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Few biomarker-based validation studies have examined error in online self-report dietary assessment instruments, and food records (FRs) have been considered less than food frequency questionnaires (FFQs) and 24-hour recalls (24HRs). We investigated measurement error in online and paper-based FFQs, online 24HRs, and paper-based FRs in 3 samples drawn primarily from 3 cohorts, comprising 1,393 women and 1,455 men aged 45–86 years. Data collection occurred from January 2011 to October 2013. Attenuation factors and correlation coefficients between reported and true usual intake for energy, protein, sodium, potassium, and respective densities were estimated using recovery biomarkers. Across studies, average attenuation factors for energy were 0.07, 0.07, and 0.19 for a single FFQ, 24HR, and FR, respectively. Correlation coefficients for energy were 0.24, 0.23, and 0.40, respectively. Excluding energy, the average attenuation factors across nutrients and studies were 0.22 for a single FFQ, 0.22 for a single 24HR, and 0.51 for a single FR. Corresponding correlation coefficients were 0.31, 0.34, and 0.53, respectively. For densities (nutrient expressed relative to energy), the average attenuation factors across studies were 0.37, 0.17, and 0.50, respectively. The findings support prior research suggesting different instruments have unique strengths that should be leveraged in epidemiologic research. [ABSTRACT FROM AUTHOR]

In this paper, we advocate and expand upon a previously described monitoring strategy for efficient and robust estimation of disease prevalence and case numbers within closed and enumerated populations such as schools, workplaces, or retirement communities. The proposed design relies largely on voluntary testing, which is notoriously biased (e.g. in the case of coronavirus disease 2019) due to nonrepresentative sampling. The approach yields unbiased and comparatively precise estimates with no assumptions about factors underlying selection of individuals for voluntary testing, building on the strength of what can be a small random sampling component. This component enables the use of a recently proposed "anchor stream" estimator, a well-calibrated alternative to classical capture-recapture (CRC) estimators based on 2 data streams. We show that this estimator is equivalent to a direct standardization based on "capture," that is, selection (or not) by the voluntary testing program, made possible by means of a key parameter identified by design. This equivalency simultaneously allows for novel 2-stream CRC-like estimation of general mean values (e.g. means of continuous variables like antibody levels or biomarkers). For inference, we propose adaptations of Bayesian credible intervals when estimating case counts and bootstrapping when estimating means of continuous variables. We use simulations to demonstrate significant precision benefits relative to random sampling alone. [ABSTRACT FROM AUTHOR]

We evaluated the performance of a semiquantitative food frequency questionnaire (SFFQ), the Automated Self-Administered 24-Hour Dietary Recall (ASA24), and 7-day dietary records (7DDRs), in comparison with biomarkers, in the estimation of nutrient intakes among 627 women in the Women's Lifestyle Validation Study (United States, 2010-2012). Two paper SFFQs, 1 Web-based SFFQ, 4 ASA24s (beta version), 2 7DDRs, 4 24-hour urine samples, 1 doubly labeled water measurement (repeated among 76 participants), and 2 fasting blood samples were collected over a 15-month period. The dietary variables evaluated were energy, energy-adjusted intakes of protein, sodium, potassium, and specific fatty acids, carotenoids, a-tocopherol, retinol, and folate. In general, relative to biomarkers, averaged ASA24s had lower validity than the SFFQ completed at the end of the data-collection year (SFFQ2); SFFQ2 had slightly lower validity than 1 7DDR; the averaged SFFQs had validity similar to that of 1 7DDR; and the averaged 7DDRs had the highest validity. The deattenuated correlation of energy-adjusted protein intake assessed by SFFQ2 with its biomarker was 0.46, similar to its correlation with 7DDRs (deattenuated r = 0.54). These data indicate that the SFFQ2 provides reasonably valid measurements of energy-adjusted intake for most of the nutrients assessed in our study, consistent with earlier conclusions derived using 7DDRs as the comparison method. The ASA24 needs further evaluation for use in large population studies, but an average of 3 days of measurement will not be sufficient for some important nutrients. [ABSTRACT FROM AUTHOR]

Statistical analysis of pooled dietary intake data in multicenter and multiethnic studies is often hampered by lack of comparability due to application of different food frequency questionnaires (FFQs). To remove this deficiency, dietary intake measurements should be standardized. This paper presents a standardization procedure based on nonlinear calibration, which aims to approximate the usual intake distribution estimated by reference measurements. The method can be applied in studies with repeated standardized reference measurements that can refer to time periods different from that of the FFQ. It was developed especially for short-term reference assessment methods, such as 24-hour recalls, diet records, and biomarkers. Similar to linear calibration, the proposed method does not change the rankings of subjects in each center or group; therefore, it maintains the within-center validity of the FFQ data. In contrast to linear calibration, the mixture of nonlinearly calibrated intake measurements from different centers or groups corresponds to the mixture of usual intake expected from the reference measurements. This paper illustrates this property of achieving high between-center validity by using macronutrient intake data from the 1995–1996 European Prospective Investigation into Cancer and Nutrition–Potsdam validation study. Here, the proposed method is compared with three linear calibration methods. [ABSTRACT FROM PUBLISHER]

The majority of people living with Alzheimer disease (AD) and related dementias are women. Longer life expectancy is one factor thought to contribute to this observation, but possible sex-specific biological mechanisms have received considerable attention from the research community. In the current issue of the Journal , Buckley et al. (Am J Epidemiol. 2019;188(7):1213–1223) use death certificate information on all deaths occurring among adults aged ≥60 years in Australia between 2006 and 2014 to evaluate sex/gender differences in rates of death with dementia (all types), AD dementia, and vascular dementia listed on the death certificate. The paper by Buckley et al. highlights several important methodological challenges for research examining sex/gender differences in risk of AD and related dementias, including challenges in measurement, survival bias and competing risks, and selection bias arising from sample selection. The current evidence on possible sex-specific biological risk factors for AD is intriguing, but there are numerous alternative explanations for differences in AD dementia and AD biomarkers between women and men. Triangulation of evidence from study designs with different strengths and weaknesses and transdisciplinary collaboration will be vital to generating conclusive evidence about sex/gender differences in risk of AD and related dementias. [ABSTRACT FROM AUTHOR]

Vitamin D is a fat-soluble vitamin that is synthesized in the skin with exposure to sunlight or is ingested from dietary supplements or food. There has been a dramatic increase in research on vitamin D, linking it with health outcomes as varied as reproductive function, infection, cardiovascular disease, and cancer. The study of vitamin D has generated much excitement, partly because there is an ideal intervention: Low levels may be common and can be remedied with widely available supplements. Determination of vitamin D status is complex and has advanced dramatically in the past 5 years. In this paper, we begin by describing important considerations for measurement of total 25-hydroxyvitamin D (25(OH)D), the biomarker traditionally assessed in epidemiologic studies. While 25(OH)D remains the most commonly measured biomarker, emerging evidence suggests that other related analytes may contribute to the characterization of an individual's vitamin D status (e.g., vitamin D-binding protein, bioavailable and free 25(OH)D, the C-3 epimer of 25(OH)D, 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin D). The measurement of these analytes is also complex, and there are important considerations for deciding whether their measurement is warranted in new research studies. Herein we discuss these issues and provide the reader with an up-to-date synthesis of research on vitaminD measurement options and considerations. [ABSTRACT FROM AUTHOR]

Changes in women’s menstrual bleeding patterns precede the onset of menopause. In this paper, the authors identify population subgroups based on menstrual characteristics of the menopausal transition experience. Using the TREMIN data set (1943–1979), the authors apply a Bayesian change-point model with 8 parameters for each woman that summarize change in menstrual bleeding patterns during the menopausal transition. The authors then use estimates from this model to classify menstrual patterns into subgroups using a K-medoids algorithm. They identify 6 subgroups of women whose transition experience can be distinguished by age at onset, variability of the menstrual cycle, and duration of the early transition. These results suggest that for most women, mean and variance change points are well aligned with proposed bleeding markers of the menopausal transition, but for some women they are not clearly associated. Increasing understanding of population differences in the transition experience may lead to new insights into ovarian aging. Because of age inclusion criteria, most longitudinal studies of the menopausal transition probably include only a subset of the 6 subgroups of women identified in this paper, suggesting a potential bias in the understanding of both the menopausal transition and the linkage between the transition and chronic disease. [ABSTRACT FROM PUBLISHER]

Pooling specimens prior to performing laboratory assays has various benefits. Pooling can help to reduce cost, preserve irreplaceable specimens, meet minimal volume requirements for certain lab tests, and even reduce information loss when a limit of detection is present. Regardless of the motivation for pooling, appropriate analytical techniques must be applied in order to obtain valid inference from composite specimens. When biomarkers are treated as the outcome in a regression model, techniques applicable to individually measured specimens may not be valid when measurements are taken from pooled specimens, particularly when the biomarker is positive and right skewed. In this paper, we propose a novel semiparametric estimation method based on an adaptation of the quasi-likelihood approach that can be applied to a right-skewed outcome subject to pooling. We use simulation studies to compare this method with an existing estimation technique that provides valid estimates only when pools are formed from specimens with identical predictor values. Simulation results and analysis of a motivating example demonstrate that, when appropriate estimation techniques are applied to strategically formed pools, valid and efficient estimation of the regression coefficients can be achieved. [ABSTRACT FROM AUTHOR]

Relationships between some risk factors and breast cancer incidence are known to vary by tumor subtype. However, breast tumors can be classified according to a number of markers, which may be correlated, making it difficult to identify heterogeneity of risk factors with specific tumor markers when using standard competing-risk survival analysis. In this paper, we propose a constrained competing-risk survival model that allows for assessment of heterogeneity of risk factor associations according to specific tumor markers while controlling for other markers. These methods are applied to Nurses’ Health Study data from 1980–2006, during which 3,398 incident invasive breast cancers occurred over 1.4 million person-years of follow-up. Results suggested that when estrogen receptor (ER) and progesterone receptor (PR) status are mutually considered, some risk factors thought to be characteristic of “estrogen-positive tumors,” such as high body mass index during postmenopause and increased height, are actually significantly associated with PR-positive tumors but not ER-positive tumors, while other risk factors thought to be characteristic of “estrogen-negative tumors,” such as late age at first birth, are actually significantly associated with PR-negative rather than ER-negative breast cancer. This approach provides a strategy for evaluating heterogeneity of risk factor associations by tumor marker levels while controlling for additional tumor markers. [ABSTRACT FROM PUBLISHER]

The incidence of human immunodeficiency virus (HIV) is the rate at which new HIV infections occur in populations. The development of accurate, practical, and cost-effective approaches to estimation of HIV incidence is a priority among researchers in HIV surveillance because of limitations with existing methods. In this paper, we develop methods for estimating HIV incidence rates using multiple biomarkers in biological samples collected from a cross-sectional survey. An advantage of the method is that it does not require longitudinal follow-up of individuals. We use assays for BED, avidity, viral load, and CD4 cell count data from clade B samples collected in several US epidemiologic cohorts between 1987 and 2010. Considering issues of accuracy, cost, and implementation, we identify optimal multiassay algorithms for estimating incidence. We find that the multiple-biomarker approach to cross-sectional HIV incidence estimation corrects the significant deficiencies of currently available approaches and is a potentially powerful and practical tool for HIV surveillance. [ABSTRACT FROM AUTHOR]

To date, Web-based 24-hour recalls have not been validated using objective biomarkers. From 2006 to 2009, the validity of 6 Web-based DietDay 24-hour recalls was tested among 115 black and 118 white healthy adults from Los Angeles, California, by using the doubly labeled water method, and the results were compared with the results of the Diet History Questionnaire, a food frequency questionnaire developed by the National Cancer Institute. The authors performed repeated measurements in a subset of 53 subjects approximately 6 months later to estimate the stability of the doubly labeled water measurement. The attenuation factors for the DietDay recall were 0.30 for blacks and 0.26 for whites. For the Diet History Questionnaire, the attenuation factors were 0.15 and 0.17 for blacks and whites, respectively. Adjusted correlations between true energy intake and the recalls were 0.50 and 0.47 for blacks and whites, respectively, for the DietDay recall. For the Diet History Questionnaire, they were 0.34 and 0.36 for blacks and whites, respectively. The rate of underreporting of more than 30% of calories was lower with the recalls than with the questionnaire (25% and 41% vs. 34% and 52% for blacks and whites, respectively). These findings suggest that Web-based DietDay dietary recalls offer an inexpensive and widely accessible dietary assessment alternative, the validity of which is equally strong among black and white adults. The validity of the Web-administered recall was superior to that of the paper food frequency questionnaire. [ABSTRACT FROM PUBLISHER]

In this paper, the authors describe a simple method for making longitudinal comparisons of alternative markers of a subsequent event. The method is based on the aggregate prediction gain from knowing whether or not a marker has occurred at any particular age. An attractive feature of the method is the exact decomposition of the measure into 2 components: 1) discriminatory ability, which is the difference in the mean time to the subsequent event for individuals for whom the marker has and has not occurred, and 2) prevalence factor, which is related to the proportion of individuals who are positive for the marker at a particular age. Development of the method was motivated by a study that evaluated proposed markers of the menopausal transition, where the markers are measures based on successive menstrual cycles and the subsequent event is the final menstrual period. Here, results from application of the method to 4 alternative proposed markers of the menopausal transition are compared with previous findings. [ABSTRACT FROM PUBLISHER]

The receiver operating characteristic curve is a commonly used tool for evaluating biomarker usefulness in clinical diagnosis of disease. Frequently, biomarkers being assessed have immeasurable or unreportable samples below some limit of detection. Ignoring observations below the limit of detection leads to negatively biased estimates of the area under the curve. Several correction methods are suggested in the areas of mean estimation and testing but nothing regarding the receiver operating characteristic curve or its summary measures. In this paper, the authors show that replacement values below the limit of detection, including those suggested, result in the same biased area under the curve when properly accounted for, but they also provide guidance on the usefulness of these values in limited situations. The authors demonstrate maximum likelihood techniques leading to asymptotically unbiased estimators of the area under the curve for both normally and gamma distributed biomarker levels. Confidence intervals are proposed, the coverage probability of which is scrutinized by simulation study. An example using polychlorinated biphenyl levels to classify women with and without endometriosis illustrates the potential benefits of these methods. [ABSTRACT FROM AUTHOR]

Recent studies suggest that measurement error in food frequency questionnaires includes a person-specific component correlated with that of other self-reported dietary assessments. Use of biomarkers has been recommended to adequately calibrate dietary assessment tools for unbiased estimation of associations between diet and disease. Data on biomarkers of intake are often collected only in small subsamples, because collection of biomarker data can be expensive and inconvenient for participants. In this paper, the authors propose a novel approach using itemized household grocery till receipts to calibrate dietary assessment. Till receipts are not self-recorded and the data obtained from them are not subject to person-specific bias, but the data need to be supported by self-completed diaries for foods eaten away from home. Till receipts may also prove cheaper to collect in larger samples. The authors discuss the many methodological challenges of using household-level data and discuss how till receipts might be used in practice, with or without the use of biomarkers. [ABSTRACT FROM PUBLISHER]

The use of biomarkers is of ever-increasing importance in clinical diagnosis of disease. In practice, a cutpoint is required for dichotomizing naturally continuous biomarker levels to distinguish persons at risk of disease from those who are not. Two methods commonly used for establishing the “optimal” cutpoint are the point on the receiver operating characteristic curve closest to (0,1) and the Youden index, J. Both have sound intuitive interpretations—the point closest to perfect differentiation and the point farthest from none, respectively—and are generalizable to weighted sensitivity and specificity. Under the same weighting of sensitivity and specificity, these two methods identify the same cutpoint as “optimal” in certain situations but different cutpoints in others. In this paper, the authors examine situations in which the two criteria agree or disagree and show that J is the only “optimal” cutpoint for given weighting with respect to overall misclassification rates. A data-driven example is used to clarify and demonstrate the magnitude of the differences. The authors also demonstrate a slight alteration in the (0,1) criterion that retains its intuitive meaning while resulting in consistent agreement with J. In conclusion, the authors urge that great care be taken when establishing a biomarker cutpoint for clinical use. [ABSTRACT FROM AUTHOR]

A marker strongly associated with outcome (or disease) is often assumed to be effective for classifying persons according to their current or future outcome. However, for this assumption to be true, the associated odds ratio must be of a magnitude rarely seen in epidemiologic studies. In this paper, an illustration of the relation between odds ratios and receiver operating characteristic curves shows, for example, that a marker with an odds ratio of as high as 3 is in fact a very poor classification tool. If a marker identifies 10% of controls as positive (false positives) and has an odds ratio of 3, then it will correctly identify only 25% of cases as positive (true positives). The authors illustrate that a single measure of association such as an odds ratio does not meaningfully describe a marker’s ability to classify subjects. Appropriate statistical methods for assessing and reporting the classification power of a marker are described. In addition, the serious pitfalls of using more traditional methods based on parameters in logistic regression models are illustrated. [ABSTRACT FROM AUTHOR]

This paper describes the Observing Protein and Energy Nutrition (OPEN) Study, conducted from September 1999 to March 2000. The purpose of the study was to assess dietary measurement error using two self-reported dietary instruments--the food frequency questionnaire (FFQ) and the 24-hour dietary recall (24HR)--and unbiased biomarkers of energy and protein intakes: doubly labeled water and urinary nitrogen. Participants were 484 men and women aged 40-69 years from Montgomery County, Maryland. Nine percent of men and 7% of women were defined as underreporters of both energy and protein intake on 24HRs; for FFQs, the comparable values were 35% for men and 23% for women. On average, men underreported energy intake compared with total energy expenditure by 12-14% on 24HRs and 31-36% on FFQs and underreported protein intake compared with a protein biomarker by 11-12% on 24HRs and 30-34% on FFQs. Women underreported energy intake on 24HRs by 16-20% and on FFQs by 34-38% and underreported protein intake by 11-15% on 24HRs and 27-32% on FFQs. There was little underreporting of the percentage of energy from protein for men or women. These findings have important implications for nutritional epidemiology and dietary surveillance. [ABSTRACT FROM AUTHOR]

Oxidation of biomolecules may play a role in susceptibility to a number of diseases. However, there are few large-scale survey data describing oxidative damage that occurs in humans and the demographic, physical, or nutritional factors that may be associated with it. Such information is essential for the design and analysis of studies investigating the role of oxidative stress in health and disease. This paper presents data on levels of two biomarkers of lipid peroxidation, malondialdehyde and F2-isoprostanes, in 298 healthy adults aged 19–78 years. The study was conducted in Berkeley and Oakland, California, in 1998–1999. Sex was the strongest predictor of lipid peroxidation as measured by both biomarkers (p < 0.0001); it was stronger than smoking. C-reactive protein was positively associated with lipid peroxidation (p = 0.004), as was plasma cholesterol. Plasma ascorbic acid had a strong inverse relation (p < 0.001) with both biomarkers. Plasma β-carotene was also associated with F2-isoprostanes. Other plasma antioxidants were not associated with lipid peroxidation biomarkers, once ascorbic acid was included in the multivariate model. Future surveys and epidemiologic studies should measure at least one marker of oxidative damage, as well as plasma ascorbic acid. These data would permit a better understanding of the role that oxidants and antioxidants play in the health of human populations. Am J Epidemiol 2002;156:274–85. [ABSTRACT FROM PUBLISHER]

Measurement error is a major issue in self-reported diet that can distort diet-disease relationships. Use of blood concentration biomarkers has the potential to mitigate the subjective bias inherent in self-reporting. As part of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) baseline visit (2008–2011), self-reported information on diet was collected from all participants (n  = 16,415). The HCHS/SOL also included annual telephone follow-up, as well as a second (2014–2017) and third (2020–2023) clinic visit. Blood concentration biomarkers for carotenoids, tocopherols, retinol, vitamin B12, and folate were measured in a subset of participants (n  = 476) as part of the Study of Latinos: Nutrition and Physical Activity Assessment Study (SOLNAS) (2010–2012). We examined the relationships among biomarker levels, self-reported intake, Hispanic/Latino background (Central American, Cuban, Dominican, Mexican, Puerto Rican, or South American), and other participant characteristics in this diverse cohort. We built regression calibration–based prediction equations for 10 nutritional biomarkers and used a simulation to study the power of detecting a diet-disease association in a multivariable Cox model using a predicted concentration level. Good statistical power was observed for some nutrients with high prediction model R 2 values, but further research is needed to understand how best to realize the potential of these dietary biomarkers. This study provides a comprehensive examination of several nutritional biomarkers within the HCHS/SOL, characterizing their associations with subject characteristics and the influence of the measurement characteristics on the power to detect associations with health outcomes. [ABSTRACT FROM AUTHOR]

We recently evaluated associations of biomarker-calibrated protein intake, protein density, carbohydrate intake, and carbohydrate density with the incidence of cardiovascular disease, cancer, and diabetes among postmenopausal women in the Women's Health Initiative (1993–present, 40 US clinical centers). The biomarkers relied on serum and urine metabolomics profiles, and biomarker calibration used regression of biomarkers on food frequency questionnaires. Here we develop corresponding calibration equations using food records and dietary recalls. In addition, we use calibrated intakes based on food records in disease association estimation in a cohort subset (n  = 29,294) having food records. In this analysis, more biomarker variation was explained by food records than by FFQs for absolute macronutrient intake, with 24-hour recalls being intermediate. However, the percentage of biomarker variation explained was similar for each assessment approach for macronutrient densities. Invasive breast cancer risk was related inversely to carbohydrate and protein densities using food records, in analyses that included (calibrated) total energy intake and body mass index. Corresponding analyses for absolute intakes did not differ from the null, nor did absolute or relative intakes associate significantly with colorectal cancer or coronary heart disease. These analyses do not suggest major advantages for food records or dietary recalls in comparison with less costly and logistically simpler food frequency questionnaires for these nutritional variables. [ABSTRACT FROM AUTHOR]

The precise quantitation of smoking during pregnancy is difficult in retrospective studies. Routinely collected blood specimens from newborns, stored as dried blood spots, may provide a low-cost method to objectively measure maternal smoking close to the time of delivery. This article compares cotinine levels in dried blood spots to those in umbilical cord blood to assess cotinine in dried blood spots as a biomarker of maternal smoking close to the time of delivery. The California Genetic Disease Screening Program provided dried blood spots from 428 newborns delivered in 2001–2003 with known umbilical cord blood cotinine levels. Cotinine in dried blood spots was measured in 6.35­-mm punches by using liquid chromatography­–tandem mass spectrometry (quantitation limit, 3.1 ng/mL). Repeated measures of cotinine in dried blood spots were highly correlated (R2 = 0.99, P < 0.001) among 100 dried blood spots with cotinine quantitated in 2 separate punches. Linear regression revealed that cotinine levels in dried blood spots were slightly lower than those in umbilical cord blood and predicted umbilical cord blood cotinine levels well (β = 0.95, R2 = 0.80, and P < 0.001 for both cotinine levels in log10 scale). When defining active smoking as a cotinine level of 10 ng/mL or more and using umbilical cord blood cotinine as the criterion standard, we found that measurements of cotinine in dried blood spots had high sensitivity (92.3%) and specificity (99.7%) in the prediction of maternal active smoking. Cotinine levels in dried blood spots are an accurate biomarker of maternal smoking close to the time of delivery. [ABSTRACT FROM PUBLISHER]

The concept of covariate adjustment is well established in therapeutic and etiologic studies. However, it has received little attention in the growing area of medical research devoted to the development of markers for disease diagnosis, screening, or prognosis, where classification accuracy, rather than association, is of primary interest. In this paper, the authors demonstrate the need for covariate adjustment in studies of classification accuracy, discuss methods for adjusting for covariates, and distinguish covariate adjustment from several other related, but fundamentally different, uses for covariates. They draw analogies and contrasts throughout with studies of association. [ABSTRACT FROM AUTHOR]

Morbidity and mortality have been increasing among middle-aged and young-old Americans since the turn of the century. We investigated whether these unfavorable trends extend to younger cohorts and their underlying physiological, psychological, and behavioral mechanisms. Applying generalized linear mixed-effects models to data from 62,833 adults from the National Health and Nutrition Examination Surveys (1988–2016) and 625,221 adults from the National Health Interview Surveys (1997–2018), we found that for all sex and racial groups, physiological dysregulation has increased continuously from Baby Boomers through late-Generation X and Generation Y. The magnitude of the increase was higher for White men than for other groups, while Black men had a steepest increase in low urinary albumin (a marker of chronic inflammation). In addition, Whites underwent distinctive increases in anxiety, depression, and heavy drinking, and they had a higher level than Blacks and Hispanics of smoking and drug use in recent cohorts. Smoking is not responsible for the increasing physiological dysregulation across cohorts. The obesity epidemic contributes to the increase in metabolic syndrome but not in low urinary albumin. The worsening physiological and mental health profiles among younger generations imply a challenging morbidity and mortality prospect for the United States, one that might be particularly inauspicious for Whites. [ABSTRACT FROM AUTHOR]

Among 626 participants of the Men's Lifestyle Validation Study (2011–2013), we evaluated the validity and reproducibility of a self-administered 152-item semiquantitative food frequency questionnaire (SFFQ) using two 7-day dietary records (7DDRs), 4 Automated Self-Administered 24-hour dietary recalls (ASA24s), four 24-hour urine samples, 1 doubly labeled water measurement (repeated in 104 participants), and 2 fasting blood samples, collected over 15 months. Compared with 7DDRs, SFFQs underestimated energy intake, macronutrients, and sodium intake but overestimated some micronutrients. The mean of the Spearman correlation coefficients was 0.66 (range, 0.38–0.88) between 46 energy-adjusted nutrients estimated from 7DDRs and the final SFFQ, deattenuated for within-person variation in the 7DDRs. These deattenuated correlations were similar using ASA24s as the comparison. Relative to biomarkers, SFFQs underestimated energy, sodium, and protein intakes, as well as the sodium:potassium ratio. The energy-adjusted correlations between the final SFFQ and the biomarkers were slightly lower than the correlations between the SFFQ and 7DDRs. Using the method of triads to calculate validity coefficients, the median validity coefficient between SFFQ and true intake was 0.65 and 0.69 using 7DDRs and ASA24s, respectively, as the third method. These data indicate that this SFFQ provided reasonably valid estimates for a wide range of nutrients when evaluated by multiple comparison methods. [ABSTRACT FROM AUTHOR]

The evidence that fetal life and early infancy are "critical" or "sensitive" ages for later development of cardiometabolic disease is based on flawed methods for comparing different age periods. Moreover, most previous studies have limited their focus to weight gain, rather than growth in length/height or body mass index (weight (kg)/height (m)2). We undertook a secondary analysis of data from the Promotion of Breastfeeding Intervention Trial (1996–2010), a birth cohort study nested within a large cluster-randomized trial in the Republic of Belarus, that had repeated measurements of weight and length/height taken from birth to 11.5 years of age. We used mixed-effects linear models to analyze associations of changes in standardized weight, length/height, and body mass index during 5 age periods (conception to birth, birth to age 3 months, ages 3–12 months, ages 12 months–6.5 years, and ages 6.5–11.5 years) with fasting glucose, insulin, insulin resistance, β-cell function, and adiponectin at age 11.5 years. We observed strong associations between the metabolic markers and all 3 growth measures, with the largest magnitudes being observed during the latest age period (ages 6.5–11.5 years) and negligible associations during gestation and the first year of life. Later age periods appear more "sensitive" than earlier periods to the adverse metabolic association with rapid growth in childhood. [ABSTRACT FROM AUTHOR]

Blood biomarkers provide critical information about the health of older populations, especially in large developing countries where self-reports of health are often inaccurate due to lack of access to health care. However, it is very difficult to collect blood samples in representative population surveys in such countries. The China Health and Retirement Longitudinal Study (CHARLS), a nationally representative study of middle-aged and older Chinese, represents one of the first efforts to include blood biomarkers in a nationally representative survey of China. In the 2015 wave of CHARLS, 13,013 respondents located in 150 counties around China donated whole blood, which was assayed on a range of indicators. Here we describe the process of the sample collection, transportation, storage, and analysis and present basic statistics. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Receiver Operating Characteristic Curve Inference From a Sample With a Limit of Detection" by N. J. Perkins and colleagues, published in a previous issue.

A response by Sarah Rosner Preis and colleagues to a letter to the editor about their article "Application of a repeat-measure biomarker measurement error model to 2 validation studies: Examination of the effect of within-person variation in biomarker measurements" in the March 15, 2011 issue is presented.

Leukocyte telomere length (LTL) is ostensibly a biomarker of human aging. Cross-sectional analyses have found that LTL is relatively short in a host of aging-related diseases. These studies have also provided indirect estimates of age-dependent LTL shortening. In this paper, the authors report findings of the first comprehensive longitudinal study of 450 whites and 185 African Americans in Louisiana (aged 31.4 and 37.4 years at baseline (1995–1996) and follow-up (2001–2006) examinations, respectively) participating in the Bogalusa Heart Study. Rate of change in LTL was highly variable among individuals, with some displaying a paradoxical gain in LTL during the follow-up period. The most striking observation was that age-dependent LTL shortening was proportional to LTL at baseline examination. At both baseline and follow-up examinations, African Americans had longer LTLs than whites, and smokers had shorter LTLs than nonsmokers. The longer LTL in African Americans than in whites explained in part the faster rate of LTL shortening observed among African Americans. These findings underscore the complexity of leukocyte telomere dynamics in vivo and suggest that determinants in addition to the “end-replication problem” contribute to telomere shortening in vivo. [ABSTRACT FROM AUTHOR]

This paper examines the reporting of sexual and other risk behaviors within a randomized experiment using a computerized versus face-to-face interview mode. Biomarkers for sexually transmitted infection (STI) were used to validate self-reported behavior by interview mode. As part of a parent study evaluating home versus clinic screening and diagnosis for STIs, 818 women aged 18−40 years were recruited in 2004 at or near a primary care clinic in São Paulo, Brazil, and were randomized to a face-to-face interview or audio computer-assisted self-interviewing. Ninety-six percent of participants were tested for chlamydia, gonorrhea, and trichomoniasis. Reporting of STI risk behavior was consistently higher with the computerized mode of interview. Stronger associations between risk behaviors and STI were found with the computerized interview after controlling for sociodemographic factors. These results were obtained by using logistic regression approaches, as well as statistical methods that address potential residual confounding and covariate endogeneity. Furthermore, STI-positive participants were more likely than STI-negative participants to underreport risk behavior in the face-to-face interview. Results strongly suggest that computerized interviewing provides more accurate and reliable behavioral data. The analyses also confirm the benefits of using data on prevalent STIs for externally validating behavioral reporting. [ABSTRACT FROM AUTHOR]

This study explored the association between exposure to acetaminophen during pregnancy and pubertal development using data from 15,822 boys and girls in the longitudinal Puberty Cohort, nested within the Danish National Birth Cohort. Use of acetaminophen was reported 3 times during pregnancy and 6 months postpartum. In total, 54% of mothers indicated use at least once during pregnancy. Between 2012 and 2017, sons and daughters provided information on a wide range of pubertal milestones—including Tanner stages, axillary hair growth, and age at menarche or voice break and first ejaculation—every 6 months from 11 years of age until full sexual maturation. Data were analyzed using a regression model for interval-censored data, providing adjusted mean monthly differences in age at attaining the pubertal milestones according to intrauterine cumulative (weeks) and trimester-specific acetaminophen exposure. Our results suggested a tendency towards slightly earlier attainment of almost all studied markers of female pubertal development with increasing number of weeks of exposure (i.e. about 1.5–3 months earlier age at pubic hair, axillary hair, and acne development comparing unexposed with those prenatally exposed for more than 12 weeks). Male pubertal development had no strong association with acetaminophen exposure. [ABSTRACT FROM AUTHOR]

The Earned Income Tax Credit (EITC) is the largest US poverty-alleviation program, yet few studies examine its effects on the health of recipients' children. We employed quasiexperimental techniques to test the hypothesis that EITC refund receipt is associated with short-term improvements in child health. The data set included children in families surveyed in the Third National Health and Nutrition Examination Survey (n = 7,444). We employed a difference-in-differences approach, exploiting the seasonal nature of EITC refund receipt. We compared children of EITC-eligible families interviewed immediately after refund receipt (February to April) with those interviewed during other months (May to January), differencing out seasonal variation among non-EITC-eligible families. We examined outcomes that were likely to be affected immediately after refund receipt, including general health, nutrition, metabolic and inflammatory biomarkers, and test scores. There were improvements in physician-reported overall health after refund receipt but no changes in infection, serum metabolic or inflammatory markers, or test scores, and there were contradictory findings for food insufficiency. In summary, EITC refunds are not strongly associated with most short-term health outcomes among recipients' children, although numerous previous studies have demonstrated impacts on longer-term outcomes. This highlights the importance of examining the effects of public policies on beneficiaries and their children using varying study designs. [ABSTRACT FROM AUTHOR]

Improving estimates of individuals' dietary intakes is key to obtaining more reliable evidence for diet-health relationships from nutritional cohort studies. One approach to improvement is combining information from different self-report instruments. Previous work evaluated the gains obtained from combining information from a food frequency questionnaire (FFQ) and multiple 24-hour recalls (24HRs), based on assuming that 24HRs provide unbiased measures of individual intakes. Here we evaluate the same approach of combining instruments but base it on the better assumption that recovery biomarkers provide unbiased measures of individual intakes. Our analysis uses data from the 5 large validation studies included in the Validation Studies Pooling Project: the Observing Protein and Energy Nutrition Study (1999–2000), the Automated Multiple-Pass Method validation study (2002–2004), the Energetics Study (2006–2009), the Nutrition Biomarker Study (2004–2005), and the Nutrition and Physical Activity Assessment Study (2007–2009). The data included intakes of energy, protein, potassium, and sodium. Under a time-varying usual-intake model analysis, the combination of an FFQ with 4 24HRs improved correlations with true intake for predicted protein density, potassium density, and sodium density (range, 0.39–0.61) in comparison with use of a single FFQ (range, 0.34–0.50). Absolute increases in correlation ranged from 0.02 to 0.26, depending on nutrient and sex, with an average increase of 0.14. Based on unbiased recovery biomarker evaluation for these nutrients, we confirm that combining an FFQ with multiple 24HRs modestly improves the accuracy of estimates of individual intakes. [ABSTRACT FROM AUTHOR]

The inconsistent findings from epidemiologic studies relating total sugars (TS) consumption to cardiovascular disease (CVD) or type 2 diabetes (T2D) risk may be partly due to measurement error in self-reported intake. Using regression calibration equations developed based on the predictive biomarker for TS and recovery biomarker for energy, we examined the association of TS with T2D and CVD risk, before and after dietary calibration, in 82,254 postmenopausal women participating in the Women's Health Initiative Observational Study. After up to 16 years of follow-up (1993–2010), 6,621 T2D and 5,802 CVD incident cases were identified. The hazard ratio for T2D per 20% increase in calibrated TS was 0.94 (95% confidence interval (CI): 0.77, 1.15) in multivariable energy substitution, and 1.00 (95% CI: 0.85, 1.18) in energy partition models. Multivariable hazard ratios for total CVD were 0.97 (95% CI: 0.87, 1.09) from energy substitution, and 0.91 (95% CI: 0.80, 1.04) from energy partition models. Uncalibrated TS generated a statistically significant inverse association with T2D and total CVD risk in multivariable energy substitution and energy partition models. The lack of conclusive findings from our calibrated analyses may be due to the low explanatory power of the calibration equations for TS, which could have led to incomplete deattenuation of the risk estimates. [ABSTRACT FROM AUTHOR]

Inflammatory processes are known to drive the pathogenesis of several chronic diseases, including cardiovascular disease and Alzheimer disease, as well as all-cause mortality. Emerging research indicates that women who have a longer reproductive life span—roughly determined as the period from menarche to menopause or lifetime number of ovulatory cycles after accounting for anovulatory time spans—are at lower risk for these inflammation-related chronic diseases. The paradox is that ovulation is known to induce acute inflammation. Given the limited research assessing the relationship between reproductive life span and later inflammatory profiles, Huang et al. (Am J Epidemiol. 2020;189(7):660–670) set out to investigate this relationship within 2 of the most robust longitudinal cohort studies of women, the Nurses' Health studies. They found that after adjustment for other inflammation-related factors, including adiposity, exercise, and diet, lifetime ovulatory years was associated with lower C-reactive protein levels in both premenopausal and postmenopausal women. Huang et al. call attention to several challenges in research on women's reproductive life spans, including how to appropriately capture lifetime ovulatory cycles and the need for repeated measurements of inflammatory biomarkers across the life course if we wish to understand pathogenic processes linking reproductive factors to subsequent chronic disease. [ABSTRACT FROM AUTHOR]

In this issue of the American Journal of Epidemiology , Huang et al. (Am J Epidemiol. 2020;189(7):660–670) report an inverse relationship between lifetime ovulatory years (LOY) and circulating levels of C-reactive protein (CRP), counter to their hypothesis. CRP is a nonspecific systemic marker of chronic inflammation, and there is evidence that there are other drivers of systemic inflammation as measured by CRP. There also is a body of evidence supporting the possibility that ovulation may be responsible for a localized inflammatory response. Because ovarian cancer is the fifth most common cause of cancer death in women, preventive strategies are urgently needed. The findings of this report underscore the need for new research initiatives to determine the relationship between incessant ovulation and ovarian cancer risk in order to identify mechanisms of carcinogenesis. [ABSTRACT FROM AUTHOR]

Loss to follow-up is an endemic feature of time-to-event analyses that precludes observation of the event of interest. To our knowledge, in typical cohort studies with encounters occurring at regular or irregular intervals, there is no consensus on how to handle person-time between participants' last study encounter and the point at which they meet a definition of loss to follow-up. We demonstrate, using simulation and an example, that when the event of interest is captured outside of a study encounter (e.g., in a registry), person-time should be censored when the study-defined criterion for loss to follow-up is met (e.g., 1 year after last encounter), rather than at the last study encounter. Conversely, when the event of interest must be measured within the context of a study encounter (e.g., a biomarker value), person-time should be censored at the last study encounter. An inappropriate censoring scheme has the potential to result in substantial bias that may not be easily corrected. [ABSTRACT FROM AUTHOR]

Evidence indicates that gaining weight in adult life is associated with an elevated risk of colorectal cancer; however, biological mechanisms that may explain this association remain unclear. We evaluated the mediation effect of 20 different biomarkers on the relationship between adult weight gain and colorectal cancer, using data from a prospective nested case-control study of 452 incident cases diagnosed between 1992 and 2003 and matched within risk sets to 452 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The proportions of mediated effects (%) were estimated on the basis of differences in percent effect changes in conditional logistic regression models with and without additional adjustment for individual biomarkers. Greater adult weight gain (≥300 g/year vs. <300 g/year) was associated with a higher risk of colon cancer (multivariableadjusted relative risk = 1.54, 95% confidence interval: 1.07, 2.24) but not rectal cancer (relative risk = 1.07, 95% confidence interval: 0.68, 1.66). This association was accounted for mostly by attained waist circumference (reduction of 61%) and by the biomarkers soluble leptin receptor (reduction of 43%) and glycated hemoglobin (reduction of 28%). These novel data suggest that the observed association between adult weight gain and colon cancer could be primarily explained by attained abdominal fatness and biomarkers of metabolic dysfunction. [ABSTRACT FROM AUTHOR]

Limitations of extant research on neighborhood disadvantage and health include general reliance on point-intime neighborhood measures and sensitivity to residential self-selection. Using data from the US Census and the 1995-2008 National Longitudinal Study of Adolescent to Adult Health, we applied conventional methods and coarsened exact matching to assess how cardiometabolic health varies among those entering, exiting, or remaining in poor and nonpoor neighborhoods. Within the full sample (n = 11,767), we found significantly higher systolic and diastolic blood pressures among those who entered or consistently lived in poor neighborhoods relative to those who never lived in poor neighborhoods. Obesity was similarly more common among those who originated from poor neighborhoods than among those who originated from nonpoor neighborhoods. Having exited poor neighborhoods was associated with lower systolic blood pressure than was consistent residence in low-income communities. Among the matched sample (n = 9,727), results adjusted for confounders and residential selfselection revealed fewer significant contrasts. Compared with peers who had no neighborhood poverty exposure, those who consistently lived in poor neighborhoods had 46% and 52% higher odds of being obese or hypertensive, respectively. Those who exited neighborhood poverty had significantly higher diastolic blood pressures than those who had never lived in poor neighborhoods. These findings underscore the importance of past as well as current residential circumstances for cardiometabolic health. [ABSTRACT FROM AUTHOR]

At high levels, inorganic arsenic exposure is linked to peripheral arterial disease (PAD) and cardiovascular disease. To our knowledge, no prior study has evaluated the association between low-to-moderate arsenic exposure and incident PAD by ankle brachial index (ABI). We evaluated this relationship in the Strong Heart Study, a large population-based cohort study of American Indian communities. A total of 2,977 and 2,966 PAD-free participants who were aged 45-74 years in 1989-1991 were reexamined in 1993-1995 and 1997-1999, respectively, for incident PAD defined as either ABI <0.9 or ABI >1.4. A total of 286 and 206 incident PAD cases were identified for ABI <0.9 and ABI >1.4, respectively. The sum of inorganic and methylated urinary arsenic species (ΣAs) at baseline was used as a biomarker of long-term exposure. Comparing the highest tertile of ΣAs with the lowest, the adjusted hazard ratios were 0.57 (95% confidence interval (CI): 0.32, 1.01) for ABI <0.9 and 2.24 (95% CI: 1.01, 4.32) for ABI >1.4. Increased arsenic methylation (as percent dimethylarsinate) was associated with a 2-fold increased risk of ABI >1.4 (hazard ratio = 2.04, 95% CI: 1.02, 3.41). Long-term low-to-moderate ΣAs and increased arsenic methylation were associated with ABI >1.4 but not with ABI <0.9. Further studies are needed to clarify whether diabetes and enhanced arsenic metabolism increase susceptibility to the vasculotoxic effects of arsenic exposure. [ABSTRACT FROM AUTHOR]

Recent studies suggest that epigenetic programming may mediate the relationship between early life environment, including parental socioeconomic position, and adult cardiometabolic health. However, interpreting associations between early environment and adult DNA methylation may be difficult because of time-dependent confounding by life-course exposures. Among 613 adult women (mean age = 32 years) of the Jerusalem Perinatal Study Family Follow-up (2007-2009), we investigated associations between early life socioeconomic position (paternal occupation and parental education) and mean adult DNA methylation at 5 frequently studied cardiometabolic and stress-response genes (ABCA1, INS-IGF2, LEP, HSD11B2, and NR3C1). We used multivariable linear regression and marginal structural models to estimate associations under 2 causal structures for life-course exposures and timing of methylation measurement. We also examined whether methylation was associated with adult cardiometabolic phenotype. Higher maternal education was consistently associated with higher HSD11B2 methylation (e.g., 0.5%-point higher in 9-12 years vs. ≤8 years, 95% confidence interval: 0.1, 0.8). Higher HSD11B2 methylation was also associated with lower adult weight and total and low-density lipoprotein cholesterol. We found that associations with early life socioeconomic position measures were insensitive to different causal assumption; however, exploratory analysis did not find evidence for a mediating role of methylation in socioeconomic position-cardiometabolic risk associations. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Application of a repeat-measure biomarker measurement error model to 2 validation studies: Examination of the effect of within-person variation in biomarker measurements" by Sarah Rosner Preis and colleagues in the March 15, 2011 issue.

Previous studies have suggested an association between fetal growth restriction and the risk of spontaneous preterm birth (sPTB). However, addressing this association is methodologically challenging. We conducted a prospective cohort study of nulliparous women with a singleton pregnancy in Cambridge, United Kingdom (2008-2012). Ultrasonic fetal biometry was performed at 20 weeks of gestation as per routine clinical care. Participants also had blinded research ultrasonography performed at approximately 28 weeks. Biometric measurements were expressed as gestational-age-adjusted z scores. Fetal growth velocity was quantified by change in z score between 20 weeks and 28 weeks. Risk of sPTB, defined as delivery at ≥28 weeks and <37 weeks associated with labor in the absence of induction, was analyzed using cause-specific Cox regression. Of 3,892 women, 98 (2.5%) had sPTB. When compared with the other decile groups, the lowest decile of growth velocity of the fetal femur between 20 and 28 weeks was associated with increased risk of sPTB (hazard ratio = 2.37, 95% confidence interval: 1.43, 3.93; P < 0.001). Adjustment for maternal characteristics had no material effect (hazard ratio = 2.50, 95% confidence interval: 1.50, 4.14; P < 0.001). There were no significant associations between other fetal measurements and risk of sPTB. To conclude, slow growth velocity of the fetal femur is associated with an increased risk of sPTB. [ABSTRACT FROM AUTHOR]

The role of inhalation behaviors as predictors of nicotine uptake was examined in the Pennsylvania Adult Smoking Study (2012-2014), a study of 332 adults whose cigarette smoking was measured in a naturalistic environment (e.g., at home) with portable handheld topography devices. Piecewise regression analyses showed that levels of salivary continence, Trans-3'-hydroxycotinine, and total salivary nicotine metabolites (cotinine + trans-3'- hydroxycotinine) increased linearly up to a level of about 1 pack per day (20 cigarettes per day (CPD)) (P < 0.01). Total daily puff volume (TDPV; in mL) (P < 0.05) and total daily number of puffs (P < 0.05), but not other topographical measures, increased linearly with CPD up to a level of about 1 pack per day. The mean level of cotinine per cigarette did not change above 20 CPD and was 36% lower in heavy smokers (≥20 CPD) than in lighter smokers (<20 CPD) (15.6 ng/mL vs. 24.5 ng/mL, respectively; P < 0.01). Mediation models showed that TDPV accounted for 43%-63% of the association between CPD and nicotine metabolites for smokers of <20 CPD. TDPV was the best predictor of nicotine metabolite levels in light-to-moderate smokers (1-19 CPD). In contrast, neither CPD, total daily number of puffs, nor TDPV predicted nicotine metabolite levels above 20 CPD (up to 40 CPD). Finally, although light smokers are traditionally considered less dependent on nicotine, these findings suggest that they are exposed to more nicotine per cigarette than are heavy smokers due to more frequent, intensive puffing. [ABSTRACT FROM AUTHOR]

In interdisciplinary biomedical, epidemiologic, and population research, it is increasingly necessary to consider pathogenesis and inherent heterogeneity of any given health condition and outcome. As the unique disease principle implies, no single biomarker can perfectly define disease subtypes. The complex nature of molecular pathology and biology necessitates biostatistical methodologies to simultaneously analyze multiple biomarkers and subtypes. To analyze and test for heterogeneity hypotheses across subtypes defined by multiple categorical and/or ordinal markers, we developed a meta-regression method that can utilize existing statistical software for mixed-model analysis. This method can be used to assess whether the exposure-subtype associations are different across subtypes defined by 1 marker while controlling for other markers and to evaluate whether the difference in exposure-subtype association across subtypes defined by 1 marker depends on any other markers. To illustrate this method in molecular pathological epidemiology research, we examined the associations between smoking status and colorectal cancer subtypes defined by 3 correlated tumor molecular characteristics (CpG island methylator phenotype, microsatellite instability, and the B-Raf protooncogene, serine/threonine kinase (BRAF), mutation) in the Nurses' Health Study (1980-2010) and the Health Professionals Follow-up Study (1986-2010). This method can be widely useful as molecular diagnostics and genomic technologies become routine in clinical medicine and public health. [ABSTRACT FROM AUTHOR]

We pooled data from 5 large validation studies (1999-2009) of dietary self-report instruments that used recovery biomarkers as referents, to assess food frequency questionnaires (FFQs) and 24-hour recalls (24HRs). Here we report on total potassium and sodium intakes, their densities, and their ratio. Results were similar by sex but were heterogeneous across studies. For potassium, potassium density, sodium, sodium density, and sodium:potassium ratio, average correlation coefficients for the correlation of reported intake with true intake on the FFQs were 0.37, 0.47, 0.16, 0.32, and 0.49, respectively. For the same nutrients measured with a single 24HR, they were 0.47, 0.46, 0.32, 0.31, and 0.46, respectively, rising to 0.56, 0.53, 0.41, 0.38, and 0.60 for the average of three 24HRs. Average underreporting was 5%-6% with an FFQ and 0%-4% with a single 24HR for potassium but was 28%-39% and 4%-13%, respectively, for sodium. Higher body mass index was related to under reporting of sodium. Calibration equations for true intake that included personal characteristics provided improved prediction, except for sodium density. In summary, self-reports capture potassium intake quite well but sodium intake less well. Using densities improves the measurement of potassium and sodium on an FFQ. Sodium:potassium ratio is measured much better than sodium itself on both FFQs and 24HRs. [ABSTRACT FROM AUTHOR]

Total energy consumption and activity-related energy expenditure (AREE) estimates that have been calibrated using biomarkers to correct for measurement error were simultaneously associated with the risks of cardiovascular disease, cancer, and diabetes among postmenopausal women who were enrolled in the Women's Health Initiative at 40 US clinical centers and followed from 1994 to the present. Calibrated energy consumption was found to be positively related, and AREE inversely related, to the risks of various cardiovascular diseases, cancers, and diabetes. These associations were not evident in most corresponding analyses that did not correct for measurement error. However, an important analytical caveat relates to the role of body mass index (BMI) (weight (kg)/height (m)2). In the calibrated variable analyses, BMI was regarded, along with self-reported data, as a source of information on energy consumption and physical activity, and BMI was otherwise excluded from the disease risk models. This approach cannot be fully justified with available data, and the analyses herein imply a need for improved dietary and physical activity assessment methods and for longitudinal self-reported and biomarker data to test and relax modeling assumptions. Estimated hazard ratios for 20% increases in total energy consumption and AREE, respectively, were as follows: 1.49 (95% confidence interval: 1.18, 1.88) and 0.80 (95% confidence interval: 0.69, 0.92) for total cardiovascular disease; 1.43 (95% confidence interval: 1.17, 1.73) and 0.84 (95% confidence interval: 0.73, 0.96) for total invasive cancer; and 4.17 (95% confidence interval: 2.68, 6.49) and 0.60 (95% confidence interval: 0.44, 0.83) for diabetes. [ABSTRACT FROM PUBLISHER]

We pooled data from 5 large validation studies of dietary self-report instruments that used recovery biomarkers as references to clarify the measurement properties of food frequency questionnaires (FFQs) and 24-hour recalls. The studies were conducted in widely differing US adult populations from 1999 to 2009. We report on total energy, protein, and protein density intakes. Results were similar across sexes, but there was heterogeneity across studies. Using a FFQ, the average correlation coefficients for reported versus true intakes for energy, protein, and protein density were 0.21, 0.29, and 0.41, respectively. Using a single 24-hour recall, the coefficients were 0.26, 0.40, and 0.36, respectively, for the same nutrients and rose to 0.31, 0.49, and 0.46 when three 24-hour recalls were averaged. The average rate of under-reporting of energy intake was 28% with a FFQ and 15% with a single 24-hour recall, but the percentages were lower for protein. Personal characteristics related to under-reporting were body mass index, educational level, and age. Calibration equations for true intake that included personal characteristics provided improved prediction. This project establishes that FFQs have stronger correlations with truth for protein density than for absolute protein intake, that the use of multiple 24-hour recalls substantially increases the correlations when compared with a single 24-hour recall, and that body mass index strongly predicts under-reporting of energy and protein intakes. [ABSTRACT FROM PUBLISHER]

Second-generation assays for anti-cyclic citrullinated peptide (anti-CCP), a highly sensitive and specific marker for rheumatoid arthritis (RA), have redefined the epidemiology of RA. In the Women's Health Initiative (WHI) RA study (2009–2011), we evaluated the prevalence of anti-CCP positivity among 15,691 (10.2% of 161,808) WHI participants aged 50–79 years who reported RA. Using stored baseline specimens, we measured serum anti-CCP, rheumatoid factor (RF), and antinuclear antibody in a defined sample of 9,988 of black, white, and Hispanic women. In a subset of women, we measured plasma cytokine levels and number of copies of the human leukocyte antigen (HLA)-DRB1 (HLA-DRB1) shared epitope in DNA by means of Luminex polymerase chain reaction typing (Luminex Corporation, Austin, Texas). We validated classification of probable clinical RA in 2 clinics as anti-CCP positivity or self-reported validated use of disease-modifying antirheumatic drugs (DMARDs). The prevalence of anti-CCP positivity was 8.1%, and the prevalence of RF positivity was approximately 16.0%. DMARD use including prednisone was reported by 1,140 (11.4%) participants (841 excluding prednisone) but by 57.5% of anti-CCP-positive women. The prevalence of 2 shared epitopes was also much higher for anti-CCP-positive women (18.2%, as opposed to only 5.5% for women with anti-CCP-negative DMARD-positive RA and 6.6% for anti-CCP-negative, RF-negative DMARD nonusers). Median cytokine levels were much higher for anti-CCP-positive/RF-positive women. Women with anti-CCP-positive RA and anti-CCP-negative RA had different characteristics with regard to HLA shared epitope, cigarette smoking, and inflammation (cytokines). [ABSTRACT FROM AUTHOR]

Given that the primordial ovarian follicular pool is established in utero, it may be influenced by parental characteristics and the intrauterine environment. Anti-Müllerian hormone (AMH) levels are increasingly recognized as a biomarker of ovarian reserve in females in adulthood and adolescence. We examined and compared associations of maternal and paternal prenatal exposures with AMH levels in adolescent (mean age, 15.4 years) female offspring (n = 1,399) using data from the Avon Longitudinal Study of Parents and Children, a United Kingdom birth cohort study that originated in 1991 and is still ongoing (data are from 1991–2008). The median AMH level was 3.67 ng/mL (interquartile range: 2.46–5.57). Paternal but not maternal smoking prior to and during pregnancy were inversely associated with AMH levels. No or irregular maternal menstrual cycles before pregnancy were associated with higher AMH levels in daughter during adolescence. High maternal gestational weight gain (top fifth versus the rest of the distribution) was associated with lower AMH levels in daughters. Parental age, body mass index, and alcohol intake during pregnancy, child's birth weight, and maternal parity and time to conception were not associated with daughters' AMH levels. Our results suggest that some parental preconceptual characteristics and environmental exposures while the child is in utero may influence the long-term ovarian development and function in female offspring. [ABSTRACT FROM PUBLISHER]