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 dev...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.展开更多
Proton pump inhibitors(PPIs)are widely utilized in oncology to treat gastroeso-phageal reflux disease,peptic ulcer disease,and chemotherapy-induced mucosal injury.Emerging evidence has suggested that prolonged use of ...Proton pump inhibitors(PPIs)are widely utilized in oncology to treat gastroeso-phageal reflux disease,peptic ulcer disease,and chemotherapy-induced mucosal injury.Emerging evidence has suggested that prolonged use of PPIs is associated with increased mortality in patients with cancer.The findings of Krishnan et al are proof of this but need to be considered cautiously due to potential confounding factors.This letter raised important methodological concerns,including con-founding by indication,reverse causality,and polypharmacy that can influence the observed association.While PPIs are important in oncology,their advantages and disadvantages should be weighed judiciously by clinicians.Future prospective studies with robust analytical approaches will be required to ascertain more definite causality.展开更多
This paper uses three size metrics,which are collectable during the design phase,to analyze the potentially confounding effect of class size on the associations between object-oriented（OO）metrics and maintainability...This paper uses three size metrics,which are collectable during the design phase,to analyze the potentially confounding effect of class size on the associations between object-oriented（OO）metrics and maintainability.To draw as many general conclusions as possible,the confounding effect of class size is analyzed on 127 C＋＋ systems and 113 Java systems.For each OO metric,the indirect effect that represents the distortion of the association caused by class size and its variance for individual systems is first computed.Then,a statistical meta-analysis technique is used to compute the average indirect effect over all the systems and to determine if it is significantly different from zero.The experimental results show that the confounding effects of class size on the associations between OO metrics and maintainability generally exist,regardless of whatever size metric is used.Therefore,empirical studies validating OO metrics on maintainability should consider class size as a confounding variable.展开更多
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 cl...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.展开更多
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 prov...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.展开更多
Confounding effect is a critical issue in clinical research of otolaryngology because it can distort the research's conclusion. In this review, we introduce the definition of confounding effect, the methods of ver...Confounding effect is a critical issue in clinical research of otolaryngology because it can distort the research's conclusion. In this review, we introduce the definition of confounding effect, the methods of verifying and controlling the effect. Confounding effect can be prevented by research's design, and adjusted by data analysis. Clinicians would be aware and cautious about confounding effect in their research. They would be able to set up a research's design in which appropriate methods have been applied to prevent this effect.They would know how to adjust confounding effect after data collection. It is important to remember that sometimes it is impossible to eliminate confounding effect completely, and statistical method is not a master key. Solid research knowledge and critical thinking of our brain are the most important in controlling confounding effect.展开更多
In this paper, the concept of distribution effect is proposed without the causal diagram. Following the notation of Stone [11], we assume that the exposure treatment X is an unknown deterministic function of the confo...In this paper, the concept of distribution effect is proposed without the causal diagram. Following the notation of Stone [11], we assume that the exposure treatment X is an unknown deterministic function of the confounder set Pa（X） and a random error ε. We discuss sufficient and necessary conditions for homogeneity, collapsibility and nonconfounding for distribution effects and discuss relations among them.展开更多
This letter to editor discusses on the publication on admission hemoglobin level and prognosis of type 2 diabetes mellitus.A comment on published article is raised.The specific confounding conditions on the hemoglobin...This letter to editor discusses on the publication on admission hemoglobin level and prognosis of type 2 diabetes mellitus.A comment on published article is raised.The specific confounding conditions on the hemoglobin level are mentioned.Concerns on clinal application are raised and discussed.展开更多
The author, who has published numerous meta-analyses of epidemiological studies, particularly on tobacco, comments on various aspects of their content. While such meta-analyses, even when well conducted, are more diff...The author, who has published numerous meta-analyses of epidemiological studies, particularly on tobacco, comments on various aspects of their content. While such meta-analyses, even when well conducted, are more difficult to draw inferences from than are meta-analyses of clinical trials, they allow greater insight into an association than do simple qualitative reviews. This editorial starts with a discussion of some problems relating to hypothesis definition. These include the definition of the outcome, the exposure and the population to be considered, as well as the study inclusion and exclusion criteria. Under literature searching, the author argues against restriction to studies published in peer-reviewed journals, emphasising the fact that relevant data may be available from other sources. Problems of identifying studies and double counting are discussed, as are various issues in regard to data entry. The need to check published effect estimates is emphasised, and techniques to calculate estimates from material provided in the source publication are described. Once the data have been collected and an overall effect estimate obtained, tests for heterogeneity should be conducted in relation to different study characteristics. Though some meta-analysts recommend classifying studies by an overall index of study quality, the author prefers to separately investigate heterogeneity by those factors which contribute to the assessment of quality. Reasons why an association may not actually reflect a true causal relationship are also discussed, with the editorial describing techniques for investigating the relevance of confounding, and referring to problems resulting from misclassification of key variables. Misclassification of disease, exposure and confounding variables can all produce a spurious association, as can misclassification of the variable used to determine whether an individual can enter the study, and the author points to techniques to adjust for this. Issues relating to publication bias and the interpretation of "statistically significant" results are also discussed. The editorial should give the reader insight into the difficulties of producing a good meta-analysis.展开更多
The DOE methodology is an effective tool for upgrading the level of measurement and assessment. In any design, planning or control problem the designer is faced with many alternatives. He/she is challenged to develop ...The DOE methodology is an effective tool for upgrading the level of measurement and assessment. In any design, planning or control problem the designer is faced with many alternatives. He/she is challenged to develop design approaches that can meet both quality and cost criteria. The way experiments are designed greatly affects the effective use of the experimental resources and the easiness with which the measured results can be analyzed. This paper does not present new evidence based on designed experiments. Its objective is solely to show how useful application of multifactor experiments is in a variety of circumstances and decision making scenarios. The paper reviews three published examples where this method was used in different contexts: quality control, flexible manufacturing systems (FMS) and logistics systems. The physical experiment has been carried out to improve the quality of a special type of batteries. The simulation experiment has been carried out to investigate the impact of several flexibility factors in a flexible manufacturing system. The numerical value of a complex analytical expression representing a customer oriented logistics performance measure has been calculated for different values of its parameters, i.e. the given numerical values of the investigated factors. It enabled a methodical examination of all factor effects and especially their interactions, thus shedding light on complex aspects of the logistics decision problem. In these examples, cases from different contexts were presented, enabling to view design of experiments as a powerful ingredient for improving decision making in a variety of circumstances.展开更多
Confounding of three binary-variable counterfactual model with directed acyclic graph (DAG) is discussed in this paper. According to the effect between the control variable and the covariate variable, we investigate t...Confounding of three binary-variable counterfactual model with directed acyclic graph (DAG) is discussed in this paper. According to the effect between the control variable and the covariate variable, we investigate three causal counterfactual models: the control variable is independent of the covariate variable, the control variable has the effect on the covariate variable and the covariate variable affects the control variable. Using the ancillary information based on conditional independence hypotheses and ignorability, the sufficient conditions to determine whether the covariate variable is an irrelevant factor or whether there is no confounding in each counterfactual model are obtained.展开更多
The purpose of this study was to determine the effects of skin pigmentation regarding Near Infrared Spectroscopy (NIRS) tissue oxygen saturation values (StO2). The study examined NIRS values in individuals with varyin...The purpose of this study was to determine the effects of skin pigmentation regarding Near Infrared Spectroscopy (NIRS) tissue oxygen saturation values (StO2). The study examined NIRS values in individuals with varying skin pigmentation on the anterior compartment of the lower leg and volar forearm to determine if correlation exists among three NIRS devices, the EQUANOX, Casmed, and INVOS. Skin pigmentation was measured on the anterior lower leg (AL) and volar forearm (VF) of participants using a noninvasive colorimeter that employed reflective spectroscopy to produce a quantitative value for erythema (skin “redness”) and melanin (skin pigment). Muscle oxygenation was measured using three oximetry devices with sensors placed in the same areas. The EQUANOX device showed no significant correlation with skin pigmentation, while the Casmed and INVOS devices showed moderate and significant correlation with skin pigmentation, respectively. Different devices have different abilities to remove confounding variables, such as skin pigmentation and erythema, which may affect clinical decision-making, and affect the use of NIRS technology.展开更多
Fractional factorial split-plot design has been widely used in many fields due to its advantage of saving experimental cost. The general minimum lower order confounding criterion is usually used as one of the attracti...Fractional factorial split-plot design has been widely used in many fields due to its advantage of saving experimental cost. The general minimum lower order confounding criterion is usually used as one of the attractive design criterion for selecting fractional factorial split-plot design. In this paper, we are interested in the theoretical construction methods of the optimal fractional factorial split-plot designs under the general minimum lower order confounding criterion. We present the theoretical construction methods of optimal fractional factorial split-plot designs under general minimum lower order confounding criterion under several conditions.展开更多
Background Dietary variation has been identified as a key contributor to microbiome diversification.However,assessing its true impact in a cross-sectional setting is complicated by biological confounders and methodolo...Background Dietary variation has been identified as a key contributor to microbiome diversification.However,assessing its true impact in a cross-sectional setting is complicated by biological confounders and methodological hurdles.We aimed to estimate the impact of a reduction of dietary variation(dietary convergence)on faecal microbiota composition among individuals consuming a Western-type diet.Methods 18 healthy volunteers recruited in the region of Flanders(Belgium)were followed up for 21 days.Participants were allowed to consume their habitual diet during a baseline and follow-up period(7 and 8 days,respectively),intersected by a 6-day intervention during which dietary options were restricted to oat flakes,whole milk and still water.Faecal samples were collected on a daily basis.Quantitative microbiome profiles were constructed,combining 16S rRNA gene amplicon sequencing with flow cytometry cell counting.Blood samples were taken at the beginning and end of each study week.Results While the intervention did not affect transit time(as assessed through the analysis of stool moisture),consumption of the restricted diet resulted in an increased prevalence of the Bacteroides2 microbiome community type.Microbial load and Faecalibacterium abundance decreased markedly.Despite dietary restrictions,no convergence of microbial communities(reduction of interindividual and intraindividual variation)was observed.The effect size(ES)of the intervention on genus-level microbiome community differentiation was estimated as 3.4%,but substantial interindividual variation was observed(1.67%–16.42%).Conclusion The impact of dietary variation on microbiome composition in a Western population is significant but limited in ES,with notable individual exceptions.Dietary convergence does not invariably translate into interindividual convergence of faecal microbial communities.展开更多
Building simulation(BS)increasingly relies on data-driven models that extract patterns directly from measured data.However,these models often conflate statistical dependency with causal relationship.The idea of a caus...Building simulation(BS)increasingly relies on data-driven models that extract patterns directly from measured data.However,these models often conflate statistical dependency with causal relationship.The idea of a causal lens introduces structural causal diagrams and do-operators to distinguish true causations from spurious associations.The“causal lens”perspective highlights how confounding bias can arise in observational modeling and emphasizes the importance of extracting true causality from building data.This suggests that BS move beyond pattern replication to enable counterfactual reasoning,thereby supporting reliable decision-making.展开更多
In this paper,we consider the regular s-level fractional factorial split-plot(FFSP)designs when the subplot(SP)factors are more important.The idea of general minimum lower-order confounding criterion is applied to suc...In this paper,we consider the regular s-level fractional factorial split-plot(FFSP)designs when the subplot(SP)factors are more important.The idea of general minimum lower-order confounding criterion is applied to such designs,and the general minimum lower-order confounding criterion of type SP(SP-GMC)is proposed.Using a finite projective geometric formulation,we derive explicit formulae connecting the key terms for the criterion with the complementary set.These results are applied to choose optimal FFSP designs under the SP-GMC criterion.Some two-and three-level SP-GMC FFSP designs are constructed.展开更多
A recent study by Lu et al examined the potential benefits of postoperative combined therapy(PCT)using anti-programmed cell death protein-1/PD-ligand-1 and anti-vascular endothelial growth factor agents for patients w...A recent study by Lu et al examined the potential benefits of postoperative combined therapy(PCT)using anti-programmed cell death protein-1/PD-ligand-1 and anti-vascular endothelial growth factor agents for patients with hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC).At the same time,the findings offer important insights;however,several methodological and statistical limitations should be noted.These limitations include selection bias from the study’s retrospective design,variability in treatment regimens,a small sample size,and inadequate monitoring of hepatitis B virus(HBV)reactivation.The study’s conclusions about PCT efficacy warrant cautious interpretation due to unresolved biases.Prospective trials with biomarker stratification are critical to confirm these preliminary findings.These findings underscore the need for prospective,biomarker-driven trials to validate the efficacy of PCT.Future research should prioritize standardized regimens,HBV reactivation monitoring,and global collaborations to optimize therapeutic strategies for HBV-HCC.展开更多
Experimental design is an effective statistical tool that is extensively applied in modern industry,engineering,and science.It is proved that experimental design is a powerful and efficient means to screen the relatio...Experimental design is an effective statistical tool that is extensively applied in modern industry,engineering,and science.It is proved that experimental design is a powerful and efficient means to screen the relationships between input factors and their responses,and to distinguish significant and unimportant factor effects.In many practical situations,experimenters are faced with large experiments having four-level factors.Even though there are several techniques provided to design such experiments,the challenge faced by the experimenters is still daunting.The practice has demonstrated that the existing techniques are highly time-consuming optimization procedures,satisfactory outcomes are not guaranteed,and non-mathematicians face a significant challenge in dealing with them.A new technique that can overcome these defects of the existing techniques is presented in this paper.The results demonstrated that the proposed technique outperformed the current techniques in terms of construction simplicity,computational efficiency and achieving satisfactory results capability.For non-mathematician experimenters,the new technique is much easier and simpler than the current techniques,as it allows them to design optimal large experiments without the recourse to optimization softwares.The optimality is discussed from four basic perspectives:maximizing the dissimilarity among experimental runs,maximizing the number of independent factors,minimizing the confounding among factors,and filling the experimental domain uniformly with as few gaps as possible.展开更多
Excessive urbanization leads to considerable nature deficiency and abundant artificial infrastructure in urban areas,which triggered intensive discussions on people's exposure to green space and outdoor artificial...Excessive urbanization leads to considerable nature deficiency and abundant artificial infrastructure in urban areas,which triggered intensive discussions on people's exposure to green space and outdoor artificial light at night(ALAN).Recent academic progress highlights that people's exposure to green space and outdoor ALAN may be confounders of each other but lacks systematic investigations.This study investigates the associations between people's exposure to green space and outdoor ALAN by adopting the three most used research paradigms:population-level residence-based,individual-level residencebased,and individual-level mobility-oriented paradigms.We employed the green space and outdoor ALAN data of 291 Tertiary Planning Units in Hong Kong for population-level analysis.We also used data from 940 participants in six representative communities for individual-level analyses.Hong Kong green space and outdoor ALAN were derived from high-resolution remote sensing data.The total exposures were derived using the spatiotemporally weighted approaches.Our results confirm that the negative associations between people's exposure to green space and outdoor ALAN are universal across different research paradigms,spatially non-stationary,and consistent among different socio-demographic groups.We also observed that mobility-oriented measures may lead to stronger negative associations than residence-based measures by mitigating the contextual errors of residence-based measures.Our results highlight the potential confounding associations between people's exposure to green space and outdoor ALAN,and we strongly recommend relevant studies to consider both of them in modeling people's health outcomes,especially for those health outcomes impacted by the co-exposure to them.展开更多
文摘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.
文摘Proton pump inhibitors(PPIs)are widely utilized in oncology to treat gastroeso-phageal reflux disease,peptic ulcer disease,and chemotherapy-induced mucosal injury.Emerging evidence has suggested that prolonged use of PPIs is associated with increased mortality in patients with cancer.The findings of Krishnan et al are proof of this but need to be considered cautiously due to potential confounding factors.This letter raised important methodological concerns,including con-founding by indication,reverse causality,and polypharmacy that can influence the observed association.While PPIs are important in oncology,their advantages and disadvantages should be weighed judiciously by clinicians.Future prospective studies with robust analytical approaches will be required to ascertain more definite causality.
基金The National Natural Science Foundation of China(No.60425206,60633010)
文摘This paper uses three size metrics,which are collectable during the design phase,to analyze the potentially confounding effect of class size on the associations between object-oriented（OO）metrics and maintainability.To draw as many general conclusions as possible,the confounding effect of class size is analyzed on 127 C＋＋ systems and 113 Java systems.For each OO metric,the indirect effect that represents the distortion of the association caused by class size and its variance for individual systems is first computed.Then,a statistical meta-analysis technique is used to compute the average indirect effect over all the systems and to determine if it is significantly different from zero.The experimental results show that the confounding effects of class size on the associations between OO metrics and maintainability generally exist,regardless of whatever size metric is used.Therefore,empirical studies validating OO metrics on maintainability should consider class size as a confounding variable.
文摘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.
文摘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.
文摘Confounding effect is a critical issue in clinical research of otolaryngology because it can distort the research's conclusion. In this review, we introduce the definition of confounding effect, the methods of verifying and controlling the effect. Confounding effect can be prevented by research's design, and adjusted by data analysis. Clinicians would be aware and cautious about confounding effect in their research. They would be able to set up a research's design in which appropriate methods have been applied to prevent this effect.They would know how to adjust confounding effect after data collection. It is important to remember that sometimes it is impossible to eliminate confounding effect completely, and statistical method is not a master key. Solid research knowledge and critical thinking of our brain are the most important in controlling confounding effect.
文摘In this paper, the concept of distribution effect is proposed without the causal diagram. Following the notation of Stone [11], we assume that the exposure treatment X is an unknown deterministic function of the confounder set Pa（X） and a random error ε. We discuss sufficient and necessary conditions for homogeneity, collapsibility and nonconfounding for distribution effects and discuss relations among them.
文摘This letter to editor discusses on the publication on admission hemoglobin level and prognosis of type 2 diabetes mellitus.A comment on published article is raised.The specific confounding conditions on the hemoglobin level are mentioned.Concerns on clinal application are raised and discussed.
文摘The author, who has published numerous meta-analyses of epidemiological studies, particularly on tobacco, comments on various aspects of their content. While such meta-analyses, even when well conducted, are more difficult to draw inferences from than are meta-analyses of clinical trials, they allow greater insight into an association than do simple qualitative reviews. This editorial starts with a discussion of some problems relating to hypothesis definition. These include the definition of the outcome, the exposure and the population to be considered, as well as the study inclusion and exclusion criteria. Under literature searching, the author argues against restriction to studies published in peer-reviewed journals, emphasising the fact that relevant data may be available from other sources. Problems of identifying studies and double counting are discussed, as are various issues in regard to data entry. The need to check published effect estimates is emphasised, and techniques to calculate estimates from material provided in the source publication are described. Once the data have been collected and an overall effect estimate obtained, tests for heterogeneity should be conducted in relation to different study characteristics. Though some meta-analysts recommend classifying studies by an overall index of study quality, the author prefers to separately investigate heterogeneity by those factors which contribute to the assessment of quality. Reasons why an association may not actually reflect a true causal relationship are also discussed, with the editorial describing techniques for investigating the relevance of confounding, and referring to problems resulting from misclassification of key variables. Misclassification of disease, exposure and confounding variables can all produce a spurious association, as can misclassification of the variable used to determine whether an individual can enter the study, and the author points to techniques to adjust for this. Issues relating to publication bias and the interpretation of "statistically significant" results are also discussed. The editorial should give the reader insight into the difficulties of producing a good meta-analysis.
文摘The DOE methodology is an effective tool for upgrading the level of measurement and assessment. In any design, planning or control problem the designer is faced with many alternatives. He/she is challenged to develop design approaches that can meet both quality and cost criteria. The way experiments are designed greatly affects the effective use of the experimental resources and the easiness with which the measured results can be analyzed. This paper does not present new evidence based on designed experiments. Its objective is solely to show how useful application of multifactor experiments is in a variety of circumstances and decision making scenarios. The paper reviews three published examples where this method was used in different contexts: quality control, flexible manufacturing systems (FMS) and logistics systems. The physical experiment has been carried out to improve the quality of a special type of batteries. The simulation experiment has been carried out to investigate the impact of several flexibility factors in a flexible manufacturing system. The numerical value of a complex analytical expression representing a customer oriented logistics performance measure has been calculated for different values of its parameters, i.e. the given numerical values of the investigated factors. It enabled a methodical examination of all factor effects and especially their interactions, thus shedding light on complex aspects of the logistics decision problem. In these examples, cases from different contexts were presented, enabling to view design of experiments as a powerful ingredient for improving decision making in a variety of circumstances.
文摘Confounding of three binary-variable counterfactual model with directed acyclic graph (DAG) is discussed in this paper. According to the effect between the control variable and the covariate variable, we investigate three causal counterfactual models: the control variable is independent of the covariate variable, the control variable has the effect on the covariate variable and the covariate variable affects the control variable. Using the ancillary information based on conditional independence hypotheses and ignorability, the sufficient conditions to determine whether the covariate variable is an irrelevant factor or whether there is no confounding in each counterfactual model are obtained.
文摘The purpose of this study was to determine the effects of skin pigmentation regarding Near Infrared Spectroscopy (NIRS) tissue oxygen saturation values (StO2). The study examined NIRS values in individuals with varying skin pigmentation on the anterior compartment of the lower leg and volar forearm to determine if correlation exists among three NIRS devices, the EQUANOX, Casmed, and INVOS. Skin pigmentation was measured on the anterior lower leg (AL) and volar forearm (VF) of participants using a noninvasive colorimeter that employed reflective spectroscopy to produce a quantitative value for erythema (skin “redness”) and melanin (skin pigment). Muscle oxygenation was measured using three oximetry devices with sensors placed in the same areas. The EQUANOX device showed no significant correlation with skin pigmentation, while the Casmed and INVOS devices showed moderate and significant correlation with skin pigmentation, respectively. Different devices have different abilities to remove confounding variables, such as skin pigmentation and erythema, which may affect clinical decision-making, and affect the use of NIRS technology.
文摘Fractional factorial split-plot design has been widely used in many fields due to its advantage of saving experimental cost. The general minimum lower order confounding criterion is usually used as one of the attractive design criterion for selecting fractional factorial split-plot design. In this paper, we are interested in the theoretical construction methods of the optimal fractional factorial split-plot designs under the general minimum lower order confounding criterion. We present the theoretical construction methods of optimal fractional factorial split-plot designs under general minimum lower order confounding criterion under several conditions.
基金funded by CREA grant ZKC7861 of the KU Leuven.SV-S,GK,JFV-C,RYT and JS were funded by a(post)doctoral fellowship from Research Foundation Flanders(FWO-Vlaanderen)GF was funded by the ReALity Innovation Fund,a Research Initiative of the State of Rhineland-Palatinate,GermanyThe Raes Lab received funding from VIB,KU Leuven,the Rega Institute for Medical Research and Novo Nordisk(PRIMA project).
文摘Background Dietary variation has been identified as a key contributor to microbiome diversification.However,assessing its true impact in a cross-sectional setting is complicated by biological confounders and methodological hurdles.We aimed to estimate the impact of a reduction of dietary variation(dietary convergence)on faecal microbiota composition among individuals consuming a Western-type diet.Methods 18 healthy volunteers recruited in the region of Flanders(Belgium)were followed up for 21 days.Participants were allowed to consume their habitual diet during a baseline and follow-up period(7 and 8 days,respectively),intersected by a 6-day intervention during which dietary options were restricted to oat flakes,whole milk and still water.Faecal samples were collected on a daily basis.Quantitative microbiome profiles were constructed,combining 16S rRNA gene amplicon sequencing with flow cytometry cell counting.Blood samples were taken at the beginning and end of each study week.Results While the intervention did not affect transit time(as assessed through the analysis of stool moisture),consumption of the restricted diet resulted in an increased prevalence of the Bacteroides2 microbiome community type.Microbial load and Faecalibacterium abundance decreased markedly.Despite dietary restrictions,no convergence of microbial communities(reduction of interindividual and intraindividual variation)was observed.The effect size(ES)of the intervention on genus-level microbiome community differentiation was estimated as 3.4%,but substantial interindividual variation was observed(1.67%–16.42%).Conclusion The impact of dietary variation on microbiome composition in a Western population is significant but limited in ES,with notable individual exceptions.Dietary convergence does not invariably translate into interindividual convergence of faecal microbial communities.
文摘Building simulation(BS)increasingly relies on data-driven models that extract patterns directly from measured data.However,these models often conflate statistical dependency with causal relationship.The idea of a causal lens introduces structural causal diagrams and do-operators to distinguish true causations from spurious associations.The“causal lens”perspective highlights how confounding bias can arise in observational modeling and emphasizes the importance of extracting true causality from building data.This suggests that BS move beyond pattern replication to enable counterfactual reasoning,thereby supporting reliable decision-making.
基金supported by the National Natural Science Foundation of China(No.12171277,12271294).
文摘In this paper,we consider the regular s-level fractional factorial split-plot(FFSP)designs when the subplot(SP)factors are more important.The idea of general minimum lower-order confounding criterion is applied to such designs,and the general minimum lower-order confounding criterion of type SP(SP-GMC)is proposed.Using a finite projective geometric formulation,we derive explicit formulae connecting the key terms for the criterion with the complementary set.These results are applied to choose optimal FFSP designs under the SP-GMC criterion.Some two-and three-level SP-GMC FFSP designs are constructed.
文摘A recent study by Lu et al examined the potential benefits of postoperative combined therapy(PCT)using anti-programmed cell death protein-1/PD-ligand-1 and anti-vascular endothelial growth factor agents for patients with hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC).At the same time,the findings offer important insights;however,several methodological and statistical limitations should be noted.These limitations include selection bias from the study’s retrospective design,variability in treatment regimens,a small sample size,and inadequate monitoring of hepatitis B virus(HBV)reactivation.The study’s conclusions about PCT efficacy warrant cautious interpretation due to unresolved biases.Prospective trials with biomarker stratification are critical to confirm these preliminary findings.These findings underscore the need for prospective,biomarker-driven trials to validate the efficacy of PCT.Future research should prioritize standardized regimens,HBV reactivation monitoring,and global collaborations to optimize therapeutic strategies for HBV-HCC.
基金partially supported by the UIC Grants(Nos.R201810,R201912 and R202010)the Zhuhai Premier Discipline Grant.
文摘Experimental design is an effective statistical tool that is extensively applied in modern industry,engineering,and science.It is proved that experimental design is a powerful and efficient means to screen the relationships between input factors and their responses,and to distinguish significant and unimportant factor effects.In many practical situations,experimenters are faced with large experiments having four-level factors.Even though there are several techniques provided to design such experiments,the challenge faced by the experimenters is still daunting.The practice has demonstrated that the existing techniques are highly time-consuming optimization procedures,satisfactory outcomes are not guaranteed,and non-mathematicians face a significant challenge in dealing with them.A new technique that can overcome these defects of the existing techniques is presented in this paper.The results demonstrated that the proposed technique outperformed the current techniques in terms of construction simplicity,computational efficiency and achieving satisfactory results capability.For non-mathematician experimenters,the new technique is much easier and simpler than the current techniques,as it allows them to design optimal large experiments without the recourse to optimization softwares.The optimality is discussed from four basic perspectives:maximizing the dissimilarity among experimental runs,maximizing the number of independent factors,minimizing the confounding among factors,and filling the experimental domain uniformly with as few gaps as possible.
基金supported by grants from the Hong Kong Research Grants Council(General Research Fund Grant no.14605920,14611621,14606922Collaborative Research Fund Grant no.C4023-20GF+1 种基金Research Matching Grants RMG 8601219,8601242)a grant from the Research Committee on Research Sustainability of Major Research Grants Council Funding Schemes(3133235)of the Chinese University of Hong Kong.
文摘Excessive urbanization leads to considerable nature deficiency and abundant artificial infrastructure in urban areas,which triggered intensive discussions on people's exposure to green space and outdoor artificial light at night(ALAN).Recent academic progress highlights that people's exposure to green space and outdoor ALAN may be confounders of each other but lacks systematic investigations.This study investigates the associations between people's exposure to green space and outdoor ALAN by adopting the three most used research paradigms:population-level residence-based,individual-level residencebased,and individual-level mobility-oriented paradigms.We employed the green space and outdoor ALAN data of 291 Tertiary Planning Units in Hong Kong for population-level analysis.We also used data from 940 participants in six representative communities for individual-level analyses.Hong Kong green space and outdoor ALAN were derived from high-resolution remote sensing data.The total exposures were derived using the spatiotemporally weighted approaches.Our results confirm that the negative associations between people's exposure to green space and outdoor ALAN are universal across different research paradigms,spatially non-stationary,and consistent among different socio-demographic groups.We also observed that mobility-oriented measures may lead to stronger negative associations than residence-based measures by mitigating the contextual errors of residence-based measures.Our results highlight the potential confounding associations between people's exposure to green space and outdoor ALAN,and we strongly recommend relevant studies to consider both of them in modeling people's health outcomes,especially for those health outcomes impacted by the co-exposure to them.
