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Fetal alcohol spectrum disorders (FASD) describe a range of physical, behavioral, and neurologic deficits in individuals exposed to alcohol prenatally. Reduced palpebral fissure length is one of the cardinal facial features of FASD. However, other ocular measurements have not been studied extensively in FASD. Using the Fetal Alcohol Syndrome Epidemiologic Research (FASER) database, we investigated how inner canthal distance (ICD), interpupillary distance (IPD), and outer canthal distance (OCD) centiles differed between FASD and non-FASD individuals. We compared ocular measurement centiles in children with FASD to non-FASD individuals and observed reductions in all three centiles for ICD, IPD, and OCD. However, when our non-FASD children who had various forms of growth deficiency (microcephaly, short-stature, or underweight) were compared to controls, we did not observe a similar reduction in ocular measurements. This suggests that reductions in ocular measurements are a direct effect of alcohol on ocular development independent of its effect on growth parameters, which is consistent with animal models showing a negative effect of alcohol on developing neural crest cells. Interpupillary distance centile appeared to be the most significantly reduced ocular measure we evaluated, suggesting it may be a useful measure to be considered in the diagnosis of FASD.

As attrition of telomeres, DNA caps that protect chromosome integrity, is accelerated by various forms of stress, telomere length (TL) has been proposed as an indicator of lifetime accumulated stress. In ecological studies, it has been used to provide insights into ageing, life history trade-offs, the costs of reproduction and disease. qPCR is a high-throughput and cost-effective tool to measure relative TL (rTL) that can be applied to newly collected and archived ecological samples. However, qPCR is susceptible to error both from the method itself and pre-analytical steps. Here, repeatability was assessed overall and separately across multiple levels (intra-assay, inter-assay and inter-extraction) to elucidate the causes of measurement error, as a step towards improving precision. We also tested how accuracy, defined as the correlation between the "gold standard" for TL estimation (telomere restriction fragment length analysis with in-gel hybridization), could be improved. We find qPCR repeatability (intra- and inter-assay levels) to be at similar levels across three common storage media (ethanol, Longmire's and Queen's). However, inter-extraction repeatability was 50% lower for samples stored in Queen's lysis buffer, indicating storage medium can influence precision. Precision as well as accuracy could be increased by estimating rTL from multiple qPCR reactions and from multiple extractions. Repetition increased statistical power equivalent to a 25% (single extraction analysed twice) and 17% (two extractions) increase in sample size. Overall, this study identifies novel sources of variability in high-throughput telomere quantification and provides guidance on sampling strategy design and how to increase rTL precision and accuracy.

Background Moderate alcohol consumption has been associated with a lower risk of cardiovascular disease (CVD) and all‐cause mortality compared with heavy drinkers and abstainers. To date, studies have relied on self‐reported consumption, which may be prone to misclassification. Urinary ethyl glucuronide (EtG) is an alcohol metabolite and validated biomarker for recent alcohol consumption. We aimed to examine and compare the associations of self‐reported alcohol consumption and EtG with CVD and all‐cause mortality. Methods and Results In 5676 participants of the PREVEND (Prevention of Renal and Vascular End‐Stage Disease) study cohort, EtG was measured in 24‐hour urine samples and alcohol consumption questionnaires were administered. Participants were followed up for occurrence of first CVD and all‐cause mortality. Cox proportional hazards regression models, adjusted for age, sex, and CVD risk factors, were fitted for self‐reported consumption, divided into 5 categories: abstention, 1 to 4 units/month (reference), 2 to 7 units/week, 1 to 3 units/day, and ≥4 units/day. Similar models were fitted for EtG, analyzed as both continuous and categorical variables. Follow‐up times differed for CVD (8 years; 385 CVD events) and all‐cause mortality (14 years; 724 deaths). For both self‐reported alcohol consumption and EtG, nonsignificant trends were found toward J‐shaped associations between alcohol consumption and CVD, with higher risk in the lowest (hazard ratio for abstention versus 1–4 units/month, 1.42; 95% CI, 1.02–1.98) and highest drinking categories (hazard ratio for ≥4 units/day versus 1–4 units/month, 1.11; 95% CI, 0.68–1.84). Neither self‐report nor EtG was associated with all‐cause mortality. Conclusions Comparable associations with CVD events and all‐cause mortality were found for self‐report and EtG. This argues for the validity of self‐reported alcohol consumption in epidemiologic research.

Aims The aim of most pelvic floor disorders (PFD) research is to obtain an unbiased effect estimate and to make causal inferences. New developments in epidemiologic research, including the use of causal directed acyclic graphs (DAGs), have shown that traditional analytical strategies for research can be inadequate, leading to unintended consequences such as introducing additional bias. Although DAGs have been proven to be useful in other medical fields, their use has been limited in PFD research. The aim of this paper is to introduce DAGs and then demonstrate their application in PFD research. This paper will also illustrate how relying purely on statistical techniques can lead to pitfalls in reducing bias in research studies. Methods/Results DAGs are a graphical epidemiologic tool that provide a method to select for potential confounders and minimize bias in the design and analysis of research studies. We start by providing an introduction to DAGs. We then describe six scenarios in PFD research in which DAGs can be helpful: (1) identifying appropriate confounding variables for adjustment; (2) identifying potential over-adjustment when conditioning on a mediator; (3) identifying unintended confounding due to inappropriate adjustment; (4) identifying unintended selection bias due to inappropriate adjustment; (5) planning analyses in cross-sectional studies; and (6) using DAGs as a framework to help plan data collection and analyses in PFD research. Conclusions We demonstrate how the application of DAGs as an aid to PFD research can help to decrease bias and discuss the insights and implications for study design and analytical approaches. Neurourol. Urodynam. 31:115–120, 2012. © 2011 Wiley Periodicals, Inc.

Summary Research aimed at deciphering the aetiology of obesity and the metabolic syndrome remains focused on two behavioural factors, namely diet and physical activity, even though epidemiologic research suggests that these two cornerstones of treatment and prevention account for only a small-to-moderate portion of the variance in these phenotypes. In recent years, this observation has prompted the intensified investigation of the pathogenic potential of factors that extend beyond the traditional concept of energy imbalance and examine the putative causes of this imbalance. Psychosocial stress has emerged as one such factor, raising the need for researchers to be informed about this expansive and complex literature. The purpose of this review is twofold (i) To introduce obesity researchers to fundamental concepts and historically important theoretical developments in the stress field and (ii) To outline the dyadic and triadic interactions between stress, physical activity and the metabolic syndrome. Although the expansion of the research focus to multiple, diverse and interacting putative causal agents will certainly increase the complexity of the research enterprise, this step seems essential for the comprehension and effective response to the continuing rise in the prevalence of obesity and the metabolic syndrome.

K x-ray fluorescence (KXRF) technology has been used to make in vivo measurements of lead in bone for more than three decades. The data obtained are beneficial to research on lead toxicity as well as, in certain circumstances, the practice of occupational and environmental medicine. This paper reviews the impact of KXRF data on epidemiologic research involving lead toxicity and demonstrates that bone lead is and will continue to be a valuable biomarker in addressing long-term health effects related to cumulative exposure. The KXRF system has been improved and upgraded several times ever since it was first used. The consistency of the data obtained from these KXRF systems has been investigated in many studies. This paper provides an overview of the factors that will affect the data generated by the KXRF systems. A calibration problem encountered in one of the major KXRF laboratories is described, and the approach taken to solve the problem is discussed. Despite all the theoretical considerations, there are still some important practical challenges to the intercalibration of KXRF instruments both within the laboratory, and between laboratories. Copyright © 2007 John Wiley & Sons, Ltd.

The United Kingdom General Practice Research Database (GPRD) is an office-based, computer-generated, medical resource designed from its inception to be used for epidemiologic research. A distinct version of the GPRD is maintained by the Boston Collaborative Drug Surveillance Program and has been the source of more than 130 scientific articles primarily addressing drug safety issues. We reviewed evidence related to the validity of the GPRD. Specifically, with our extensive experience with this automated database, we evaluated the quality and completeness of the data that it contains.

To evaluate the effects of physical exercise on breast cancer risk, a large-scale case-referent study of 2376 incident breast cancer cases and 18,977 non-cancer referents was conducted using data from the hospital-based epidemiologic research program at Aichi Cancer Center (HERPACC). To adjust appropriately for possible confounders, we examined the effects within subgroups of the study population. The multivariable-adjusted odds ratio (OR) was 0.81 (95% confidence interval (CI): 0.69-0.94) for twice a week or more regular exercise. We observed a decreased risk of breast cancer for women who regularly exercised for health twice a week or more, irrespective of menopausal status, and were able to detect greater risk reductions within particular subgroups, including women who were parous, without a family history or non-drinkers. Among premenopausal women, a particularly strong protective effect of physical exercise was observed (OR=0.57, 95%CI: 0.28-1.15) for those women whose body mass index (BMI) was high (BMor = 25). In contrast, risk reduction was found (OR=0.71, 95%CI: 0.50-1.01) among postmenopausal women whose BMI was medium (BMI: 22-25). Stratification of history of stomach cancer screening to adjust modifying effects of healthy consciousness allows a more precise assessment of the protective effect of exercise twice a week or more, independent of stomach cancer screening history. This study provides evidence that physical exercise, especially exercise twice a week or more, reduces the risk of breast cancer among Japanese women.

Background To design questionnaires for epidemiologic research among children of migrant farmworkers, researchers need to consider ways to best solicit information about pesticide exposures. Methods Bilingual facilitators conducted five focus groups with either migrant farmworker mothers or their children (age range 8–16 years) in southern Texas and northeastern Colorado. Guided questions were used to assess activities of migrant farmworker children and the ways to best elicit information about exposure to pesticides. Results Participants reported a large number of activities that may potentially expose children to pesticides through both direct and indirect routes. Prompting, indirect questions about chemical use, and use of local and trusted facilitators increased information elicited from focus group participants. Conclusions These focus groups helped to provide information for developing questionnaire items related to pesticide exposure among migrant farmworker children, and highlighted the importance of using bilingual community interviewers and including children as respondents. Am. J. Ind. Med. 40:531–537, 2001. © 2001 Wiley-Liss, Inc.

Misclassification of exposure can lead to biased results in the epidemiologic research. Available methods accounting for misclassification often require the use of a gold standard or assume non-differential misclassification of exposure. We present a regression approach which can detect and account for different types of misclassification when estimating the exposure and disease relationship. This approach uses two imperfect measures of a dichotomous exposure and does not require a gold standard. Standard statistical packages with a logistic regression module can be used for estimation of parameters through the EM algorithm process. Two examples are used to illustrate the methodology.

Measuring exposure levels for epidemiologic research is time consuming and expensive and therefore subjective exposure estimates are sometimes used instead. In this study we related the subjective dust exposure estimates of workers in California agriculture to personal dust exposure measurements. One hundred and twenty-four observations were available for comparison of subjective dust estimates and inhalable dust measurements and 129 observations for comparison of subjective dust estimates and respirable dust measurements. Individual subjective dust estimates showed weak to moderate correlations with measured dust concentrations for both the inhalable (Rs = 0.67) and respirable dust fraction (Rs = 0.36). The within-worker reliability coefficients were low (0.2 and 0.1, respectively). Grouped subjective dust estimates performed better and showed a consistent increase with average measured dust levels, in particular for the inhalable dust fraction (R2 = 0.81). Age, the number of years working in agriculture, education level, the presence of any respiratory symptoms, and the language of the questionnaire did not have a significant independent effect on the relationship between measured dust levels and subjective dust estimates. California agricultural workers appear to be reasonably good at estimating inhalable dust levels, in particular if an average of many different workers is taken, but they are unable to provide good estimates of respirable dust levels. Measuring dust levels remains the preferred option.

An historic perspective on the development of the National Cancer Institute's series of cancer atlases is provided. Emphasis is placed on the role which emergent questions concerning environmental determinants of cancer played in the acquisition and utilization of data resources. Studies which were fielded as a consequence of the atlases are highlighted. The legacy of the collective effort of many persons who worked on the development of the cancer atlases – the facilitation of many current epidemiologic investigations – is discussed.

Report of a workshop held on 18 July 1991 at the National Institutes of Health in Bethesda, MD. Workshop participants were: William J. Blot, National Cancer Institute, Bethesda, MD; Ronald S. Brookmeyer, Johns Hopkins University, Baltimore, MD; Theodore Colton, Boston University, Boston, MA; Genrose D. Copley, National Cancer Institute, Rockville, MD; Mitchell Gail, National Cancer Institute, Rockville, MD; Nancy L. Geller, National Heart, Lung and Blood Institute, Bethesda, MD; Frank E. Harrell, Jr., Duke University, Durham, NC; Marthana Hjortland, National Cancer Institute, Rockville, MD; Elizabeth Holly, Northern California Cancer Center, Belmont, CA; Michel Ibrahim, University of North Carolina, Chapel Hill, NC; Stephen W. Lagakos, Dana-Farber Cancer Institute, Boston, MA (written report only); G. Iris Obrams, National Cancer Institute, Rockville, MD; Wasema Rida, National Institute of Allergy and Infectious Diseases, Rockville, MD; Jonathan Samet, New Mexico Tumor Registry, Albuquerque, NM; Robert F. Woolson, University of Iowa, Iowa City, IA; and Mimi C. Yu, University of Southern California, Los Angeles, CA (Chair).

We review the scope of the scientific discipline genetic epidemiology by considering the steps of genetic epidemiologic research. Starting from the classical definition of genetic epidemiology as provided by Morton and Chung [1978, ISBN-13: 9780125080507], we propose a slightly modernized definition of the term genetic epidemiology.

This review describes the development of periodontal index systems which during the last 50 yr have made it possible to gradually expand our understanding of the etiology and pathogenesis of periodontal diseases. Modern epidemiologic research on the prevalence and severity of periodontal diseases is based on a substantial amount of scientific data collected since the early 1940's. The work of a number of innovative researchers has eventually resulted in the clarification of one unsolved problem after the other. At the same time new ideas have been developed for the inclusion of public health aspects in the epidemiologic analyses. The assessment of periodontal treatment needs has become an issue of great importance in many countries of the world and has initiated a discussion and studies on the role of the possibilities for self-assessment of treatment needs. A completely new area of interest has developed when recent epidemiologic surveys demonstrated a substantial increase in the numbers of elderly people together with a substantial increase in the number of teeth per elderly person.

The assessment of subjects' 'usual' intake of nutrients is important in assessing relationships between diet and disease and in identifying malnourished sub-groups of the populations. Estimation of the variation in intakes within subjects over time ('within variation') has importance in epidemiologic research; estimation of the between subject variation in the sample has use in defining the recommended dietary allowances that take into account the inter-individual differences. This paper estimates the between and within variances in the energy and protein intakes of 1189 Filipino children, based on 4 rounds of 24-hour recall data within a dynamic framework by means of maximum likelihood. The main findings are that the proportion of variation due to the within variance is higher for children from poorer households. Also, from the estimates of dynamic regression models for nutrient intakes of children and adults, it appears that school programmes that provide subsidized foods with good sources of protein to the poorest among school attendees will be cost effective.

The problems of estimation and hypotheses testing on the parameters of two correlated linear models are discussed. Such models are known to have direct applications in epidemiologic research, particularly in the field of family studies. When the data are unbalanced, the maximum-likelihood estimation of the parameters is achieved by adopting a fairly simple numerical algorithm. The asymptotic variances and covariances of the estimators are derived, and the procedures are illustrated on arterial-blood-pressure data from the literature. On traite de l'estimation et de tests d'hypotheses pour les parametres de deux modeles lineaires avec structure de correlation. De tels modeles s'appliquent dans la recherche epidemiologique, plus particulierement dans le domaine des etudes familiales. Un algorithme relativement simple permet d'obtenir les estimateurs de maximum de vraisemblance lorsque les donnees ne sont pas equilibrees. On presente les variances et les covariances asymptotiques des estimateurs. Les methodes sont illustrees a l'aide de donnees publiees a propos de la pression arterielle.

Nested case–control studies refer to a class of cohort sampling designs used in epidemiologic research. This article describes the general principles, analysis methods, statistical properties, and relationship to other approaches. Methods are illustrated by studies from the epidemiological literature. Keywords: case–control studies; cohort studies; failure time data; epidemiology; martingales; matching; partial likelihood; proportional hazards model; sampling; stochastic processes

This entry describes the need for confidentiality in conducting clinical and epidemiologic research, particularly with respect to informational privacy of individuals. Ethical principles (including beneficence, nonmalfeasance, autonomy, and justice) are reviewed, and mention is made of the legal framework and guidelines to prevent the violation of confidentiality. Keywords: privacy; ethics; legal framework; record linkage

The Society for Pediatric Epidemiologic Research: Third Annual Meeting, Snowbird, Utah, 12 Tune 1990

The potential interactions between marine and freshwater harmful algal blooms (HABs) and humans are increasing. Humans are exposed through food, drinking water, and recreational and occupational water use to an increasing number of organisms and their toxins. Nevertheless, the amount of clinical and epidemiologic research concerning acute and chronic human health effects from the HAB organisms and their toxins is relatively sparse. At the same time, the public is increasingly aware of and interested in the potential dangers associated with exposure to HABs. Public health authorities and researchers must respond to these public health concerns. The development of appropriate educational and outreach materials based on limited scientific databases is the challenge of informing the public concerning the possible human health effects of HAB organisms and their toxins, and their prevention. Educational materials developed by a group of researchers and public health personnel for general HABs, Florida Red Tide Toxins (brevetoxins), Cyanobacteria, and Ciguatera are discussed, as well as methods for their dissemination.

A composite review of a series of hospital-based, clinical studies on the prevalence of simultaneous and nonsimultaneous multiple primary cancers, including those in which data were recorded by the life table method for six different series of cancer patients and one "control" series of patients who did not have cancer at first contact is provided. The studies came from Barnes Hospital and the Ellis Fischel State Cancer Hospital (EFSCH) and span the period from 1914 through 1964. The conclusions of the studies support the concept that the presence of one primary cancer neither increases nor decreases the chances for developing additional cancers with the possible exception of a few "target organ" areas. One study of this period showed a nonrandom distribution of patients with multiple primary cancers referred to EFSCH and this observation merits further epidemiologic research.

In the United States about 15% of cancer in men and 5% of cancer in women is probably due to occupational exposures. Yet, among the populations actually exposed, occupational cancer is a major health hazard. Further, occupational carcinogenesis should be studied because of it scientific interest and the likely generalizability of findings to non-occupational exposures. The alert clinician remains the most important source of leads to occupational cancer. When groups of cases occur, particularly cases of rare tumors among relatively young persons, an occupational exposure should be suspect. A reasonably detailed occupation history should be included in every medical record. Formal evaluation, measurement of risk and identification of specific hazards is usually done by epidemiologic methods. Several approaches to the improvement of these methods and, possibly, to disease control are presented.

'Gusella, J., Wexler, N., Conneally, P., Naylor S., et. al.: A polymorphic DNA marker genetically linked to Huntington's Disease, Nature, 306:234-238, November 17, 1983. 2Commission for the Control of Huntington's Disease and its Consequences: Report: Volume II Techincal Report, DHEW Pub. No. (NIH) 78-1502, Washington, D.C., 1977. 3Commission for the Control of Huntington's Disease and its Consequences: Report: Volume I: Overview, DHEW Pub. No. (NIH) 78-1501, Washington, D.C., 1977. 4Hemphill, M.: "Pretesting for Huntington's Disease," Hastings Center Report, 3 (No.3):12-13, June, 1973; MacKay, C. and Shea, J.: "Ethical Considerations in Research on Huntington's Disease," Clinical Research, 24:241-247, 1977. 5President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research: Screening and Counseling for Genetic Conditions, Washington, D.C., February, 1983.

In their article in the July/August 1984 issue of IRB: A Review of Human Subjects Research, Cristina Cann and Kenneth Rothman describe practices of some IRBs in connection with epidemiologic research. The authors charge IRBs with imposing unjustified requirements or conditions (those not required by the current federal regulations). They call on investigators to challenge aggressively imposition of such requirements on their research, both to minimize their own burdens