Confounding factors affect the pathophysiology of eosinophilic esophagitis

Eosinophilic esophagitis is a newly diagnosed esophageal disease in adult and children. The clinical and pathological characteristics of this disease have been established and were recently summarized in the expert clinical guideline published in 2011. In spite of the wide knowledge accumulated on this disease, there are many areas where scientific data are missing, especially in regard to the disease's pathophysiology. Recent publications have suggested that other confounding factors modify the disease and may affect its clinicalphenotypic presentation. Those factors may include place of living, air pollution, race, genetic factors and other. In the present report we discussed and review those confounding factors, the new developments, and what direction we should go to further advance our knowledge of this disease.

Diet and Rat Strain as Factors in Nervous System Function and Influence of Confounders

The necessity for understanding normal human cognitive processes and behavior, and themechanisrns which result in dysfunction in these processes are dependant on utilization of a suitable animal model. In order to develop pharmaceutical agents to alleviate mental disturbances and enable the individual to cope within the norms of society, it is incumbent upon investigators to choose a species in which pharmacokinetic principles are established and resemble those of hurnans. The choice of rats in cognition research studies has specific advantages in that these anirnals possess similar pharrnacodynamic parameters to hurnans. Further advantages include availability, low cost, ease of breeding, maintenance and an extensive literature database which enable comparisons to present findings. However, there are substantial differences in the perforrnance of various rat strains in tasks of learning, memory, attention, and responses to stress or drugs. In addition to rat strain, quantity of thed also exerts profound consequences on animal behavior. The aim of this review is to demonstrate that there are differences in the central nervous systern responsivencess of rat strains to chemicals and these could be related to factors such as source of supplier, type and quantity of feed, or season of the year. It is also evident that the genotype differs amongst strains and this may be responsible for the observed differences in CNS sensitivity to chemicals. Strain differences must be identified and taken into consideration in interpretation of assessrnent of neurobehavioural functions. It is also incumbent upon the investigators to utilize healthy (diet-controlled) animal models.

Environmental tobacco smoke exposure and lung cancer:A systematic review

AIM： To review evidence relating passive smoking to lung cancer risk in never smokers, considering various major sources of bias.METHODS： Epidemiological prospective or case-control studies were identifed which provide estimates of relative risk （RR） and 95%CI for never smokers for one or more of seven different indices of exposure to environmental tobacco smoke （ETS）： The spouse; household; workplace; childhood; travel; social and other; and total. A wide range of study details were entered into a database, and the RRs for each study, including descriptions of the comparisons made, were entered into a linked database. RRs were derived where necessary. Results were entered, where available, for all lung cancer, and for squamous cell cancer and adenocarcinoma. “Most adjusted” results were entered based on results available, adjusted for the greatest number of potential confounding variables. “Least adjusted” results were also entered, with a preference for results adjusted at least for age for prospective studies. A pre-planned series of fxed-effects and random-effects meta-analyses were conducted. Overall analyses and analyses by continent were run for each exposure index,with results for spousal smoking given by sex, and results for childhood exposure given by source of ETS exposure. For spousal exposure, more extensive analyses provide results by various aspects of study design and defnition of the RR. For smoking by the husband （or nearest equivalent）, additional analyses were carried out both for overall risk, and for risk per 10 cigarettes per day smoked by the husband. These adjusted for uncontrolled confounding by four factors （fruit, vegetable and dietary fat consumption, and education）, and corrected for misclassification of smoking status of the wife. For the confounding adjustment, estimates for never smoking women were derived from publications on the relationship of the four factors to both lung cancer risk and at home ETS exposure, and on the correlations between the factors. The bias due to misclassifcation was calculated on the basis that the proportion of ever smokers denying smoking is 10% in Asian studies and 2.5% elsewhere, and that those who deny smoking have the same risk as those who admit it. This approach, justifed in previous work, balances higher true denial rates and lower risk in deniers compared to non-deniers.RESULTS： One hundred and two studies were identifed for inclusion, published in 1981 onwards, 45 in Asia, 31 in North America, 21 in Europe, and fve elsewhere. Eighty-fve were of case-control design and 17 were prospective. Significant （P 〈 0.05） associations were noted, with random-effects of （RR = 1.22, 95%CI： 1.14-1.31, n = 93） for smoking by the husband （RR = 1.14, 95%CI： 1.01-1.29, n = 45） for smoking by the wife （RR = 1.22, 95%CI： 1.15-1.30, n = 47） for workplace exposure （RR = 1.15, 95%CI： 1.02-1.29, n = 41） for childhood exposure, and （RR = 1.31, 95%CI： 1.19-1.45, n = 48） for total exposure. No signifcant association was seen for ETS exposure in travel （RR = 1.34, 95%CI： 0.94-1.93, n = 8） or in social situations （RR = 1.01, 95%CI： 0.82-1.24, n = 15）. A signifcant negative association （RR = 0.78, 95%CI： 0.64-0.94, n = 8） was seen for ETS exposure in childhood, specifically from the parents. Significant associations were also seen for spousal smoking for both squamous cell carcinoma （RR = 1.44, 95%CI： 1.15-1.80, n = 24） and adenocarcinoma （RR = 1.33,95%CI： 1.17-1.51, n = 30）. Results generally showed marked heterogeneity between studies. For smoking by either the husband or wife, where 119 RR estimates gave an overall estimate of （RR = 1.21, 95%CI： 1.14-1.29）, the heterogeneity was highly significant （P 〈 0.001）, with evidence that the largest RRs were seen in studies published in 1981-89, in small studies （1-49 cases）, and for estimates unadjusted by age. For smoking by the husband, the additional analyses showed that adjustment for the four factors reduced the overall （RR = 1.22, 95%CI： 1.14-1.31） based on 93 estimates to （RR = 1.14, 95%CI： 1.06-1.22）, implying bias due to uncontrolled confounding of 7%. Further correction for misclassification reduced the estimate to a marginally non-signifcant （RR = 1.08, 95%CI： 0.999-1.16）. In the fully adjusted and corrected analyses, there was evidence of an increase in Asia （RR = 1.18, 95%CI： 1.07-1.30, n = 44）, but not in other regions （RR = 0.96, 95%CI： 0.86-1.07, n = 49）. Studies published in the 1980’s, studies providing dose-response data, and studies only providing results unadjusted for age showed elevated RRs, but later published studies, studies not providing dose-response data, and studies adjusting for age did not. The pattern of results for RRs per 10 cigs/d was similar, with no signifcant association in the adjusted and corrected results （RR = 1.03, 95%CI： 0.994-1.07）.CONCLUSION： Most, if not all, of the ETS/lung cancer association can be explained by confounding adjustment and misclassifcation correction. Any causal relationship is not convincingly demonstrated.

A practical guide to promote informatics-driven efficient biotopographic material development

Micro/nano topographic structures have shown great utility in many biomedical areas including cell therapies,tissue engineering,and implantable devices.Computer-assisted informatics methods hold great promise for the design of topographic structures with targeted properties for a specific medical application.To benefit from these methods,researchers and engineers require a highly reusable“one structural parameter-one set of cell responses”database.However,existing confounding factors in topographic cell culture devices seriously impede the acquisition of this kind of data.Through carefully dissecting the confounding factors and their possible reasons for emergence,we developed corresponding guideline requirements for topographic cell culture device development to remove or control the influence of such factors.Based on these requirements,we then suggested potential strategies to meet them.In this work,we also experimentally demonstrated a topographic cell culture device with controlled confounding factors based on these guideline requirements and corresponding strategies.A“guideline for the development of topographic cell culture devices”was summarized to instruct researchers to develop topographic cell culture devices with the confounding factors removed or well controlled.This guideline aims to promote the establishment of a highly reusable“one structural parameter-one set of cell responses”database that could facilitate the application of informatics methods,such as artificial intelligence,in the rational design of future biotopographic structures with high efficacy.

Methods for Population-Based eQTL Analysis in Human Genetics

Gene expression is a critical process in biological system that is influenced and modulated by many factors including genetic variation. Expression Quantitative Trait Loci（e QTL） analysis provides a powerful way to understand how genetic variants affect gene expression. For genome wide e QTL analysis, the number of genetic variants and that of genes are large and thus the search space is tremendous. Therefore, e QTL analysis brings about computational and statistical challenges. In this paper, we provide a comprehensive review of recent advances in methods for e QTL analysis in population-based studies. We first present traditional pairwise association methods, which are widely used in human genetics. To account for expression heterogeneity, we investigate the methods for correcting confounding factors. Next, we discuss newly developed statistical learning methods including Lasso-based models. In the conclusion, we provide an overview of future method development in analyzing e QTL associations. Although we focus on human genetics in this review, the methods are applicable to many other organisms.