Approximate and Pseudo-Likelihood Analysis for Logistic Regression Using External Validation Data to Model Log Exposure

A common goal in environmental epidemiologic studies is to undertake logistic regression modeling to associate a continuous measure of exposure with binary disease status, adjusting for covariates. A frequent complication is that exposure may only be measurable indirectly, through a collection of subject-specific variables assumed associated with it. Motivated by a specific study to investigate the association between lung function and exposure to metal working fluids, we focus on a multiplicative-lognormal structural measurement error scenario and approaches to address it when external validation data are available. Conceptually, we emphasize the case in which true untransformed exposure is of interest in modeling disease status, but measurement error is additive on the log scale and thus multiplicative on the raw scale. Methodologically, we favor a pseudo-likelihood (PL) approach that exhibits fewer computational problems than direct full maximum likelihood (ML) yet maintains consistency under the assumed models without necessitating small exposure effects and/or small measurement error assumptions. Such assumptions are required by computationally convenient alternative methods like regression calibration (RC) and ML based on probit approximations. We summarize simulations demonstrating considerable potential for bias in the latter two approaches, while supporting the use of PL across a variety of scenarios. We also provide accessible strategies for obtaining adjusted standard errors to accompany RC and PL estimates

Effect of tissue fit on corneal shape after transplantation

Postkeratoplasty astigmatism is now a major problem preventing visual recovery. Certain postopertive topographic characteristics are felt to be dictated by the fit of the donor corneal button in its recipient bed. Deficient tissue at the wound is predicted to contribute to the location of the steep meridian and excess tissue to the location of the flat meridian. In an eight-cat sample using our Fit Assessment Method and Photogrammetric Index Method, the authors tested the relationship between button fit in recipient bed and resulting corneal curvature at approximately 42, 161, and 289 postoperative days. Corneal symmetry improved between the first and second postoperative periods. Deficient tissue led to steepened curvature and ample tissue to flattened curvature in the first measurement period. When buttons fit poorly, deficient tissue led to steepness in the first postoperative period, but led to flattened curvature 90 deg away from the deficient tissue meridian in the second and third periods. The relationship between ample tissue and flattest postoperative curvature did not depend on the magnitude of button-bed disparity in any period. Corneal elasticity appeared to influence the way tissue disparity affected postoperative topography. Our findings support Troutman's balloon mode. When there was a large amount of uncompensated tissue disparity, the tissue deficiency exerted a force that shortened the translimbal chord. This produced both steepened curvature parallel to this chord soon after surgery and flattened curvature at 90 deg to the chord in the stable postoperative cornea

A new photogrammetric method for quantifying corneal topography

Attempts to describe normal corneal shape and to represent corneal topography by an array of discrete points have limited usefulness. A quantitative photogrammetric method that produces indices to describe corneal shape was developed. Four indices depict the departure of keratographic rings from circularity, and two indices express the trends and consistencies of all the rings from one keratograph. This photogrammetric index method (PIM) was evaluated against established measurement techniques. Values for the six indices were computed for groups (10 corneas each) of symmetrical, regularly astigmatic, and keratoconic corneas that had been defined by keratometry and clinical criteria. Predictions of the differences among groups were formulated for each index based on group descriptions and anticipated manual tracing and/or digitization error. Parametric and nonparametric tests of significance supported most predictions. The asymmetry of irregularly astigmatic keratoconic corneas, the variability of their orthogonal principal meridians, and an increasing symmetry toward their peripheries were documented clearly. The circularity of symmetrical group rings and the ellipticity of regularly astigmatic group rings were also evident. Preliminary norms are offered to illustrate the usefulness of the PIM in defining groups of corneas with the same histories and in classifying individual corneas

Correlates of antioxidant nutrients and oxidative DNA damage differ by race in a cross-sectional study of healthy African American and white adults

Although antioxidant nutrients and oxidative DNA damage have been associated with carcinogenesis, few studies have investigated the factors that influence antioxidant intake and oxidative DNA damage in racially diverse populations. Demographic, behavioral, and diet-related psychosocial correlates of plasma antioxidant (carotenoids, vitamin C, and vitamin E) concentrations and oxidative DNA damage were examined using data from a cross-sectional study of 147 generally healthy, non-smoking African American and White adults in North Carolina, age 20 to 45 years. All participants completed self-administered demographic, diet, and health questionnaires and provided semi-fasting (≥ 6 hours) blood samples. Multivariate regression analyses were computed separately for each race to determine associations between the potential correlates with plasma antioxidant concentrations and oxidative DNA damage, separately. Our findings suggest appreciable differences by race. Only a few factors (age, supplement use, and several psychosocial factors) were associated with antioxidant concentrations in African Americans, whereas these and additional factors, including physical activity, waist circumference, and passive smoke exposure, were associated with antioxidant concentrations in Whites. For oxidative DNA damage, passive smoke exposure was significantly associated with oxidative DNA damage in African Americans, and age and alcohol were significant in Whites. In addition, the regression models generally explained more of the variance in plasma antioxidant concentrations and oxidative DNA damage in Whites than in African Americans. Considering the salient correlates differed by race, this work has important implications for the design and implementation of future research studies investigating antioxidant nutrients and/or oxidative stress, especially those in racially diverse populations

Meta-Analyses of the Relation between Silicone Breast Implants and the Risk of Connective-Tissue Diseases

BACKGROUND: The postulated relation between silicone breast implants and the risk of connective-tissue and autoimmune diseases has generated intense medical and legal interest during the past decade. The salience of the issue persists, despite the fact that a great deal of research has been conducted on this subject. To provide a stronger quantitative basis for addressing the postulated relation, we applied several techniques of meta-analysis that combine, compare, and summarize the results of existing relevant studies. METHODS: We searched data bases and reviewed citations in relevant articles to identify studies that met prestated inclusion criteria. Nine cohort studies, nine case-control studies, and two cross-sectional studies were included in our meta-analyses. We conducted meta-analyses of the results of these studies, both with and without adjustment for confounding factors, and a separate analysis restricted to studies of silicone-gel-filled breast implants. Finally, we estimated the annual number of new cases of connective-tissue disease that could be attributed to breast implants. RESULTS: There was no evidence that breast implants were associated with a significant increase in the summary adjusted relative risk of individual connective-tissue diseases (rheumatoid arthritis, 1.04 [95 percent confidence interval, 0.72 to 1.51]; systemic lupus erythematosus, 0.65 [95 percent confidence interval, 0.35 to 1.23]; scleroderma or systemic sclerosis, 1.01 [95 percent confidence interval, 0.59 to 1.73]; and Sjögren's syndrome, 1.42 [95 percent confidence interval, 0.65 to 3.11]); all definite connective-tissue diseases combined (0.80; 95 percent confidence interval, 0.62 to 1.04); or other autoimmune or rheumatic conditions (0.96; 95 percent confidence interval, 0.74 to 1.25). Nor was there evidence of significantly increased risk in the unadjusted analyses or in the analysis restricted to silicone-gel-filled implants. CONCLUSIONS: On the basis of our meta-analyses, there was no evidence of an association between breast implants in general, or silicone-gel-filled breast implants specifically, and any of the individual connective-tissue diseases, all definite connective-tissue diseases combined, or other autoimmune or rheumatic conditions. From a public health perspective, breast implants appear to have a minimal effect on the number of women in whom connective-tissue diseases develop, and the elimination of implants would not be likely to reduce the incidence of connective-tissue diseases

Patterns of Intimate Partner Violence Victimization from Adolescence to Young Adulthood in a Nationally Representative Sample

To determine the prevalence of patterns of intimate partner violence (IPV) victimization from adolescence to young adulthood, and document associations with selected sociodemographic and experiential factors

Numeric score-based conditional and overall change-in-status indices for ordered categorical data

Planned interventions and/or natural conditions often effect change on an ordinal categorical outcome (e.g., symptom severity). In such scenarios it is sometimes desirable to assign a priori scores to observed changes in status, typically giving higher weight to changes of greater magnitude. We define change indices for such data based upon a multinomial model for each row of a c×c table, where the rows represent the baseline status categories. We distinguish an index designed to assess conditional changes within each baseline category from two others designed to capture overall change. One of these overall indices measures expected change across a target population. The other is scaled to capture the proportion of total possible change in the direction indicated by the data, so that it ranges from −1 (when all subjects finish in the least favorable category) to +1 (when all finish in the most favorable category). The conditional assessment of change can be informative regardless of how subjects are sampled into the baseline categories. In contrast, the overall indices become relevant when subjects are randomly sampled at baseline from the target population of interest, or when the investigator is able to make certain assumptions about the baseline status distribution in that population. We use a Dirichlet-multinomial model to obtain Bayesian credible intervals for the conditional change index that exhibit favorable small-sample frequentist properties. Simulation studies illustrate the methods, and we apply them to examples involving changes in ordinal responses for studies of sleep deprivation and activities of daily living

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

Somatic Symptoms Among US Adolescent Females: Associations with Sexual and Physical Violence Exposure

To examine the association between physical and sexual violence exposure and somatic symptoms among female adolescents

Selenium, Folate, and Colon Cancer

Selenium is an essential trace element which has been implicated in cancer risk; however, study results have been inconsistent with regard to colon cancer. Our objectives were to 1) investigate the association between selenium and colon cancer 2) evaluate possible effect measure modifiers and 3) evaluate potential biases associated with the use of post-diagnostic serum selenium measure