tape-strip sampling, passive monitoring, and glass bulbs, respectively. Levels of urinary 1- and 2-naphthols were determined in urine samples and used as biomarkers of JP-8 exposure. Multiple linear regression analyses were conducted to investigate the relative contributions of dermal and inhalation exposure to JP-8, and demographic and work-related covariates, to the levels of urinary naphthols. Our results show that both inhalation exposure and smoking significantly contributed to urinary 1-naphthol levels. The contribution of dermal exposure was significantly associated with levels of urinary 2-naphthol but not with urinary 1-naphthol among fuel-cell maintenance workers who wore supplied-air respirators. We conclude that dermal exposure to JP-8 significantly contributes to the systemic dose and affects the levels of urinary naphthalene metabolites. Future work on dermal xenobiotic metabolism and toxicokinetic studies are warranted in order to gain additional knowledge on naphthalene metabolism in the skin and the contribution to systemic exposure.

Administration, Cutaneous↗

PubMed2005

Genetic testing for colon cancer among African-Americans in North Carolina.

OBJECTIVE: To describe attitudes and correlates of intention to take a genetic test for colon cancer in a population-based sample of African-Americans. METHODS: African-Americans (n = 658), age 18-70, in North Carolina completed an 11-page questionnaire between June-October 2003 that assessed attitudes (familiarity, perceived benefits and risks, anxiety, and confidentiality) and intention to take a genetic test for colon cancer and various participant characteristics. RESULTS: Respondents expressed favorable attitudes and high intention regarding genetic testing for colon cancer: 87% would definitely/probably take a genetic test, although only 42% had read/heard a lot or some about genetic testing. Most agreed that genetic test results should be available to healthcare providers (79%) but not to health insurers (62%) or employers (82%). About a third were concerned that genetic testing could lead to discrimination. Correlates of intention differed by sex. Perceived benefits were significantly positively associated with intention among all respondents. However, being married (OR = 2.1, 95% CI: 1.2, 3.7), doctor as the main source of health information (OR = 2.4, 95% CI: 1.4, 3.9), and colon cancer family history (OR = 4.3, 95% CI: 1.6, 11.6) were significant only for women; some college education (OR = 4.1, 95% CI: 1.7, 9.7), importance of sharing test results with relatives (OR = 5.5, 95% CI: 1.6, 18.7), and colon cancer screening history (OR = 3.4, 95% CI: 1.6, 7.5) were only significant for men. CONCLUSIONS: Respondents expressed high interest in genetic testing for colon cancer risk, although confidentiality of test results is a concern. Guidelines and policies for genetic testing specific to African-Americans should be established and future research should examine the prevalence of genetic testing.

Adolescent↗

PubMed2004

Prevalence of partner violence in same-sex romantic and sexual relationships in a national sample of adolescents.

PURPOSE: To present the first national prevalence estimates of psychological and physical intimate partner violence between adolescents in same-sex relationships. METHODS: Analyses focus on 117 adolescents aged 12-21 years (50% female) from Wave II of the National Longitudinal Study of Adolescent Health who reported exclusively same-sex romantic or sexual relationships in the 18 months before interview. Items from the Conflict Tactics Scale were used to measure partner violence victimization. Data analysis included computation of prevalence estimates and a logistic regression analysis to assess associations between sociodemographic characteristics and violence victimization. RESULTS: Almost one-quarter of adolescents with same-sex romantic or sexual partners reported some type of partner violence victimization; about 1 in 10 reported physical victimization. Significant sex differences were found (OR = .29, CI = 0.08, 1.00), with males being less likely than females to report "any violence." Of six other sociodemographic characteristics examined, importance of religion (OR = .27, CI = 0.07-1.07) and school size (OR = .32, CI = 0.09-1.11) were associated with victimization at the p < .10 level. Adolescents who reported that religion was important to them and adolescents who attended larger schools were at lower risk of "any violence." CONCLUSIONS: As with opposite-sex relationships, psychological and minor physical violence victimization is common among adolescents involved in same-sex intimate relationships. Males reporting exclusively same-sex relationships were less likely than females to report experiencing the violence behaviors examined.

Adolescent↗

PubMed2004

Variability of environmental exposures to volatile organic compounds.

Although studies of occupational exposure to volatile organic compounds (VOCs) often partition variability across groups, and between and within persons, those of environmental exposure to VOCs have not involved such partitioning. Using data from the Environmental Protection Agency's total exposure assessment methodology (TEAM) studies, we partitioned exposure variability across cities, and between and within persons for nine VOCs. The estimated variance components decreased in the order: within-person > between-person > across city. Despite their smaller magnitudes, estimates of between-person and across-city variance components were sufficiently large to provide reasonable contrast for informative epidemiology studies of most VOCs. Estimates of between-person variance components for environmental VOCs were similar to those published for occupational VOCs (groups defined by job and factory). However, estimates of within-person variance components were much greater for environmental VOCs, probably due to the greater diversity of locations (including the workplace) visited by the general public over time. For benzene and perchloroethylene, we used a simple model to calculate numbers of personal measurements required to relate the exposure level to health outcome statistically. About 10 times more personal measurements would be required to investigate perchloroethylene exposure as compared to benzene exposure; this disparity reflects the greater within-subject variability of perchloroethylene data compared to benzene data. We conclude that variability should be partitioned for environmental VOC exposures in much the same manner as for occupational exposures. There should be sufficient variability in the levels of most VOCs across cities and between subjects to provide reasonable contrast for informative epidemiology studies, as we illustrate for exposures to benzene. Yet, epidemiologists should be wary of investigating environmental VOCs without preliminary data with which to estimate the variance structure of exposure variables.

Air Pollutants↗

PubMed2004

Estimating dermal exposure to jet fuel (naphthalene) using adhesive tape strip samples.

A simple, non-invasive dermal sampling technique was developed and tested on 22 human volunteers under laboratory conditions to estimate acute dermal exposure to jet fuel (JP-8). Two sites on the ventral surface of each forearm were exposed to 25 micro l of JP-8 and the non-viable epidermis (stratum corneum) was sequentially tape-stripped using an adhesive tape. Samples were extracted with acetone and analyzed by gas chromatography/mass spectrometry. Analysis of the first tape strips indicated that JP-8 was rapidly removed from the stratum corneum over the 20 min study period. On average, after 5 min of exposure the first two tape strips removed 69.8% of the applied dose. The amount recovered with two tape strips decreased over time to a recovery of 0.9% 20 min after exposure. By fitting a mixed-effects linear regression model to the tape strip data, we were able to estimate accurately the amount of JP-8 initially applied. This study indicates that naphthalene has a short retention time in the human stratum corneum and that the tape stripping method, if used within 20 min of the initial exposure, can be used to measure reliably the amount of naphthalene initially in the stratum corneum due to a single exposure to jet fuel. We are currently investigating the applicability of the developed mixed-effects linear regression model to estimate acute JP-8 exposure levels based upon naphthalene measurements from tape strips collected from occupationally exposed workers.

Adult↗

PubMed2004

Birthweight differences among infants of North African immigrants and Belgians in Belgium.

BACKGROUND: Infants of North African immigrants are reported to have higher birthweights than their Belgian counterparts. It is unclear what mechanism contributes to this difference. METHODS: Analyses were based on a hospital-based cohort of 1,162 women. RESULTS: Infants of North African immigrants were less likely to be born preterm, compared to infants of Belgian women. After adjusting for sociodemographic and maternal factors, the estimated difference in mean birthweight was 74 g (p=0.05). When limited to term births, this difference was 28 g (p=0.42). CONCLUSION: The difference in mean birthweight between North African and Belgian infants was explained by differences in preterm birth and other risk factors.

Adult↗

PubMed2004

A parametric model for studying organism fitness using step-stress experiments.

We propose a method based on parametric survival analysis to analyze step-stress data. Step-stress studies are failure time studies in which the experimental stressor is increased at specified time intervals. While this protocol has been frequently employed in industrial reliability studies, it is less common in the life sciences. Possible biological applications include experiments on swimming performance of fish using a step function defining increasing water velocity over time, and treadmill tests on humans. A likelihood-ratio test is developed for comparing the failure times in two groups based on a piecewise constant hazard assumption. The test can be extended to other piecewise distributions and to include covariates. An example data set is used to illustrate the method and highlight experimental design issues. A small simulation study compares this analysis procedure to currently used methods with regard to type I error rate and power.

Analysis of Variance↗

PubMed2003

Substance use before and during pregnancy: links to intimate partner violence.

Although some research has found links between women's experiences of intimate partner violence and their use of substances, little research has examined how this potential relationship changes when women become pregnant. Furthermore, most of the past research examining women's experiences of intimate partner violence and their use of substances has focused on only one type of violence, typically, physical assault. Thus less is known concerning how other important forms of violence, such as psychological aggression and sexual coercion, may be related to women's substance use and substance abuse disorders. This research studies 85 prenatal care patients to describe the women's use of alcohol and illicit drugs, both before and during pregnancy, in relation to their experiences of various types of intimate partner violence before and during pregnancy (including psychological aggression, physical abuse, and sexual coercion). The Conflict Tactics Scales 2 was used to assess the women's experiences of intimate partner violence. The women were asked about their frequency of alcohol use, and alcohol using women were administered a short version of the Michigan Alcohol Screening Test to assess the women for symptoms of alcohol disorder. The women's use of illicit drugs was assessed by asking the women about their frequencies of various types of drug use and drug using women were administered the Drug Abuse Screening Test to assess the women for symptoms of drug disorder. The results showed that before pregnancy, women who were physically assaulted by their partners were somewhat more likely to drink alcohol and use illicit drugs compared with women who did not experience such violence, even though these differences did not reach the traditional level of statistical significance; however, among the substance using women, those who experienced each type of violence were more likely to be frequent users of substances compared with the non-victims, and they evidenced a greater number of substance disorder symptoms compared with the non-victims. After the women became pregnant, the links between women's experiences of intimate partner violence and their use of substances became stronger, with the women who experienced each type of partner violence being more likely to use both alcohol and illicit drugs. Furthermore, among the substance-using women, those who were psychologically and physically abused had somewhat elevated levels of substance disorder symptoms during pregnancy compared with women who did not suffer such victimization. These findings underscore the importance of providing routine screening for various types of violent victimization and substance use within the context of many types of women's health care settings, including substance abuse treatment programs, domestic violence programs, and prenatal care services.

Adolescent↗

PubMed2003

A new method for choosing sample size for confidence interval-based inferences.

Scientists often need to test hypotheses and construct corresponding confidence intervals. In designing a study to test a particular null hypothesis, traditional methods lead to a sample size large enough to provide sufficient statistical power. In contrast, traditional methods based on constructing a confidence interval lead to a sample size likely to control the width of the interval. With either approach, a sample size so large as to waste resources or introduce ethical concerns is undesirable. This work was motivated by the concern that existing sample size methods often make it difficult for scientists to achieve their actual goals. We focus on situations which involve a fixed, unknown scalar parameter representing the true state of nature. The width of the confidence interval is defined as the difference between the (random) upper and lower bounds. An event width is said to occur if the observed confidence interval width is less than a fixed constant chosen a priori. An event validity is said to occur if the parameter of interest is contained between the observed upper and lower confidence interval bounds. An event rejection is said to occur if the confidence interval excludes the null value of the parameter. In our opinion, scientists often implicitly seek to have all three occur: width, validity, and rejection. New results illustrate that neglecting rejection or width (and less so validity) often provides a sample size with a low probability of the simultaneous occurrence of all three events. We recommend considering all three events simultaneously when choosing a criterion for determining a sample size. We provide new theoretical results for any scalar (mean) parameter in a general linear model with Gaussian errors and fixed predictors. Convenient computational forms are included, as well as numerical examples to illustrate our methods.

Biometry↗

PubMed2002

Improved approximate confidence intervals for the mean of a log-normal random variable.

Data analysts often compute approximate 100 (1-alpha) per cent confidence intervals for the mean of a log-normal random variable due to the computational effort required for exact intervals. We evaluate two simple approximations and demonstrate that the probabilities with which the intervals fail to capture the population mean (that is, the coverage error) can range from well above the desired level, alpha, to very near zero in small to moderate sample sizes (n < or = 100). The performance of a more sophisticated approximation, implemented via numerical integration or bootstrap sampling, is noticeably improved, but also suffers from coverage errors that are too large when n < or = 25. A new procedure is developed which outperforms existing approximations. Computing these improved intervals requires the integration of standard distribution functions. The calculations are straightforward, however, and lead to satisfactory coverage errors for n as small as 5. A related method that avoids the integration step generally outperforms existing simple approximations for n < or = 100, while maintaining the coverage error at or below alpha. Programs to implement the new procedures are provided in an Appendix.

Benzene↗

PubMed2002

Domestic violence across generations: findings from northern India.

BACKGROUND: Although one cannot underestimate the importance of macrosystem-level forces (such as cultural and social norms) in the aetiology of gender-based violence within any country, including India, individual-level variables (such as observing violence between one's parents while growing up) may also play important roles in the development of such violence. Therefore, this research studies men residing in northern India to: (1) estimate the prevalence of men's childhood experiences of witnessing parent-to-parent violence within their families of origin; (2) examine whether men raised in violent homes were more likely than men raised in non-violent homes to have attitudes supportive of husbands' control of their wives; (3) examine whether men raised in violent homes were more likely than men raised in non-violent homes to be abusive toward their own wives; and (4) estimate the extent to which wife abuse in this second generation could have been prevented had there not been parent-to-parent violence in the men's natal families. METHODS: Married men (n = 6902) were surveyed concerning: their childhood experiences of witnessing parent-to-parent violence in their families of origin; their attitudes regarding the appropriateness of husbands' control of their wives; their physically and sexually abusive behaviours toward their own wives; and sociodemographic variables. Descriptive statistics, multivariable modelling procedures, and estimation of a population attributable fraction were used to address the study questions. RESULTS: Approximately one-third of the men had witnessed parent-to-parent violence as a child. Compared to men raised in non-violent homes, men from violent homes were significantly more likely to believe in husbands' rights to control their wives, and to be physically/sexually abusive toward their own wives. Non-violence in the earlier generation was strongly predictive of non-violence in the second generation, with about a third of the wife abuse in the second generation being attributable to parent-to-parent violence in the first generation. CONCLUSIONS: These findings from northern India are congruent with those from other geographical/cultural settings in suggesting that witnessing violence between one's parents while growing up is an important risk factor for the perpetration of partner violence in adulthood.

Adult↗

PubMed2002

Stability of hemoglobin and albumin adducts of naphthalene oxide, 1,2-naphthoquinone, and 1,4-naphthoquinone.

Naphthalene is an important industrial chemical, which has recently been shown to cause tumors of the respiratory tract in rodents. It is thought that one or more reactive metabolites of naphthalene, namely, naphthalene-1,2-oxide (NPO), 1,2-naphthoquinone (1,2-NPQ), and 1,4-naphthoquinone (1,4-NPQ) contribute to the tumorigenicity of this chemical. These electrophiles are all capable of covalent binding to macromolecules including DNA and proteins. The stability of cysteinyl adducts of NPO, 1,2-NPQ, and 1,4-NPQ were investigated in both hemoglobin (Hb) and albumin (Alb) of male F344 rats following a single administration of 2 different doses (400 or 800 mg naphthalene per kg body weight). To assess the stability of Alb adducts, we compared the rates of NPO-Alb turnover (half-life of approximately 2 days) and 1,2-NPQ-Alb (half-life of approximately 1 day) to the normal turnover rate of Alb in the rat (half-life = 2.5-3 days). Based on the rapid turnover of these adducts relative to Alb itself, we concluded that they were unstable. However, the stability of Alb adducts was not affected by the dose of naphthalene administered (400 or 800 mg/kg). In contrast, NPO-Hb adducts were relatively stable (rate constant of adduct instability <or= 0.01) following a 400 mg/kg dose of naphthalene, but their stability could not be estimated following an 800 mg/kg dose due to high variability among animals. The rate constants of adduct instability obtained in this study allow application of NPO and NPQ adducts to estimate the exposure to reactive electrophilic metabolites of naphthalene in the rat. In addition, some limitations of current methods for estimating adduct instability were identified.

Albumins↗