Serum Retinol and Carotenoids in Association with Biomarkers of Insulin Resistance among Premenopausal Women.

Objective: The aim of this study was to investigate how serum retinol and carotenoids (-carotene, -cryptoxanthin, lutein/zeaxanthin, lycopene) are associated with biomarkers of insulin resistance.

Research Methods And Procedures: The BioCycle Study (2005-2007) is a prospective cohort of 259 healthy premenopausal women. Fasting serum samples were collected at up to sixteen clinic visits, from which retinol, carotenoids, insulin, glucose, and sex hormone-binding globulin (SHBG) were measured.

Accuracy loss due to selection bias in cohort studies with left truncation.

Background: Selection is a common problem in paediatric and perinatal epidemiology, and truncation can be thought of as missing person time that can result in selection bias. Left truncation, also known as late or staggered entry, may induce selection bias and/or adversely affect precision. There are two kinds of left truncation: fixed left truncation where the start of follow-up is initiated at a set time, and variable left truncation where follow-up begins at a stochastically varying time-point.

A gene-specific method for predicting hemophilia-causing point mutations.

A fundamental goal of medical genetics is the accurate prediction of genotype-phenotype correlations. As an approach to develop more accurate in silico tools for prediction of disease-causing mutations of structural proteins, we present a gene- and disease-specific prediction tool based on a large systematic analysis of missense mutations from hemophilia A (HA) patients. Our HA-specific prediction tool, HApredictor, showed disease prediction accuracy comparable to other publicly available prediction software.

Multivariate normally distributed biomarkers subject to limits of detection and receiver operating characteristic curve inference.

Rationale And Objectives: Biomarkers are of ever-increasing importance to clinical practice and epidemiologic research. Multiple biomarkers are often measured per patient. Measurement of true biomarker levels is limited by laboratory precision, specifically measuring relatively low, or high, biomarker levels resulting in undetectable levels below, or above, a limit of detection (LOD).

Habitual dietary isoflavone intake is associated with decreased C-reactive protein concentrations among healthy premenopausal women.

Isoflavones have been associated with lower cardiovascular disease risk, but existing research focused on very high isoflavone intakes, as seen in Asian populations, as well as on risk factor reductions primarily in postmenopausal women. We investigated whether habitual low isoflavone intake among premenopausal women was associated with serum C-reactive protein (CRP) concentration, a commonly used biomarker associated with prediction of cardiovascular disease risk in healthy women. Between 2005 and 2007, 259 healthy, regularly menstruating women were enrolled in the BioCycle Study, and followed for up to 2 menstrual cycles.

An additive selection of markers to improve diagnostic accuracy based on a discriminatory measure.

Rationale And Objectives: The estimation of the area under the receiver operating characteristic (ROC) curve (AUC) often relies on the assumption that the truly positive population tends to have higher marker results than the truly negative population. The authors propose a discriminatory measure to relax such an assumption and apply the measure to identify the appropriate set of markers for combination.

Materials And Methods: The proposed measure is based on the maximum of the AUC and 1-AUC.

The influence of sporadic anovulation on hormone levels in ovulatory cycles.

Study Question: Do ovulatory hormone profiles among healthy premenopausal women differ between women with and without sporadic anovulation?

Summary Answer: Women with one anovulatory cycle tended to have lower estradiol, progesterone and LH peak levels during their ovulatory cycle.

What Is Known Already: Anovulation occurs sporadically in healthy premenopausal women, but the influence of hormones in a preceding cycle and the impact on a subsequent cycle's hormone levels is unknown.

Study Design, Size, Duration: The BioCycle Study was a prospective cohort including 250 healthy regularly menstruating women, 18-44 years of age, from Western New York with no history of menstrual or ovulation disorders.

Serum uric acid in relation to endogenous reproductive hormones during the menstrual cycle: findings from the BioCycle study.

Study Question: Do uric acid levels across the menstrual cycle show associations with endogenous estradiol (E2) and reproductive hormone concentrations in regularly menstruating women?

Summary Answer: Mean uric acid concentrations were highest during the follicular phase, and were inversely associated with E2 and progesterone, and positively associated with FSH.

What Is Known Already: E2 may decrease serum levels of uric acid in post-menopausal women; however, the interplay between endogenous reproductive hormones and uric acid levels among regularly menstruating women has not been elucidated.

Study Design, Size, Duration: The BioCycle study was a prospective cohort study conducted at the University at Buffalo research centre from 2005 to 2007, which followed healthy women for one (n = 9) or 2 (n = 250) menstrual cycle(s).

Self-report of fruit and vegetable intake that meets the 5 a day recommendation is associated with reduced levels of oxidative stress biomarkers and increased levels of antioxidant defense in premenopausal women.

Background: Oxidative stress has been associated with a variety of chronic diseases and reproductive disorders. Fruits and vegetables (F/V) may contribute to antioxidant vitamin and micronutrient levels and reduce oxidative stress.

Objective: To investigate the effect of meeting the 5 A Day For Better Health Program recommendation for F/V consumption on biomarkers of oxidative damage and antioxidant defense.

Validation of different instruments for caffeine measurement among premenopausal women in the BioCycle study.

Effects of caffeine on women's health are inconclusive, in part because of inadequate exposure assessment. In this study we determined 1) validity of a food frequency questionnaire compared with multiple 24-hour dietary recalls (24HDRs) for measuring monthly caffeine and caffeinated beverage intakes; and 2) validity of the 24HDR compared with the prior day's diary record for measuring daily caffeinated coffee intake. BioCycle Study (2005-2007) participants, women (n = 259) aged 18-44 years from western New York State, were followed for 2 menstrual cycles.

Adherence to the Mediterranean diet and body fat distribution in reproductive aged women.

Background/objectives: Adherence to the Mediterranean diet (MD), high in fruits, vegetables and monounsaturated fats, has been associated with lower body mass index. Associations with measured body fat, including regional adiposity, have not been previously investigated. We examined the associations between the alternate Mediterranean diet score (aMED), anthropometry and measured adiposity by dual-energy x-ray absorptiometry (DXA).

Energy-containing beverages: reproductive hormones and ovarian function in the BioCycle Study.

Background: Energy-containing beverages are widely consumed among premenopausal women, but their association with reproductive hormones is not well understood.

Objective: The objective was to assess the association of energy-containing beverages, added sugars, and total fructose intake with reproductive hormones among ovulatory cycles and sporadic anovulation in healthy premenopausal women.

Design: Women (n = 259) in the BioCycle Study were followed for up to 2 menstrual cycles; they provided fasting blood specimens during up to 8 visits/cycle and four 24-h dietary recalls/cycle.

Correlated biomarker measurement error: an important threat to inference in environmental epidemiology.

Utilizing multiple biomarkers is increasingly common in epidemiology. However, the combined impact of correlated exposure measurement error, unmeasured confounding, interaction, and limits of detection (LODs) on inference for multiple biomarkers is unknown. We conducted data-driven simulations evaluating bias from correlated measurement error with varying reliability coefficients (R), odds ratios (ORs), levels of correlation between exposures and error, LODs, and interactions.

Persistent environmental pollutants and couple fecundity: the LIFE study.

Background: Evidence suggesting that persistent environmental pollutants may be reproductive toxicants underscores the need for prospective studies of couples for whom exposures are measured.

Objectives: We examined the relationship between selected persistent pollutants and couple fecundity as measured by time to pregnancy.

Methods: A cohort of 501 couples who discontinued contraception to become pregnant was prospectively followed for 12 months of trying to conceive or until a human chorionic gonadotrophin (hCG) test confirmed pregnancy.

Bone mineral density and blood metals in premenopausal women.

Exposure to metals, specifically cadmium, lead, and mercury, is widespread and is associated with reduced bone mineral density (BMD) in older populations, but the associations among premenopausal women are unclear. Therefore, we evaluated the relationship between these metals in blood and BMD (whole body, total hip, lumbar spine, and non-dominant wrist) quantified by dual energy X-ray absorptiometry in 248 premenopausal women, aged 18-44. Participants were of normal body mass index (mean BMI 24.

Nonparametric ROC summary statistics for correlated diagnostic marker data.

We propose efficient nonparametric statistics to compare medical imaging modalities in multi-reader multi-test data and to compare markers in longitudinal ROC data. The proposed methods are based on the weighted area under the ROC curve, which includes the area under the curve and the partial area under the curve as special cases. The methods maximize the local power for detecting the difference between imaging modalities.

The impact of dietary folate intake on reproductive function in premenopausal women: a prospective cohort study.

Background: Folic acid is recommended to reproductive-aged women to prevent birth defects, though little is known about the effects of dietary intake on other reproductive outcomes. Improved pregnancy rates have been documented after folic acid supplement use, suggesting a possible link with ovulation, however research is limited. Our objective was to evaluate the association between dietary folate intake, hormone levels, and sporadic anovulation in healthy, regularly menstruating women.

An information criterion for marginal structural models.

Marginal structural models were developed as a semiparametric alternative to the G-computation formula to estimate causal effects of exposures. In practice, these models are often specified using parametric regression models. As such, the usual conventions regarding regression model specification apply.

Pancreatic beta-cell function and type 2 diabetes risk: quantify the causal effect using a Mendelian randomization approach based on meta-analyses.

The objective of the study is to quantify the causal effect of β-cell function on type 2 diabetes by minimizing residual confounding and reverse causation. We employed a Mendelian randomization (MR) approach using TCF7L2 variant rs7903146 as an instrument for lifelong levels of β-cell function. We first conducted two sets of meta-analyses to quantify the association of the TCF7L2 variant with the risk of type 2 diabetes among 55 436 cases and 106 020 controls from 66 studies by calculating pooled odds ratio (OR) and to quantify the associations with multiple direct or indirect measures of β-cell function among 35 052 non-diabetic individuals from 31 studies by calculating pooled mean difference.

"Toward a clearer definition of confounding" revisited with directed acyclic graphs.

In a 1993 paper (Am J Epidemiol. 1993;137(1):1-8), Weinberg considered whether a variable that is associated with the outcome and is affected by exposure but is not an intermediate variable between exposure and outcome should be considered a confounder in etiologic studies. As an example, she examined the common practice of adjusting for history of spontaneous abortion when estimating the effect of an exposure on the risk of spontaneous abortion.