“Fecal microbiome in epidemiologic studies” - Letter

We congratulate Sinha et al. on their recent report (1) comparing fecal sample collection methods for epidemiologic studies of the gut microbiome. These data contribute to the increasing body of literature describing robust methodological frameworks for specimen collection and processing (2, 3). However, their claim that fixation of stool using RNAlater® results in “considerable changes to the microbiome diversity” contrasts with previous findings (2, 3), including those from their earlier reports (4, 5). We have previously demonstrated that self-collected stool stabilized with RNAlater® or other fixatives yields high fidelity and reproducibility in compositional profiling of DNA and RNA from shotgun sequence data, compared to immediately-frozen specimens (3). Additionally, fixation offers several distinct advantages crucial for large-scale population-based studies: a straightforward self-collection procedure; sample stabilization without deep-freezing during shipping, receiving, and processing; and versatility for multiple molecular analyses. The authors’ finding that specimens preserved in RNAlater® had poor correlation with immediately frozen specimens (1) could be explained, for example, by improper fixation resulting from an excess of specimen relative to preservative volume (1–2 g:2.5 ml, compared to the manufacturer-recommended ratio of 1 g:5–10 ml; Thermo Fisher Scientific Inc., Waltham, MA)

Atrazine and cancer incidence among pesticide applicators in the agricultural health study (1994-2007).

Atrazine is a triazine herbicide used widely in the United States. Although it is an animal carcinogen, the mechanism in rodents does not appear to operate in humans. Few epidemiologic studies have provided evidence for an association

On robust and efficient designs for risk estimation in epidemiologic studies

We consider the design problem for the estimation of several scalar measures suggested in the epidemiological literature for comparing the success rate in two samples. The designs considered so far in the literature are local in the sense that they depend on the unknown probabilities of success in the two groups and are not necessarily robust with respect to their misspecification. A maximin approach is proposed to obtain efficient and robust designs for the estimation of the relative risk, attributable risk and odds ratio, whenever a range for the success rates can be specified by the experimenter. It is demonstrated that the designs obtained by this method are usually more efficient than the uniform design, which allocates equal sample sizes to the two groups. --two by two table,odds ratio,relativ risk,attributable risk,optimal design,efficient design

Assessing exposure in epidemiologic studies to disinfection by-products in drinking water: report from an international workshop.

The inability to accurately assess exposure has been one of the major shortcomings of epidemiologic studies of disinfection by-products (DBPs) in drinking water. A number of contributing factors include a) limited information on the identity, occurrence, toxicity, and pharmacokinetics of the many DBPs that can be formed from chlorine, chloramine, ozone, and chlorine dioxide disinfection; b) the complex chemical interrelationships between DBPs and other parameters within a municipal water distribution system; and c) difficulties obtaining accurate and reliable information on personal activity and water consumption patterns. In May 2000, an international workshop was held to bring together various disciplines to develop better approaches for measuring DBP exposure for epidemiologic studies. The workshop reached consensus about the clear need to involve relevant disciplines (e.g., chemists, engineers, toxicologists, biostatisticians and epidemiologists) as partners in developing epidemiologic studies of DBPs in drinking water. The workshop concluded that greater collaboration of epidemiologists with water utilities and regulators should be encouraged in order to make regulatory monitoring data more useful for epidemiologic studies. Similarly, exposure classification categories in epidemiologic studies should be chosen to make results useful for regulatory or policy decision making

Epidemiologic Studies of Isoflavones & Mammographic Density

Isoflavones, phytoestrogens in soy beans with estrogen-like properties, have been examined for their cancer protective effects. Mammographic density is a strong predictor of breast cancer. This review summarizes studies that have examined the association between isoflavones and breast density. Observational investigations in Hawaii and Singapore suggest slightly lower breast density among women of Asian descent with regular soy intake, but two larger studies from Japan and Singapore did not observe a protective effect. The findings from seven randomized trials with primarily Caucasian women indicate that soy or isoflavones do not modify mammographic density. Soy foods and isoflavone supplements within a nutritional range do not appear to modify breast cancer risk as assessed by mammographic density

Reconciling animal and human data in a cancer risk assessment of acrylonitrile

Objectives Bioassays of rats exposed to acrylonitrile have consistently detected an elevated incidence of central nervous system (CNS) cancer. In contrast, epidemiologic studies have not found a statistically stable increase in CNS cancer mortality. The purpose of this paper is to examine whether or not CNS cancers predicted from the most appropriate inhalation bioassay in rats are consistent with CNS cancers observed in 3 recent, large epidemiologic studies. Methods A linearized multistage model was fit to dose-response data from a rat inhalation bioassay to estimate carcinogenic potency. This potency was applied to epidemiologic studies of acrylonitrile-exposed workers. After adjustment for less than complete lifetime follow-up in the epidemiologic studies, consistency was examined between CNS cancers predicted by the model fit to the animal data for the exposure levels and sample sizes of the epidemiologicy studies and the CNS cancers observed in the epidemiologic studies. Results The model predicted totals of 17.7, 3.6, and 7.6 CNS cancer deaths for the studies. These predictions were not far from the observed CNS cancer deaths (12, 6, and 6) and were well within their 95% confidence intervals of 6.9—22.3, 2.2—13.1, and 2.2—13.1, respectively. Conclusions The CNS cancer potency estimated from the best available inhalation bioassay was consistent with the observed deaths in the epidemiologic studies as long as continuous lifetime exposure was chosen as the exposure metric. The lack of observed excess in CNS cancer among the studied workers may have been due to low exposures, insufficient follow-up times, or both

Distributions of Human Exposure to Ozone During Commuting Hours in Connecticut using the Cellular Device Network

Epidemiologic studies have established associations between various air pollutants and adverse health outcomes for adults and children. Due to high costs of monitoring air pollutant concentrations for subjects enrolled in a study, statisticians predict exposure concentrations from spatial models that are developed using concentrations monitored at a few sites. In the absence of detailed information on when and where subjects move during the study window, researchers typically assume that the subjects spend their entire day at home, school or work. This assumption can potentially lead to large exposure assignment bias. In this study, we aim to determine the distribution of the exposure assignment bias for an air pollutant (ozone) when subjects are assumed to be static as compared to accounting for individual mobility. To achieve this goal, we use cell-phone mobility data on approximately 400,000 users in the state of Connecticut during a week in July, 2016, in conjunction with an ozone pollution model, and compare individual ozone exposure assuming static versus mobile scenarios. Our results show that exposure models not taking mobility into account often provide poor estimates of individuals commuting into and out of urban areas: the average 8-hour maximum difference between these estimates can exceed 80 parts per billion (ppb). However, for most of the population, the difference in exposure assignment between the two models is small, thereby validating many current epidemiologic studies focusing on exposure to ozone

Epidemiologic studies on arterial calcification : The Rotterdam Study

Cardiovascular disease leads to a high morbidity and mortality and consequently puts a large burden on the health care system. Therefore, early identification of high-risk subjects is needed. Several non-invasive measures of atherosclerosis exist and may be useful in identifying subjects at high risk. Existing non-invasive measures of atherosclerosis include intima media thickness (IMT) and number of plaques of the carotid arteries by ultrasound and the ankle brachial index, measuring peripheral atherosclerosis. The introduction of electron beam computed tomography (EBCT) and multislice computed tomography (MSCT) has enabled the non-invasive visualization and accurate quantification of calcification in different arteries