Duration perception of emotional stimuli: Using evaluative conditioning to avoid sensory confounds.

PubMed

Kliegl, Katrin M; Watrin, Luc; Huckauf, Anke

2015-01-01

It has been found that emotional pictures are estimated to last longer than neutral ones. However, emotional and neutral stimuli often differ in their physical characteristics, too. Since this might also affect time perception, we present a method disentangling a possible confounding regarding the processing of physically different stimulus material. In the evaluative condition paradigm, participants, at first, learnt the association of neutral images with a certain Landolt ring and of emotional images with another Landolt ring with a different gap position. The conditioned Landolt rings were subsequently used in a temporal bisection task. In two experiments, the results revealed a temporal overestimation of Landolt rings conditioned with emotional pictures compared to neutral pictures showing that the temporal overestimation of emotional stimuli cannot be attributed to perceptual differences between neutral and emotional stimuli. The method provides the potential for investigating emotional effects on various perceptual processes.

Beyond total treatment effects in randomised controlled trials: Baseline measurement of intermediate outcomes needed to reduce confounding in mediation investigations.

PubMed

Landau, Sabine; Emsley, Richard; Dunn, Graham

2018-06-01

Random allocation avoids confounding bias when estimating the average treatment effect. For continuous outcomes measured at post-treatment as well as prior to randomisation (baseline), analyses based on (A) post-treatment outcome alone, (B) change scores over the treatment phase or (C) conditioning on baseline values (analysis of covariance) provide unbiased estimators of the average treatment effect. The decision to include baseline values of the clinical outcome in the analysis is based on precision arguments, with analysis of covariance known to be most precise. Investigators increasingly carry out explanatory analyses to decompose total treatment effects into components that are mediated by an intermediate continuous outcome and a non-mediated part. Traditional mediation analysis might be performed based on (A) post-treatment values of the intermediate and clinical outcomes alone, (B) respective change scores or (C) conditioning on baseline measures of both intermediate and clinical outcomes. Using causal diagrams and Monte Carlo simulation, we investigated the performance of the three competing mediation approaches. We considered a data generating model that included three possible confounding processes involving baseline variables: The first two processes modelled baseline measures of the clinical variable or the intermediate variable as common causes of post-treatment measures of these two variables. The third process allowed the two baseline variables themselves to be correlated due to past common causes. We compared the analysis models implied by the competing mediation approaches with this data generating model to hypothesise likely biases in estimators, and tested these in a simulation study. We applied the methods to a randomised trial of pragmatic rehabilitation in patients with chronic fatigue syndrome, which examined the role of limiting activities as a mediator. Estimates of causal mediation effects derived by approach (A) will be biased if one of the three processes involving baseline measures of intermediate or clinical outcomes is operating. Necessary assumptions for the change score approach (B) to provide unbiased estimates under either process include the independence of baseline measures and change scores of the intermediate variable. Finally, estimates provided by the analysis of covariance approach (C) were found to be unbiased under all the three processes considered here. When applied to the example, there was evidence of mediation under all methods but the estimate of the indirect effect depended on the approach used with the proportion mediated varying from 57% to 86%. Trialists planning mediation analyses should measure baseline values of putative mediators as well as of continuous clinical outcomes. An analysis of covariance approach is recommended to avoid potential biases due to confounding processes involving baseline measures of intermediate or clinical outcomes, and not simply for increased precision.

Attachment, attractiveness, and social interaction: a diary study.

PubMed

Tidwell, M C; Reis, H T; Shaver, P R

1996-10-01

To what extent are attachment styles manifested in natural social activity? A total of 125 participants categorized as possessing secure, avoidant, or anxious-ambivalent attachment styles kept structured social interaction diaries for 1 week. Several theoretically important findings emerged. First, compared with secure and anxious-ambivalent persons, avoidant persons reported lower levels of intimacy, enjoyment, promotive interaction, and positive emotions, and higher levels of negative emotions, primarily in opposite-sex interactions. Analyses indicated that avoidant persons may structure social activities in ways that minimize closeness. Second, secure people differentiated more clearly than either insecure group between romantic and other opposite-sex partners. Third, the subjective experiences of anxious-ambivalent persons were more variable than those of the other groups. Finally, the authors examined and rejected the possibility that attachment effects might be confounded with physical attractiveness. These findings suggest that feeling and behaviors that arise during spontaneous, everyday social activity may contribute to the maintenance of attachment styles in adulthood.

On the Confounding Effect of Temperature on Chemical Shift-Encoded Fat Quantification

PubMed Central

Hernando, Diego; Sharma, Samir D.; Kramer, Harald; Reeder, Scott B.

2014-01-01

Purpose To characterize the confounding effect of temperature on chemical shift-encoded (CSE) fat quantification. Methods The proton resonance frequency of water, unlike triglycerides, depends on temperature. This leads to a temperature dependence of the spectral models of fat (relative to water) that are commonly used by CSE-MRI methods. Simulation analysis was performed for 1.5 Tesla CSE fat–water signals at various temperatures and echo time combinations. Oil–water phantoms were constructed and scanned at temperatures between 0 and 40°C using spectroscopy and CSE imaging at three echo time combinations. An explanted human liver, rejected for transplantation due to steatosis, was scanned using spectroscopy and CSE imaging. Fat–water reconstructions were performed using four different techniques: magnitude and complex fitting, with standard or temperature-corrected signal modeling. Results In all experiments, magnitude fitting with standard signal modeling resulted in large fat quantification errors. Errors were largest for echo time combinations near TEinit ≈ 1.3 ms, ΔTE ≈ 2.2 ms. Errors in fat quantification caused by temperature-related frequency shifts were smaller with complex fitting, and were avoided using a temperature-corrected signal model. Conclusion Temperature is a confounding factor for fat quantification. If not accounted for, it can result in large errors in fat quantifications in phantom and ex vivo acquisitions. PMID:24123362

Conflict adaptation in patients diagnosed with schizophrenia.

PubMed

Abrahamse, Elger; Ruitenberg, Marit; Boddewyn, Sarah; Oreel, Edith; de Schryver, Maarten; Morrens, Manuel; van Dijck, Jean-Philippe

2017-11-01

Cognitive control impairments may contribute strongly to the overall cognitive deficits observed in patients diagnosed with schizophrenia. In the current study we explore a specific cognitive control function referred to as conflict adaptation. Previous studies on conflict adaptation in schizophrenia showed equivocal results, and, moreover, were plagued by confounded research designs. Here we assessed for the first time conflict adaptation in schizophrenia with a design that avoided the major confounds of feature integration and stimulus-response contingency learning. Sixteen patients diagnosed with schizophrenia and sixteen healthy, matched controls performed a vocal Stroop task to determine the congruency sequence effect - a marker of conflict adaptation. A reliable congruency sequence effect was observed for both healthy controls and patients diagnosed with schizophrenia. These findings indicate that schizophrenia is not necessarily accompanied by impaired conflict adaptation. As schizophrenia has been related to abnormal functioning in core conflict adaptation areas such as anterior cingulate and dorsolateral prefrontal cortex, further research is required to better understand the precise impact of such abnormal brain functioning at the behavioral level. Copyright © 2017 Elsevier B.V. All rights reserved.

The development of a modified spectral ripple test.

PubMed

Aronoff, Justin M; Landsberger, David M

2013-08-01

Poor spectral resolution can be a limiting factor for hearing impaired listeners, particularly for complex listening tasks such as speech understanding in noise. Spectral ripple tests are commonly used to measure spectral resolution, but these tests contain a number of potential confounds that can make interpretation of the results difficult. To measure spectral resolution while avoiding those confounds, a modified spectral ripple test with dynamically changing ripples was created, referred to as the spectral-temporally modulated ripple test (SMRT). This paper describes the SMRT and provides evidence that it is sensitive to changes in spectral resolution.

Confounding of the Association between Radiation Exposure from CT Scans and Risk of Leukemia and Brain Tumors by Cancer Susceptibility Syndromes.

PubMed

Meulepas, Johanna M; Ronckers, Cécile M; Merks, Johannes; Weijerman, Michel E; Lubin, Jay H; Hauptmann, Michael

2016-01-01

Recent studies linking radiation exposure from pediatric computed tomography (CT) to increased risks of leukemia and brain tumors lacked data to control for cancer susceptibility syndromes (CSS). These syndromes might be confounders because they are associated with an increased cancer risk and may increase the likelihood of CT scans performed in children. We identify CSS predisposing to leukemia and brain tumors through a systematic literature search and summarize prevalence and risk estimates. Because there is virtually no empirical evidence in published literature on patterns of CT use for most types of CSS, we estimate confounding bias of relative risks (RR) for categories of radiation exposure based on expert opinion about the current and previous patterns of CT scans among CSS patients. We estimate that radiation-related RRs for leukemia are not meaningfully confounded by Down syndrome, Noonan syndrome, or other CSS. In contrast, RRs for brain tumors may be overestimated due to confounding by tuberous sclerosis complex (TSC) while von Hippel-Lindau disease, neurofibromatosis type 1, or other CSS do not meaningfully confound. Empirical data on the use of CT scans among CSS patients are urgently needed. Our assessment indicates that associations with leukemia reported in previous studies are unlikely to be substantially confounded by unmeasured CSS, whereas brain tumor risks might have been overestimated due to confounding by TSC. Future studies should identify TSC patients in order to avoid overestimation of brain tumor risks due to radiation exposure from CT scans. ©2015 American Association for Cancer Research.

Manipulability impairs association-memory: revisiting effects of incidental motor processing on verbal paired-associates.

PubMed

Madan, Christopher R

2014-06-01

Imageability is known to enhance association-memory for verbal paired-associates. High-imageability words can be further subdivided by manipulability, the ease by which the named object can be functionally interacted with. Prior studies suggest that motor processing enhances item-memory, but impairs association-memory. However, these studies used action verbs and concrete nouns as the high- and low-manipulability words, respectively, confounding manipulability with word class. Recent findings demonstrated that nouns can serve as both high- and low-manipulability words (e.g., CAMERA and TABLE, respectively), allowing us to avoid this confound. Here participants studied pairs of words that consisted of all possible pairings of high- and low-manipulability words and were tested with immediate cued recall. Recall was worse for pairs that contained high-manipulability words. In free recall, participants recalled more high- than low-manipulability words. Our results provide further evidence that manipulability influences memory, likely occurring through automatic motor imagery. Copyright © 2014 Elsevier B.V. All rights reserved.

Understanding logistic regression analysis.

PubMed

Sperandei, Sandro

2014-01-01

Logistic regression is used to obtain odds ratio in the presence of more than one explanatory variable. The procedure is quite similar to multiple linear regression, with the exception that the response variable is binomial. The result is the impact of each variable on the odds ratio of the observed event of interest. The main advantage is to avoid confounding effects by analyzing the association of all variables together. In this article, we explain the logistic regression procedure using examples to make it as simple as possible. After definition of the technique, the basic interpretation of the results is highlighted and then some special issues are discussed.

Being Forward Not Backward: Lexical Limits to Masked Priming

ERIC Educational Resources Information Center

Davis, Chris; Kim, Jeesun; Forster, Kenneth I.

2008-01-01

This study investigated whether masked priming is mediated by existing memory representations by determining whether nonwords targets would show repetition priming. To avoid the potential confound that nonword repetition priming would be obscured by a familiarity response bias, the standard lexical decision and naming tasks were modified to make…

Iterative Usage of Fixed and Random Effect Models for Powerful and Efficient Genome-Wide Association Studies

PubMed Central

Liu, Xiaolei; Huang, Meng; Fan, Bin; Buckler, Edward S.; Zhang, Zhiwu

2016-01-01

False positives in a Genome-Wide Association Study (GWAS) can be effectively controlled by a fixed effect and random effect Mixed Linear Model (MLM) that incorporates population structure and kinship among individuals to adjust association tests on markers; however, the adjustment also compromises true positives. The modified MLM method, Multiple Loci Linear Mixed Model (MLMM), incorporates multiple markers simultaneously as covariates in a stepwise MLM to partially remove the confounding between testing markers and kinship. To completely eliminate the confounding, we divided MLMM into two parts: Fixed Effect Model (FEM) and a Random Effect Model (REM) and use them iteratively. FEM contains testing markers, one at a time, and multiple associated markers as covariates to control false positives. To avoid model over-fitting problem in FEM, the associated markers are estimated in REM by using them to define kinship. The P values of testing markers and the associated markers are unified at each iteration. We named the new method as Fixed and random model Circulating Probability Unification (FarmCPU). Both real and simulated data analyses demonstrated that FarmCPU improves statistical power compared to current methods. Additional benefits include an efficient computing time that is linear to both number of individuals and number of markers. Now, a dataset with half million individuals and half million markers can be analyzed within three days. PMID:26828793

Effect of information seeking and avoidance behavior on self-rated health status among cancer survivors.

PubMed

Jung, Minsoo; Ramanadhan, Shoba; Viswanath, Kasisomayajula

2013-07-01

Social determinants, such as socioeconomic status (SES) and race/ethnicity are linked to striking health disparities across the cancer continuum. One important mechanism linking social determinants and health disparities may be communication inequalities that are caused by differences in accessing, processing and utilizing cancer information. In this context, we examined health information-seeking/avoidance as a potential mediator between social determinants and self-rated health (SRH) status among cancer survivors. Data came from the 2008 well-informed, thriving and surviving (WITS) study of post-treatment cancer survivors (n=501). We examined the mediating effect of health communication-related behavior between SES and disparities in SRH. The likelihood of belonging to the Low SRH group was higher among patients who had avoided health information and whose family members had not sought health information on behalf of the survivor, those in the lowest household income bracket, and those who had high school or less education after adjusting for potential confounders. Differences in SRH among cancer survivors are associated with SES as well as communication inequalities. It is necessary to provide a supportive environment in which health information is made available if disparities in health-related quality of life among cancer survivors are to be reduced. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The Role of Language in Nonlinguistic Stimuli: Comparing Inhibition in Children with Language Impairment

ERIC Educational Resources Information Center

Roebuck, Hettie; Sindberg, Heidi; Weismer, Susan Ellis

2018-01-01

Purpose: There is conflicting evidence regarding if and how a deficit in executive function may be associated with developmental language impairment (LI). Nonlinguistic stimuli are now frequently used when testing executive function to avoid a language confound. However, it is possible that increased stimulus processing demands for nonlinguistic…

Experimental Design in Clinical 'Omics Biomarker Discovery.

PubMed

Forshed, Jenny

2017-11-03

This tutorial highlights some issues in the experimental design of clinical 'omics biomarker discovery, how to avoid bias and get as true quantities as possible from biochemical analyses, and how to select samples to improve the chance of answering the clinical question at issue. This includes the importance of defining clinical aim and end point, knowing the variability in the results, randomization of samples, sample size, statistical power, and how to avoid confounding factors by including clinical data in the sample selection, that is, how to avoid unpleasant surprises at the point of statistical analysis. The aim of this Tutorial is to help translational clinical and preclinical biomarker candidate research and to improve the validity and potential of future biomarker candidate findings.

Factors influencing tests of auditory processing: a perspective on current issues and relevant concerns.

PubMed

Cacace, Anthony T; McFarland, Dennis J

2013-01-01

Tests of auditory perception, such as those used in the assessment of central auditory processing disorders ([C]APDs), represent a domain in audiological assessment where measurement of this theoretical construct is often confounded by nonauditory abilities due to methodological shortcomings. These confounds include the effects of cognitive variables such as memory and attention and suboptimal testing paradigms, including the use of verbal reproduction as a form of response selection. We argue that these factors need to be controlled more carefully and/or modified so that their impact on tests of auditory and visual perception is only minimal. To advocate for a stronger theoretical framework than currently exists and to suggest better methodological strategies to improve assessment of auditory processing disorders (APDs). Emphasis is placed on adaptive forced-choice psychophysical methods and the use of matched tasks in multiple sensory modalities to achieve these goals. Together, this approach has potential to improve the construct validity of the diagnosis, enhance and develop theory, and evolve into a preferred method of testing. Examination of methods commonly used in studies of APDs. Where possible, currently used methodology is compared to contemporary psychophysical methods that emphasize computer-controlled forced-choice paradigms. In many cases, the procedures used in studies of APD introduce confounding factors that could be minimized if computer-controlled forced-choice psychophysical methods were utilized. Ambiguities of interpretation, indeterminate diagnoses, and unwanted confounds can be avoided by minimizing memory and attentional demands on the input end and precluding the use of response-selection strategies that use complex motor processes on the output end. Advocated are the use of computer-controlled forced-choice psychophysical paradigms in combination with matched tasks in multiple sensory modalities to enhance the prospect of obtaining a valid diagnosis. American Academy of Audiology.

Approach and Avoidance Tendencies Toward Picture Stimuli of (Pre-)Pubescent Children and Adults: An Investigation in Pedophilic and Nonpedophilic Samples.

PubMed

Weidacker, K; Kärgel, C; Massau, C; Weiß, S; Kneer, J; Krueger, T H C; Schiffer, B

2017-03-01

The presence of pedophilic sexual interests is considered of high importance for predicting recidivism among individuals who have committed sexual offenses. However, objective and valid assessment methods that are robust against confounding issues such as cognitive capacity and manipulation are sparse. We applied the Approach-Avoidance Task (AAT) for detecting sexual interests in 38 pedophilic men (18 primarily attracted to boys) and 27 male nonpedophilic (11 gay) participants. The AAT relies on automatic approach and avoidance tendencies, independent of cognitive abilities such as memory capacity and intelligence. Approach-avoidance tendencies toward stimuli depicting seminude prepubescent boys and girls as well as men and women are reported. The results were consistent with previous research on the utility of the AAT: Except for pedophiles attracted to girls, the mean AAT scores (approach minus avoidance reaction time for each stimulus category) were positive only for stimuli of the preferred category. A multivariate binary logistic regression approach revealed 80% overall accuracy in differentiating pedophilic from nonpedophilic participants.

Poppers, Kaposi's sarcoma, and HIV infection: empirical example of a strong confounding effect?

PubMed

Morabia, A

1995-01-01

Are there empirical examples of strong confounding effects? Textbooks usually show examples of weak confounding or use hypothetical examples of strong confounding to illustrate the paradoxical consequences of not separating out the effect of the studied exposure from that of second factor acting as a confounder. HIV infection is a candidate strong confounder of the spuriously high association reported between consumption of poppers, a sexual stimulant, and risk of Kaposi's sarcoma in the early phase of the AIDS epidemic. To examine this hypothesis, assumptions must be made on the prevalence of HIV infection among cases of Kaposi's sarcoma and on the prevalence of heavy popper consumption according to HIV infection in cases and controls. Results show that HIV infection may have confounded the poppers-Kaposi's sarcoma association. However, it cannot be ruled out that HIV did not qualify as a confounder because it was either an intermediate variable or an effect modifier of the association between popper inhalation and Kaposi's sarcoma. This example provides a basis to discuss the mechanism by which confounding occurs as well as the practical importance of confounding in epidemiologic research.

Predicting Adult Physical Illness from Infant Attachment: A Prospective Longitudinal Study

PubMed Central

Puig, Jennifer; Englund, Michelle M.; Simpson, Jeffry A.; Collins, W. Andrew

2012-01-01

Objective Recent epidemiological and longitudinal studies indicate that attachment relationships may be a significant predictor of physical health in adulthood. This study is among the few to prospectively link attachment classifications assessed in infancy to physical health outcomes thirty years later in adulthood, controlling for various health-related confounds. Methods Participants were 163 individuals involved in a 32-year longitudinal study of risk and adaptation who have been followed since birth. Attachment classifications were assessed at ages 12 and 18 months using the Ainsworth Strange Situation Procedure. Stability of attachment security was derived from these assessments. At age 32, participants completed a questionnaire asking about the presence of or treatment for current physical illnesses. Results Binary logistic regression analyses controlling for health-related confounds at age 32 indicated that individuals who were insecurely attached (i.e., anxious-resistant or anxious-avoidant) during infancy were more likely to report an inflammation-based illness in adulthood than those classified as securely attached during infancy. There also was a trend whereby individuals classified as anxious-resistant reported more non-specific symptoms in adulthood than those classified as either anxious-avoidant or secure. Individuals who were continuously insecure during infancy were more likely to report all types of physical illness in adulthood. Conclusion These findings reveal the lasting effect of early interpersonal relationships on physical health and suggests that infancy may be a fruitful point for prevention efforts. The widespread influence that attachment has on endogenous and exogenous health-related processes may make it particularly potent in the prevention of later physical health problems. PMID:22823067

An overview of confounding. Part 1: the concept and how to address it.

PubMed

Howards, Penelope P

2018-04-01

Confounding is an important source of bias, but it is often misunderstood. We consider how confounding occurs and how to address confounding using examples. Study results are confounded when the effect of the exposure on the outcome, mixes with the effects of other risk and protective factors for the outcome. This problem arises when these factors are present to different degrees among the exposed and unexposed study participants, but not all differences between the groups result in confounding. Thinking about an ideal study where all of the population of interest is exposed in one universe and is unexposed in a parallel universe helps to distinguish confounders from other differences. In an actual study, an observed unexposed population is chosen to stand in for the unobserved parallel universe. Differences between this substitute population and the parallel universe result in confounding. Confounding by identified factors can be addressed analytically and through study design, but only randomization has the potential to address confounding by unmeasured factors. Nevertheless, a given randomized study may still be confounded. Confounded study results can lead to incorrect conclusions about the effect of the exposure of interest on the outcome. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

Strange Words: Autistic Traits and the Processing of Non-Literal Language.

PubMed

McKenna, Peter E; Glass, Alexandra; Rajendran, Gnanathusharan; Corley, Martin

2015-11-01

Previous investigations into metonymy comprehension in ASD have confounded metonymy with anaphora, and outcome with process. Here we show how these confounds may be avoided, using data from non-diagnosed participants classified using Autism Quotient. Participants read sentences containing target words with novel or established metonymic senses (e.g., Finland, Vietnam) in literal- or figurative-supporting contexts. Participants took longer to read target words in figurative contexts, especially where the metonymic sense was novel. Importantly, participants with higher AQs took longer still to read novel metonyms. This suggests a focus for further exploration, in terms of potential differences between individuals diagnosed with ASD and their neurotypical counterparts, and more generally in terms of the processes by which comprehension is achieved.

Event-related potentials to event-related words: grammatical class and semantic attributes in the representation of knowledge.

PubMed

Barber, Horacio A; Kousta, Stavroula-Thaleia; Otten, Leun J; Vigliocco, Gabriella

2010-05-21

A number of recent studies have provided contradictory evidence on the question of whether grammatical class plays a role in the neural representation of lexical knowledge. Most of the previous studies comparing the processing of nouns and verbs, however, confounded word meaning and grammatical class by comparing verbs referring to actions with nouns referring to objects. Here, we recorded electrical brain activity from native Italian speakers reading single words all referring to events (e.g., corsa [the run]; correre [to run]), thus avoiding confounding nouns and verbs with objects and actions. We manipulated grammatical class (noun versus verb) as well as semantic attributes (motor versus sensory events). Activity between 300 and 450ms was more negative for nouns than verbs, and for sensory than motor words, over posterior scalp sites. These grammatical class and semantic effects were not dissociable in terms of latency, duration, or scalp distribution. In a later time window (450-110ms) and at frontal regions, grammatical class and semantic effects interacted; motor verbs were more positive than the other three word categories. We suggest that the lack of a temporal and topographical dissociation between grammatical class and semantic effects in the time range of the N400 component is compatible with an account in which both effects reflect the same underlying process related to meaning retrieval, and we link the later effect with working memory operations associated to the experimental task. Copyright 2010 Elsevier B.V. All rights reserved.

Promoting interaction during sociodramatic play: teaching scripts to typical preschoolers and classmates with disabilities.

PubMed

Goldstein, H; Cisar, C L

1992-01-01

We investigated the effects of teaching sociodramatic scripts on subsequent interaction among three triads, each containing 2 typical children and 1 child with autistic characteristics. The same type and rate of teacher prompts were implemented throughout structured play observations to avoid the confounding effects of script training and teacher prompting. After learning the scripts, all children demonstrated more frequent theme-related social behavior. These improvements in social-communicative interaction were replicated with the training of three sociodramatic scripts (i.e., pet shop, carnival, magic show) according to a multiple baseline design. These effects were maintained during the training of successive scripts and when the triads were reconstituted to include new but similarly trained partners. Results provided support for the inclusion of systematic training of scripts to enhance interaction among children with and without disabilities during sociodramatic play.

Effect of motion artifacts and their correction on near-infrared spectroscopy oscillation data: a study in healthy subjects and stroke patients.

PubMed

Selb, Juliette; Yücel, Meryem A; Phillip, Dorte; Schytz, Henrik W; Iversen, Helle K; Vangel, Mark; Ashina, Messoud; Boas, David A

2015-05-01

Functional near-infrared spectroscopy is prone to contamination by motion artifacts (MAs). Motion correction algorithms have previously been proposed and their respective performance compared for evoked rain activation studies. We study instead the effect of MAs on "oscillation" data which is at the basis of functional connectivity and autoregulation studies. We use as our metric of interest the interhemispheric correlation (IHC), the correlation coefficient between symmetrical time series of oxyhemoglobin oscillations. We show that increased motion content results in a decreased IHC. Using a set of motion-free data on which we add real MAs, we find that the best motion correction approach consists of discarding the segments of MAs following a careful approach to minimize the contamination due to band-pass filtering of data from "bad" segments spreading into adjacent "good" segments. Finally, we compare the IHC in a stroke group and in a healthy group that we artificially contaminated with the MA content of the stroke group, in order to avoid the confounding effect of increased motion incidence in the stroke patients. After motion correction, the IHC remains lower in the stroke group in the frequency band around 0.1 and 0.04 Hz, suggesting a physiological origin for the difference. We emphasize the importance of considering MAs as a confounding factor in oscillation-based functional near-infrared spectroscopy studies.

Neuroticism explains unwanted variance in Implicit Association Tests of personality: possible evidence for an affective valence confound.

PubMed

Fleischhauer, Monika; Enge, Sören; Miller, Robert; Strobel, Alexander; Strobel, Anja

2013-01-01

Meta-analytic data highlight the value of the Implicit Association Test (IAT) as an indirect measure of personality. Based on evidence suggesting that confounding factors such as cognitive abilities contribute to the IAT effect, this study provides a first investigation of whether basic personality traits explain unwanted variance in the IAT. In a gender-balanced sample of 204 volunteers, the Big-Five dimensions were assessed via self-report, peer-report, and IAT. By means of structural equation modeling (SEM), latent Big-Five personality factors (based on self- and peer-report) were estimated and their predictive value for unwanted variance in the IAT was examined. In a first analysis, unwanted variance was defined in the sense of method-specific variance which may result from differences in task demands between the two IAT block conditions and which can be mirrored by the absolute size of the IAT effects. In a second analysis, unwanted variance was examined in a broader sense defined as those systematic variance components in the raw IAT scores that are not explained by the latent implicit personality factors. In contrast to the absolute IAT scores, this also considers biases associated with the direction of IAT effects (i.e., whether they are positive or negative in sign), biases that might result, for example, from the IAT's stimulus or category features. None of the explicit Big-Five factors was predictive for method-specific variance in the IATs (first analysis). However, when considering unwanted variance that goes beyond pure method-specific variance (second analysis), a substantial effect of neuroticism occurred that may have been driven by the affective valence of IAT attribute categories and the facilitated processing of negative stimuli, typically associated with neuroticism. The findings thus point to the necessity of using attribute category labels and stimuli of similar affective valence in personality IATs to avoid confounding due to recoding.

A Principled Way of Assessing Visualization Literacy.

PubMed

Boy, Jeremy; Rensink, Ronald A; Bertini, Enrico; Fekete, Jean-Daniel

2014-12-01

We describe a method for assessing the visualization literacy (VL) of a user. Assessing how well people understand visualizations has great value for research (e. g., to avoid confounds), for design (e. g., to best determine the capabilities of an audience), for teaching (e. g., to assess the level of new students), and for recruiting (e. g., to assess the level of interviewees). This paper proposes a method for assessing VL based on Item Response Theory. It describes the design and evaluation of two VL tests for line graphs, and presents the extension of the method to bar charts and scatterplots. Finally, it discusses the reimplementation of these tests for fast, effective, and scalable web-based use.

Examining the Error of Mis-Specifying Nonlinear Confounding Effect with Application on Accelerometer-Measured Physical Activity

ERIC Educational Resources Information Center

Lee, Paul H.

2017-01-01

Purpose: Some confounders are nonlinearly associated with dependent variables, but they are often adjusted using a linear term. The purpose of this study was to examine the error of mis-specifying the nonlinear confounding effect. Methods: We carried out a simulation study to investigate the effect of adjusting for a nonlinear confounder in the…

Examining the Error of Mis-Specifying Nonlinear Confounding Effect With Application on Accelerometer-Measured Physical Activity.

PubMed

Lee, Paul H

2017-06-01

Some confounders are nonlinearly associated with dependent variables, but they are often adjusted using a linear term. The purpose of this study was to examine the error of mis-specifying the nonlinear confounding effect. We carried out a simulation study to investigate the effect of adjusting for a nonlinear confounder in the estimation of a causal relationship between the exposure and outcome in 3 ways: using a linear term, binning into 5 equal-size categories, or using a restricted cubic spline of the confounder. Continuous, binary, and survival outcomes were simulated. We examined the confounder across varying measurement error. In addition, we performed a real data analysis examining the 3 strategies to handle the nonlinear effects of accelerometer-measured physical activity in the National Health and Nutrition Examination Survey 2003-2006 data. The mis-specification of a nonlinear confounder had little impact on causal effect estimation for continuous outcomes. For binary and survival outcomes, this mis-specification introduced bias, which could be eliminated using spline adjustment only when there is small measurement error of the confounder. Real data analysis showed that the associations between high blood pressure, high cholesterol, and diabetes and mortality adjusted for physical activity with restricted cubic spline were about 3% to 11% larger than their counterparts adjusted with a linear term. For continuous outcomes, confounders with nonlinear effects can be adjusting with a linear term. Spline adjustment should be used for binary and survival outcomes on confounders with small measurement error.

An overview of confounding. Part 2: how to identify it and special situations.

PubMed

Howards, Penelope P

2018-04-01

Confounding biases study results when the effect of the exposure on the outcome mixes with the effects of other risk and protective factors for the outcome that are present differentially by exposure status. However, not all differences between the exposed and unexposed group cause confounding. Thus, sources of confounding must be identified before they can be addressed. Confounding is absent in an ideal study where all of the population of interest is exposed in one universe and is unexposed in a parallel universe. In an actual study, an observed unexposed population represents the unobserved parallel universe. Thinking about differences between this substitute population and the unexposed parallel universe helps identify sources of confounding. These differences can then be represented in a diagram that shows how risk and protective factors for the outcome are related to the exposure. Sources of confounding identified in the diagram should be addressed analytically and through study design. However, treating all factors that differ by exposure status as confounders without considering the structure of their relation to the exposure can introduce bias. For example, conditions affected by the exposure are not confounders. There are also special types of confounding, such as time-varying confounding and unfixable confounding. It is important to evaluate carefully whether factors of interest contribute to confounding because bias can be introduced both by ignoring potential confounders and by adjusting for factors that are not confounders. The resulting bias can result in misleading conclusions about the effect of the exposure of interest on the outcome. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

Improving the Power of GWAS and Avoiding Confounding from Population Stratification with PC-Select

PubMed Central

Tucker, George; Price, Alkes L.; Berger, Bonnie

2014-01-01

Using a reduced subset of SNPs in a linear mixed model can improve power for genome-wide association studies, yet this can result in insufficient correction for population stratification. We propose a hybrid approach using principal components that does not inflate statistics in the presence of population stratification and improves power over standard linear mixed models. PMID:24788602

Subliminal action priming modulates the perceived intensity of sensory action consequences.

PubMed

Stenner, Max-Philipp; Bauer, Markus; Sidarus, Nura; Heinze, Hans-Jochen; Haggard, Patrick; Dolan, Raymond J

2014-02-01

The sense of control over the consequences of one's actions depends on predictions about these consequences. According to an influential computational model, consistency between predicted and observed action consequences attenuates perceived stimulus intensity, which might provide a marker of agentic control. An important assumption of this model is that these predictions are generated within the motor system. However, previous studies of sensory attenuation have typically confounded motor-specific perceptual modulation with perceptual effects of stimulus predictability that are not specific to motor action. As a result, these studies cannot unambiguously attribute sensory attenuation to a motor locus. We present a psychophysical experiment on auditory attenuation that avoids this pitfall. Subliminal masked priming of motor actions with compatible prime-target pairs has previously been shown to modulate both reaction times and the explicit feeling of control over action consequences. Here, we demonstrate reduced perceived loudness of tones caused by compatibly primed actions. Importantly, this modulation results from a manipulation of motor processing and is not confounded by stimulus predictability. We discuss our results with respect to theoretical models of the mechanisms underlying sensory attenuation and subliminal motor priming. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Subliminal action priming modulates the perceived intensity of sensory action consequences☆

PubMed Central

Stenner, Max-Philipp; Bauer, Markus; Sidarus, Nura; Heinze, Hans-Jochen; Haggard, Patrick; Dolan, Raymond J.

2014-01-01

The sense of control over the consequences of one’s actions depends on predictions about these consequences. According to an influential computational model, consistency between predicted and observed action consequences attenuates perceived stimulus intensity, which might provide a marker of agentic control. An important assumption of this model is that these predictions are generated within the motor system. However, previous studies of sensory attenuation have typically confounded motor-specific perceptual modulation with perceptual effects of stimulus predictability that are not specific to motor action. As a result, these studies cannot unambiguously attribute sensory attenuation to a motor locus. We present a psychophysical experiment on auditory attenuation that avoids this pitfall. Subliminal masked priming of motor actions with compatible prime–target pairs has previously been shown to modulate both reaction times and the explicit feeling of control over action consequences. Here, we demonstrate reduced perceived loudness of tones caused by compatibly primed actions. Importantly, this modulation results from a manipulation of motor processing and is not confounded by stimulus predictability. We discuss our results with respect to theoretical models of the mechanisms underlying sensory attenuation and subliminal motor priming. PMID:24333539

The same analysis approach: Practical protection against the pitfalls of novel neuroimaging analysis methods.

PubMed

Görgen, Kai; Hebart, Martin N; Allefeld, Carsten; Haynes, John-Dylan

2017-12-27

Standard neuroimaging data analysis based on traditional principles of experimental design, modelling, and statistical inference is increasingly complemented by novel analysis methods, driven e.g. by machine learning methods. While these novel approaches provide new insights into neuroimaging data, they often have unexpected properties, generating a growing literature on possible pitfalls. We propose to meet this challenge by adopting a habit of systematic testing of experimental design, analysis procedures, and statistical inference. Specifically, we suggest to apply the analysis method used for experimental data also to aspects of the experimental design, simulated confounds, simulated null data, and control data. We stress the importance of keeping the analysis method the same in main and test analyses, because only this way possible confounds and unexpected properties can be reliably detected and avoided. We describe and discuss this Same Analysis Approach in detail, and demonstrate it in two worked examples using multivariate decoding. With these examples, we reveal two sources of error: A mismatch between counterbalancing (crossover designs) and cross-validation which leads to systematic below-chance accuracies, and linear decoding of a nonlinear effect, a difference in variance. Copyright © 2017 Elsevier Inc. All rights reserved.

The Problem of Confounding in Studies of the Effect of Maternal Drug Use on Pregnancy Outcome

PubMed Central

Källén, Bengt

2012-01-01

In most epidemilogical studies, the problem of confounding adds to the uncertainty in conclusions drawn. This is also true for studies on the effect of maternal drug use on birth defect risks. This paper describes various types of such confounders and discusses methods to identify and adjust for them. Such confounders can be found in maternal characteristics like age, parity, smoking, use of alcohol, and body mass index, subfertility, and previous pregnancies including previous birth of a malformed child, socioeconomy, race/ethnicity, or country of birth. Confounding by concomitant maternal drug use may occur. A geographical or seasonal confounding can exist. In rare instances, infant sex and multiple birth can appear as confounders. The most difficult problem to solve is often confounding by indication. The problem of confounding is less important for congenital malformations than for many other pregnancy outcomes. PMID:22190949

Psychosocial job conditions, fear avoidance beliefs and expected return to work following acute coronary syndrome: a cross-sectional study of fear-avoidance as a potential mediator.

PubMed

Söderberg, Mia; Rosengren, Annika; Gustavsson, Sara; Schiöler, Linus; Härenstam, Annika; Torén, Kjell

2015-12-21

Despite improvements in treatment, acute coronary syndrome remains a substantial cause for prolonged sick absences and premature retirement. Knowledge regarding what benefits return to work is limited, especially the effect of psychological processes and psychosocial work factors. The purposes of this cross-sectional study were two-fold: to examine associations between adverse psychosocial job conditions and fear-avoidance beliefs towards work, and to determine whether such beliefs mediated the relationship between work conditions and expected return to work in acute coronary syndrome survivors. Study inclusion criteria: acute myocardial infarction or unstable angina diagnosis, below 65 years of age, being a resident in the West county of Sweden and currently working. In all, 509 individuals (21.8 % women) accepted study participation and for whom all data of study interest were available for analysis. Psychosocial work variables; job demand-control and effort-reward imbalance, were assessed with standard questionnaire batteries. Linear regression models were used to investigate relationships between psychosocial factors and fear-avoidance, and to evaluate mediator effects for fear-avoidance. Both total sample and gender stratified analyses were calculated. Fear-avoidance beliefs about work were associated to psychosocial job environments characterized by high strain (β 1.4; CI 1.2-1.6), active and passive work and high effort-reward imbalance (β 0.6; CI 0.5-0.7). Further, such beliefs also mediated the relationship between adverse work conditions and expected time for return to work. However, these results were only observed in total sample analyses or among or male participants. For women only high strain was linked to fear-avoidance, and these relationships became non-significant when entering chosen confounders. This cross-sectional study showed that acute coronary syndrome survivors, who laboured under adverse psychosocial work conditions, held fear-avoidance beliefs towards their workplace. Furthermore, these beliefs mediated the relationships between - high strained or high effort-reward imbalanced work - and expected return to work. However, mentioned results were primarily found among men, which could results from few female study participants or gender differences in return to work mechanisms. Still, an earlier return to work might be promoted by interventions focusing on improved psychosocial work conditions and cognitive behavioural therapy targeting fear-avoidance beliefs.

Shared processing in multiple object tracking and visual working memory in the absence of response order and task order confounds

PubMed Central

Howe, Piers D. L.

2017-01-01

To understand how the visual system represents multiple moving objects and how those representations contribute to tracking, it is essential that we understand how the processes of attention and working memory interact. In the work described here we present an investigation of that interaction via a series of tracking and working memory dual-task experiments. Previously, it has been argued that tracking is resistant to disruption by a concurrent working memory task and that any apparent disruption is in fact due to observers making a response to the working memory task, rather than due to competition for shared resources. Contrary to this, in our experiments we find that when task order and response order confounds are avoided, all participants show a similar decrease in both tracking and working memory performance. However, if task and response order confounds are not adequately controlled for we find substantial individual differences, which could explain the previous conflicting reports on this topic. Our results provide clear evidence that tracking and working memory tasks share processing resources. PMID:28410383

Shared processing in multiple object tracking and visual working memory in the absence of response order and task order confounds.

PubMed

Lapierre, Mark D; Cropper, Simon J; Howe, Piers D L

2017-01-01

To understand how the visual system represents multiple moving objects and how those representations contribute to tracking, it is essential that we understand how the processes of attention and working memory interact. In the work described here we present an investigation of that interaction via a series of tracking and working memory dual-task experiments. Previously, it has been argued that tracking is resistant to disruption by a concurrent working memory task and that any apparent disruption is in fact due to observers making a response to the working memory task, rather than due to competition for shared resources. Contrary to this, in our experiments we find that when task order and response order confounds are avoided, all participants show a similar decrease in both tracking and working memory performance. However, if task and response order confounds are not adequately controlled for we find substantial individual differences, which could explain the previous conflicting reports on this topic. Our results provide clear evidence that tracking and working memory tasks share processing resources.

Sensitivity analysis for direct and indirect effects in the presence of exposure-induced mediator-outcome confounders

PubMed Central

Chiba, Yasutaka

2014-01-01

Questions of mediation are often of interest in reasoning about mechanisms, and methods have been developed to address these questions. However, these methods make strong assumptions about the absence of confounding. Even if exposure is randomized, there may be mediator-outcome confounding variables. Inference about direct and indirect effects is particularly challenging if these mediator-outcome confounders are affected by the exposure because in this case these effects are not identified irrespective of whether data is available on these exposure-induced mediator-outcome confounders. In this paper, we provide a sensitivity analysis technique for natural direct and indirect effects that is applicable even if there are mediator-outcome confounders affected by the exposure. We give techniques for both the difference and risk ratio scales and compare the technique to other possible approaches. PMID:25580387

Assessment of Confounders in Comparative Effectiveness Studies From Secondary Databases.

PubMed

Franklin, Jessica M; Schneeweiss, Sebastian; Solomon, Daniel H

2017-03-15

Secondary clinical databases are an important and growing source of data for comparative effectiveness research (CER) studies. However, measurement of confounders, such as biomarker values or patient-reported health status, in secondary clinical databases may not align with the initiation of a new treatment. In many published CER analyses of registry data, investigators assessed confounders based on the first questionnaire in which the new exposure was recorded. However, it is known that adjustment for confounders measured after the start of exposure can lead to biased treatment effect estimates. In the present study, we conducted simulations to compare assessment strategies for a dynamic clinical confounder in a registry-based comparative effectiveness study of 2 therapies. As expected, we found that adjustment for the confounder value at the time of the first questionnaire after the start of exposure creates a biased estimate the total effect of exposure choice on outcome when the confounder mediates part of the effect. However, adjustment for the prior value can also be badly biased when measured long before exposure initiation. Thus, investigators should carefully consider the timing of confounder measurements relative to exposure initiation and the rate of change in the confounder in order to choose the most relevant measure for each patient. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The effect of music on cognitive performance: insight from neurobiological and animal studies.

PubMed

Rickard, Nikki S; Toukhsati, Samia R; Field, Simone E

2005-12-01

The past 50 years have seen numerous claims that music exposure enhances human cognitive performance. Critical evaluation of studies across a variety of contexts, however, reveals important methodological weaknesses. The current article argues that an interdisciplinary approach is required to advance this research. A case is made for the use of appropriate animal models to avoid many confounds associated with human music research. Although such research has validity limitations for humans, reductionist methodology enables a more controlled exploration of music's elementary effects. This article also explores candidate mechanisms for this putative effect. A review of neurobiological evidence from human and comparative animal studies confirms that musical stimuli modify autonomic and neurochemical arousal indices, and may also modify synaptic plasticity. It is proposed that understanding how music affects animals provides a valuable conjunct to human research and may be vital in uncovering how music might be used to enhance cognitive performance.

Promoting interaction during sociodramatic play: teaching scripts to typical preschoolers and classmates with disabilities.

PubMed Central

Goldstein, H; Cisar, C L

1992-01-01

We investigated the effects of teaching sociodramatic scripts on subsequent interaction among three triads, each containing 2 typical children and 1 child with autistic characteristics. The same type and rate of teacher prompts were implemented throughout structured play observations to avoid the confounding effects of script training and teacher prompting. After learning the scripts, all children demonstrated more frequent theme-related social behavior. These improvements in social-communicative interaction were replicated with the training of three sociodramatic scripts (i.e., pet shop, carnival, magic show) according to a multiple baseline design. These effects were maintained during the training of successive scripts and when the triads were reconstituted to include new but similarly trained partners. Results provided support for the inclusion of systematic training of scripts to enhance interaction among children with and without disabilities during sociodramatic play. PMID:1386068

Perceived displacement explains wolfpack effect

PubMed Central

Šimkovic, Matúš; Träuble, Birgit

2014-01-01

We investigate the influence of perceived displacement of moving agent-like stimuli on the performance in dynamic interactive tasks. In order to reliably measure perceived displacement we utilize multiple tasks with different task demands. The perceived center of an agent's body is displaced in the direction in which the agent is facing and this perceived displacement is larger than the theoretical position of the center of mass would predict. Furthermore, the displacement in the explicit judgment is dissociated from the displacement obtained by the implicit measures. By manipulating the location of the pivot point, we show that it is not necessary to postulate orientation as an additional cue utilized by perception, as has been suggested by earlier studies. These studies showed that the agent's orientation influences the detection of chasing motion and the detection-related performance in interactive tasks. This influence has been labeled wolfpack effect. In one of the demonstrations of the wolfpack effect participants control a green circle on a display with a computer mouse. It has been shown that participants avoid display areas with agents pointing toward the green circle. Participants do so in favor of areas where the agents point in the direction perpendicular to the circle. We show that this avoidance behavior arises because the agent's pivot point selected by the earlier studies is different from where people locate the center of agent's body. As a consequence, the nominal rotation confounds rotation and translation. We show that the avoidance behavior disappears once the pivot point is set to the center of agent's body. PMID:25566114

Do clinically anxious children cluster according to their expression of factors that maintain child anxiety?

PubMed

Pearcey, Samantha; Alkozei, Anna; Chakrabarti, Bhismadev; Dodd, Helen; Murayama, Kou; Stuijfzand, Suzannah; Creswell, Cathy

2018-03-15

Cognitive Behaviour Therapy (CBT) is an effective treatment for childhood anxiety disorders, yet a significant proportion of children do not benefit from it. CBT for child anxiety disorders typically includes a range of strategies that may not all be applicable for all affected children. This study explored whether there are distinct subgroups of children with anxiety disorders who are characterized by their responses to measures of the key mechanisms that are targeted in CBT (i.e. interpretation bias, perceived control, avoidance, physiological arousal, and social communication). 379 clinically anxious children (7-12 years) provided indices of threat interpretation, perceived control, expected negative emotions and avoidance and measures of heart rate recovery following a speech task. Parents also reported on their children's social communication difficulties using the Social Communication Questionnaire (SCQ). Latent profile analysis identified three groups, reflecting (i) 'Typically anxious' (the majority of the sample and more likely to have Generalized anxiety disorder); (ii) 'social difficulties' (characterized by high SCQ and more likely to have social anxiety disorder and be male); (iii) 'Avoidant' (characterized by low threat interpretation but high avoidance and low perceived control). Some measures may have been influenced by confounding variables (e.g. physical variability in heart rate recovery). Sample characteristics of the group may limit the generalizability of the results. Clinically anxious children appear to fall in to subgroups that might benefit from more targeted treatments that focus on specific maintenance factors. Treatment studies are now required to establish whether this approach would lead to more effective and efficient treatments. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Assessing Omitted Confounder Bias in Multilevel Mediation Models.

PubMed

Tofighi, Davood; Kelley, Ken

2016-01-01

To draw valid inference about an indirect effect in a mediation model, there must be no omitted confounders. No omitted confounders means that there are no common causes of hypothesized causal relationships. When the no-omitted-confounder assumption is violated, inference about indirect effects can be severely biased and the results potentially misleading. Despite the increasing attention to address confounder bias in single-level mediation, this topic has received little attention in the growing area of multilevel mediation analysis. A formidable challenge is that the no-omitted-confounder assumption is untestable. To address this challenge, we first analytically examined the biasing effects of potential violations of this critical assumption in a two-level mediation model with random intercepts and slopes, in which all the variables are measured at Level 1. Our analytic results show that omitting a Level 1 confounder can yield misleading results about key quantities of interest, such as Level 1 and Level 2 indirect effects. Second, we proposed a sensitivity analysis technique to assess the extent to which potential violation of the no-omitted-confounder assumption might invalidate or alter the conclusions about the indirect effects observed. We illustrated the methods using an empirical study and provided computer code so that researchers can implement the methods discussed.

Use of electronic healthcare records in large-scale simple randomized trials at the point of care for the documentation of value-based medicine.

PubMed

van Staa, T-P; Klungel, O; Smeeth, L

2014-06-01

A solid foundation of evidence of the effects of an intervention is a prerequisite of evidence-based medicine. The best source of such evidence is considered to be randomized trials, which are able to avoid confounding. However, they may not always estimate effectiveness in clinical practice. Databases that collate anonymized electronic health records (EHRs) from different clinical centres have been widely used for many years in observational studies. Randomized point-of-care trials have been initiated recently to recruit and follow patients using the data from EHR databases. In this review, we describe how EHR databases can be used for conducting large-scale simple trials and discuss the advantages and disadvantages of their use. © 2014 The Association for the Publication of the Journal of Internal Medicine.

The sentence wrap-up dogma.

PubMed

Stowe, Laurie A; Kaan, Edith; Sabourin, Laura; Taylor, Ryan C

2018-03-30

Current sentence processing research has focused on early effects of the on-line incremental processes that are performed at each word or constituent during processing. However, less attention has been devoted to what happens at the end of the clause or sentence. More specifically, over the last decade and a half, a lot of effort has been put into avoiding measuring event-related brain potentials (ERPs) at the final word of a sentence, because of the possible effects of sentence wrap-up. This article reviews the evidence on how and when sentence wrap-up impacts behavioral and ERP results. Even though the end of the sentence is associated with a positive-going ERP wave, thus far this effect has not been associated with any factors hypothesized to affect wrap-up. In addition, ERP responses to violations have not been affected by this positivity. "Sentence-final" negativities reported in the literature are not unique to sentence final positions, nor do they obscure or distort ERP effects associated with linguistic manipulations. Finally, the empirical evidence used to argue that sentence-final ERPs are different from those recorded at sentence-medial positions is weak at most. Measuring ERPs at sentence-final positions is therefore certainly not to be avoided at all costs, especially not in cases where the structure of the language under investigation requires it. More importantly, researchers should follow rigorous method in their experimental design, avoid decision tasks which may induce ERP confounds, and ensure all other possible explanations for results are considered. Although this article is directed at a particular dogma from a particular literature, this review shows that it is important to reassess what is regarded as "general knowledge" from time to time. Copyright © 2018 Elsevier B.V. All rights reserved.

Epidemiologic methods in clinical trials.

PubMed

Rothman, K J

1977-04-01

Epidemiologic methods developed to control confounding in non-experimental studies are equally applicable for experiments. In experiments, most confounding is usually controlled by random allocation of subjects to treatment groups, but randomization does not preclude confounding except for extremely large studies, the degree of confounding expected being inversely related to the size of the treatment groups. In experiments, as in non-experimental studies, the extent of confounding for each risk indicator should be assessed, and if sufficiently large, controlled. Confounding is properly assessed by comparing the unconfounded effect estimate to the crude effect estimate; a common error is to assess confounding by statistical tests of significance. Assessment of confounding involves its control as a prerequisite. Control is most readily and cogently achieved by stratification of the data, though with many factors to control simultaneously, multivariate analysis or a combination of multivariate analysis and stratification might be necessary.

Impact of land-use on carbon storage as dependent on soil texture: evidence from a desertified dryland using repeated paired sampling design.

PubMed

Ye, Xuehua; Tang, Shuangli; Cornwell, William K; Gao, Shuqin; Huang, Zhenying; Dong, Ming; Cornelissen, Johannes H C

2015-03-01

Desertification resulting from land-use affects large dryland areas around the world, accompanied by carbon loss. However it has been difficult to interpret different land-use contributions to carbon pools owing to confounding factors related to climate, topography, soil texture and other original soil properties. To avoid such confounding effects, a unique systematic and extensive repeated design of paired sampling plots of different land-use types was adopted on Ordos Plateau, N China. The sampling enabled to quantify the effects of the predominant land-use types on carbon storage as dependent on soil texture, and to define the most promising land-use choices for carbon storage, both in grassland on sandy soil and in desert grassland on brown calcareous soil. The results showed that (1) desertification control should be an effective measure to improve the carbon sequestration in sandy grassland, and shrub planting should be better than grass planting; (2) development of man-made grassland should be a good choice to solve the contradictions of ecology and economy in desert grassland; (3) grassland on sandy soil is more vulnerable to soil degradation than desert grassland on brown calcareous soil. The results may be useful for the selection of land-use types, aiming at desertification prevention in drylands. Follow-up studies should directly investigate the role of soil texture on the carbon storage dynamic caused by land-use change. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cardiovascular health, traffic-related air pollution and noise: are associations mutually confounded? A systematic review.

PubMed

Tétreault, Louis-François; Perron, Stéphane; Smargiassi, Audrey

2013-10-01

This review assessed the confounding effect of one traffic-related exposure (noise or air pollutants) on the association between the other exposure and cardiovascular outcomes. A systematic review was conducted with the databases Medline and Embase. The confounding effects in studies were assessed by using change in the estimate with a 10 % cutoff point. The influence on the change in the estimate of the quality of the studies, the exposure assessment methods and the correlation between road noise and air pollutions were also assessed. Nine publications were identified. For most studies, the specified confounders produced changes in estimates <10 %. The correlation between noise and pollutants, the quality of the study and of the exposure assessment do not seem to influence the confounding effects. Results from this review suggest that confounding of cardiovascular effects by noise or air pollutants is low, though with further improvements in exposure assessment, the situation may change. More studies using pollution indicators specific to road traffic are needed to properly assess if noise and air pollution are subjected to confounding.

Disentangle the Causes of the Road Barrier Effect in Small Mammals through Genetic Patterns.

PubMed

Ascensão, Fernando; Mata, Cristina; Malo, Juan E; Ruiz-Capillas, Pablo; Silva, Catarina; Silva, André P; Santos-Reis, Margarida; Fernandes, Carlos

2016-01-01

Road barrier effect is among the foremost negative impacts of roads on wildlife. Knowledge of the factors responsible for the road barrier effect is crucial to understand and predict species' responses to roads, and to improve mitigation measures in the context of management and conservation. We built a set of hypothesis aiming to infer the most probable cause of road barrier effect (traffic effect or road surface avoidance), while controlling for the potentially confounding effects road width, traffic volume and road age. The wood mouse Apodemus sylvaticus was used as a model species of small and forest-dwelling mammals, which are more likely to be affected by gaps in cover such as those resulting from road construction. We confront genetic patterns from opposite and same roadsides from samples of three highways and used computer simulations to infer migration rates between opposite roadsides. Genetic patterns from 302 samples (ca. 100 per highway) suggest that the highway barrier effect for wood mouse is due to road surface avoidance. However, from the simulations we estimated a migration rate of about 5% between opposite roadsides, indicating that some limited gene flow across highways does occur. To reduce highway impact on population genetic diversity and structure, possible mitigation measures could include retrofitting of culverts and underpasses to increase their attractiveness and facilitate their use by wood mice and other species, and setting aside roadside strips without vegetation removal to facilitate establishment and dispersal of small mammals.

Disentangle the Causes of the Road Barrier Effect in Small Mammals through Genetic Patterns

PubMed Central

Ascensão, Fernando; Mata, Cristina; Malo, Juan E.; Ruiz-Capillas, Pablo; Silva, Catarina; Silva, André P.; Santos-Reis, Margarida; Fernandes, Carlos

2016-01-01

Road barrier effect is among the foremost negative impacts of roads on wildlife. Knowledge of the factors responsible for the road barrier effect is crucial to understand and predict species’ responses to roads, and to improve mitigation measures in the context of management and conservation. We built a set of hypothesis aiming to infer the most probable cause of road barrier effect (traffic effect or road surface avoidance), while controlling for the potentially confounding effects road width, traffic volume and road age. The wood mouse Apodemus sylvaticus was used as a model species of small and forest-dwelling mammals, which are more likely to be affected by gaps in cover such as those resulting from road construction. We confront genetic patterns from opposite and same roadsides from samples of three highways and used computer simulations to infer migration rates between opposite roadsides. Genetic patterns from 302 samples (ca. 100 per highway) suggest that the highway barrier effect for wood mouse is due to road surface avoidance. However, from the simulations we estimated a migration rate of about 5% between opposite roadsides, indicating that some limited gene flow across highways does occur. To reduce highway impact on population genetic diversity and structure, possible mitigation measures could include retrofitting of culverts and underpasses to increase their attractiveness and facilitate their use by wood mice and other species, and setting aside roadside strips without vegetation removal to facilitate establishment and dispersal of small mammals. PMID:26978779

Evaluation of uncontrolled confounding in studies of environmental exposures and neurobehavioral testing in children.

PubMed

Mink, Pamela J; Goodman, Michael; Barraj, Leila M; Imrey, Harriet; Kelsh, Michael A; Yager, Janice

2004-07-01

Neurobehavioral tests are commonly used in studies of children exposed to low-level environmental concentrations of compounds known to be neurotoxic at higher levels. However, uncontrolled or incomplete control for confounding makes interpretation of results problematic because effects of confounders are often stronger than the effects of primary interest. We examined a priori the potential impact of confounding in a hypothetical study evaluating the association of a potentially neurotoxic environmental exposure with neurobehavioral function in children. We used 2 outcome measures: the Bayley Scales of Infant Development Mental Development Index and the Stanford-Binet Intelligence Scale Composite Score. We selected 3 potential confounders: maternal intelligence, home environment, and socioeconomic status as measured by years of parental education. We conducted 3 sets of analyses measuring the effect of each of the 3 confounding factors alone, 2 confounders acting simultaneously, and all 3 confounders acting simultaneously. Relatively small differences (0.5 standard deviations) in confounding variables between "exposed" and "unexposed" groups, if unmeasured and unaccounted for in the analysis, could produce spurious differences in cognitive test scores. The magnitude of this difference (3-10 points) has been suggested to have a meaningful impact in populations. The method of measuring confounders (eg, maternal intelligence) could also substantially affect the results. It is important to carefully consider the impact of potential confounders during the planning stages of an observational study. Study-to-study differences in neurobehavioral outcomes with similar environmental exposures could be partially explained by differences in the adjustment for confounding variables. Copyright 2004 Lippincott Williams and Wilkins

Large-scale monitoring of effects of clothianidin dressed oilseed rape seeds on pollinating insects in Northern Germany: implementation of the monitoring project and its representativeness.

PubMed

Heimbach, Fred; Russ, Anja; Schimmer, Maren; Born, Katrin

2016-11-01

Monitoring studies at the landscape level are complex, expensive and difficult to conduct. Many aspects have to be considered to avoid confounding effects which is probably the reason why they are not regularly performed in the context of risk assessments of plant protection products to pollinating insects. However, if conducted appropriately their contribution is most valuable. In this paper we identify the requirements of a large-scale monitoring study for the assessment of side-effects of clothianidin seed-treated winter oilseed rape on three species of pollinating insects (Apis mellifera, Bombus terrestris and Osmia bicornis) and present how these requirements were implemented. Two circular study sites were delineated next to each other in northeast Germany and comprised almost 65 km 2 each. At the reference site, study fields were drilled with clothianidin-free OSR seeds while at the test site the oilseed rape seeds contained a coating with 10 g clothianidin and 2 g beta-cyfluthrin per kg seeds (Elado®). The comparison of environmental conditions at the study sites indicated that they are as similar as possible in terms of climate, soil, land use, history and current practice of agriculture as well as in availability of oilseed rape and non-crop bee forage. Accordingly, local environmental conditions were considered not to have had any confounding effect on the results of the monitoring of the bee species. Furthermore, the study area was found to be representative for other oilseed rape cultivation regions in Europe.

Methodological challenges to control for immortal time bias in addressing drug effects in type 2 diabetes

PubMed Central

Yang, Xi-Lin; Huo, Xiao-Xu; Chan, Juliana CN

2015-01-01

There are multiple biases in using observational studies to examine treatment effects such as those from prevalent drug users, immortal time and drug indications. We used renin angiotensin system (RAS) inhibitors and statins as reference drugs with proven efficacies in randomized clinical trials (RCTs) and examined their effectiveness in the prospective Hong Kong Diabetes Registry using adjustment methods proposed in the literature. Using time-dependent exposures to drug treatments yielded greatly inflated hazard ratios (HR) regarding the treatment effects of these drugs for cardiovascular disease (CVD) in type 2 diabetes. These errors were probably due to changing indications to use these drugs during follow up periods, especially at the time of drug commencement making time-dependent analysis extremely problematic. Using time-fixed analysis with exclusion of immortal time and adjustment for confounders at baseline and/or during follow-up periods, the HR of RAS inhibitors for CVD was comparable to that in RCT. The result supported the use of the Registry for performing pharmacoepidemiological analysis which revealed an attenuated low low-density lipoprotein cholesterol related cancer risk with RAS inhibitors. On the other hand, time-fixed analysis with including immortal time and adjustment for confounders at baseline and/or during follow-up periods, the HR of statins for CVD was similar to that in the RCT. Our results highlight the complexity and difficulty in removing these biases. We call for validations of the methods to cope with immortal time and drug use indications before applying them to particular research questions, so to avoid making erroneous conclusions. PMID:26413484

Methodological challenges to control for immortal time bias in addressing drug effects in type 2 diabetes.

PubMed

Yang, Xi-Lin; Huo, Xiao-Xu; Chan, Juliana Cn

2015-09-26

There are multiple biases in using observational studies to examine treatment effects such as those from prevalent drug users, immortal time and drug indications. We used renin angiotensin system (RAS) inhibitors and statins as reference drugs with proven efficacies in randomized clinical trials (RCTs) and examined their effectiveness in the prospective Hong Kong Diabetes Registry using adjustment methods proposed in the literature. Using time-dependent exposures to drug treatments yielded greatly inflated hazard ratios (HR) regarding the treatment effects of these drugs for cardiovascular disease (CVD) in type 2 diabetes. These errors were probably due to changing indications to use these drugs during follow up periods, especially at the time of drug commencement making time-dependent analysis extremely problematic. Using time-fixed analysis with exclusion of immortal time and adjustment for confounders at baseline and/or during follow-up periods, the HR of RAS inhibitors for CVD was comparable to that in RCT. The result supported the use of the Registry for performing pharmacoepidemiological analysis which revealed an attenuated low low-density lipoprotein cholesterol related cancer risk with RAS inhibitors. On the other hand, time-fixed analysis with including immortal time and adjustment for confounders at baseline and/or during follow-up periods, the HR of statins for CVD was similar to that in the RCT. Our results highlight the complexity and difficulty in removing these biases. We call for validations of the methods to cope with immortal time and drug use indications before applying them to particular research questions, so to avoid making erroneous conclusions.

Examining the role of unmeasured confounding in mediation analysis with genetic and genomic applications.

PubMed

Lutz, Sharon M; Thwing, Annie; Schmiege, Sarah; Kroehl, Miranda; Baker, Christopher D; Starling, Anne P; Hokanson, John E; Ghosh, Debashis

2017-07-19

In mediation analysis if unmeasured confounding is present, the estimates for the direct and mediated effects may be over or under estimated. Most methods for the sensitivity analysis of unmeasured confounding in mediation have focused on the mediator-outcome relationship. The Umediation R package enables the user to simulate unmeasured confounding of the exposure-mediator, exposure-outcome, and mediator-outcome relationships in order to see how the results of the mediation analysis would change in the presence of unmeasured confounding. We apply the Umediation package to the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) study to examine the role of unmeasured confounding due to population stratification on the effect of a single nucleotide polymorphism (SNP) in the CHRNA5/3/B4 locus on pulmonary function decline as mediated by cigarette smoking. Umediation is a flexible R package that examines the role of unmeasured confounding in mediation analysis allowing for normally distributed or Bernoulli distributed exposures, outcomes, mediators, measured confounders, and unmeasured confounders. Umediation also accommodates multiple measured confounders, multiple unmeasured confounders, and allows for a mediator-exposure interaction on the outcome. Umediation is available as an R package at https://github.com/SharonLutz/Umediation A tutorial on how to install and use the Umediation package is available in the Additional file 1.

Review of methodological challenges in comparing the effectiveness of neoadjuvant chemotherapy versus primary debulking surgery for advanced ovarian cancer in the United States.

PubMed

Cole, Ashley L; Austin, Anna E; Hickson, Ryan P; Dixon, Matthew S; Barber, Emma L

2018-05-11

Randomized trials outside the U.S. have found non-inferior survival for neoadjuvant chemotherapy (NACT) versus primary debulking surgery (PDS) for advanced ovarian cancer (AOC). However, these trials reported lower overall survival and lower rates of optimal debulking than U.S. studies, leading to questions about generalizability to U.S. practice, where aggressive debulking is more common. Consequently, comparative effectiveness in the U.S. remains controversial. We reviewed U.S. comparative effectiveness studies of NACT versus PDS for AOC. Here we describe methodological challenges, compare results to trials outside the U.S., and make suggestions for future research. We identified U.S. studies published in 2010 or later that evaluated the comparative effectiveness of NACT versus PDS on survival in AOC through a PubMed search. Two independent reviewers abstracted data from eligible articles. Nine of 230 articles were eligible for review. Methodological challenges included unmeasured confounders, heterogeneous treatment effects, treatment variations over time, and inconsistent measurement of treatment and survival. Whereas some limitations were unavoidable, several limitations noted across studies were avoidable, including conditioning on mediating factors and immortal time introduced by measuring survival beginning from diagnosis. Without trials in the U.S., non-randomized studies are an important source of evidence for the ideal treatment for AOC. However, several methodological challenges exist when assessing the comparative effectiveness of NACT versus PDS in a non-randomized setting. Future observational studies must ensure that treatment is consistent throughout the study period and that treatment groups are comparable. Rapidly-evolving oncology data networks may allow for identification of treatment intent and other important confounders. Copyright © 2018 Elsevier Ltd. All rights reserved.

Paradoxical cardiovascular effects of implementing adaptive emotion regulation strategies in generalized anxiety disorder.

PubMed

Aldao, Amelia; Mennin, Douglas S

2012-02-01

Recent models of generalized anxiety disorder (GAD) have expanded on Borkovec's avoidance theory by delineating emotion regulation deficits associated with the excessive worry characteristic of this disorder (see Behar, DiMarco, Hekler, Mohlman, & Staples, 2009). However, it has been difficult to determine whether emotion regulation is simply a useful heuristic for the avoidant properties of worry or an important extension to conceptualizations of GAD. Some of this difficulty may arise from a focus on purported maladaptive regulation strategies, which may be confounded with symptomatic distress components of the disorder (such as worry). We examined the implementation of adaptive regulation strategies by participants with and without a diagnosis of GAD while watching emotion-eliciting film clips. In a between-subjects design, participants were randomly assigned to accept, reappraise, or were not given specific regulation instructions. Implementation of adaptive regulation strategies produced differential effects in the physiological (but not subjective) domain across diagnostic groups. Whereas participants with GAD demonstrated lower cardiac flexibility when implementing adaptive regulation strategies than when not given specific instructions on how to regulate, healthy controls showed the opposite pattern, suggesting they benefited from the use of adaptive regulation strategies. We discuss the implications of these findings for the delineation of emotion regulation deficits in psychopathology. Copyright © 2011 Elsevier Ltd. All rights reserved.

The Effectiveness of the Personality Assessment Inventory With Feigned PTSD: An Initial Investigation of Resnick's Model of Malingering.

PubMed

Wooley, Chelsea N; Rogers, Richard

2015-08-01

Malingered posttraumatic stress disorder (PTSD) poses a formidable clinical challenge because of the apparent ease in feigning PTSD. As an additional confound, some patients with genuine PTSD produce elevated profiles on feigning indicators that are difficult to distinguish from feigned PTSD. The current study utilized 109 inpatients from a trauma unit to examine whether the Personality Assessment Inventory and the Detailed Assessment of Posttraumatic Stress can effectively differentiate between genuine and feigned PTSD. As a primary focus, Resnick's model of malingered PTSD was evaluated with its three subtypes: pure malingering, partial malingering, and false imputation. They were tested on their ability to (a) effectively simulate PTSD and (b) avoid being classified as feigning. The partial malingering group proved to be the best feigning group in achieving these two goals. Overall, the Personality Assessment Inventory Malingering Index and Negative Distortion Scale were the most effective at identifying feigning. © The Author(s) 2014.

Prosody and parsing in coordination structures.

PubMed

Schepman, A; Rodway, P

2000-05-01

The effect of prosodic boundary cues on the off-line disambiguation and on-line parsing of coordination structures was examined. It was found that relative clauses were attached to coordinated object noun phrases in preference to second conjuncts in sentences like: The lawyer greeted the powerful barrister and the wise judge who was/were walking to the courtroom. Naive speakers signalled the syntactic contrast between the two structures by a prosodic break between the conjuncts when the relative clause was attached to the second conjunct. Listeners were able to use this prosodic information in both off-line syntactic disambiguation and on-line syntactic parsing. The findings are compatible with a model in which prosody has a strong immediate effect on parsing. It is argued that the current experimental design has avoided confounds present in earlier studies on the on-line integration of prosodic and syntactic information.

The Sander parallelogram illusion dissociates action and perception despite control for the litany of past confounds.

PubMed

Whitwell, Robert L; Goodale, Melvyn A; Merritt, Kate E; Enns, James T

2018-01-01

The two visual systems hypothesis proposes that human vision is supported by an occipito-temporal network for the conscious visual perception of the world and a fronto-parietal network for visually-guided, object-directed actions. Two specific claims about the fronto-parietal network's role in sensorimotor control have generated much data and controversy: (1) the network relies primarily on the absolute metrics of target objects, which it rapidly transforms into effector-specific frames of reference to guide the fingers, hands, and limbs, and (2) the network is largely unaffected by scene-based information extracted by the occipito-temporal network for those same targets. These two claims lead to the counter-intuitive prediction that in-flight anticipatory configuration of the fingers during object-directed grasping will resist the influence of pictorial illusions. The research confirming this prediction has been criticized for confounding the difference between grasping and explicit estimates of object size with differences in attention, sensory feedback, obstacle avoidance, metric sensitivity, and priming. Here, we address and eliminate each of these confounds. We asked participants to reach out and pick up 3D target bars resting on a picture of the Sander Parallelogram illusion and to make explicit estimates of the length of those bars. Participants performed their grasps without visual feedback, and were permitted to grasp the targets after making their size-estimates to afford them an opportunity to reduce illusory error with haptic feedback. The results show unequivocally that the effect of the illusion is stronger on perceptual judgments than on grasping. Our findings from the normally-sighted population provide strong support for the proposal that human vision is comprised of functionally and anatomically dissociable systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

Intelligence and all-cause mortality in the 6-Day Sample of the Scottish Mental Survey 1947 and their siblings: testing the contribution of family background.

PubMed

Iveson, Matthew H; Cukic, Iva; Der, Geoff; Batty, G David; Deary, Ian J

2018-02-01

Higher early-life intelligence is associated with a reduced risk of mortality in adulthood, though this association is apparently hardly attenuated when accounting for early-life socio-economic status (SES). However, the use of proxy measures of SES means that residual confounding may underestimate this attenuation. In the present study, the potential confounding effect of early-life SES was instead accounted for by examining the intelligence-mortality association within families. The association between early-life intelligence and mortality in adulthood was assessed in 727 members of the 6-Day Sample of the Scottish Mental Survey 1947 and, for the first time, 1580 of their younger siblings. These individuals were born between 1936 and 1958, and were followed up into later life, with deaths recorded up to 2015. Cox regression was used to estimate the relative risk of mortality associated with higher IQ scores after adjusting for shared family factors. A standard-deviation advantage in IQ score was associated with a significantly reduced mortality risk [hazard ratio = 0.76, p < 0.001, 95% confidence interval (CI) (0.68-0.84)]. This reduction in hazard was only slightly attenuated by adjusting for sex and shared family factors [hazard ratio = 0.79, p = 0.002, 95% CI (0.68-0.92)]. Although somewhat conservative, adjusting for all variance shared by a family avoids any potential residual confounding of the intelligence-mortality association arising from the use of proxy measures of early-life SES. The present study demonstrates that the longevity associated with higher early-life intelligence cannot be explained by early-life SES or within-family factors. © The Author 2017; Published by Oxford University Press on behalf of the International Epidemiological Association

High angular resolution diffusion imaging with stimulated echoes: compensation and correction in experiment design and analysis.

PubMed

Lundell, Henrik; Alexander, Daniel C; Dyrby, Tim B

2014-08-01

Stimulated echo acquisition mode (STEAM) diffusion MRI can be advantageous over pulsed-gradient spin-echo (PGSE) for diffusion times that are long compared with T2 . It therefore has potential for biomedical diffusion imaging applications at 7T and above where T2 is short. However, gradient pulses other than the diffusion gradients in the STEAM sequence contribute much greater diffusion weighting than in PGSE and lead to a disrupted experimental design. Here, we introduce a simple compensation to the STEAM acquisition that avoids the orientational bias and disrupted experiment design that these gradient pulses can otherwise produce. The compensation is simple to implement by adjusting the gradient vectors in the diffusion pulses of the STEAM sequence, so that the net effective gradient vector including contributions from diffusion and other gradient pulses is as the experiment intends. High angular resolution diffusion imaging (HARDI) data were acquired with and without the proposed compensation. The data were processed to derive standard diffusion tensor imaging (DTI) maps, which highlight the need for the compensation. Ignoring the other gradient pulses, a bias in DTI parameters from STEAM acquisition is found, due both to confounds in the analysis and the experiment design. Retrospectively correcting the analysis with a calculation of the full B matrix can partly correct for these confounds, but an acquisition that is compensated as proposed is needed to remove the effect entirely. © 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.

The interpersonally sensitive disposition and health: an integrative review.

PubMed

Marin, Teresa J; Miller, Gregory E

2013-09-01

This article reviews studies that have examined the association between constructs related to interpersonal sensitivity (IS) and morbidity and mortality from major medical illnesses. We define IS as a stable trait characterized by ongoing concerns about negative social evaluation. This disposition makes people vigilant for as well as sensitive to others' evaluations of them. To avoid negative social evaluation, they adopt defensive behaviors such as submission and inhibition. Aspects of IS are captured by various constructs, including introversion, rejection sensitivity, social inhibition, social anxiety, and submissiveness. The review includes 76 long-term prospective studies across 4 outcome categories, namely, infectious disease, cancer, cardiovascular disease (CVD), and all-cause mortality. Three general conclusions are established. First, IS individuals are at increased risk of infectious diseases and possibly CVD, but not cancer and not all-cause mortality. Second, the positive studies provide evidence that IS temporally precedes disease, and go a long way toward ruling out the most plausible alternative explanations based on confounders, supporting a tentative causal interpretation of the data. However, unmeasured potential confounders make it impossible to be certain about whether IS drives the effects on mortality and morbidity. Third, the effects of introversion are accentuated and may only become apparent in contexts that activate social-evaluative concerns (e.g., exposure to early life residential mobility, living with the stigma of human immunodeficiency virus). Findings are discussed in regard to potential psychosocial and psychobiological mechanisms as well as implications for future work concerning IS and health. (c) 2013 APA, all rights reserved.

Helicase-Dependent Isothermal Amplification of DNA and RNA by Using Self-Avoiding Molecular Recognition Systems.

PubMed

Yang, Zunyi; McLendon, Chris; Hutter, Daniel; Bradley, Kevin M; Hoshika, Shuichi; Frye, Carole B; Benner, Steven A

2015-06-15

Assays that detect DNA or RNA (xNA) are highly sensitive, as small amounts of xNA can be amplified by PCR. Unfortunately, PCR is inconvenient in low-resource environments, and requires equipment and power that might not be available in these environments. Isothermal procedures, which avoid thermal cycling, are often confounded by primer dimers, off-target priming, and other artifacts. Here, we show how a "self avoiding molecular recognition system" (SAMRS) eliminates these artifacts and gives clean amplicons in a helicase-dependent isothermal amplification (SAMRS-HDA). We also show that incorporating SAMRS into the 3'-ends of primers facilitates the design and screening of primers for HDA assays. Finally, we show that SAMRS-HDA can be twofold multiplexed, difficult to achieve with HDA using standard primers. Thus, SAMRS-HDA is a more versatile approach than standard HDA, with a broader applicability for xNA-targeted diagnostics and research. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Helicase Dependent Isothermal Amplification of DNA and RNA using Self-Avoiding Molecular Recognition Systems

PubMed Central

Yang, Zunyi; McLendon, Chris; Hutter, Daniel; Bradley, Kevin M.; Hoshika, Shuichi; Frye, Carole; Benner, Steven A.

2015-01-01

Assays that target DNA or RNA (xNA) are highly sensitive, as small amounts of xNA can be amplified by PCR. Unfortunately, PCR is inconvenient in low resource environments, requiring equipment and power that may not be available in these environments. However, isothermal procedures that avoid thermal cycling are often confounded by primer dimers, off-target priming, and other artifacts. Here, we show how a “self avoiding molecular recognition system” (SAMRS) eliminates these artifacts to give clean amplicons in a helicase-dependent isothermal amplification (SAMRS-HDA). We also show that incorporating SAMRS into the 3′-ends of primers facilitates the design and screening of primers for HDA assays. Finally, we show that SAMRS-HDA can be twofold multiplexed, something difficult to achieve with HDA using standard primers. This shows that SAMRS-HDA is a more versatile approach than standard HDA with a broader applicability for xNA-targeted diagnostics and research. PMID:25953623

JIM-13-0560 R1: Propensity scores for confounder adjustment when assessing the effects of medical interventions using non-experimental study designs

PubMed Central

Stürmer, Til; Wyss, Richard; Glynn, Robert J.; Brookhart, M. Alan

2014-01-01

Treatment effects, especially when comparing two or more therapeutic alternatives as in comparative effectiveness research, are likely to be heterogeneous across age, gender, co-morbidities, and co-medications. Propensity scores (PSs), an alternative to multivariable outcome models to control for measured confounding, have specific advantages in the presence of heterogeneous treatment effects. Implementing PSs using matching or weighting allows us to estimate different overall treatment effects in differently defined populations. Heterogeneous treatment effects can also be due to unmeasured confounding concentrated in those treated contrary to prediction. Sensitivity analyses based on PSs can help to assess such unmeasured confounding. PSs should be considered a primary or secondary analytic strategy in non-experimental medical research, including pharmacoepidemiology and non-experimental comparative effectiveness research. PMID:24520806

The time course of symbolic number adaptation: oscillatory EEG activity and event-related potential analysis.

PubMed

Hsu, Yi-Fang; Szűcs, Dénes

2012-02-15

Several functional magnetic resonance imaging (fMRI) studies have used neural adaptation paradigms to detect anatomical locations of brain activity related to number processing. However, currently not much is known about the temporal structure of number adaptation. In the present study, we used electroencephalography (EEG) to elucidate the time course of neural events in symbolic number adaptation. The numerical distance of deviants relative to standards was manipulated. In order to avoid perceptual confounds, all levels of deviants consisted of perceptually identical stimuli. Multiple successive numerical distance effects were detected in event-related potentials (ERPs). Analysis of oscillatory activity further showed at least two distinct stages of neural processes involved in the automatic analysis of numerical magnitude, with the earlier effect emerging at around 200ms and the later effect appearing at around 400ms. The findings support for the hypothesis that numerical magnitude processing involves a succession of cognitive events. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

What does testosterone do for red deer males?

PubMed Central

Malo, A.F.; Roldan, E.R.S.; Garde, J.J.; Soler, A.J.; Vicente, J.; Gortazar, C.; Gomendio, M.

2008-01-01

Testosterone has been proposed to have a dual effect, enhancing sexual traits while depressing parasite resistance in males. Here, we test this hypothesis in red deer, examining males from captive populations during the whole annual cycle and males from natural populations during the breeding season. We first explored the effects of body size, age and sampling date on testosterone to avoid confounding effects. Our results show that in captive populations seasonal changes in testosterone levels were mirrored by changes in testes size, and that during the rut there was a strong correlation between both. In natural populations, males with higher testosterone levels had larger testes, improved sperm quality, smaller burr diameter, stronger antlers, higher haematocrit levels, and increased nematode parasite load. By contrast, no significant relationship was found between testosterone and spleen size or tick parasite load. We conclude that testosterone (i) improves males' reproductive investment and physical stamina, (ii) improves antler strength but reduces burr diameter, and (iii) imposes a cost in terms of depressed parasite resistance. PMID:19129132

Elevated C-reactive protein and posttraumatic stress pathology among survivors of the 9/11 World Trade Center attacks.

PubMed

Rosen, Rebecca L; Levy-Carrick, Nomi; Reibman, Joan; Xu, Ning; Shao, Yongzhao; Liu, Mengling; Ferri, Lucia; Kazeros, Angeliki; Caplan-Shaw, Caralee E; Pradhan, Deepak R; Marmor, Michael; Galatzer-Levy, Isaac R

2017-06-01

Systemic inflammation has emerged as a promising marker and potential mechanism underlying post-traumatic stress disorder (PTSD). The relationship between posttraumatic stress pathology and systemic inflammation has not, however, been consistently replicated and is potentially confounded by comorbid illness or injury, common complications of trauma exposure. We analyzed a large naturalistic cohort sharing a discrete physical and mental health trauma from the destruction of the World Trade Center (WTC) towers on September 11, 2001 (n = 641). We evaluated the relationship between multiple physical and mental health related indices collected through routine evaluations at the WTC Environmental Health Center (WTC EHC), a treatment program for community members exposed to the disaster. C-Reactive Protein (CRP), a marker of systemic inflammation, was examined in relation to scores for PTSD, PTSD symptom clusters (re-experiencing, avoidance, negative cognitions/mood, arousal), depression and anxiety, while controlling for WTC exposures, lower respiratory symptoms, age, sex, BMI and smoking as potential risks or confounders. CRP was positively associated with PTSD severity (p < 0.001), trending toward association with depression (p = 0.06), but not with anxiety (p = 0.27). CRP was positively associated with re-experiencing (p < 0.001) and avoidance (p < 0.05) symptom clusters, and trended toward associations with negative cognitions/mood (p = 0.06) and arousal (p = 0.08). In this large study of the relationship between CRP and posttraumatic stress pathology, we demonstrated an association between systemic inflammation and stress pathology (PTSD; trending with depression), which remained after adjusting for potentially confounding variables. These results contribute to research findings suggesting a salient relationship between inflammation and posttraumatic stress pathology. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Can statistic adjustment of OR minimize the potential confounding bias for meta-analysis of case-control study? A secondary data analysis.

PubMed

Liu, Tianyi; Nie, Xiaolu; Wu, Zehao; Zhang, Ying; Feng, Guoshuang; Cai, Siyu; Lv, Yaqi; Peng, Xiaoxia

2017-12-29

Different confounder adjustment strategies were used to estimate odds ratios (ORs) in case-control study, i.e. how many confounders original studies adjusted and what the variables are. This secondary data analysis is aimed to detect whether there are potential biases caused by difference of confounding factor adjustment strategies in case-control study, and whether such bias would impact the summary effect size of meta-analysis. We included all meta-analyses that focused on the association between breast cancer and passive smoking among non-smoking women, as well as each original case-control studies included in these meta-analyses. The relative deviations (RDs) of each original study were calculated to detect how magnitude the adjustment would impact the estimation of ORs, compared with crude ORs. At the same time, a scatter diagram was sketched to describe the distribution of adjusted ORs with different number of adjusted confounders. Substantial inconsistency existed in meta-analysis of case-control studies, which would influence the precision of the summary effect size. First, mixed unadjusted and adjusted ORs were used to combine individual OR in majority of meta-analysis. Second, original studies with different adjustment strategies of confounders were combined, i.e. the number of adjusted confounders and different factors being adjusted in each original study. Third, adjustment did not make the effect size of original studies trend to constringency, which suggested that model fitting might have failed to correct the systematic error caused by confounding. The heterogeneity of confounder adjustment strategies in case-control studies may lead to further bias for summary effect size in meta-analyses, especially for weak or medium associations so that the direction of causal inference would be even reversed. Therefore, further methodological researches are needed, referring to the assessment of confounder adjustment strategies, as well as how to take this kind of bias into consideration when drawing conclusion based on summary estimation of meta-analyses.

Breast milk and cognitive development—the role of confounders: a systematic review

PubMed Central

Walfisch, Asnat; Sermer, Corey; Cressman, Alex; Koren, Gideon

2013-01-01

Objectives The association between breastfeeding and child cognitive development is conflicted by studies reporting positive and null effects. This relationship may be confounded by factors associated with breastfeeding, specifically maternal socioeconomic class and IQ. Design Systematic review of the literature. Setting and participants Any prospective or retrospective study, in any language, evaluating the association between breastfeeding and cognitive development using a validated method in healthy term infants, children or adults, was included. Primary and secondary outcome measures Extracted data included the study design, target population and sample size, breastfeeding exposure, cognitive development assessment tool used and participants’ age, summary of the results prior to, and following, adjustment for confounders, and all confounders adjusted for. Study quality was assessed as well. Results 84 studies met our inclusion criteria (34 rated as high quality, 26 moderate and 24 low quality). Critical assessment of accepted studies revealed the following associations: 21 null, 28 positive, 18 null after adjusting for confounders and 17 positive—diminished after adjusting for confounders. Directionality of effect did not correlate with study quality; however, studies showing a decreased effect after multivariate analysis were of superior quality compared with other study groupings (14/17 high quality, 82%). Further, studies that showed null or diminished effect after multivariate analysis corrected for significantly more confounders (7.7±3.4) as compared with those that found no change following adjustment (5.6±4.5, p=0.04). The majority of included studies were carried out during childhood (75%) and set in high-income countries (85.5%). Conclusions Much of the reported effect of breastfeeding on child neurodevelopment is due to confounding. It is unlikely that additional work will change the current synthesis. Future studies should attempt to rigorously control for all important confounders. Alternatively, study designs using sibling cohorts discordant for breastfeeding may yield more robust conclusions. PMID:23975102

Robustness of meta-analyses in finding gene × environment interactions

PubMed Central

Shi, Gang; Nehorai, Arye

2017-01-01

Meta-analyses that synthesize statistical evidence across studies have become important analytical tools for genetic studies. Inspired by the success of genome-wide association studies of the genetic main effect, researchers are searching for gene × environment interactions. Confounders are routinely included in the genome-wide gene × environment interaction analysis as covariates; however, this does not control for any confounding effects on the results if covariate × environment interactions are present. We carried out simulation studies to evaluate the robustness to the covariate × environment confounder for meta-regression and joint meta-analysis, which are two commonly used meta-analysis methods for testing the gene × environment interaction or the genetic main effect and interaction jointly. Here we show that meta-regression is robust to the covariate × environment confounder while joint meta-analysis is subject to the confounding effect with inflated type I error rates. Given vast sample sizes employed in genome-wide gene × environment interaction studies, non-significant covariate × environment interactions at the study level could substantially elevate the type I error rate at the consortium level. When covariate × environment confounders are present, type I errors can be controlled in joint meta-analysis by including the covariate × environment terms in the analysis at the study level. Alternatively, meta-regression can be applied, which is robust to potential covariate × environment confounders. PMID:28362796

Confounding in statistical mediation analysis: What it is and how to address it.

PubMed

Valente, Matthew J; Pelham, William E; Smyth, Heather; MacKinnon, David P

2017-11-01

Psychology researchers are often interested in mechanisms underlying how randomized interventions affect outcomes such as substance use and mental health. Mediation analysis is a common statistical method for investigating psychological mechanisms that has benefited from exciting new methodological improvements over the last 2 decades. One of the most important new developments is methodology for estimating causal mediated effects using the potential outcomes framework for causal inference. Potential outcomes-based methods developed in epidemiology and statistics have important implications for understanding psychological mechanisms. We aim to provide a concise introduction to and illustration of these new methods and emphasize the importance of confounder adjustment. First, we review the traditional regression approach for estimating mediated effects. Second, we describe the potential outcomes framework. Third, we define what a confounder is and how the presence of a confounder can provide misleading evidence regarding mechanisms of interventions. Fourth, we describe experimental designs that can help rule out confounder bias. Fifth, we describe new statistical approaches to adjust for measured confounders of the mediator-outcome relation and sensitivity analyses to probe effects of unmeasured confounders on the mediated effect. All approaches are illustrated with application to a real counseling intervention dataset. Counseling psychologists interested in understanding the causal mechanisms of their interventions can benefit from incorporating the most up-to-date techniques into their mediation analyses. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

The alarming problems of confounding equivalence using logistic regression models in the perspective of causal diagrams.

PubMed

Yu, Yuanyuan; Li, Hongkai; Sun, Xiaoru; Su, Ping; Wang, Tingting; Liu, Yi; Yuan, Zhongshang; Liu, Yanxun; Xue, Fuzhong

2017-12-28

Confounders can produce spurious associations between exposure and outcome in observational studies. For majority of epidemiologists, adjusting for confounders using logistic regression model is their habitual method, though it has some problems in accuracy and precision. It is, therefore, important to highlight the problems of logistic regression and search the alternative method. Four causal diagram models were defined to summarize confounding equivalence. Both theoretical proofs and simulation studies were performed to verify whether conditioning on different confounding equivalence sets had the same bias-reducing potential and then to select the optimum adjusting strategy, in which logistic regression model and inverse probability weighting based marginal structural model (IPW-based-MSM) were compared. The "do-calculus" was used to calculate the true causal effect of exposure on outcome, then the bias and standard error were used to evaluate the performances of different strategies. Adjusting for different sets of confounding equivalence, as judged by identical Markov boundaries, produced different bias-reducing potential in the logistic regression model. For the sets satisfied G-admissibility, adjusting for the set including all the confounders reduced the equivalent bias to the one containing the parent nodes of the outcome, while the bias after adjusting for the parent nodes of exposure was not equivalent to them. In addition, all causal effect estimations through logistic regression were biased, although the estimation after adjusting for the parent nodes of exposure was nearest to the true causal effect. However, conditioning on different confounding equivalence sets had the same bias-reducing potential under IPW-based-MSM. Compared with logistic regression, the IPW-based-MSM could obtain unbiased causal effect estimation when the adjusted confounders satisfied G-admissibility and the optimal strategy was to adjust for the parent nodes of outcome, which obtained the highest precision. All adjustment strategies through logistic regression were biased for causal effect estimation, while IPW-based-MSM could always obtain unbiased estimation when the adjusted set satisfied G-admissibility. Thus, IPW-based-MSM was recommended to adjust for confounders set.

Validation sampling can reduce bias in health care database studies: an illustration using influenza vaccination effectiveness.

PubMed

Nelson, Jennifer Clark; Marsh, Tracey; Lumley, Thomas; Larson, Eric B; Jackson, Lisa A; Jackson, Michael L

2013-08-01

Estimates of treatment effectiveness in epidemiologic studies using large observational health care databases may be biased owing to inaccurate or incomplete information on important confounders. Study methods that collect and incorporate more comprehensive confounder data on a validation cohort may reduce confounding bias. We applied two such methods, namely imputation and reweighting, to Group Health administrative data (full sample) supplemented by more detailed confounder data from the Adult Changes in Thought study (validation sample). We used influenza vaccination effectiveness (with an unexposed comparator group) as an example and evaluated each method's ability to reduce bias using the control time period before influenza circulation. Both methods reduced, but did not completely eliminate, the bias compared with traditional effectiveness estimates that do not use the validation sample confounders. Although these results support the use of validation sampling methods to improve the accuracy of comparative effectiveness findings from health care database studies, they also illustrate that the success of such methods depends on many factors, including the ability to measure important confounders in a representative and large enough validation sample, the comparability of the full sample and validation sample, and the accuracy with which the data can be imputed or reweighted using the additional validation sample information. Copyright © 2013 Elsevier Inc. All rights reserved.

Validation sampling can reduce bias in healthcare database studies: an illustration using influenza vaccination effectiveness

PubMed Central

Nelson, Jennifer C.; Marsh, Tracey; Lumley, Thomas; Larson, Eric B.; Jackson, Lisa A.; Jackson, Michael

2014-01-01

Objective Estimates of treatment effectiveness in epidemiologic studies using large observational health care databases may be biased due to inaccurate or incomplete information on important confounders. Study methods that collect and incorporate more comprehensive confounder data on a validation cohort may reduce confounding bias. Study Design and Setting We applied two such methods, imputation and reweighting, to Group Health administrative data (full sample) supplemented by more detailed confounder data from the Adult Changes in Thought study (validation sample). We used influenza vaccination effectiveness (with an unexposed comparator group) as an example and evaluated each method’s ability to reduce bias using the control time period prior to influenza circulation. Results Both methods reduced, but did not completely eliminate, the bias compared with traditional effectiveness estimates that do not utilize the validation sample confounders. Conclusion Although these results support the use of validation sampling methods to improve the accuracy of comparative effectiveness findings from healthcare database studies, they also illustrate that the success of such methods depends on many factors, including the ability to measure important confounders in a representative and large enough validation sample, the comparability of the full sample and validation sample, and the accuracy with which data can be imputed or reweighted using the additional validation sample information. PMID:23849144

Environmental confounding in gene-environment interaction studies.

PubMed

Vanderweele, Tyler J; Ko, Yi-An; Mukherjee, Bhramar

2013-07-01

We show that, in the presence of uncontrolled environmental confounding, joint tests for the presence of a main genetic effect and gene-environment interaction will be biased if the genetic and environmental factors are correlated, even if there is no effect of either the genetic factor or the environmental factor on the disease. When environmental confounding is ignored, such tests will in fact reject the joint null of no genetic effect with a probability that tends to 1 as the sample size increases. This problem with the joint test vanishes under gene-environment independence, but it still persists if estimating the gene-environment interaction parameter itself is of interest. Uncontrolled environmental confounding will bias estimates of gene-environment interaction parameters even under gene-environment independence, but it will not do so if the unmeasured confounding variable itself does not interact with the genetic factor. Under gene-environment independence, if the interaction parameter without controlling for the environmental confounder is nonzero, then there is gene-environment interaction either between the genetic factor and the environmental factor of interest or between the genetic factor and the unmeasured environmental confounder. We evaluate several recently proposed joint tests in a simulation study and discuss the implications of these results for the conduct of gene-environment interaction studies.

Bias, Confounding, and Interaction: Lions and Tigers, and Bears, Oh My!

PubMed

Vetter, Thomas R; Mascha, Edward J

2017-09-01

Epidemiologists seek to make a valid inference about the causal effect between an exposure and a disease in a specific population, using representative sample data from a specific population. Clinical researchers likewise seek to make a valid inference about the association between an intervention and outcome(s) in a specific population, based upon their randomly collected, representative sample data. Both do so by using the available data about the sample variable to make a valid estimate about its corresponding or underlying, but unknown population parameter. Random error in an experiment can be due to the natural, periodic fluctuation or variation in the accuracy or precision of virtually any data sampling technique or health measurement tool or scale. In a clinical research study, random error can be due to not only innate human variability but also purely chance. Systematic error in an experiment arises from an innate flaw in the data sampling technique or measurement instrument. In the clinical research setting, systematic error is more commonly referred to as systematic bias. The most commonly encountered types of bias in anesthesia, perioperative, critical care, and pain medicine research include recall bias, observational bias (Hawthorne effect), attrition bias, misclassification or informational bias, and selection bias. A confounding variable is a factor associated with both the exposure of interest and the outcome of interest. A confounding variable (confounding factor or confounder) is a variable that correlates (positively or negatively) with both the exposure and outcome. Confounding is typically not an issue in a randomized trial because the randomized groups are sufficiently balanced on all potential confounding variables, both observed and nonobserved. However, confounding can be a major problem with any observational (nonrandomized) study. Ignoring confounding in an observational study will often result in a "distorted" or incorrect estimate of the association or treatment effect. Interaction among variables, also known as effect modification, exists when the effect of 1 explanatory variable on the outcome depends on the particular level or value of another explanatory variable. Bias and confounding are common potential explanations for statistically significant associations between exposure and outcome when the true relationship is noncausal. Understanding interactions is vital to proper interpretation of treatment effects. These complex concepts should be consistently and appropriately considered whenever one is not only designing but also analyzing and interpreting data from a randomized trial or observational study.

Addressing unmeasured confounding in comparative observational research.

PubMed

Zhang, Xiang; Faries, Douglas E; Li, Hu; Stamey, James D; Imbens, Guido W

2018-04-01

Observational pharmacoepidemiological studies can provide valuable information on the effectiveness or safety of interventions in the real world, but one major challenge is the existence of unmeasured confounder(s). While many analytical methods have been developed for dealing with this challenge, they appear under-utilized, perhaps due to the complexity and varied requirements for implementation. Thus, there is an unmet need to improve understanding the appropriate course of action to address unmeasured confounding under a variety of research scenarios. We implemented a stepwise search strategy to find articles discussing the assessment of unmeasured confounding in electronic literature databases. Identified publications were reviewed and characterized by the applicable research settings and information requirements required for implementing each method. We further used this information to develop a best practice recommendation to help guide the selection of appropriate analytical methods for assessing the potential impact of unmeasured confounding. Over 100 papers were reviewed, and 15 methods were identified. We used a flowchart to illustrate the best practice recommendation which was driven by 2 critical components: (1) availability of information on the unmeasured confounders; and (2) goals of the unmeasured confounding assessment. Key factors for implementation of each method were summarized in a checklist to provide further assistance to researchers for implementing these methods. When assessing comparative effectiveness or safety in observational research, the impact of unmeasured confounding should not be ignored. Instead, we suggest quantitatively evaluating the impact of unmeasured confounding and provided a best practice recommendation for selecting appropriate analytical methods. Copyright © 2018 John Wiley & Sons, Ltd.

Quasi-Experimental Approaches to Evaluating the Impact of Air Pollution on Children’s Health

PubMed Central

Heep, Samantha; Neidell, Matthew

2016-01-01

Many studies have shown a correlation between air pollution and poor children’s health. This paper focuses on recent studies that employ quasi-experimental designs in an effort to minimize the effect of confounding factors. These studies are complementary to studies using other designs and confirm that reducing air pollution reduces infant mortality, low birth weight, prematurity, congenital anomalies, asthma hospitalizations, and school absences. These results suggest that lowering the thresholds for acceptable air pollution levels may be prudent, as research has consistently found that some pollutants have negative impacts even at levels below current regulatory thresholds. Policy makers should also consider providing more information to pregnant women and families about when and where the risk of pollution exposure is highest so that they can employ avoidance behavior. PMID:22147868

Explicit processing demands reveal language modality-specific organization of working memory.

PubMed

Rudner, Mary; Rönnberg, Jerker

2008-01-01

The working memory model for Ease of Language Understanding (ELU) predicts that processing differences between language modalities emerge when cognitive demands are explicit. This prediction was tested in three working memory experiments with participants who were Deaf Signers (DS), Hearing Signers (HS), or Hearing Nonsigners (HN). Easily nameable pictures were used as stimuli to avoid confounds relating to sensory modality. Performance was largely similar for DS, HS, and HN, suggesting that previously identified intermodal differences may be due to differences in retention of sensory information. When explicit processing demands were high, differences emerged between DS and HN, suggesting that although working memory storage in both groups is sensitive to temporal organization, retrieval is not sensitive to temporal organization in DS. A general effect of semantic similarity was also found. These findings are discussed in relation to the ELU model.

Differential roles of childhood adversities and stressful war experiences in the development of mental health symptoms in post-war adolescents in northern Uganda.

PubMed

Okello, James; De Schryver, Maarten; Musisi, Seggane; Broekaert, Eric; Derluyn, Ilse

2014-09-09

Previous studies have shown a relationship between stressful war experiences and mental health symptoms in children and adolescents. To date, no comprehensive studies on the role of childhood adversities have been conducted with war-exposed adolescents living in post-war, low-resource settings in Sub-Saharan Africa. A cross-sectional study of 551 school-going adolescents aged 13-21 years old was undertaken four years post-war in northern Uganda. Participants completed self-administered questionnaires assessing demographics, stressful war experiences, childhood adversities, posttraumatic stress disorder (PTSD), depression, and anxiety symptoms. Our analyses revealed a main effect of gender on all mental health outcomes except avoidance symptoms, with girls reporting higher scores than boys. Stressful war experiences were associated with all mental health symptoms, after adjusting for potential confounders. Childhood adversity was independently associated with depression symptoms but not PTSD, anxiety, and PTSD cluster symptoms. However, in situations of high childhood adversity, our analyses showed that stressful war experiences were less associated with vulnerability to avoidance symptoms than in situations of low childhood adversity. Both stressful war experiences and childhood adversities are risk factors for mental health symptoms among war-affected adolescents. Adolescents with histories of high childhood adversities may be less likely to develop avoidance symptoms in situations of high stressful war experiences. Further exploration of the differential roles of childhood adversities and stressful war experiences is needed.

Case-control vaccine effectiveness studies: Data collection, analysis and reporting results.

PubMed

Verani, Jennifer R; Baqui, Abdullah H; Broome, Claire V; Cherian, Thomas; Cohen, Cheryl; Farrar, Jennifer L; Feikin, Daniel R; Groome, Michelle J; Hajjeh, Rana A; Johnson, Hope L; Madhi, Shabir A; Mulholland, Kim; O'Brien, Katherine L; Parashar, Umesh D; Patel, Manish M; Rodrigues, Laura C; Santosham, Mathuram; Scott, J Anthony; Smith, Peter G; Sommerfelt, Halvor; Tate, Jacqueline E; Victor, J Chris; Whitney, Cynthia G; Zaidi, Anita K; Zell, Elizabeth R

2017-06-05

The case-control methodology is frequently used to evaluate vaccine effectiveness post-licensure. The results of such studies provide important insight into the level of protection afforded by vaccines in a 'real world' context, and are commonly used to guide vaccine policy decisions. However, the potential for bias and confounding are important limitations to this method, and the results of a poorly conducted or incorrectly interpreted case-control study can mislead policies. In 2012, a group of experts met to review recent experience with case-control studies evaluating vaccine effectiveness; we summarize the recommendations of that group regarding best practices for data collection, analysis, and presentation of the results of case-control vaccine effectiveness studies. Vaccination status is the primary exposure of interest, but can be challenging to assess accurately and with minimal bias. Investigators should understand factors associated with vaccination as well as the availability of documented vaccination status in the study context; case-control studies may not be a valid method for evaluating vaccine effectiveness in settings where many children lack a documented immunization history. To avoid bias, it is essential to use the same methods and effort gathering vaccination data from cases and controls. Variables that may confound the association between illness and vaccination are also important to capture as completely as possible, and where relevant, adjust for in the analysis according to the analytic plan. In presenting results from case-control vaccine effectiveness studies, investigators should describe enrollment among eligible cases and controls as well as the proportion with no documented vaccine history. Emphasis should be placed on confidence intervals, rather than point estimates, of vaccine effectiveness. Case-control studies are a useful approach for evaluating vaccine effectiveness; however careful attention must be paid to the collection, analysis and presentation of the data in order to best inform evidence-based vaccine policies. Published by Elsevier Ltd.

Which Propensity Score Method Best Reduces Confounder Imbalance? An Example From a Retrospective Evaluation of a Childhood Obesity Intervention.

PubMed

Schroeder, Krista; Jia, Haomiao; Smaldone, Arlene

Propensity score (PS) methods are increasingly being employed by researchers to reduce bias arising from confounder imbalance when using observational data to examine intervention effects. The purpose of this study was to examine PS theory and methodology and compare application of three PS methods (matching, stratification, weighting) to determine which best improves confounder balance. Baseline characteristics of a sample of 20,518 school-aged children with severe obesity (of whom 1,054 received an obesity intervention) were assessed prior to PS application. Three PS methods were then applied to the data to determine which showed the greatest improvement in confounder balance between the intervention and control group. The effect of each PS method on the outcome variable-body mass index percentile change at one year-was also examined. SAS 9.4 and Comprehensive Meta-analysis statistical software were used for analyses. Prior to PS adjustment, the intervention and control groups differed significantly on seven of 11 potential confounders. PS matching removed all differences. PS stratification and weighting both removed one difference but created two new differences. Sensitivity analyses did not change these results. Body mass index percentile at 1 year decreased in both groups. The size of the decrease was smaller in the intervention group, and the estimate of the decrease varied by PS method. Selection of a PS method should be guided by insight from statistical theory and simulation experiments, in addition to observed improvement in confounder balance. For this data set, PS matching worked best to correct confounder imbalance. Because each method varied in correcting confounder imbalance, we recommend that multiple PS methods be compared for ability to improve confounder balance before implementation in evaluating treatment effects in observational data.

Nonlinear Predictive Models for Multiple Mediation Analysis: With an Application to Explore Ethnic Disparities in Anxiety and Depression Among Cancer Survivors.

PubMed

Yu, Qingzhao; Medeiros, Kaelen L; Wu, Xiaocheng; Jensen, Roxanne E

2018-04-02

Mediation analysis allows the examination of effects of a third variable (mediator/confounder) in the causal pathway between an exposure and an outcome. The general multiple mediation analysis method (MMA), proposed by Yu et al., improves traditional methods (e.g., estimation of natural and controlled direct effects) to enable consideration of multiple mediators/confounders simultaneously and the use of linear and nonlinear predictive models for estimating mediation/confounding effects. Previous studies find that compared with non-Hispanic cancer survivors, Hispanic survivors are more likely to endure anxiety and depression after cancer diagnoses. In this paper, we applied MMA on MY-Health study to identify mediators/confounders and quantify the indirect effect of each identified mediator/confounder in explaining ethnic disparities in anxiety and depression among cancer survivors who enrolled in the study. We considered a number of socio-demographic variables, tumor characteristics, and treatment factors as potential mediators/confounders and found that most of the ethnic differences in anxiety or depression between Hispanic and non-Hispanic white cancer survivors were explained by younger diagnosis age, lower education level, lower proportions of employment, less likely of being born in the USA, less insurance, and less social support among Hispanic patients.

On the definition of a confounder

PubMed Central

VanderWeele, Tyler J.; Shpitser, Ilya

2014-01-01

Summary The causal inference literature has provided a clear formal definition of confounding expressed in terms of counterfactual independence. The causal inference literature has not, however, produced a clear formal definition of a confounder, as it has given priority to the concept of confounding over that of a confounder. We consider a number of candidate definitions arising from various more informal statements made in the literature. We consider the properties satisfied by each candidate definition, principally focusing on (i) whether under the candidate definition control for all “confounders” suffices to control for “confounding” and (ii) whether each confounder in some context helps eliminate or reduce confounding bias. Several of the candidate definitions do not have these two properties. Only one candidate definition of those considered satisfies both properties. We propose that a “confounder” be defined as a pre-exposure covariate C for which there exists a set of other covariates X such that effect of the exposure on the outcome is unconfounded conditional on (X, C) but such that for no proper subset of (X, C) is the effect of the exposure on the outcome unconfounded given the subset. A variable that helps reduce bias but not eliminate bias we propose referring to as a “surrogate confounder.” PMID:25544784

Structural confounding of area-level deprivation and segreation: an empirical example

EPA Science Inventory

The neighborhood effects literature has grown, but its utility is limited by the lack of attention paid to non-random selection into neighborhoods. Confounding occurs when an exposure and an outcome share an underlying common cause. Confounding resulting from differential allocat...

Statistical primer: propensity score matching and its alternatives.

PubMed

Benedetto, Umberto; Head, Stuart J; Angelini, Gianni D; Blackstone, Eugene H

2018-06-01

Propensity score (PS) methods offer certain advantages over more traditional regression methods to control for confounding by indication in observational studies. Although multivariable regression models adjust for confounders by modelling the relationship between covariates and outcome, the PS methods estimate the treatment effect by modelling the relationship between confounders and treatment assignment. Therefore, methods based on the PS are not limited by the number of events, and their use may be warranted when the number of confounders is large, or the number of outcomes is small. The PS is the probability for a subject to receive a treatment conditional on a set of baseline characteristics (confounders). The PS is commonly estimated using logistic regression, and it is used to match patients with similar distribution of confounders so that difference in outcomes gives unbiased estimate of treatment effect. This review summarizes basic concepts of the PS matching and provides guidance in implementing matching and other methods based on the PS, such as stratification, weighting and covariate adjustment.

Electronic magnification and perceived contrast of video

PubMed Central

Haun, Andrew; Woods, Russell L; Peli, Eli

2012-01-01

Electronic magnification of an image results in a decrease in its perceived contrast. The decrease in perceived contrast could be due to a perceived blur or to limited sampling of the range of contrasts in the original image. We measured the effect on perceived contrast of magnification in two contexts: either a small video was enlarged to fill a larger area, or a portion of a larger video was enlarged to fill the same area as the original. Subjects attenuated the source video contrast to match the perceived contrast of the magnified videos, with the effect increasing with magnification and decreasing with viewing distance. These effects are consistent with expectations based on both the contrast statistics of natural images and the contrast sensitivity of the human visual system. We demonstrate that local regions within videos usually have lower physical contrast than the whole, and that this difference accounts for a minor part of the perceived differences. Instead, visibility of ‘missing content’ (blur) in a video is misinterpreted as a decrease in contrast. We detail how the effects of magnification on perceived contrast can be measured while avoiding confounding factors. PMID:23483111

An introduction to instrumental variables analysis: part 1.

PubMed

Bennett, Derrick A

2010-01-01

There are several examples in the medical literature where the associations of treatment effects predicted by observational studies have been refuted by evidence from subsequent large-scale randomised trials. This is because of the fact that non-experimental studies are subject to confounding - and confounding cannot be entirely eliminated even if all known confounders have been measured in the study as there may be unknown confounders. The aim of this 2-part methodological primer is to introduce an emerging methodology for estimating treatment effects using observational data in the absence of good randomised evidence known as the method of instrumental variables. Copyright © 2010 S. Karger AG, Basel.

Using instrumental variables to estimate a Cox's proportional hazards regression subject to additive confounding

PubMed Central

Tosteson, Tor D.; Morden, Nancy E.; Stukel, Therese A.; O'Malley, A. James

2014-01-01

The estimation of treatment effects is one of the primary goals of statistics in medicine. Estimation based on observational studies is subject to confounding. Statistical methods for controlling bias due to confounding include regression adjustment, propensity scores and inverse probability weighted estimators. These methods require that all confounders are recorded in the data. The method of instrumental variables (IVs) can eliminate bias in observational studies even in the absence of information on confounders. We propose a method for integrating IVs within the framework of Cox's proportional hazards model and demonstrate the conditions under which it recovers the causal effect of treatment. The methodology is based on the approximate orthogonality of an instrument with unobserved confounders among those at risk. We derive an estimator as the solution to an estimating equation that resembles the score equation of the partial likelihood in much the same way as the traditional IV estimator resembles the normal equations. To justify this IV estimator for a Cox model we perform simulations to evaluate its operating characteristics. Finally, we apply the estimator to an observational study of the effect of coronary catheterization on survival. PMID:25506259

Using instrumental variables to estimate a Cox's proportional hazards regression subject to additive confounding.

PubMed

MacKenzie, Todd A; Tosteson, Tor D; Morden, Nancy E; Stukel, Therese A; O'Malley, A James

2014-06-01

The estimation of treatment effects is one of the primary goals of statistics in medicine. Estimation based on observational studies is subject to confounding. Statistical methods for controlling bias due to confounding include regression adjustment, propensity scores and inverse probability weighted estimators. These methods require that all confounders are recorded in the data. The method of instrumental variables (IVs) can eliminate bias in observational studies even in the absence of information on confounders. We propose a method for integrating IVs within the framework of Cox's proportional hazards model and demonstrate the conditions under which it recovers the causal effect of treatment. The methodology is based on the approximate orthogonality of an instrument with unobserved confounders among those at risk. We derive an estimator as the solution to an estimating equation that resembles the score equation of the partial likelihood in much the same way as the traditional IV estimator resembles the normal equations. To justify this IV estimator for a Cox model we perform simulations to evaluate its operating characteristics. Finally, we apply the estimator to an observational study of the effect of coronary catheterization on survival.

Dietary and lifestyle correlates of passive smoking in Hong Kong, Japan, Sweden, and the U.S.A.

PubMed

Koo, L C; Kabat, G C; Rylander, R; Tominaga, S; Kato, I; Ho, J H

1997-07-01

From epidemiologic studies in several countries, passive smoking has been associated with increased risk for lung cancer, respiratory diseases, and coronary heart disease. Since the relative risks derived from those studies are weak, i.e. relative risk less than two, we investigated whether poorer diets and less healthy lifestyles might act as confounders and be correlated with having a smoking husband on a cross-cultural basis. Characteristics of never-smoked wives with or without smoking husbands were compared between 530 women from Hong Kong, 13,047 from Japan, 87 from Sweden, and 144 from the U.S. In all four sites, wives with smoking husbands generally ate less healthy diets. They had a tendency to eat more fried food but less fruit than wives with nonsmoking husbands. Other healthy traits, e.g. avoiding obesity, dietary cholesterol and alcohol, or taking vitamins and participating in preventive screening were also less prevalent among wives with smoking husbands. These patterns suggest that never-smoked wives with smoking husbands tend to share the same less healthy dietary traits characteristic of smokers, and to have dietary habits associated with increased risk for lung cancer and heart disease in their societies. These results emphasize the need to take into account the potential confounding effects of diet and lifestyle in studies evaluating the health effects of passive smoking, especially since it is known that the current prevalence rates of smoking among men is indirectly associated with social class and education in affluent urban societies.

Interpretational confounding is due to misspecification, not to type of indicator: comment on Howell, Breivik, and Wilcox (2007).

PubMed

Bollen, Kenneth A

2007-06-01

R. D. Howell, E. Breivik, and J. B. Wilcox (2007) have argued that causal (formative) indicators are inherently subject to interpretational confounding. That is, they have argued that using causal (formative) indicators leads the empirical meaning of a latent variable to be other than that assigned to it by a researcher. Their critique of causal (formative) indicators rests on several claims: (a) A latent variable exists apart from the model when there are effect (reflective) indicators but not when there are causal (formative) indicators, (b) causal (formative) indicators need not have the same consequences, (c) causal (formative) indicators are inherently subject to interpretational confounding, and (d) a researcher cannot detect interpretational confounding when using causal (formative) indicators. This article shows that each claim is false. Rather, interpretational confounding is more a problem of structural misspecification of a model combined with an underidentified model that leaves these misspecifications undetected. Interpretational confounding does not occur if the model is correctly specified whether a researcher has causal (formative) or effect (reflective) indicators. It is the validity of a model not the type of indicator that determines the potential for interpretational confounding. Copyright 2007 APA, all rights reserved.

A New Method for Partial Correction of Residual Confounding in Time-Series and Other Observational Studies.

PubMed

Flanders, W Dana; Strickland, Matthew J; Klein, Mitchel

2017-05-15

Methods exist to detect residual confounding in epidemiologic studies. One requires a negative control exposure with 2 key properties: 1) conditional independence of the negative control and the outcome (given modeled variables) absent confounding and other model misspecification, and 2) associations of the negative control with uncontrolled confounders and the outcome. We present a new method to partially correct for residual confounding: When confounding is present and our assumptions hold, we argue that estimators from models that include a negative control exposure with these 2 properties tend to be less biased than those from models without it. Using regression theory, we provide theoretical arguments that support our claims. In simulations, we empirically evaluated the approach using a time-series study of ozone effects on asthma emergency department visits. In simulations, effect estimators from models that included the negative control exposure (ozone concentrations 1 day after the emergency department visit) had slightly or modestly less residual confounding than those from models without it. Theory and simulations show that including the negative control can reduce residual confounding, if our assumptions hold. Our method differs from available methods because it uses a regression approach involving an exposure-based indicator rather than a negative control outcome to partially correct for confounding. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Efficient Bayesian mixed model analysis increases association power in large cohorts

PubMed Central

Loh, Po-Ru; Tucker, George; Bulik-Sullivan, Brendan K; Vilhjálmsson, Bjarni J; Finucane, Hilary K; Salem, Rany M; Chasman, Daniel I; Ridker, Paul M; Neale, Benjamin M; Berger, Bonnie; Patterson, Nick; Price, Alkes L

2014-01-01

Linear mixed models are a powerful statistical tool for identifying genetic associations and avoiding confounding. However, existing methods are computationally intractable in large cohorts, and may not optimize power. All existing methods require time cost O(MN2) (where N = #samples and M = #SNPs) and implicitly assume an infinitesimal genetic architecture in which effect sizes are normally distributed, which can limit power. Here, we present a far more efficient mixed model association method, BOLT-LMM, which requires only a small number of O(MN)-time iterations and increases power by modeling more realistic, non-infinitesimal genetic architectures via a Bayesian mixture prior on marker effect sizes. We applied BOLT-LMM to nine quantitative traits in 23,294 samples from the Women’s Genome Health Study (WGHS) and observed significant increases in power, consistent with simulations. Theory and simulations show that the boost in power increases with cohort size, making BOLT-LMM appealing for GWAS in large cohorts. PMID:25642633

Assessing mediation using marginal structural models in the presence of confounding and moderation

PubMed Central

Coffman, Donna L.; Zhong, Wei

2012-01-01

This paper presents marginal structural models (MSMs) with inverse propensity weighting (IPW) for assessing mediation. Generally, individuals are not randomly assigned to levels of the mediator. Therefore, confounders of the mediator and outcome may exist that limit causal inferences, a goal of mediation analysis. Either regression adjustment or IPW can be used to take confounding into account, but IPW has several advantages. Regression adjustment of even one confounder of the mediator and outcome that has been influenced by treatment results in biased estimates of the direct effect (i.e., the effect of treatment on the outcome that does not go through the mediator). One advantage of IPW is that it can properly adjust for this type of confounding, assuming there are no unmeasured confounders. Further, we illustrate that IPW estimation provides unbiased estimates of all effects when there is a baseline moderator variable that interacts with the treatment, when there is a baseline moderator variable that interacts with the mediator, and when the treatment interacts with the mediator. IPW estimation also provides unbiased estimates of all effects in the presence of non-randomized treatments. In addition, for testing mediation we propose a test of the null hypothesis of no mediation. Finally, we illustrate this approach with an empirical data set in which the mediator is continuous, as is often the case in psychological research. PMID:22905648

Assessing mediation using marginal structural models in the presence of confounding and moderation.

PubMed

Coffman, Donna L; Zhong, Wei

2012-12-01

This article presents marginal structural models with inverse propensity weighting (IPW) for assessing mediation. Generally, individuals are not randomly assigned to levels of the mediator. Therefore, confounders of the mediator and outcome may exist that limit causal inferences, a goal of mediation analysis. Either regression adjustment or IPW can be used to take confounding into account, but IPW has several advantages. Regression adjustment of even one confounder of the mediator and outcome that has been influenced by treatment results in biased estimates of the direct effect (i.e., the effect of treatment on the outcome that does not go through the mediator). One advantage of IPW is that it can properly adjust for this type of confounding, assuming there are no unmeasured confounders. Further, we illustrate that IPW estimation provides unbiased estimates of all effects when there is a baseline moderator variable that interacts with the treatment, when there is a baseline moderator variable that interacts with the mediator, and when the treatment interacts with the mediator. IPW estimation also provides unbiased estimates of all effects in the presence of nonrandomized treatments. In addition, for testing mediation we propose a test of the null hypothesis of no mediation. Finally, we illustrate this approach with an empirical data set in which the mediator is continuous, as is often the case in psychological research. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Avoiding false discoveries in association studies.

PubMed

Sabatti, Chiara

2007-01-01

We consider the problem of controlling false discoveries in association studies. We assume that the design of the study is adequate so that the "false discoveries" are potentially only because of random chance, not to confounding or other flaws. Under this premise, we review the statistical framework for hypothesis testing and correction for multiple comparisons. We consider in detail the currently accepted strategies in linkage analysis. We then examine the underlying similarities and differences between linkage and association studies and document some of the most recent methodological developments for association mapping.

Are personality disorders associated with social welfare burden in the United States?

PubMed

Vaughn, Michael G; Fu, Quana; Beaver, Devin; DeLisi, Matt; Perron, Brian; Howard, Matthew

2010-12-01

This study examined the association between personality disorders and use of major social welfare services in a nationally representative sample of U.S. adults (N = 43,093). Social welfare services received and diagnoses of personality, substance use, mood, and anxiety disorders were assessed with the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV-version. Analyses quantified the association between personality disorders and forms of public assistance while controlling for numerous confounds. Logistic regression analyses revealed dependent personality disorder, paranoid personality disorder, antisocial personality disorder, and avoidant personality disorder were significantly associated with increased odds of receiving public assistance. In contrast, persons diagnosed with histrionic, schizoid, and obsessive-personality disorder were not significantly more likely to receive any public welfare service. Development of effective prevention and treatment of personality disorders would likely lead to reductions in overall social welfare burden.

The role of kinetic context in apparent biased agonism at GPCRs

PubMed Central

Klein Herenbrink, Carmen; Sykes, David A.; Donthamsetti, Prashant; Canals, Meritxell; Coudrat, Thomas; Shonberg, Jeremy; Scammells, Peter J.; Capuano, Ben; Sexton, Patrick M.; Charlton, Steven J.; Javitch, Jonathan A.; Christopoulos, Arthur; Lane, J. Robert

2016-01-01

Biased agonism describes the ability of ligands to stabilize different conformations of a GPCR linked to distinct functional outcomes and offers the prospect of designing pathway-specific drugs that avoid on-target side effects. This mechanism is usually inferred from pharmacological data with the assumption that the confounding influences of observational (that is, assay dependent) and system (that is, cell background dependent) bias are excluded by experimental design and analysis. Here we reveal that ‘kinetic context', as determined by ligand-binding kinetics and the temporal pattern of receptor-signalling processes, can have a profound influence on the apparent bias of a series of agonists for the dopamine D2 receptor and can even lead to reversals in the direction of bias. We propose that kinetic context must be acknowledged in the design and interpretation of studies of biased agonism. PMID:26905976

Regular Tooth Brushing is Associated with a Decreased Risk of Metabolic Syndrome According to a Medical Check-Up Database.

PubMed

Tsutsumi, Chiyo; Kakuma, Tatsuyuki

2015-01-01

Associations have been reported between periodontal disease and increased cardiovascular disease risk, as well as between healthy self-reported tooth brushing behavior and reduced cardiovascular disease risk. We examined the association between self-reported tooth brushing behavior and the risk of metabolic syndrome (MetS) using a large medical check-up database. A total of 12,548 medical checkup records from a medical screening center in a city in southwest Japan were assessed. Subjects were aged 30 to 59 years. As lifestyle is associated with both tooth brushing and MetS, many lifestyle variables were considered as potential confounders. Logistic regression model were employed with a list of 127 lifestyle variables. Twenty variables associated with both tooth brushing and MetS were selected for both males and females. Furthermore, final confounding variables were selected by principal component analysis to avoid collinearity problems. The association of tooth brushing and MetS was evaluated for males and females separately by calculating adjusted odds ratios (ORs) with selected confounders plus age. The association between daily tooth brushing frequency and MetS risk for both genders was significant after adjusting for confounders, with the risk of MetS decreasing with increased frequency of daily tooth brushing (adjusted OR = 0.57 (95%Cl:0.48-0.81), 0.50 (95%Cl:0.35-0.71), 0.42 (95%Cl: 0.29-0.61) for males and adjusted OR = 0.65 (95%Cl:0.48-0.87), 0.44 (95%Cl:0.32-0.62) for females). Therefore, oral hygiene, including the frequency of tooth brushing as a significant component, may be an important factor in preventing MetS.

Effect decomposition in the presence of an exposure-induced mediator-outcome confounder

PubMed Central

VanderWeele, Tyler J.; Vansteelandt, Stijn; Robins, James M.

2014-01-01

Methods from causal mediation analysis have generalized the traditional approach to direct and indirect effects in the epidemiologic and social science literature by allowing for interaction and non-linearities. However, the methods from the causal inference literature have themselves been subject to a major limitation in that the so-called natural direct and indirect effects that are employed are not identified from data whenever there is a variable that is affected by the exposure, which also confounds the relationship between the mediator and the outcome. In this paper we describe three alternative approaches to effect decomposition that give quantities that can be interpreted as direct and indirect effects, and that can be identified from data even in the presence of an exposure-induced mediator-outcome confounder. We describe a simple weighting-based estimation method for each of these three approaches, illustrated with data from perinatal epidemiology. The methods described here can shed insight into pathways and questions of mediation even when an exposure-induced mediator-outcome confounder is present. PMID:24487213

Open field exposure facilitates recovery from an aversive emotional event: Involvement of adrenergic and cholinergic transmitter systems.

PubMed

Psyrdellis, Mariana; Pautassi, Ricardo Marcos; Justel, Nadia

2016-10-28

Successive negative contrast (SNC) is an incentive relativity procedure that has been widely used to model emotional reactivity in rodents. The reward downshift experienced during SNC is thought to result in frustration. The exploration of a novel open field (OF), a complex situation involving stress induction and novelty detection, can enhance or block the acquisition of associative and non-associative memories. Previous experiments found a modulatory effect of OF, applied before downshift trials, on SNC. This schedule, however, can affect retention performance by influencing attentional, motivational, motor or sensory-perceptual mechanisms at training or retention testing. The use of post-training OF exposure avoids these confounds. This work assessed the effect of OF exposure after the acquisition of the downshifted memory, with the goal of targeting the consolidation of this mnemonic trace. We also investigated the involvement of the cholinergic and adrenergic systems in this phenomenon. The results indicated that OF facilitates recovery from reward loss and that both transmitter systems, cholinergic and adrenergic, play a role in this effect of OF. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Causal Methods for Observational Research: A Primer.

PubMed

Almasi-Hashiani, Amir; Nedjat, Saharnaz; Mansournia, Mohammad Ali

2018-04-01

The goal of many observational studies is to estimate the causal effect of an exposure on an outcome after adjustment for confounders, but there are still some serious errors in adjusting confounders in clinical journals. Standard regression modeling (e.g., ordinary logistic regression) fails to estimate the average effect of exposure in total population in the presence of interaction between exposure and covariates, and also cannot adjust for time-varying confounding appropriately. Moreover, stepwise algorithms of the selection of confounders based on P values may miss important confounders and lead to bias in effect estimates. Causal methods overcome these limitations. We illustrate three causal methods including inverse-probability-of-treatment-weighting (IPTW) and parametric g-formula, with an emphasis on a clever combination of these 2 methods: targeted maximum likelihood estimation (TMLE) which enjoys a double-robust property against bias. © 2018 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The role of life events and psychological factors in the onset of first and recurrent mood episodes in bipolar offspring: results from the Dutch Bipolar Offspring Study.

PubMed

Kemner, S M; Mesman, E; Nolen, W A; Eijckemans, M J C; Hillegers, M H J

2015-01-01

Life events are an established risk factor for the onset and recurrence of unipolar and bipolar mood episodes, especially in the presence of genetic vulnerability. The dynamic interplay between life events and psychological context, however, is less studied. In this study, we investigated the impact of life events on the onset and recurrence of mood episodes in bipolar offspring, as well as the effects of temperament, coping and parenting style on this association. Bipolar offspring (n = 108) were followed longitudinally from adolescence to adulthood. Mood disorders were assessed with: the Kiddie Schedule of Affective Disorders and Schizophrenia - Present and Lifetime Version or the Structured Clinical Interview for DSM-IV Axis I disorders; life events with the Life Events and Difficulties Schedule; and psychological measures using the Utrecht Coping List, Temperament and Character Inventory and short-EMBU (memories of upbringing instrument). Anderson-Gill models (an extension of the Cox proportional hazard model) were utilized. Life events were associated with an increased risk for first and, although less pronounced, subsequent mood episodes. There was a large confounding effect for the number of previous mood episodes; findings suggest a possible kindling effect. Passive coping style increased the risk of mood episode onset and recurrent episodes, but also altered the effect of life events on mood disorders. Harm avoidance temperament was associated with mood episode recurrence. Life events are especially a risk factor in the onset of mood disorders, though less so in recurrent episodes. Psychological features (passive coping and harm-avoidant temperament) contribute to the risk of an episode occurring, and also have a moderating effect on the association between life events and mood episodes. These findings create potential early intervention strategies for bipolar offspring.

More Precise Estimation of Lower-Level Interaction Effects in Multilevel Models.

PubMed

Loeys, Tom; Josephy, Haeike; Dewitte, Marieke

2018-01-01

In hierarchical data, the effect of a lower-level predictor on a lower-level outcome may often be confounded by an (un)measured upper-level factor. When such confounding is left unaddressed, the effect of the lower-level predictor is estimated with bias. Separating this effect into a within- and between-component removes such bias in a linear random intercept model under a specific set of assumptions for the confounder. When the effect of the lower-level predictor is additionally moderated by another lower-level predictor, an interaction between both lower-level predictors is included into the model. To address unmeasured upper-level confounding, this interaction term ought to be decomposed into a within- and between-component as well. This can be achieved by first multiplying both predictors and centering that product term next, or vice versa. We show that while both approaches, on average, yield the same estimates of the interaction effect in linear models, the former decomposition is much more precise and robust against misspecification of the effects of cross-level and upper-level terms, compared to the latter.

Brain activation related to the perception of minimal agency cues: the role of the mirror system.

PubMed

Stosic, Marina; Brass, Marcel; Van Hoeck, Nicole; Ma, Ning; Van Overwalle, Frank

2014-02-01

Recent fMRI studies indicate that the posterior superior temporal sulcus (pSTS) and the mirror system are involved in analyzing goal-directed actions performed by non-human objects. However, these studies have some limitations: the animations showed moving shapes that resemble humans and human movement, or showed the interaction of two moving shapes rather than one alone. This may have prompted participants to assume a human agent instead of an object. To avoid this potential confound, in this study, animations showed a small circular shape (agent) jumping toward a bigger circular shape (goal) with an obstacle separating them. We manipulated agency of the small circular shape by showing its movements as self-propelled (Agent condition) or as launched by a lever mechanism (Non-agent condition). The small shape succeeded in avoiding an obstacle and reaching the goal object or failed to do so. Our results showed that goal-directed actions performed by an agentic shape recruited the mirror system (the inferior parietal lobe and the premotor cortex) in comparison with shapes that were launched. Success or failure to avoid the obstacle had no effect on these areas. These results complement and further extend previous findings indicating that the mirror system does not appear to be selective for biological actions and their goals, nor does it require the presence of a human, human body parts or human-made objects. Instead, it seems to play a general role in representing goal-directed actions of agents regardless of their form. © 2013.

The Combined Effects of Measurement Error and Omitting Confounders in the Single-Mediator Model

PubMed Central

Fritz, Matthew S.; Kenny, David A.; MacKinnon, David P.

2016-01-01

Mediation analysis requires a number of strong assumptions be met in order to make valid causal inferences. Failing to account for violations of these assumptions, such as not modeling measurement error or omitting a common cause of the effects in the model, can bias the parameter estimates of the mediated effect. When the independent variable is perfectly reliable, for example when participants are randomly assigned to levels of treatment, measurement error in the mediator tends to underestimate the mediated effect, while the omission of a confounding variable of the mediator to outcome relation tends to overestimate the mediated effect. Violations of these two assumptions often co-occur, however, in which case the mediated effect could be overestimated, underestimated, or even, in very rare circumstances, unbiased. In order to explore the combined effect of measurement error and omitted confounders in the same model, the impact of each violation on the single-mediator model is first examined individually. Then the combined effect of having measurement error and omitted confounders in the same model is discussed. Throughout, an empirical example is provided to illustrate the effect of violating these assumptions on the mediated effect. PMID:27739903

Bayesian effect estimation accounting for adjustment uncertainty.

PubMed

Wang, Chi; Parmigiani, Giovanni; Dominici, Francesca

2012-09-01

Model-based estimation of the effect of an exposure on an outcome is generally sensitive to the choice of which confounding factors are included in the model. We propose a new approach, which we call Bayesian adjustment for confounding (BAC), to estimate the effect of an exposure of interest on the outcome, while accounting for the uncertainty in the choice of confounders. Our approach is based on specifying two models: (1) the outcome as a function of the exposure and the potential confounders (the outcome model); and (2) the exposure as a function of the potential confounders (the exposure model). We consider Bayesian variable selection on both models and link the two by introducing a dependence parameter, ω, denoting the prior odds of including a predictor in the outcome model, given that the same predictor is in the exposure model. In the absence of dependence (ω= 1), BAC reduces to traditional Bayesian model averaging (BMA). In simulation studies, we show that BAC, with ω > 1, estimates the exposure effect with smaller bias than traditional BMA, and improved coverage. We, then, compare BAC, a recent approach of Crainiceanu, Dominici, and Parmigiani (2008, Biometrika 95, 635-651), and traditional BMA in a time series data set of hospital admissions, air pollution levels, and weather variables in Nassau, NY for the period 1999-2005. Using each approach, we estimate the short-term effects of on emergency admissions for cardiovascular diseases, accounting for confounding. This application illustrates the potentially significant pitfalls of misusing variable selection methods in the context of adjustment uncertainty. © 2012, The International Biometric Society.

Effect of Hydration State of Martian Perchlorate Salts on Their Decomposition Temperatures During Thermal Extraction

NASA Astrophysics Data System (ADS)

Royle, Samuel H.; Montgomery, Wren; Kounaves, Samuel P.; Sephton, Mark A.

2017-12-01

Three Mars missions have analyzed the composition of surface samples using thermal extraction techniques. The temperatures of decomposition have been used as diagnostic information for the materials present. One compound of great current interest is perchlorate, a relatively recently discovered component of Mars' surface geochemistry that leads to deleterious effects on organic matter during thermal extraction. Knowledge of the thermal decomposition behavior of perchlorate salts is essential for mineral identification and possible avoidance of confounding interactions with organic matter. We have performed a series of experiments which reveal that the hydration state of magnesium perchlorate has a significant effect on decomposition temperature, with differing temperature releases of oxygen corresponding to different perchlorate hydration states (peak of O2 release shifts from 500 to 600°C as the proportion of the tetrahydrate form in the sample increases). Changes in crystallinity/crystal size may also have a secondary effect on the temperature of decomposition, and although these surface effects appear to be minor for our samples, further investigation may be warranted. A less than full appreciation of the hydration state of perchlorate salts during thermal extraction analyses could lead to misidentification of the number and the nature of perchlorate phases present.

Doubly robust matching estimators for high dimensional confounding adjustment.

PubMed

Antonelli, Joseph; Cefalu, Matthew; Palmer, Nathan; Agniel, Denis

2018-05-11

Valid estimation of treatment effects from observational data requires proper control of confounding. If the number of covariates is large relative to the number of observations, then controlling for all available covariates is infeasible. In cases where a sparsity condition holds, variable selection or penalization can reduce the dimension of the covariate space in a manner that allows for valid estimation of treatment effects. In this article, we propose matching on both the estimated propensity score and the estimated prognostic scores when the number of covariates is large relative to the number of observations. We derive asymptotic results for the matching estimator and show that it is doubly robust in the sense that only one of the two score models need be correct to obtain a consistent estimator. We show via simulation its effectiveness in controlling for confounding and highlight its potential to address nonlinear confounding. Finally, we apply the proposed procedure to analyze the effect of gender on prescription opioid use using insurance claims data. © 2018, The International Biometric Society.

An operant-based detection method for inferring tinnitus in mice.

PubMed

Zuo, Hongyan; Lei, Debin; Sivaramakrishnan, Shobhana; Howie, Benjamin; Mulvany, Jessica; Bao, Jianxin

2017-11-01

Subjective tinnitus is a hearing disorder in which a person perceives sound when no external sound is present. It can be acute or chronic. Because our current understanding of its pathology is incomplete, no effective cures have yet been established. Mouse models are useful for studying the pathophysiology of tinnitus as well as for developing therapeutic treatments. We have developed a new method for determining acute and chronic tinnitus in mice, called sound-based avoidance detection (SBAD). The SBAD method utilizes one paradigm to detect tinnitus and another paradigm to monitor possible confounding factors, such as motor impairment, loss of motivation, and deficits in learning and memory. The SBAD method has succeeded in monitoring both acute and chronic tinnitus in mice. Its detection ability is further validated by functional studies demonstrating an abnormal increase in neuronal activity in the inferior colliculus of mice that had previously been identified as having tinnitus by the SBAD method. The SBAD method provides a new means by which investigators can detect tinnitus in a single mouse accurately and with more control over potential confounding factors than existing methods. This work establishes a new behavioral method for detecting tinnitus in mice. The detection outcome is consistent with functional validation. One key advantage of mouse models is they provide researchers the opportunity to utilize an extensive array of genetic tools. This new method could lead to a deeper understanding of the molecular pathways underlying tinnitus pathology. Copyright © 2017 Elsevier B.V. All rights reserved.

Adaptive design of visual perception experiments

NASA Astrophysics Data System (ADS)

O'Connor, John D.; Hixson, Jonathan; Thomas, James M., Jr.; Peterson, Matthew S.; Parasuraman, Raja

2010-04-01

Meticulous experimental design may not always prevent confounds from affecting experimental data acquired during visual perception experiments. Although experimental controls reduce the potential effects of foreseen sources of interference, interaction, or noise, they are not always adequate for preventing the confounding effects of unforeseen forces. Visual perception experimentation is vulnerable to unforeseen confounds because of the nature of the associated cognitive processes involved in the decision task. Some confounds are beyond the control of experimentation, such as what a participant does immediately prior to experimental participation, or the participant's attitude or emotional state. Other confounds may occur through ignorance of practical control methods on the part of the experiment's designer. The authors conducted experiments related to experimental fatigue and initially achieved significant results that were, upon re-examination, attributable to a lack of adequate controls. Re-examination of the original results and the processes and events that led to them yielded a second experimental design with more experimental controls and significantly different results. The authors propose that designers of visual perception experiments can benefit from planning to use a test-fix-test or adaptive experimental design cycle, so that unforeseen confounds in the initial design can be remedied.

Instrumental Variable Methods for Continuous Outcomes That Accommodate Nonignorable Missing Baseline Values.

PubMed

Ertefaie, Ashkan; Flory, James H; Hennessy, Sean; Small, Dylan S

2017-06-15

Instrumental variable (IV) methods provide unbiased treatment effect estimation in the presence of unmeasured confounders under certain assumptions. To provide valid estimates of treatment effect, treatment effect confounders that are associated with the IV (IV-confounders) must be included in the analysis, and not including observations with missing values may lead to bias. Missing covariate data are particularly problematic when the probability that a value is missing is related to the value itself, which is known as nonignorable missingness. In such cases, imputation-based methods are biased. Using health-care provider preference as an IV method, we propose a 2-step procedure with which to estimate a valid treatment effect in the presence of baseline variables with nonignorable missing values. First, the provider preference IV value is estimated by performing a complete-case analysis using a random-effects model that includes IV-confounders. Second, the treatment effect is estimated using a 2-stage least squares IV approach that excludes IV-confounders with missing values. Simulation results are presented, and the method is applied to an analysis comparing the effects of sulfonylureas versus metformin on body mass index, where the variables baseline body mass index and glycosylated hemoglobin have missing values. Our result supports the association of sulfonylureas with weight gain. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Long-term therapy in COPD: any evidence of adverse effect on bone?

PubMed Central

Langhammer, Arnulf; Forsmo, Siri; Syversen, Unni

2009-01-01

Patients with COPD have high risk for osteoporosis and fractures. Hip and vertebral fractures might impair mobility, and vertebral fractures further reduce lung function. This review discusses the evidence of bone loss due to medical treatment opposed to disease severity and risk factors for COPD, and therapeutic options for the prevention and treatment of osteoporosis in these patients. A review of the English-language literature was conducted using the MEDLINE database until June 2009. Currently used bronchodilators probably lack adverse effect on bone. Oral corticosteroids (OCS) increase bone resorption and decrease bone formation in a dose response relationship, but the fracture risk is increased more than reflected by bone densitometry. Inhaled corticosteroids (ICS) have been associated with both increased bone loss and fracture risk. This might be a result of confounding by disease severity, but high doses of ICS have similar effects as equipotent doses of OCS. The life-style factors should be modified, use of regular OCS avoided and use of ICS restricted to those with evidenced effect and probably kept at moderate doses. The health care should actively reveal risk factors, include bone densitometry in fracture risk evaluation, and give adequate prevention and treatment for osteoporosis. PMID:19888355

An education gradient in health, a health gradient in education, or a confounded gradient in both?

PubMed

Lynch, Jamie L; von Hippel, Paul T

2016-04-01

There is a positive gradient associating educational attainment with health, yet the explanation for this gradient is not clear. Does higher education improve health (causation)? Do the healthy become highly educated (selection)? Or do good health and high educational attainment both result from advantages established early in the life course (confounding)? This study evaluates these competing explanations by tracking changes in educational attainment and Self-rated Health (SRH) from age 15 to age 31 in the National Longitudinal Study of Youth, 1997 cohort. Ordinal logistic regression confirms that high-SRH adolescents are more likely to become highly educated. This is partly because adolescent SRH is associated with early advantages including adolescents' academic performance, college plans, and family background (confounding); however, net of these confounders adolescent SRH still predicts adult educational attainment (selection). Fixed-effects longitudinal regression shows that educational attainment has little causal effect on SRH at age 31. Completion of a high school diploma or associate's degree has no effect on SRH, while completion of a bachelor's or graduate degree have effects that, though significant, are quite small (less than 0.1 points on a 5-point scale). While it is possible that educational attainment would have greater effect on health at older ages, at age 31 what we see is a health gradient in education, shaped primarily by selection and confounding rather than by a causal effect of education on health. Copyright © 2016 Elsevier Ltd. All rights reserved.

The ACCE method: an approach for obtaining quantitative or qualitative estimates of residual confounding that includes unmeasured confounding

PubMed Central

Smith, Eric G.

2015-01-01

Background:  Nonrandomized studies typically cannot account for confounding from unmeasured factors.  Method:  A method is presented that exploits the recently-identified phenomenon of  “confounding amplification” to produce, in principle, a quantitative estimate of total residual confounding resulting from both measured and unmeasured factors.  Two nested propensity score models are constructed that differ only in the deliberate introduction of an additional variable(s) that substantially predicts treatment exposure.  Residual confounding is then estimated by dividing the change in treatment effect estimate between models by the degree of confounding amplification estimated to occur, adjusting for any association between the additional variable(s) and outcome. Results:  Several hypothetical examples are provided to illustrate how the method produces a quantitative estimate of residual confounding if the method’s requirements and assumptions are met.  Previously published data is used to illustrate that, whether or not the method routinely provides precise quantitative estimates of residual confounding, the method appears to produce a valuable qualitative estimate of the likely direction and general size of residual confounding. Limitations:  Uncertainties exist, including identifying the best approaches for: 1) predicting the amount of confounding amplification, 2) minimizing changes between the nested models unrelated to confounding amplification, 3) adjusting for the association of the introduced variable(s) with outcome, and 4) deriving confidence intervals for the method’s estimates (although bootstrapping is one plausible approach). Conclusions:  To this author’s knowledge, it has not been previously suggested that the phenomenon of confounding amplification, if such amplification is as predictable as suggested by a recent simulation, provides a logical basis for estimating total residual confounding. The method's basic approach is straightforward.  The method's routine usefulness, however, has not yet been established, nor has the method been fully validated. Rapid further investigation of this novel method is clearly indicated, given the potential value of its quantitative or qualitative output. PMID:25580226

Teacher Quality at the High-School Level: The Importance of Accounting for Tracks. Working Paper 17722. Revised

ERIC Educational Resources Information Center

Jackson, C. Kirabo

2013-01-01

Unlike in elementary school, high-school teacher effects may be confounded with both selection to tracks and unobserved track-level treatments. I document sizable confounding track effects, and show that traditional tests for the existence of teacher effects are likely biased. After accounting for these biases, high-school algebra and English…

Avoidance of sun exposure as a risk factor for major causes of death: a competing risk analysis of the Melanoma in Southern Sweden cohort.

PubMed

Lindqvist, P G; Epstein, E; Nielsen, K; Landin-Olsson, M; Ingvar, C; Olsson, H

2016-10-01

Women with active sunlight exposure habits experience a lower mortality rate than women who avoid sun exposure; however, they are at an increased risk of skin cancer. We aimed to explore the differences in main causes of death according to sun exposure. We assessed the differences in sun exposure as a risk factor for all-cause mortality in a competing risk scenario for 29 518 Swedish women in a prospective 20-year follow-up of the Melanoma in Southern Sweden (MISS) cohort. Women were recruited from 1990 to 1992 (aged 25-64 years at the start of the study). We obtained detailed information at baseline on sun exposure habits and potential confounders. The data were analysed using modern survival statistics. Women with active sun exposure habits were mainly at a lower risk of cardiovascular disease (CVD) and noncancer/non-CVD death as compared to those who avoided sun exposure. As a result of their increased survival, the relative contribution of cancer death increased in these women. Nonsmokers who avoided sun exposure had a life expectancy similar to smokers in the highest sun exposure group, indicating that avoidance of sun exposure is a risk factor for death of a similar magnitude as smoking. Compared to the highest sun exposure group, life expectancy of avoiders of sun exposure was reduced by 0.6-2.1 years. The longer life expectancy amongst women with active sun exposure habits was related to a decrease in CVD and noncancer/non-CVD mortality, causing the relative contribution of death due to cancer to increase. © 2016 The Association for the Publication of the Journal of Internal Medicine.

Do hedonic motives moderate regulatory focus motives? Evidence from the framing of persuasive messages.

PubMed

Malaviya, Prashant; Brendl, C Miguel

2014-01-01

Research on regulatory focus has established a regulatory matching effect: The persuasiveness of a message is enhanced when regulatory orientations of message and perceiver match (i.e., both are promotion or both are prevention). We report evidence that varying the hedonic outcome reverses this effect. We manipulated hedonic outcome by explicitly stating pleasurable versus painful outcomes as part of the message frame as well as by priming perceivers to focus on either pleasurable or painful outcomes. When both message and perceiver were focused on pleasurable outcomes, we replicated the regulatory matching effect. However, the matching effect reversed when the hedonic outcome of the message was opposed to that of the perceiver (i.e., one was pleasurable and the other painful). Under these conditions, messages that mismatched the perceivers' regulatory orientation were more persuasive (i.e., promotion message for a prevention oriented perceiver or vice versa). We also examined the persuasion effects when both message and perceiver were focused on painful outcomes and found that the regulatory matching effect re-emerged. The reversal of the regulatory matching effect by hedonic outcome strongly suggests that hedonic motives (approach of pleasure vs. avoidance of pain) and regulatory focus motives are distinct constructs. This is important because contrary to theoretical statements these constructs have often been confounded.

Confounding adjustment in comparative effectiveness research conducted within distributed research networks.

PubMed

Toh, Sengwee; Gagne, Joshua J; Rassen, Jeremy A; Fireman, Bruce H; Kulldorff, Martin; Brown, Jeffrey S

2013-08-01

A distributed research network (DRN) of electronic health care databases, in which data reside behind the firewall of each data partner, can support a wide range of comparative effectiveness research (CER) activities. An essential component of a fully functional DRN is the capability to perform robust statistical analyses to produce valid, actionable evidence without compromising patient privacy, data security, or proprietary interests. We describe the strengths and limitations of different confounding adjustment approaches that can be considered in observational CER studies conducted within DRNs, and the theoretical and practical issues to consider when selecting among them in various study settings. Several methods can be used to adjust for multiple confounders simultaneously, either as individual covariates or as confounder summary scores (eg, propensity scores and disease risk scores), including: (1) centralized analysis of patient-level data, (2) case-centered logistic regression of risk set data, (3) stratified or matched analysis of aggregated data, (4) distributed regression analysis, and (5) meta-analysis of site-specific effect estimates. These methods require different granularities of information be shared across sites and afford investigators different levels of analytic flexibility. DRNs are growing in use and sharing of highly detailed patient-level information is not always feasible in DRNs. Methods that incorporate confounder summary scores allow investigators to adjust for a large number of confounding factors without the need to transfer potentially identifiable information in DRNs. They have the potential to let investigators perform many analyses traditionally conducted through a centralized dataset with detailed patient-level information.

Restricted spatial regression in practice: Geostatistical models, confounding, and robustness under model misspecification

USGS Publications Warehouse

Hanks, Ephraim M.; Schliep, Erin M.; Hooten, Mevin B.; Hoeting, Jennifer A.

2015-01-01

In spatial generalized linear mixed models (SGLMMs), covariates that are spatially smooth are often collinear with spatially smooth random effects. This phenomenon is known as spatial confounding and has been studied primarily in the case where the spatial support of the process being studied is discrete (e.g., areal spatial data). In this case, the most common approach suggested is restricted spatial regression (RSR) in which the spatial random effects are constrained to be orthogonal to the fixed effects. We consider spatial confounding and RSR in the geostatistical (continuous spatial support) setting. We show that RSR provides computational benefits relative to the confounded SGLMM, but that Bayesian credible intervals under RSR can be inappropriately narrow under model misspecification. We propose a posterior predictive approach to alleviating this potential problem and discuss the appropriateness of RSR in a variety of situations. We illustrate RSR and SGLMM approaches through simulation studies and an analysis of malaria frequencies in The Gambia, Africa.

Attentional bias for affective visual stimuli in posttraumatic stress disorder and the role of depression.

PubMed

Hauschildt, Marit; Wittekind, Charlotte; Moritz, Steffen; Kellner, Michael; Jelinek, Lena

2013-05-15

An attentional bias for trauma-related verbal cues was frequently demonstrated in posttraumatic stress disorder (PTSD) using variants of the emotional Stroop task (EST). However, the mechanisms underlying the Stroop-effect are ill-defined and it is yet unclear how the findings apply to different paradigms and stimulus modalities. To address these open questions, for the first time a spatial-cuing task with pictorial cues of different emotional valence was administered to trauma-exposed individuals with and without PTSD, and non-trauma-exposed controls. Groups did not show different response profiles across affective conditions. However, a group effect was evident when comparing depressed with non-depressed individuals: Those with depression showed delayed attending towards trauma-related cues and faster attending away from negative cues. In correlational analyses, attentional avoidance was associated with both depression and PTSD symptom severity. These findings highlight the need for research on trauma populations and anxiety in general to pay closer attention to depression as an important confound in the study of emotional information processing. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Altered 5-HT2A Receptor Binding after Recovery from Bulimia-Type Anorexia Nervosa: Relationships to Harm Avoidance and Drive for Thinness

PubMed Central

Bailer, Ursula F; Price, Julie C; Meltzer, Carolyn C; Mathis, Chester A; Frank, Guido K; Weissfeld, Lisa; McConaha, Claire W; Henry, Shannan E; Brooks-Achenbach, Sarah; Barbarich, Nicole C; Kaye, Walter H

2015-01-01

Several lines of evidence suggest that a disturbance of serotonin neuronal pathways may contribute to the pathogenesis of anorexia nervosa (AN) and bulimia nervosa (BN). This study applied positron emission tomography (PET) to investigate the brain serotonin 2A (5-HT2A) receptor, which could contribute to disturbances of appetite and behavior in AN and BN. To avoid the confounding effects of malnutrition, we studied 10 women recovered from bulimia-type AN (REC AN–BN, >1 year normal weight, regular menstrual cycles, no binging, or purging) compared with 16 healthy control women (CW) using PET imaging and a specific 5-HT2A receptor antagonist, [18F]altanserin. REC AN–BN women had significantly reduced [18F]altanserin binding potential relative to CW in the left subgenual cingulate, the left parietal cortex, and the right occipital cortex. [18F]altanserin binding potential was positively related to harm avoidance and negatively related to novelty seeking in cingulate and temporal regions only in REC AN–BN subjects. In addition, REC AN–BN had negative relationships between [18F]altanserin binding potential and drive for thinness in several cortical regions. In conclusion, this study extends research suggesting that altered 5-HT neuronal system activity persists after recovery from bulimia-type AN, particularly in subgenual cingulate regions. Altered 5-HT neurotransmission after recovery also supports the possibility that this may be a trait-related disturbance that contributes to the pathophysiology of eating disorders. It is possible that subgenual cingulate findings are not specific for AN–BN, but may be related to the high incidence of lifetime major depressive disorder diagnosis in these subjects. PMID:15054474

Using propensity scores to estimate the effects of insecticides on stream invertebrates from observational data

USGS Publications Warehouse

Lester L. Yuan,; Amina I. Pollard,; Carlisle, Daren M.

2009-01-01

Analyses of observational data can provide insights into relationships between environmental conditions and biological responses across a broader range of natural conditions than experimental studies, potentially complementing insights gained from experiments. However, observational data must be analyzed carefully to minimize the likelihood that confounding variables bias observed relationships. Propensity scores provide a robust approach for controlling for the effects of measured confounding variables when analyzing observational data. Here, we use propensity scores to estimate changes in mean invertebrate taxon richness in streams that have experienced insecticide concentrations that exceed aquatic life use benchmark concentrations. A simple comparison of richness in sites exposed to elevated insecticides with those that were not exposed suggests that exposed sites had on average 6.8 fewer taxa compared to unexposed sites. The presence of potential confounding variables makes it difficult to assert a causal relationship from this simple comparison. After controlling for confounding factors using propensity scores, the difference in richness between exposed and unexposed sites was reduced to 4.1 taxa, a difference that was still statistically significant. Because the propensity score analysis controlled for the effects of a wide variety of possible confounding variables, we infer that the change in richness observed in the propensity score analysis was likely caused by insecticide exposure.

Using propensity scores to estimate the effects of insecticides on stream invertebrates from observational data

USGS Publications Warehouse

Yuan, L.L.; Pollard, A.I.; Carlisle, D.M.

2009-01-01

Analyses of observational data can provide insights into relationships between environmental conditions and biological responses across a broader range of natural conditions than experimental studies, potentially complementing insights gained from experiments. However, observational data must be analyzed carefully to minimize the likelihood that confounding variables bias observed relationships. Propensity scores provide a robust approach for controlling for the effects of measured confounding variables when analyzing observational data. Here, we use propensity scores to estimate changes in mean invertebrate taxon richness in streams that have experienced insecticide concentrations that exceed aquatic life use benchmark concentrations. A simple comparison of richness in sites exposed to elevated insecticides with those that were not exposed suggests that exposed sites had on average 6.8 fewer taxa compared to unexposed sites. The presence of potential confounding variables makes it difficult to assert a causal relationship from this simple comparison. After controlling for confounding factors using propensity scores, the difference in richness between exposed and unexposed sites was reduced to 4.1 taxa, a difference that was still statistically significant. Because the propensity score analysis controlled for the effects of a wide variety of possible confounding variables, we infer that the change in richness observed in the propensity score analysis was likely caused by insecticide exposure. ?? 2009 SETAC.

Toxicity of the molybdate anion in soil is partially explained by effects of the accompanying cation or by soil pH.

PubMed

Buekers, Jurgen; Mertens, Jelle; Smolders, Erik

2010-06-01

Previous studies have shown that toxicity of cationic trace metals in soil is partially confounded by effects of the accompanying anions. A similar assessment is reported here for toxicity of an oxyanion, i.e., molybdate (MoO(4) (2-)), the soil toxicity of which is relatively unexplored. Solubility and toxicity were compared between the soluble sodium molybdate (Na(2)MoO(4)) and the sparingly soluble molybdenum trioxide (MoO(3)). Confounding effects of salinity were excluded by referencing the Na(2)MoO(4) effect to that of sodium chloride (NaCl). The pH decrease from the acid MoO(3) amendment was equally referenced to a hydrochloric (HCl) treatment or a lime-controlled MoO(3) treatment. The concentrations of molybdenum (Mo) in soil solution or calcium chloride (CaCl(2)) 0.01 M extracts were only marginally affected by either MoO(3) or Na(2)MoO(4) as an Mo source after 10 to 13 days of equilibration. Effects of Mo on soil nitrification were fully confounded by associated changes in salinity or pH. Effects of Mo on growth of wheat seedlings (Triticum aestivum L) were more pronounced than those on nitrification, and toxicity thresholds were unaffected by the form of added Mo. The Mo thresholds for wheat growth were not confounded by pH or salinity at incipient toxicity. It is concluded that oxyanion toxicity might be confounded in relatively insensitive tests for which reference treatments should be included. Copyright 2010 SETAC.

Patient perceptions about illness self-management in ANCA-associated small vessel vasculitis.

PubMed

Thorpe, C T; DeVellis, R F; Blalock, S J; Hogan, S L; Lewis, M A; DeVellis, B M

2008-06-01

To characterize patient perceptions, related to eight self-management behaviours relevant for adults with ANCA-associated small vessel vasculitis (ANCA-SVV), and to determine if these perceptions were associated with performance of each behaviour. Adults with ANCA-SVV (n = 202) completed a self-administered questionnaire that assessed eight self-management behaviours (adherence to recommendations for medication, health service use, diet, exercise, infection avoidance and symptom monitoring; prompt reporting of symptoms and side effects; and adjusting activities in response to symptoms), perceptions about these behaviours, socio-demographics, clinical factors and social desirability bias. Descriptive statistics were generated to characterize patients' perceptions about difficulty of, importance of, and specific barriers to performing each behaviour. Regression analyses explored whether these variables were associated with performing each behaviour, controlling for potential confounders. With few exceptions, higher perceived importance and lower perceived difficulty of each behaviour were associated with more frequent performance of the behaviour. For each behaviour, several specific barriers were frequently endorsed by patients and a number of these were associated with lower levels of self-management. This study reveals that patient perceptions about the illness and its treatment influence ANCA-SVV self-management. Perceived barriers to medication, health services, diet and exercise adherence were similar to those in other illnesses. This study also provides insight into barriers experienced by patients in performing behaviours (infection avoidance, symptom monitoring, reporting symptoms and side-effects and adjusting activities) not often previously studied. How the identification of these barriers can help inform future interventions for ANCA-SVV patients is to be discussed.

Good research practices for comparative effectiveness research: approaches to mitigate bias and confounding in the design of nonrandomized studies of treatment effects using secondary data sources: the International Society for Pharmacoeconomics and Outcomes Research Good Research Practices for Retrospective Database Analysis Task Force Report--Part II.

PubMed

Cox, Emily; Martin, Bradley C; Van Staa, Tjeerd; Garbe, Edeltraut; Siebert, Uwe; Johnson, Michael L

2009-01-01

The goal of comparative effectiveness analysis is to examine the relationship between two variables, treatment, or exposure and effectiveness or outcome. Unlike data obtained through randomized controlled trials, researchers face greater challenges with causal inference with observational studies. Recognizing these challenges, a task force was formed to develop a guidance document on methodological approaches to addresses these biases. The task force was commissioned and a Chair was selected by the International Society for Pharmacoeconomics and Outcomes Research Board of Directors in October 2007. This report, the second of three reported in this issue of the Journal, discusses the inherent biases when using secondary data sources for comparative effectiveness analysis and provides methodological recommendations to help mitigate these biases. The task force report provides recommendations and tools for researchers to mitigate threats to validity from bias and confounding in measurement of exposure and outcome. Recommendations on design of study included: the need for data analysis plan with causal diagrams; detailed attention to classification bias in definition of exposure and clinical outcome; careful and appropriate use of restriction; extreme care to identify and control for confounding factors, including time-dependent confounding. Design of nonrandomized studies of comparative effectiveness face several daunting issues, including measurement of exposure and outcome challenged by misclassification and confounding. Use of causal diagrams and restriction are two techniques that can improve the theoretical basis for analyzing treatment effects in study populations of more homogeneity, with reduced loss of generalizability.

Yield and Pitfalls of Ajmaline Testing in the Evaluation of Unexplained Cardiac Arrest and Sudden Unexplained Death: Single-Center Experience With 482 Families.

PubMed

Tadros, Rafik; Nannenberg, Eline A; Lieve, Krystien V; Škorić-Milosavljević, Doris; Lahrouchi, Najim; Lekanne Deprez, Ronald H; Vendrik, Jeroen; Reckman, Yolan J; Postema, Pieter G; Amin, Ahmad S; Bezzina, Connie R; Wilde, Arthur A M; Tan, Hanno L

2017-12-11

This study evaluated the yield of ajmaline testing and assessed the occurrence of confounding responses in a large cohort of families with unexplained cardiac arrest (UCA) or sudden unexplained death (SUD). Ajmaline testing to diagnose Brugada syndrome (BrS) is routinely used in the evaluation of SUD and UCA, but its yield, limitations, and appropriate dosing have not been studied in a large cohort. We assessed ajmaline test response and genetic testing results in 637 individuals from 482 families who underwent ajmaline testing for SUD or UCA. Overall, 89 individuals (14%) from 88 families (18%) had a positive ajmaline test result. SCN5A mutations were identified in 9 of 86 ajmaline-positive cases (10%). SCN5A mutation carriers had positive test results at significantly lower ajmaline doses than noncarriers (0.75 [range: 0.64 to 0.98] mg/kg vs. 1.03 [range: 0.95 to 1.14] mg/kg, respectively; p < 0.01). In 7 of 88 families (8%), it was concluded that the positive ajmaline response was a confounder, either in the presence of an alternative genetic diagnosis accounting for UCA/SUD (5 cases) or noncosegregation of positive ajmaline response and arrhythmia (2 cases). The rate of confounding responses was significantly higher in positive ajmaline responses obtained at >1 mg/kg than in those obtained at ≤1 mg/kg (7 of 48 vs. 0 of 41 individuals; Fisher's exact test: p = 0.014). In line with previous, smaller studies, a positive ajmaline response was observed in a large proportion of UCA/SUD families. Importantly, our data emphasize the potential for confounding possibly false-positive ajmaline responses in this population, particularly at high doses, which could possibly lead to a misdiagnosis. Clinicians should consider all alternative causes in UCA/SUD and avoid ajmaline doses >1 mg/kg. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Resampling approach for anomalous change detection

NASA Astrophysics Data System (ADS)

Theiler, James; Perkins, Simon

2007-04-01

We investigate the problem of identifying pixels in pairs of co-registered images that correspond to real changes on the ground. Changes that are due to environmental differences (illumination, atmospheric distortion, etc.) or sensor differences (focus, contrast, etc.) will be widespread throughout the image, and the aim is to avoid these changes in favor of changes that occur in only one or a few pixels. Formal outlier detection schemes (such as the one-class support vector machine) can identify rare occurrences, but will be confounded by pixels that are "equally rare" in both images: they may be anomalous, but they are not changes. We describe a resampling scheme we have developed that formally addresses both of these issues, and reduces the problem to a binary classification, a problem for which a large variety of machine learning tools have been developed. In principle, the effects of misregistration will manifest themselves as pervasive changes, and our method will be robust against them - but in practice, misregistration remains a serious issue.

Flies, worms and the Free Radical Theory of ageing.

PubMed

Clancy, David; Birdsall, John

2013-01-01

Drosophila and Caenorhabditis elegans have provided the largest body of evidence addressing the Free Radical Theory of ageing, however the evidence has not been unequivocally supportive. Oxidative damage to DNA is probably not a major contributor, damage to lipids is assuming greater importance and damage to proteins probably the source of pathology. On balance the evidence does not support a primary role of oxidative damage in ageing in C. elegans, perhaps because of its particular energy metabolic and stress resistance profile. Evidence is more numerous, varied and consistent and hence more compelling for Drosophila, although not conclusive. However there is good evidence for a role of oxidative damage in later life pathology. Future work should: 1/ make more use of protein oxidative damage measurements; 2/ use inducible transgenic systems or pharmacotherapy to ensure genetic equivalence of controls and avoid confounding effects during development; 3/ to try to delay ageing, target interventions which reduce and/or repair protein oxidative damage. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Red trap colour of the carnivorous plant Drosera rotundifolia does not serve a prey attraction or camouflage function

PubMed Central

Foot, G.; Rice, S. P.; Millett, J.

2014-01-01

The traps of many carnivorous plants are red in colour. This has been widely hypothesized to serve a prey attraction function; colour has also been hypothesized to function as camouflage, preventing prey avoidance. We tested these two hypotheses in situ for the carnivorous plant Drosera rotundifolia. We conducted three separate studies: (i) prey attraction to artificial traps to isolate the influence of colour; (ii) prey attraction to artificial traps on artificial backgrounds to control the degree of contrast and (iii) observation of prey capture by D. rotundifolia to determine the effects of colour on prey capture. Prey were not attracted to green traps and were deterred from red traps. There was no evidence that camouflaged traps caught more prey. For D. rotundifolia, there was a relationship between trap colour and prey capture. However, trap colour may be confounded with other leaf traits. Thus, we conclude that for D. rotundifolia, red trap colour does not serve a prey attraction or camouflage function. PMID:24740904

Red trap colour of the carnivorous plant Drosera rotundifolia does not serve a prey attraction or camouflage function.

PubMed

Foot, G; Rice, S P; Millett, J

2014-01-01

The traps of many carnivorous plants are red in colour. This has been widely hypothesized to serve a prey attraction function; colour has also been hypothesized to function as camouflage, preventing prey avoidance. We tested these two hypotheses in situ for the carnivorous plant Drosera rotundifolia. We conducted three separate studies: (i) prey attraction to artificial traps to isolate the influence of colour; (ii) prey attraction to artificial traps on artificial backgrounds to control the degree of contrast and (iii) observation of prey capture by D. rotundifolia to determine the effects of colour on prey capture. Prey were not attracted to green traps and were deterred from red traps. There was no evidence that camouflaged traps caught more prey. For D. rotundifolia, there was a relationship between trap colour and prey capture. However, trap colour may be confounded with other leaf traits. Thus, we conclude that for D. rotundifolia, red trap colour does not serve a prey attraction or camouflage function.

Variant effect prediction tools assessed using independent, functional assay-based datasets: implications for discovery and diagnostics.

PubMed

Mahmood, Khalid; Jung, Chol-Hee; Philip, Gayle; Georgeson, Peter; Chung, Jessica; Pope, Bernard J; Park, Daniel J

2017-05-16

Genetic variant effect prediction algorithms are used extensively in clinical genomics and research to determine the likely consequences of amino acid substitutions on protein function. It is vital that we better understand their accuracies and limitations because published performance metrics are confounded by serious problems of circularity and error propagation. Here, we derive three independent, functionally determined human mutation datasets, UniFun, BRCA1-DMS and TP53-TA, and employ them, alongside previously described datasets, to assess the pre-eminent variant effect prediction tools. Apparent accuracies of variant effect prediction tools were influenced significantly by the benchmarking dataset. Benchmarking with the assay-determined datasets UniFun and BRCA1-DMS yielded areas under the receiver operating characteristic curves in the modest ranges of 0.52 to 0.63 and 0.54 to 0.75, respectively, considerably lower than observed for other, potentially more conflicted datasets. These results raise concerns about how such algorithms should be employed, particularly in a clinical setting. Contemporary variant effect prediction tools are unlikely to be as accurate at the general prediction of functional impacts on proteins as reported prior. Use of functional assay-based datasets that avoid prior dependencies promises to be valuable for the ongoing development and accurate benchmarking of such tools.

Leveraging Hierarchical Population Structure in Discrete Association Studies

PubMed Central

Carlson, Jonathan; Kadie, Carl; Mallal, Simon; Heckerman, David

2007-01-01

Population structure can confound the identification of correlations in biological data. Such confounding has been recognized in multiple biological disciplines, resulting in a disparate collection of proposed solutions. We examine several methods that correct for confounding on discrete data with hierarchical population structure and identify two distinct confounding processes, which we call coevolution and conditional influence. We describe these processes in terms of generative models and show that these generative models can be used to correct for the confounding effects. Finally, we apply the models to three applications: identification of escape mutations in HIV-1 in response to specific HLA-mediated immune pressure, prediction of coevolving residues in an HIV-1 peptide, and a search for genotypes that are associated with bacterial resistance traits in Arabidopsis thaliana. We show that coevolution is a better description of confounding in some applications and conditional influence is better in others. That is, we show that no single method is best for addressing all forms of confounding. Analysis tools based on these models are available on the internet as both web based applications and downloadable source code at http://atom.research.microsoft.com/bio/phylod.aspx. PMID:17611623

Conditioned Stimuli’s Role in Relapse: Pre-Clinical Research on Pavlovian Instrumental Transfer

PubMed Central

Lamb, R.J.; Schindler, W.; Pinkston, Jonathan W.

2016-01-01

Rationale and Objective Pavlovian learning is central to many theories of addiction. In these theories, stimuli paired with drug ingestion become Conditioned Stimuli (CS) and subsequently elicit drug-seeking and -taking. However in most relevant studies, Pavlovian and instrumental learning are confounded. This confound may be avoided in Pavlovian-Instrumental-Transfer (PIT) procedures. In PIT, Pavlovian and instrumental learning are established separately, and then combined. In order to better understand the role of CSs in addiction, we review the relevant studies using PIT. Findings We identified seven articles examining PIT effects of ethanol- or cocaine-paired CSs. Under at least one condition six of these articles reported CS-elicited increases in responding previously maintained by drug. However, the only study using the optimal control condition failed to find a CS-elicited increase. Two studies examining CS specificity found the CS also increased responding maintained by a different reinforcer. Two studies examined if CSs elicit increases in actual drug-taking. Both failed to find CS-elicited increases, i.e., no study shows CS-elicited increases in actual drug-taking. Further, CS-elicited increases in extinguished responding are short-lived. Conclusions These findings are not entirely consistent with Pavlovian learning playing a central role in addiction. However, design issues can explain most of these inconsistencies. Studies without these design issues are needed. Additionally, existing theories hypothesize drug-paired CSs increase drug-taking by increasing motivation, by eliciting conditioned responses that make drug-seeking more probable, or by a combination of these. Work distinguishing between these mechanisms would also be useful. PMID:26800688

Marked EEG worsening following Levetiracetam overdose: How a pharmacological issue can confound coma prognosis.

PubMed

Bouchier, Baptiste; Demarquay, Geneviève; Guérin, Claude; André-Obadia, Nathalie; Gobert, Florent

2017-01-01

Levetiracetam is an anti-epileptic drug commonly used in intensive care when seizure is suspected as a possible cause of coma. We propose to question the cofounding effect of Levetiracetam during the prognostication process in a case of anoxic coma. We report the story of a young woman presenting a comatose state following a hypoxic cardiac arrest. After a first EEG presenting an intermediate EEG pattern, a seizure suspicion led to prescribe Levetiracetam. The EEG showed then the appearance of burst suppression, which was compatible with a very severe pattern of post-anoxic coma. This aggravation was in fact related to an overdose of Levetiracetam (the only medication introduced recently) and was reversible after Levetiracetam cessation. The increased plasmatic dosages of Levetiracetam confirming this overdose could have been favoured by a moderate reduction of renal clearance, previously underestimated because of a low body-weight. This EEG dynamic was unexpected under Levetiracetam and could sign a functional instability after anoxia. Burst suppression is classically observed with high doses of anaesthetics, but is not expected after a minor anti-epileptic drug. This report proposes that Levetiracetam tolerance might not be straightforward after brain lesions and engages us to avoid confounding factors during the awakening prognostication, which is mainly based on the severity of the EEG. Hence, prognosis should not be decided on an isolated parameter, especially if the dynamic is atypical after a new prescription, even for well-known drugs. For any suspicion, the drug's dosage and replacement should be managed before any premature care's withdrawal. Copyright © 2016 Elsevier B.V. All rights reserved.

Correction of confounding bias in non-randomized studies by appropriate weighting.

PubMed

Schmoor, Claudia; Gall, Christine; Stampf, Susanne; Graf, Erika

2011-03-01

In non-randomized studies, the assessment of a causal effect of treatment or exposure on outcome is hampered by possible confounding. Applying multiple regression models including the effects of treatment and covariates on outcome is the well-known classical approach to adjust for confounding. In recent years other approaches have been promoted. One of them is based on the propensity score and considers the effect of possible confounders on treatment as a relevant criterion for adjustment. Another proposal is based on using an instrumental variable. Here inference relies on a factor, the instrument, which affects treatment but is thought to be otherwise unrelated to outcome, so that it mimics randomization. Each of these approaches can basically be interpreted as a simple reweighting scheme, designed to address confounding. The procedures will be compared with respect to their fundamental properties, namely, which bias they aim to eliminate, which effect they aim to estimate, and which parameter is modelled. We will expand our overview of methods for analysis of non-randomized studies to methods for analysis of randomized controlled trials and show that analyses of both study types may target different effects and different parameters. The considerations will be illustrated using a breast cancer study with a so-called Comprehensive Cohort Study design, including a randomized controlled trial and a non-randomized study in the same patient population as sub-cohorts. This design offers ideal opportunities to discuss and illustrate the properties of the different approaches. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

"A Bayesian sensitivity analysis to evaluate the impact of unmeasured confounding with external data: a real world comparative effectiveness study in osteoporosis".

PubMed

Zhang, Xiang; Faries, Douglas E; Boytsov, Natalie; Stamey, James D; Seaman, John W

2016-09-01

Observational studies are frequently used to assess the effectiveness of medical interventions in routine clinical practice. However, the use of observational data for comparative effectiveness is challenged by selection bias and the potential of unmeasured confounding. This is especially problematic for analyses using a health care administrative database, in which key clinical measures are often not available. This paper provides an approach to conducting a sensitivity analyses to investigate the impact of unmeasured confounding in observational studies. In a real world osteoporosis comparative effectiveness study, the bone mineral density (BMD) score, an important predictor of fracture risk and a factor in the selection of osteoporosis treatments, is unavailable in the data base and lack of baseline BMD could potentially lead to significant selection bias. We implemented Bayesian twin-regression models, which simultaneously model both the observed outcome and the unobserved unmeasured confounder, using information from external sources. A sensitivity analysis was also conducted to assess the robustness of our conclusions to changes in such external data. The use of Bayesian modeling in this study suggests that the lack of baseline BMD did have a strong impact on the analysis, reversing the direction of the estimated effect (odds ratio of fracture incidence at 24 months: 0.40 vs. 1.36, with/without adjusting for unmeasured baseline BMD). The Bayesian twin-regression models provide a flexible sensitivity analysis tool to quantitatively assess the impact of unmeasured confounding in observational studies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The Difficult Stoma: Challenges and Strategies

PubMed Central

Strong, Scott A.

2016-01-01

The problems that a patient experiences after the creation of a temporary or permanent stoma can result from many factors, but a carefully constructed stoma located in an ideal location is typically associated with appropriate function and an acceptable quality of life. The construction of the stoma can be confounded by many concomitant conditions that increase the distance that the bowel must traverse or shorten the bowel's capacity to reach. Stomas can be further troubled by a variety of problems that potentially arise early in the recovery period or months later. Surgeons must be familiar with these obstacles and complications to avoid their occurrence and minimize their impact. PMID:27247541

Adjusting for geographic variation in observational comparative effectiveness studies: a case study of antipsychotics using state Medicaid data.

PubMed

Root, Elisabeth Dowling; Thomas, Deborah S K; Campagna, Elizabeth J; Morrato, Elaine H

2014-08-27

Area-level variation in treatment and outcomes may be a potential source of confounding bias in observational comparative effectiveness studies. This paper demonstrates how to use exploratory spatial data analysis (ESDA) and spatial statistical methods to investigate and control for these potential biases. The case presented compares the effectiveness of two antipsychotic treatment strategies: oral second-generation antipsychotics (SGAs) vs. long-acting paliperiodone palmitate (PP). A new-start cohort study was conducted analyzing patient-level administrative claims data (8/1/2008-4/30/2011) from Missouri Medicaid. ESDA techniques were used to examine spatial patterns of antipsychotic prescriptions and outcomes (hospitalization and emergency department (ED) visits). Likelihood of mental health-related outcomes were compared between patients starting PP (N = 295) and oral SGAs (N = 8,626) using multilevel logistic regression models adjusting for patient composition (demographic and clinical factors) and geographic region. ESDA indicated significant spatial variation in antipsychotic prescription patterns and moderate variation in hospitalization and ED visits thereby indicating possible confounding by geography. In the multilevel models for this antipsychotic case example, patient composition represented a stronger source of confounding than geographic context. Because geographic variation in health care delivery is ubiquitous, it could be a comparative effectiveness research (CER) best practice to test for possible geographic confounding in observational data. Though the magnitude of the area-level geography effects were small in this case, they were still statistically significant and should therefore be examined as part of this observational CER study. More research is needed to better estimate the range of confounding due to geography across different types of observational comparative effectiveness studies and healthcare utilization outcomes.

The impact of confounder selection in propensity scores when applied to prospective cohort studies in pregnancy.

PubMed

Xu, Ronghui; Hou, Jue; Chambers, Christina D

2018-06-01

Our work was motivated by small cohort studies on the risk of birth defects in infants born to pregnant women exposed to medications. We controlled for confounding using propensity scores (PS). The extremely rare events setting renders the matching or stratification infeasible. In addition, the PS itself may be formed via different approaches to select confounders from a relatively long list of potential confounders. We carried out simulation experiments to compare different combinations of approaches: IPW or regression adjustment, with 1) including all potential confounders without selection, 2) selection based on univariate association between the candidate variable and the outcome, 3) selection based on change in effects (CIE). The simulation showed that IPW without selection leads to extremely large variances in the estimated odds ratio, which help to explain the empirical data analysis results that we had observed. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of categorization method, regression type, and variable distribution on the inflation of Type-I error rate when categorizing a confounding variable.

PubMed

Barnwell-Ménard, Jean-Louis; Li, Qing; Cohen, Alan A

2015-03-15

The loss of signal associated with categorizing a continuous variable is well known, and previous studies have demonstrated that this can lead to an inflation of Type-I error when the categorized variable is a confounder in a regression analysis estimating the effect of an exposure on an outcome. However, it is not known how the Type-I error may vary under different circumstances, including logistic versus linear regression, different distributions of the confounder, and different categorization methods. Here, we analytically quantified the effect of categorization and then performed a series of 9600 Monte Carlo simulations to estimate the Type-I error inflation associated with categorization of a confounder under different regression scenarios. We show that Type-I error is unacceptably high (>10% in most scenarios and often 100%). The only exception was when the variable categorized was a continuous mixture proxy for a genuinely dichotomous latent variable, where both the continuous proxy and the categorized variable are error-ridden proxies for the dichotomous latent variable. As expected, error inflation was also higher with larger sample size, fewer categories, and stronger associations between the confounder and the exposure or outcome. We provide online tools that can help researchers estimate the potential error inflation and understand how serious a problem this is. Copyright © 2014 John Wiley & Sons, Ltd.

Pathological gambling and alcohol dependence: neural disturbances in reward and loss avoidance processing.

PubMed

Romanczuk-Seiferth, Nina; Koehler, Saskia; Dreesen, Caspar; Wüstenberg, Torsten; Heinz, Andreas

2015-05-01

Pathological gambling (PG) shares clinical characteristics such as craving and loss of control with substance use disorders and is thus considered a behavioral addiction. While functional alterations in the mesolimbic reward system have been correlated with craving and relapse in substance use disorders, only a few studies have examined this brain circuit in PG, and no direct comparison has been conducted so far. Thus, we investigated the neuronal correlates of reward processing in PG in contrast to alcohol-dependent (AD) patients and healthy subjects. Eighteen PG patients, 15 AD patients and 17 controls were investigated with a monetary incentive delay task, in which visual cues predict the consequence (monetary gain, avoidance of loss, none) of a fast response to a subsequent target stimulus. Functional magnetic resonance imaging data were analyzed to account for possible confounding factors such as local gray matter volume. Activity in the right ventral striatum during loss anticipation was increased in PG patients compared with controls and AD patients. Moreover, PG patients showed decreased activation in the right ventral striatum and right medial prefrontal cortex during successful loss avoidance compared with controls, which was inversely associated with severity of gambling behavior. Thus, despite neurobiological similarities to substance use disorders in reward processing, as reported by previous studies, we found relevant differences with respect to the anticipation of loss as well as its avoidance (negative reinforcement), which further contributes to the understanding of PG. © 2014 Society for the Study of Addiction.

Antidepressant response in patients with major depression exposed to NSAIDs: a pharmacovigilance study.

PubMed

Gallagher, Patience J; Castro, Victor; Fava, Maurizio; Weilburg, Jeffrey B; Murphy, Shawn N; Gainer, Vivian S; Churchill, Susanne E; Kohane, Isaac S; Iosifescu, Dan V; Smoller, Jordan W; Perlis, Roy H

2012-10-01

OBJECTIVE It has been suggested that there is a mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with antidepressant response, and poorer outcomes among NSAID-treated patients were reported in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. To attempt to confirm this association in an independent population-based treatment cohort and explore potential confounding variables, the authors examined use of NSAIDs and related medications among 1,528 outpatients in a New England health care system. METHOD Treatment outcomes were classified using a validated machine learning tool applied to electronic medical records. Logistic regression was used to examine the association between medication exposure and treatment outcomes, adjusted for potential confounding variables. To further elucidate confounding and treatment specificity of the observed effects, data from the STAR*D study were reanalyzed. RESULTS NSAID exposure was associated with a greater likelihood of depression classified as treatment resistant compared with depression classified as responsive to selective serotonin reuptake inhibitors (odds ratio=1.55, 95% CI=1.21-2.00). This association was apparent in the NSAIDs-only group but not in those using other agents with NSAID-like mechanisms (cyclooxygenase-2 inhibitors and salicylates). Inclusion of age, sex, ethnicity, and measures of comorbidity and health care utilization in regression models indicated confounding; association with outcome was no longer significant in fully adjusted models. Reanalysis of STAR*D results likewise identified an association in NSAIDs but not NSAID-like drugs, with more modest effects persisting after adjustment for potential confounding variables. CONCLUSIONS These results support an association between NSAID use and poorer antidepressant outcomes in major depressive disorder but indicate that some of the observed effect may be a result of confounding.

A method for sensitivity analysis to assess the effects of measurement error in multiple exposure variables using external validation data.

PubMed

Agogo, George O; van der Voet, Hilko; van 't Veer, Pieter; Ferrari, Pietro; Muller, David C; Sánchez-Cantalejo, Emilio; Bamia, Christina; Braaten, Tonje; Knüppel, Sven; Johansson, Ingegerd; van Eeuwijk, Fred A; Boshuizen, Hendriek C

2016-10-13

Measurement error in self-reported dietary intakes is known to bias the association between dietary intake and a health outcome of interest such as risk of a disease. The association can be distorted further by mismeasured confounders, leading to invalid results and conclusions. It is, however, difficult to adjust for the bias in the association when there is no internal validation data. We proposed a method to adjust for the bias in the diet-disease association (hereafter, association), due to measurement error in dietary intake and a mismeasured confounder, when there is no internal validation data. The method combines prior information on the validity of the self-report instrument with the observed data to adjust for the bias in the association. We compared the proposed method with the method that ignores the confounder effect, and with the method that ignores measurement errors completely. We assessed the sensitivity of the estimates to various magnitudes of measurement error, error correlations and uncertainty in the literature-reported validation data. We applied the methods to fruits and vegetables (FV) intakes, cigarette smoking (confounder) and all-cause mortality data from the European Prospective Investigation into Cancer and Nutrition study. Using the proposed method resulted in about four times increase in the strength of association between FV intake and mortality. For weakly correlated errors, measurement error in the confounder minimally affected the hazard ratio estimate for FV intake. The effect was more pronounced for strong error correlations. The proposed method permits sensitivity analysis on measurement error structures and accounts for uncertainties in the reported validity coefficients. The method is useful in assessing the direction and quantifying the magnitude of bias in the association due to measurement errors in the confounders.

Does consideration of larger study areas yield more accurate estimates of air pollution health effects? An illustration of the bias-variance trade-off in air pollution epidemiology.

PubMed

Pedersen, Marie; Siroux, Valérie; Pin, Isabelle; Charles, Marie Aline; Forhan, Anne; Hulin, Agnés; Galineau, Julien; Lepeule, Johanna; Giorgis-Allemand, Lise; Sunyer, Jordi; Annesi-Maesano, Isabella; Slama, Rémy

2013-10-01

Spatially-resolved air pollution models can be developed in large areas. The resulting increased exposure contrasts and population size offer opportunities to better characterize the effect of atmospheric pollutants on respiratory health. However the heterogeneity of these areas may also enhance the potential for confounding. We aimed to discuss some analytical approaches to handle this trade-off. We modeled NO2 and PM10 concentrations at the home addresses of 1082 pregnant mothers from EDEN cohort living in and around urban areas, using ADMS dispersion model. Simulations were performed to identify the best strategy to limit confounding by unmeasured factors varying with area type. We examined the relation between modeled concentrations and respiratory health in infants using regression models with and without adjustment or interaction terms with area type. Simulations indicated that adjustment for area limited the bias due to unmeasured confounders varying with area at the costs of a slight decrease in statistical power. In our cohort, rural and urban areas differed for air pollution levels and for many factors associated with respiratory health and exposure. Area tended to modify effect measures of air pollution on respiratory health. Increasing the size of the study area also increases the potential for residual confounding. Our simulations suggest that adjusting for type of area is a good option to limit residual confounding due to area-associated factors without restricting the area size. Other statistical approaches developed in the field of spatial epidemiology are an alternative to control for poorly-measured spatially-varying confounders. © 2013 Elsevier Ltd. All rights reserved.

Are Interactions between cis-Regulatory Variants Evidence for Biological Epistasis or Statistical Artifacts?

PubMed

Fish, Alexandra E; Capra, John A; Bush, William S

2016-10-06

The importance of epistasis-or statistical interactions between genetic variants-to the development of complex disease in humans has been controversial. Genome-wide association studies of statistical interactions influencing human traits have recently become computationally feasible and have identified many putative interactions. However, statistical models used to detect interactions can be confounded, which makes it difficult to be certain that observed statistical interactions are evidence for true molecular epistasis. In this study, we investigate whether there is evidence for epistatic interactions between genetic variants within the cis-regulatory region that influence gene expression after accounting for technical, statistical, and biological confounding factors. We identified 1,119 (FDR = 5%) interactions that appear to regulate gene expression in human lymphoblastoid cell lines, a tightly controlled, largely genetically determined phenotype. Many of these interactions replicated in an independent dataset (90 of 803 tested, Bonferroni threshold). We then performed an exhaustive analysis of both known and novel confounders, including ceiling/floor effects, missing genotype combinations, haplotype effects, single variants tagged through linkage disequilibrium, and population stratification. Every interaction could be explained by at least one of these confounders, and replication in independent datasets did not protect against some confounders. Assuming that the confounding factors provide a more parsimonious explanation for each interaction, we find it unlikely that cis-regulatory interactions contribute strongly to human gene expression, which calls into question the relevance of cis-regulatory interactions for other human phenotypes. We additionally propose several best practices for epistasis testing to protect future studies from confounding. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Propensity score models in observational comparative effectiveness studies: cornerstone of design or statistical afterthought?

PubMed

Robinson, John W

2012-03-01

Propensity score models are increasingly used in observational comparative effectiveness studies to reduce confounding by covariates that are associated with both a study outcome and treatment choice. Any such potentially confounding covariate will bias estimation of the effect of treatment on the outcome, unless the distribution of that covariate is well-balanced between treatment and control groups. Constructing a subsample of treated and control subjects who are matched on estimated propensity scores is a means of achieving such balance for covariates that are included in the propensity score model. If, during study design, investigators assemble a comprehensive inventory of known and suspected potentially confounding covariates, examination of how well this inventory is covered by the chosen dataset yields an assessment of the extent of bias reduction that is possible by matching on estimated propensity scores. These considerations are explored by examining the designs of three recently published comparative effectiveness studies.

A localized flare of dermatitis may render patch tests uninterpretable in some patients with recently controlled widespread dermatitis.

PubMed

Magembe, Anna J; Davis, Mark D P; Richardson, Donna M

2009-01-01

Patch testing rarely is confounded by localized dermatitis induced in the area being tested (usually the back). Its occurrence renders the interpretation of patch tests impossible. To review our experience of the circumstances in which this phenomenon occurs during patch testing. We retrospectively reviewed patients with this phenomenon who underwent patch testing from January 1, 2002, through June 30, 2006. Of the 3,569 patients tested, 12 (0.34% [9 men and 3 women]) had development of this phenomenon. All patients previously had recent widespread dermatitis that was suppressed temporarily with topical corticosteroids and wet dressings at the time of patch testing. The period between control of the dermatitis and the initiation of patch testing was less than 1 week for all patients. Three patients (25%) had recently discontinued therapy with systemic corticosteroids (less than 1 week earlier). In patients with irritable skin either immediately after widespread dermatitis is controlled or after the cessation of systemic corticosteroid treatment, a flare of dermatitis induced by patch testing may render patch tests unreadable and therefore uninterpretable. To avoid this confounding occurrence, a waiting period between control of widespread dermatitis and initiation of patch testing is advised.

Mismeasurement and the resonance of strong confounders: uncorrelated errors.

PubMed

Marshall, J R; Hastrup, J L

1996-05-15

Greenland first documented (Am J Epidemiol 1980; 112:564-9) that error in the measurement of a confounder could resonate--that it could bias estimates of other study variables, and that the bias could persist even with statistical adjustment for the confounder as measured. An important question is raised by this finding: can such bias be more than trivial within the bounds of realistic data configurations? The authors examine several situations involving dichotomous and continuous data in which a confounder and a null variable are measured with error, and they assess the extent of resultant bias in estimates of the effect of the null variable. They show that, with continuous variables, measurement error amounting to 40% of observed variance in the confounder could cause the observed impact of the null study variable to appear to alter risk by as much as 30%. Similarly, they show, with dichotomous independent variables, that 15% measurement error in the form of misclassification could lead the null study variable to appear to alter risk by as much as 50%. Such bias would result only from strong confounding. Measurement error would obscure the evidence that strong confounding is a likely problem. These results support the need for every epidemiologic inquiry to include evaluations of measurement error in each variable considered.

Controlling for seasonal patterns and time varying confounders in time-series epidemiological models: a simulation study.

PubMed

Perrakis, Konstantinos; Gryparis, Alexandros; Schwartz, Joel; Le Tertre, Alain; Katsouyanni, Klea; Forastiere, Francesco; Stafoggia, Massimo; Samoli, Evangelia

2014-12-10

An important topic when estimating the effect of air pollutants on human health is choosing the best method to control for seasonal patterns and time varying confounders, such as temperature and humidity. Semi-parametric Poisson time-series models include smooth functions of calendar time and weather effects to control for potential confounders. Case-crossover (CC) approaches are considered efficient alternatives that control seasonal confounding by design and allow inclusion of smooth functions of weather confounders through their equivalent Poisson representations. We evaluate both methodological designs with respect to seasonal control and compare spline-based approaches, using natural splines and penalized splines, and two time-stratified CC approaches. For the spline-based methods, we consider fixed degrees of freedom, minimization of the partial autocorrelation function, and general cross-validation as smoothing criteria. Issues of model misspecification with respect to weather confounding are investigated under simulation scenarios, which allow quantifying omitted, misspecified, and irrelevant-variable bias. The simulations are based on fully parametric mechanisms designed to replicate two datasets with different mortality and atmospheric patterns. Overall, minimum partial autocorrelation function approaches provide more stable results for high mortality counts and strong seasonal trends, whereas natural splines with fixed degrees of freedom perform better for low mortality counts and weak seasonal trends followed by the time-season-stratified CC model, which performs equally well in terms of bias but yields higher standard errors. Copyright © 2014 John Wiley & Sons, Ltd.

Time-varying effect moderation using the structural nested mean model: estimation using inverse-weighted regression with residuals

PubMed Central

Almirall, Daniel; Griffin, Beth Ann; McCaffrey, Daniel F.; Ramchand, Rajeev; Yuen, Robert A.; Murphy, Susan A.

2014-01-01

This article considers the problem of examining time-varying causal effect moderation using observational, longitudinal data in which treatment, candidate moderators, and possible confounders are time varying. The structural nested mean model (SNMM) is used to specify the moderated time-varying causal effects of interest in a conditional mean model for a continuous response given time-varying treatments and moderators. We present an easy-to-use estimator of the SNMM that combines an existing regression-with-residuals (RR) approach with an inverse-probability-of-treatment weighting (IPTW) strategy. The RR approach has been shown to identify the moderated time-varying causal effects if the time-varying moderators are also the sole time-varying confounders. The proposed IPTW+RR approach provides estimators of the moderated time-varying causal effects in the SNMM in the presence of an additional, auxiliary set of known and measured time-varying confounders. We use a small simulation experiment to compare IPTW+RR versus the traditional regression approach and to compare small and large sample properties of asymptotic versus bootstrap estimators of the standard errors for the IPTW+RR approach. This article clarifies the distinction between time-varying moderators and time-varying confounders. We illustrate the methodology in a case study to assess if time-varying substance use moderates treatment effects on future substance use. PMID:23873437

A Comprehensive Analysis of the SRS-Schwab Adult Spinal Deformity Classification and Confounding Variables: A Prospective, Non-US Cross-sectional Study in 292 Patients.

PubMed

Hallager, Dennis Winge; Hansen, Lars Valentin; Dragsted, Casper Rokkjær; Peytz, Nina; Gehrchen, Martin; Dahl, Benny

2016-05-01

Cross-sectional analyses on a consecutive, prospective cohort. To evaluate the ability of the Scoliosis Research Society (SRS)-Schwab Adult Spinal Deformity Classification to group patients by widely used health-related quality-of-life (HRQOL) scores and examine possible confounding variables. The SRS-Schwab Adult Spinal Deformity Classification includes sagittal modifiers considered important for HRQOL and the clinical impact of the classification has been validated in patients from the International Spine Study Group database; however, equivocal results were reported for the Pelvic Tilt modifier and potential confounding variables were not evaluated. Between March 2013 and May 2014, all adult spinal deformity patients from our outpatient clinic with sufficient radiographs were prospectively enrolled. Analyses of HRQOL variance and post hoc analyses were performed for each SRS-Schwab modifier. Age, history of spine surgery, and aetiology of spinal deformity were considered potential confounders and their influence on the association between SRS-Schwab modifiers and aggregated Oswestry Disability Index (ODI) scores was evaluated with multivariate proportional odds regressions. P values were adjusted for multiple testing. Two hundred ninety-two of 460 eligible patients were included for analyses. The SRS-Schwab Classification significantly discriminated HRQOL scores between normal and abnormal sagittal modifier classifications. Individual grade comparisons showed equivocal results; however, Pelvic Tilt grade + versus +  + did not discriminate patients according to any HRQOL score. All modifiers showed significant proportional odds for worse aggregated ODI scores with increasing grade levels and the effects were robust to confounding. However, age group and aetiology had individual significant effects. The SRS-Schwab sagittal modifiers reliably grouped patients graded 0 versus + / +  + according to the most widely used HRQOL scores and the effects of increasing grade level on odds for worse ODI scores remained significant after adjusting for potential confounders. However, effects of age group and aetiology should not be neglected. 3.

Psychosocial Assessment of Self-Harm Patients and Risk of Repeat Presentation: An Instrumental Variable Analysis Using Time of Hospital Presentation.

PubMed

Carroll, Robert; Metcalfe, Chris; Steeg, Sarah; Davies, Neil M; Cooper, Jayne; Kapur, Nav; Gunnell, David

2016-01-01

Clinical guidelines have recommended psychosocial assessment of self-harm patients for years, yet estimates of its impact on the risk of repeat self-harm vary. Assessing the association of psychosocial assessment with risk of repeat self-harm is challenging due to the effects of confounding by indication. We analysed data from a cohort study of 15,113 patients presenting to the emergency departments of three UK hospitals to investigate the association of psychosocial assessment with risk of repeat hospital presentation for self-harm. Time of day of hospital presentation was used as an instrument for psychosocial assessment, attempting to control for confounding by indication. Conventional regression analysis suggested psychosocial assessment was not associated with risk of repeat self-harm within 12 months (Risk Difference (RD) 0.00 95% confidence interval (95%CI) -0.01 to 0.02). In contrast, IV analysis suggested risk of repeat self-harm was reduced by 18% (RD -0.18, 95%CI -0.32 to -0.03) in those patients receiving a psychosocial assessment. However, the instrument of time of day did not remove all potential effects of confounding by indication, suggesting the IV effect estimate may be biased. We found that psychosocial assessments reduce risk of repeat self-harm. This is in-line with other non-randomised studies based on populations in which allocation to assessment was less subject to confounding by indication. However, as our instrument did not fully balance important confounders across time of day, the IV effect estimate should be interpreted with caution.

On the use and misuse of scalar scores of confounders in design and analysis of observational studies.

PubMed

Pfeiffer, R M; Riedl, R

2015-08-15

We assess the asymptotic bias of estimates of exposure effects conditional on covariates when summary scores of confounders, instead of the confounders themselves, are used to analyze observational data. First, we study regression models for cohort data that are adjusted for summary scores. Second, we derive the asymptotic bias for case-control studies when cases and controls are matched on a summary score, and then analyzed either using conditional logistic regression or by unconditional logistic regression adjusted for the summary score. Two scores, the propensity score (PS) and the disease risk score (DRS) are studied in detail. For cohort analysis, when regression models are adjusted for the PS, the estimated conditional treatment effect is unbiased only for linear models, or at the null for non-linear models. Adjustment of cohort data for DRS yields unbiased estimates only for linear regression; all other estimates of exposure effects are biased. Matching cases and controls on DRS and analyzing them using conditional logistic regression yields unbiased estimates of exposure effect, whereas adjusting for the DRS in unconditional logistic regression yields biased estimates, even under the null hypothesis of no association. Matching cases and controls on the PS yield unbiased estimates only under the null for both conditional and unconditional logistic regression, adjusted for the PS. We study the bias for various confounding scenarios and compare our asymptotic results with those from simulations with limited sample sizes. To create realistic correlations among multiple confounders, we also based simulations on a real dataset. Copyright © 2015 John Wiley & Sons, Ltd.

Identification of confounders in the assessment of the relationship between lead exposure and child development.

PubMed

Tong, I S; Lu, Y

2001-01-01

To explore the best approach to identify and adjust for confounders in epidemiologic practice. In the Port Pirie cohort study, the selection of covariates was based on both a priori and an empirical consideration. In an assessment of the relationship between exposure to environmental lead and child development, change-in-estimate (CE) and significance testing (ST) criteria were compared in identifying potential confounders. The Pearson correlation coefficients were used to evaluate the potential for collinearity between pairs of major quantitative covariates. In multivariate analyses, the effects of confounding factors were assessed with multiple linear regression models. The nature and number of covariates selected varied with different confounder selection criteria and different cutoffs. Four covariates (i.e., quality of home environment, socioeconomic status (SES), maternal intelligence, and parental smoking behaviour) met the conventional CE criterion (> or =10%), whereas 14 variables met the ST criterion (p < or = 0.25). However, the magnitude of the relationship between blood lead concentration and children's IQ differed slightly after adjustment for confounding, using either the CE (partial regression coefficient: -4.4; 95% confidence interval (CI): -0.5 to -8.3) or ST criterion (-4.3; 95% CI: -0.2 to -8.4). Identification and selection of confounding factors need to be viewed cautiously in epidemiologic studies. Either the CE (e.g., > or = 10%) or ST (e.g., p < or = 0.25) criterion may be implemented in identification of a potential confounder if a study sample is sufficiently large, and both the methods are subject to arbitrariness of selecting a cut-off point. In this study, the CE criterion (i.e., > or = 10%) appears to be more stringent than the ST method (i.e., p < or = 0.25) in the identification of confounders. However, the ST rule cannot be used to determine the trueness of confounding because it cannot reflect the causal relationship between the confounder and outcome. This study shows the complexities one can expect to encounter in the identification of and adjustment for confounders.

Use of instrumental variables in the analysis of generalized linear models in the presence of unmeasured confounding with applications to epidemiological research.

PubMed

Johnston, K M; Gustafson, P; Levy, A R; Grootendorst, P

2008-04-30

A major, often unstated, concern of researchers carrying out epidemiological studies of medical therapy is the potential impact on validity if estimates of treatment are biased due to unmeasured confounders. One technique for obtaining consistent estimates of treatment effects in the presence of unmeasured confounders is instrumental variables analysis (IVA). This technique has been well developed in the econometrics literature and is being increasingly used in epidemiological studies. However, the approach to IVA that is most commonly used in such studies is based on linear models, while many epidemiological applications make use of non-linear models, specifically generalized linear models (GLMs) such as logistic or Poisson regression. Here we present a simple method for applying IVA within the class of GLMs using the generalized method of moments approach. We explore some of the theoretical properties of the method and illustrate its use within both a simulation example and an epidemiological study where unmeasured confounding is suspected to be present. We estimate the effects of beta-blocker therapy on one-year all-cause mortality after an incident hospitalization for heart failure, in the absence of data describing disease severity, which is believed to be a confounder. 2008 John Wiley & Sons, Ltd

Negative affectivity: moderator or confound in emotional dissonance-outcome relationships?

PubMed

Abraham, R

1999-01-01

This study was an examination of the impact of negative affectivity on relationships between emotional dissonance, job satisfaction, and emotional exhaustion. Negative affectivity is the predisposition to view life in negative terms. Emotional dissonance originates from the conflict between expressed and experienced emotions. In organizations that require the expression of positive emotions, high negative affectivity individuals may experience conflict between expressed, positive emotions and felt, negative emotions. A moderator effect exists when high negative affectivity individuals experience greater job dissatisfaction and emotional exhaustion. Alternatively, negative affectivity may exert a confounding effect through its relationship to both emotional dissonance and its outcomes. Empirical tests showed that negative affectivity moderated the emotional dissonance-job satisfaction relationship and confounded the emotional dissonance-emotional exhaustion relationship.

Do time-invariant confounders explain away the association between job stress and workers' mental health? Evidence from Japanese occupational panel data.

PubMed

Oshio, Takashi; Tsutsumi, Akizumi; Inoue, Akiomi

2015-02-01

It is well known that job stress is negatively related to workers' mental health, but most recent studies have not controlled for unobserved time-invariant confounders. In the current study, we attempted to validate previous observations on the association between job stress and workers' mental health, by removing the effects of unobserved time-invariant confounders. We used data from three to four waves of an occupational Japanese cohort survey, focusing on 31,382 observations of 9741 individuals who participated in at least two consecutive waves. We estimated mean-centered fixed effects models to explain psychological distress in terms of the Kessler 6 (K6) scores (range: 0-24) by eight job stress indicators related to the job demands-control, effort-reward imbalance, and organizational injustice models. Mean-centered fixed effects models reduced the magnitude of the association between jobs stress and K6 scores to 44.8-54.2% of those observed from pooled ordinary least squares. However, the association remained highly significant even after controlling for unobserved time-invariant confounders for all job stress indicators. In addition, alternatively specified models showed the robustness of the results. In all, we concluded that the validity of major job stress models, which link job stress and workers' mental health, was robust, although unobserved time-invariant confounders led to an overestimation of the association. Copyright © 2014 Elsevier Ltd. All rights reserved.

Everything that you have ever been told about assessment center ratings is confounded.

PubMed

Jackson, Duncan J R; Michaelides, George; Dewberry, Chris; Kim, Young-Jae

2016-07-01

Despite a substantial research literature on the influence of dimensions and exercises in assessment centers (ACs), the relative impact of these 2 sources of variance continues to raise uncertainties because of confounding. With confounded effects, it is not possible to establish the degree to which any 1 effect, including those related to exercises and dimensions, influences AC ratings. In the current study (N = 698) we used Bayesian generalizability theory to unconfound all of the possible effects contributing to variance in AC ratings. Our results show that ≤1.11% of the variance in AC ratings was directly attributable to behavioral dimensions, suggesting that dimension-related effects have no practical impact on the reliability of ACs. Even when taking aggregation level into consideration, effects related to general performance and exercises accounted for almost all of the reliable variance in AC ratings. The implications of these findings for recent dimension- and exercise-based perspectives on ACs are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Developing hazelnut tissue culture medium free of ion confounding

USDA-ARS?s Scientific Manuscript database

The general approach for tissue culture medium optimization is to use salts as factors in experimental design and analysis. However, using salts as factors leads to ion confounding, making it difficult to detect the effects of individual ions on particular growth responses. This study focused on tes...

Turbulence intensity's effect on liquid jet breakup from long circular pipes

NASA Astrophysics Data System (ADS)

Trettel, Ben; Ezekoye, Ofodike

2017-11-01

Long pipes which produce fully developed flow are frequently used as a nozzle in jet breakup research. We compiled experimental data from over 20 pipe jet studies for many breakup quantities and developed correlations for these quantities based on existing theories and our own theories. Previous experimental studies often had confounding between some variables (e.g., the Reynolds and Weber numbers), neglected important quantities (e.g., the turbulence intensity), or made apples to oranges comparisons (e.g., different nozzles). By independently tracking the Reynolds number, Weber number, density ratio, and turbulence intensity, and focusing only on pipe jets to keep other variables nearly constant, we minimize these issues. Turbulence is a cause of jet breakup, yet there is little quantitative research on this due to the difficulty of turbulence measurements in free surface flows. To avoid those difficulties, we exploited the fact that adjusting the roughness of a long pipe allows one to quantifiably control the turbulence intensity. We correlated turbulence intensity as a function of the friction factor. Data for rough pipes was used to include turbulence intensity in our study. Comparisons were made with theories for the effect of turbulence intensity on breakup.

Enhancing emotion-based learning in decision-making under uncertainty.

PubMed

Alarcón, David; Amián, Josué G; Sánchez-Medina, José A

2015-01-01

The Iowa Gambling Task (IGT) is widely used to study decision-making differences between several clinical and healthy populations. Unlike the healthy participants, clinical participants have difficulty choosing between advantageous options, which yield long-term benefits, and disadvantageous options, which give high immediate rewards but lead to negative profits. However, recent studies have found that healthy participants avoid the options with a higher frequency of losses regardless of whether or not they are profitable in the long run. The aim of this study was to control for the confounding effect of the frequency of losses between options to improve the performance of healthy participants on the IGT. Eighty healthy participants were randomly assigned to the original IGT or a modified version of the IGT that diminished the gap in the frequency of losses between options. The participants who used the modified IGT version learned to make better decisions based on long-term profit, as indicated by an earlier ability to discriminate good from bad options, and took less time to make their choices. This research represents an advance in the study of decision making under uncertainty by showing that emotion-based learning is improved by controlling for the loss-frequency bias effect.

Current trends in stroke rehabilitation. A review with focus on brain plasticity.

PubMed

Johansson, B B

2011-03-01

Current understanding of brain plasticity has lead to new approaches in ischemic stroke rehabilitation. Stroke units that combine good medical and nursing care with task-oriented intense training in an environment that provides confidence, stimulation and motivation significantly improve outcome. Repetitive trans-cranial magnetic stimulation (rTMS), and trans-cranial direct current stimulation (tDCS) are applied in rehabilitation of motor function. The long-term effect, optimal way of stimulation and possibly efficacy in cognitive rehabilitation need evaluation. Methods based on multisensory integration of motor, cognitive, and perceptual processes including action observation, mental training, and virtual reality are being tested. Different approaches of intensive aphasia training are described. Recent data on intensive melodic intonation therapy indicate that even patients with very severe non-fluent aphasia can regain speech through homotopic white matter tract plasticity. Music therapy is applied in motor and cognitive rehabilitation. To avoid the confounding effect of spontaneous improvement, most trials are preformed ≥3 months post stroke. Randomized controlled trials starting earlier after strokes are needed. More attention should be given to stroke heterogeneity, cognitive rehabilitation, and social adjustment and to genetic differences, including the role of BDNF polymorphism in brain plasticity. © 2010 John Wiley & Sons A/S.

Methodological Challenges in Studies Comparing Prehospital Advanced Life Support with Basic Life Support.

PubMed

Li, Timmy; Jones, Courtney M C; Shah, Manish N; Cushman, Jeremy T; Jusko, Todd A

2017-08-01

Determining the most appropriate level of care for patients in the prehospital setting during medical emergencies is essential. A large body of literature suggests that, compared with Basic Life Support (BLS) care, Advanced Life Support (ALS) care is not associated with increased patient survival or decreased mortality. The purpose of this special report is to synthesize the literature to identify common study design and analytic challenges in research studies that examine the effect of ALS, compared to BLS, on patient outcomes. The challenges discussed in this report include: (1) choice of outcome measure; (2) logistic regression modeling of common outcomes; (3) baseline differences between study groups (confounding); (4) inappropriate statistical adjustment; and (5) inclusion of patients who are no longer at risk for the outcome. These challenges may affect the results of studies, and thus, conclusions of studies regarding the effect of level of prehospital care on patient outcomes should require cautious interpretation. Specific alternatives for avoiding these challenges are presented. Li T , Jones CMC , Shah MN , Cushman JT , Jusko TA . Methodological challenges in studies comparing prehospital Advanced Life Support with Basic Life Support. Prehosp Disaster Med. 2017;32(4):444-450.

Driver self-regulation and depressive symptoms in cataract patients awaiting surgery: a cross-sectional study

PubMed Central

2013-01-01

Background Cataract is an extremely common visual condition of ageing. Evidence suggests that visual impairment influences driving patterns and self-regulatory behavior among older drivers. However, little is known about the psychological effects of driver self-regulation among older drivers. Therefore, this study aimed to describe driver self-regulation practices among older bilateral cataract patients and to determine the association between self-regulation and depressive symptoms. Methods Ninety-nine older drivers with bilateral cataract were assessed the week before first eye cataract surgery. Driver self-regulation was measured via the Driving Habits Questionnaire. Depressive symptoms were assessed using the 20-item Center for Epidemiological Studies Depression Scale. Visual, demographic and cognitive data were also collected. Differences between self-regulators and non self-regulators were described and linear regression modeling used to determine the association between driver self-regulation and depressive symptoms score. Results Among cataract patients, 48% reported self-regulating their driving to avoid at least one challenging situation. The situations most commonly avoided were driving at night (40%), on the freeway (12%), in the rain (9%) and parallel parking (8%). Self-regulators had significantly poorer contrast sensitivity in their worse eye than non self-regulators (p = 0.027). Driver self-regulation was significantly associated with increased depressive symptoms after controlling for potential confounding factors (p = 0.002). Conclusions Driver self-regulation was associated with increased depressive symptoms among cataract patients. Further research should investigate this association among the general older population. Self-regulation programs aimed at older drivers may need to incorporate mental health elements to counteract unintended psychological effects. PMID:24016307

CP-CHARM: segmentation-free image classification made accessible.

PubMed

Uhlmann, Virginie; Singh, Shantanu; Carpenter, Anne E

2016-01-27

Automated classification using machine learning often relies on features derived from segmenting individual objects, which can be difficult to automate. WND-CHARM is a previously developed classification algorithm in which features are computed on the whole image, thereby avoiding the need for segmentation. The algorithm obtained encouraging results but requires considerable computational expertise to execute. Furthermore, some benchmark sets have been shown to be subject to confounding artifacts that overestimate classification accuracy. We developed CP-CHARM, a user-friendly image-based classification algorithm inspired by WND-CHARM in (i) its ability to capture a wide variety of morphological aspects of the image, and (ii) the absence of requirement for segmentation. In order to make such an image-based classification method easily accessible to the biological research community, CP-CHARM relies on the widely-used open-source image analysis software CellProfiler for feature extraction. To validate our method, we reproduced WND-CHARM's results and ensured that CP-CHARM obtained comparable performance. We then successfully applied our approach on cell-based assay data and on tissue images. We designed these new training and test sets to reduce the effect of batch-related artifacts. The proposed method preserves the strengths of WND-CHARM - it extracts a wide variety of morphological features directly on whole images thereby avoiding the need for cell segmentation, but additionally, it makes the methods easily accessible for researchers without computational expertise by implementing them as a CellProfiler pipeline. It has been demonstrated to perform well on a wide range of bioimage classification problems, including on new datasets that have been carefully selected and annotated to minimize batch effects. This provides for the first time a realistic and reliable assessment of the whole image classification strategy.

Collider bias in trauma comparative effectiveness research: the stratification blues for systematic reviews.

PubMed

Del Junco, Deborah J; Bulger, Eileen M; Fox, Erin E; Holcomb, John B; Brasel, Karen J; Hoyt, David B; Grady, James J; Duran, Sarah; Klotz, Patricia; Dubick, Michael A; Wade, Charles E

2015-05-01

Collider bias, or stratifying data by a covariate consequence rather than cause (confounder) of treatment and outcome, plagues randomised and observational trauma research. Of the seven trials of prehospital hypertonic saline in dextran (HSD) that have been evaluated in systematic reviews, none found an overall between-group difference in survival, but four reported significant subgroup effects. We hypothesised that an avoidable type of collider bias often introduced inadvertently into trauma comparative effectiveness research could explain the incongruous findings. The two most recent HSD trials, a single-site pilot and a multi-site pivotal study, provided data for a secondary analysis to more closely examine the potential for collider bias. The two trials had followed the a priori statistical analysis plan to subgroup patients by a post-randomisation covariate and well-established surrogate for bleeding severity, massive transfusion (MT), ≥ 10 unit of red blood cells within 24h of admission. Despite favourable HSD effects in the MT subgroup, opposite effects in the non-transfused subgroup halted the pivotal trial early. In addition to analyzing the data from the two trials, we constructed causal diagrams and performed a meta-analysis of the results from all seven trials to assess the extent to which collider bias could explain null overall effects with subgroup heterogeneity. As in previous trials, HSD induced significantly greater increases in systolic blood pressure (SBP) from prehospital to admission than control crystalloid (p=0.003). Proportionately more HSD than control decedents accrued in the non-transfused subgroup, but with paradoxically longer survival. Despite different study populations and a span of over 20 years across the seven trials, the reported mortality effects were consistently null, summary RR=0.99 (p=0.864, homogeneity p=0.709). HSD delayed blood transfusion by modifying standard triggers like SBP with no detectable effect on survival. The reported heterogeneous HSD effects in subgroups can be explained by collider bias that trauma researchers can avoid by improved covariate selection and data capture strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Spatio-temporal Eigenvector Filtering: Application on Bioenergy Crop Impacts

NASA Astrophysics Data System (ADS)

Wang, M.; Kamarianakis, Y.; Georgescu, M.

2017-12-01

A suite of 10-year ensemble-based simulations was conducted to investigate the hydroclimatic impacts due to large-scale deployment of perennial bioenergy crops across the continental United States. Given the large size of the simulated dataset (about 60Tb), traditional hierarchical spatio-temporal statistical modelling cannot be implemented for the evaluation of physics parameterizations and biofuel impacts. In this work, we propose a filtering algorithm that takes into account the spatio-temporal autocorrelation structure of the data while avoiding spatial confounding. This method is used to quantify the robustness of simulated hydroclimatic impacts associated with bioenergy crops to alternative physics parameterizations and observational datasets. Results are evaluated against those obtained from three alternative Bayesian spatio-temporal specifications.

Strategies for evaluating the assumptions of the regression discontinuity design: a case study using a human papillomavirus vaccination programme.

PubMed

Smith, Leah M; Lévesque, Linda E; Kaufman, Jay S; Strumpf, Erin C

2017-06-01

The regression discontinuity design (RDD) is a quasi-experimental approach used to avoid confounding bias in the assessment of new policies and interventions. It is applied specifically in situations where individuals are assigned to a policy/intervention based on whether they are above or below a pre-specified cut-off on a continuously measured variable, such as birth date, income or weight. The strength of the design is that, provided individuals do not manipulate the value of this variable, assignment to the policy/intervention is considered as good as random for individuals close to the cut-off. Despite its popularity in fields like economics, the RDD remains relatively unknown in epidemiology where its application could be tremendously useful. In this paper, we provide a practical introduction to the RDD for health researchers, describe four empirically testable assumptions of the design and offer strategies that can be used to assess whether these assumptions are met in a given study. For illustrative purposes, we implement these strategies to assess whether the RDD is appropriate for a study of the impact of human papillomavirus vaccination on cervical dysplasia. We found that, whereas the assumptions of the RDD were generally satisfied in our study context, birth timing had the potential to confound our effect estimate in an unexpected way and therefore needed to be taken into account in the analysis. Our findings underscore the importance of assessing the validity of the assumptions of this design, testing them when possible and making adjustments as necessary to support valid causal inference. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association

Noise Pollution Filters Bird Communities Based on Vocal Frequency

PubMed Central

Francis, Clinton D.; Ortega, Catherine P.; Cruz, Alexander

2011-01-01

Background Human-generated noise pollution now permeates natural habitats worldwide, presenting evolutionarily novel acoustic conditions unprecedented to most landscapes. These acoustics not only harm humans, but threaten wildlife, and especially birds, via changes to species densities, foraging behavior, reproductive success, and predator-prey interactions. Explanations for negative effects of noise on birds include disruption of acoustic communication through energetic masking, potentially forcing species that rely upon acoustic communication to abandon otherwise suitable areas. However, this hypothesis has not been adequately tested because confounding stimuli often co-vary with noise and are difficult to separate from noise exposure. Methodology/Principal Findings Using a natural experiment that controls for confounding stimuli, we evaluate whether species vocal features or urban-tolerance classifications explain their responses to noise measured through habitat use. Two data sets representing nesting and abundance responses reveal that noise filters bird communities nonrandomly. Signal duration and urban tolerance failed to explain species-specific responses, but birds with low-frequency signals that are more susceptible to masking from noise avoided noisy areas and birds with higher frequency vocalizations remained. Signal frequency was also negatively correlated with body mass, suggesting that larger birds may be more sensitive to noise due to the link between body size and vocal frequency. Conclusions/Significance Our findings suggest that acoustic masking by noise may be a strong selective force shaping the ecology of birds worldwide. Larger birds with lower frequency signals may be excluded from noisy areas, whereas smaller species persist via transmission of higher frequency signals. We discuss our findings as they relate to interspecific relationships among body size, vocal amplitude and frequency and suggest that they are immediately relevant to the global problem of increases in noise by providing critical insight as to which species traits influence tolerance of these novel acoustics. PMID:22096517

Untangling the effects of tinnitus and hypersensitivity to sound (hyperacusis) in the gap detection test.

PubMed

Salloum, R H; Sandridge, S; Patton, D J; Stillitano, G; Dawson, G; Niforatos, J; Santiago, L; Kaltenbach, J A

2016-01-01

In recent years, there has been increasing use of the gap detection reflex test to demonstrate induction of tinnitus in animals. Animals with tinnitus show weakened gap detection ability for background noise that matches the pitch of the tinnitus. The usual explanation is that the tinnitus 'fills in the gap'. It has recently been shown, however, that tinnitus is commonly associated with hyperacusis-like enhancements of the acoustic startle response, a change which might potentially alter responses in the gap detection test. We hypothesized that such enhancements could lead to an apparent reduction of gap suppression, resembling that caused by tinnitus, by altering responses to the startle stimulus or the background noise. To test this hypothesis, we compared gap detection abilities in 3 subsets of noise-exposed animals with those in unexposed controls. The results showed that exposed animals demonstrated altered gap detection abilities, but these alterations were sometimes explained as consequences of hyper-responsiveness to either the startle stimulus or to the background noise. Two of the three subsets of animals studied, however, displayed weakened gap detection abilities that could not be explained by enhanced responses to these stimuli or by reduced sound sensitivity or a reduction of temporal processing speed, consistent with the induction of tinnitus. These results demonstrate that not only hearing loss but also changes in sensitivity to background noise or to startle stimuli are potential confounds that, when present, can underlie changes in gap detection irrespective of tinnitus. We discuss how such confounds can be recognized and how they can be avoided. Copyright © 2015 Elsevier B.V. All rights reserved.

Bi-directional associations between child fussy eating and parents' pressure to eat: Who influences whom?

PubMed

Jansen, Pauline W; de Barse, Lisanne M; Jaddoe, Vincent W V; Verhulst, Frank C; Franco, Oscar H; Tiemeier, Henning

2017-07-01

Fussy eating is common in young children, often raising concerns among parents. The use of pressuring feeding practices may provoke or worsen child fussiness, but these practices could equally be a parent's response to child fussy eating. In longitudinal analyses, we assessed directionality in the relation between fussy eating and parent's pressure to eat across childhood. Study participants were 4845 mother-child dyads from the population-based Generation R cohort in the Netherlands. The Child Behavior Checklist was used to assess fussy eating (2 items) at child ages 1½, 3 and 6years. Parents' pressure to eat was assessed with the Child Feeding Questionnaire (4 items) when children were 4years old. All scale scores were standardized. Linear regression analyses indicated that preschoolers' fussy eating prospectively predicted higher levels of parents' pressure to eat at child age 4years, independently of confounders (adjusted B=0.24, 95% CI: 0.21, 0.27). Pressure to eat at 4years also predicted more fussiness in children at age 6years, independently of confounders and of fussy eating at baseline (adjusted B=0.14, 95% CI: 0.11, 0.17). Path analyses indicated that the relation from fussy eating at 3years to parenting one year later was stronger than from pressure at 4years to fussy eating two years later (p<0.001). Our findings suggest bi-directional associations with parental pressuring feeding strategies being developed in response to children's food avoidant behaviors, but also seemingly having a counterproductive effect on fussiness. Thus, the use of pressure to eat should be reconsidered, while providing parents alternative techniques to deal with their child's fussy eating. Copyright © 2017 Elsevier Inc. All rights reserved.

Recognized Spontaneous Abortion in Mid-Pregnancy and Patterns of Pregnancy Alcohol Use

PubMed Central

Chiodo, Lisa M.; Bailey, Beth; Sokol, Robert J.; Janisse, James; Delaney-Black, Virginia; Hannigan, John H.

2012-01-01

Alcohol consumption during pregnancy is one potential risk factor for spontaneous abortion (SAb). Prior research suggested that heavy drinking during pregnancy was associated with significantly increased rates of SAb, but results for lower levels of drinking have been inconsistent. We examined the association between different levels and patterns of prenatal alcohol consumption and SAb in a high-risk inner-city sample. We hypothesized that higher levels, binge patterns, and more frequent drinking would be associated with increased rates of SAb. The quantity and frequency of self-reported peri-conceptional and repeated in-pregnancy maternal drinking volumes per beverage type were assessed with semi-structured interviews in a prospective subsample of 302 African-American mothers. Relations between various measures of prenatal alcohol exposure and SAb were assessed using logistic regression. After controlling for various potential confounders, there was a significant positive relation between average absolute alcohol use per day across pregnancy and SAb. Greater frequency of drinking episodes also predicted SAb: an average of even one day of drinking per week across pregnancy was associated with an increase in the incidence of SAb. However, contrary to our hypothesis, neither the amount of alcohol drunk per drinking day nor a measure of binge drinking were significantly related to SAb after controlling for confounders. Differences in when women who drank at risk levels initiated antenatal care may have under-estimated the impact of alcohol on SAb in this low-SES urban African American sample. Some drinking measures averaged across pregnancy may have underestimated consumption and overestimated risk of SAb, but others risk-drinking measures that avoid this limitation show similar relations to SAb. Identifying fetal risk drinking in pregnant women is critical to increasing the effectiveness of interventions that reduce risk-level alcohol consumption and protect from pregnancy loss. PMID:22440690

Identification and Sensitivity Analysis for Average Causal Mediation Effects with Time-Varying Treatments and Mediators: Investigating the Underlying Mechanisms of Kindergarten Retention Policy.

PubMed

Park, Soojin; Steiner, Peter M; Kaplan, David

2018-06-01

Considering that causal mechanisms unfold over time, it is important to investigate the mechanisms over time, taking into account the time-varying features of treatments and mediators. However, identification of the average causal mediation effect in the presence of time-varying treatments and mediators is often complicated by time-varying confounding. This article aims to provide a novel approach to uncovering causal mechanisms in time-varying treatments and mediators in the presence of time-varying confounding. We provide different strategies for identification and sensitivity analysis under homogeneous and heterogeneous effects. Homogeneous effects are those in which each individual experiences the same effect, and heterogeneous effects are those in which the effects vary over individuals. Most importantly, we provide an alternative definition of average causal mediation effects that evaluates a partial mediation effect; the effect that is mediated by paths other than through an intermediate confounding variable. We argue that this alternative definition allows us to better assess at least a part of the mediated effect and provides meaningful and unique interpretations. A case study using ECLS-K data that evaluates kindergarten retention policy is offered to illustrate our proposed approach.

Residential proximity to electromagnetic field sources and birth weight: Minimizing residual confounding using multiple imputation and propensity score matching.

PubMed

de Vocht, Frank; Lee, Brian

2014-08-01

Studies have suggested that residential exposure to extremely low frequency (50 Hz) electromagnetic fields (ELF-EMF) from high voltage cables, overhead power lines, electricity substations or towers are associated with reduced birth weight and may be associated with adverse birth outcomes or even miscarriages. We previously conducted a study of 140,356 singleton live births between 2004 and 2008 in Northwest England, which suggested that close residential proximity (≤ 50 m) to ELF-EMF sources was associated with reduced average birth weight of 212 g (95%CI: -395 to -29 g) but not with statistically significant increased risks for other adverse perinatal outcomes. However, the cohort was limited by missing data for most potentially confounding variables including maternal smoking during pregnancy, which was only available for a small subgroup, while also residual confounding could not be excluded. This study, using the same cohort, was conducted to minimize the effects of these problems using multiple imputation to address missing data and propensity score matching to minimize residual confounding. Missing data were imputed using multiple imputation using chained equations to generate five datasets. For each dataset 115 exposed women (residing ≤ 50 m from a residential ELF-EMF source) were propensity score matched to 1150 unexposed women. After doubly robust confounder adjustment, close proximity to a residential ELF-EMF source remained associated with a reduction in birth weight of -116 g (95% confidence interval: -224:-7 g). No effect was found for proximity ≤ 100 m compared to women living further away. These results indicate that although the effect size was about half of the effect previously reported, close maternal residential proximity to sources of ELF-EMF remained associated with suboptimal fetal growth. Copyright © 2014 Elsevier Ltd. All rights reserved.

On Estimation of the Survivor Average Causal Effect in Observational Studies when Important Confounders are Missing Due to Death

PubMed Central

Egleston, Brian L.; Scharfstein, Daniel O.; MacKenzie, Ellen

2008-01-01

We focus on estimation of the causal effect of treatment on the functional status of individuals at a fixed point in time t* after they have experienced a catastrophic event, from observational data with the following features: (1) treatment is imposed shortly after the event and is non-randomized, (2) individuals who survive to t* are scheduled to be interviewed, (3) there is interview non-response, (4) individuals who die prior to t* are missing information on pre-event confounders, (5) medical records are abstracted on all individuals to obtain information on post-event, pre-treatment confounding factors. To address the issue of survivor bias, we seek to estimate the survivor average causal effect (SACE), the effect of treatment on functional status among the cohort of individuals who would survive to t* regardless of whether or not assigned to treatment. To estimate this effect from observational data, we need to impose untestable assumptions, which depend on the collection of all confounding factors. Since pre-event information is missing on those who die prior to t*, it is unlikely that these data are missing at random (MAR). We introduce a sensitivity analysis methodology to evaluate the robustness of SACE inferences to deviations from the MAR assumption. We apply our methodology to the evaluation of the effect of trauma center care on vitality outcomes using data from the National Study on Costs and Outcomes of Trauma Care. PMID:18759833

Indirect effect of a transgenic wheat on aphids through enhanced powdery mildew resistance.

PubMed

von Burg, Simone; Álvarez-Alfageme, Fernando; Romeis, Jörg

2012-01-01

In agricultural ecosystems, arthropod herbivores and fungal pathogens are likely to colonise the same plant and may therefore affect each other directly or indirectly. The fungus that causes powdery mildew (Blumeria graminis tritici) and cereal aphids are important pests of wheat but interactions between them have seldom been investigated. We studied the effects of powdery mildew of wheat on two cereal aphid species, Metopolophium dirhodum and Rhopalosiphum padi. We hypothesized that aphid number and size will be smaller on powdery mildew-infected plants than on non-infected plants. In a first experiment we used six commercially available wheat varieties whereas in the second experiment we used a genetically modified (GM) mildew-resistant wheat line and its non-transgenic sister line. Because the two lines differed only in the presence of the transgene and in powdery mildew resistance, experiment 2 avoided the confounding effect of variety. In both experiments, the number of M. dirhodum but not of R. padi was reduced by powdery mildew infection. Transgenic mildew-resistant lines therefore harboured bigger aphid populations than the non-transgenic lines. For both aphid species individual size was mostly influenced by aphid number. Our results indicate that plants that are protected from a particular pest (powdery mildew) became more favourable for another pest (aphids).

Effect of soil acidity, soil strength and macropores on root growth and morphology of perennial grass species differing in acid-soil resistance.

PubMed

Haling, Rebecca E; Simpson, Richard J; Culvenor, Richard A; Lambers, Hans; Richardson, Alan E

2011-03-01

It is unclear whether roots of acid-soil resistant plants have significant advantages, compared with acid-soil sensitive genotypes, when growing in high-strength, acid soils or in acid soils where macropores may allow the effects of soil acidity and strength to be avoided. The responses of root growth and morphology to soil acidity, soil strength and macropores by seedlings of five perennial grass genotypes differing in acid-soil resistance were determined, and the interaction of soil acidity and strength for growth and morphology of roots was investigated. Soil acidity and strength altered root length and architecture, root hair development, and deformed the root tip, especially in acid-soil sensitive genotypes. Root length was restricted to some extent by soil acidity in all genotypes, but the adverse impact of soil acidity on root growth by acid-soil resistant genotypes was greater at high levels of soil strength. Roots reacted to soil acidity when growing in macropores, but elongation through high-strength soil was improved. Soil strength can confound the effect of acidity on root growth, with the sensitivity of acid-resistant genotypes being greater in high-strength soils. This highlights the need to select for genotypes that resist both acidity and high soil strength. © 2010 Blackwell Publishing Ltd.

Indirect Effect of a Transgenic Wheat on Aphids through Enhanced Powdery Mildew Resistance

PubMed Central

von Burg, Simone; Álvarez-Alfageme, Fernando; Romeis, Jörg

2012-01-01

In agricultural ecosystems, arthropod herbivores and fungal pathogens are likely to colonise the same plant and may therefore affect each other directly or indirectly. The fungus that causes powdery mildew (Blumeria graminis tritici) and cereal aphids are important pests of wheat but interactions between them have seldom been investigated. We studied the effects of powdery mildew of wheat on two cereal aphid species, Metopolophium dirhodum and Rhopalosiphum padi. We hypothesized that aphid number and size will be smaller on powdery mildew-infected plants than on non-infected plants. In a first experiment we used six commercially available wheat varieties whereas in the second experiment we used a genetically modified (GM) mildew-resistant wheat line and its non-transgenic sister line. Because the two lines differed only in the presence of the transgene and in powdery mildew resistance, experiment 2 avoided the confounding effect of variety. In both experiments, the number of M. dirhodum but not of R. padi was reduced by powdery mildew infection. Transgenic mildew-resistant lines therefore harboured bigger aphid populations than the non-transgenic lines. For both aphid species individual size was mostly influenced by aphid number. Our results indicate that plants that are protected from a particular pest (powdery mildew) became more favourable for another pest (aphids). PMID:23056284

A conveyor belt task for assessing visuo-motor coordination in the marmoset (Callithrix jacchus): effects of diazepam, chlorpromazine, pentobarbital and d-amphetamine.

PubMed

D'Mello, G D; Duffy, E A; Miles, S S

1985-01-01

A conveyor belt task for assessing visuo-motor coordination in the marmoset is described. Animals are motivated by apple, a preferred food, under a state of minimal food deprivation. The apparatus used was designed to test animals within their home cages and not restrained in any way, thus avoiding possible confounding factors associated with restraint stress. Stable baseline levels of performance were reached by all animals in a median of 24 sessions. Performance was shown to be differentially sensitive to the effects of four psychoactive drugs. Moderate doses of diazepam, chlorpromazine and pentobarbital disrupted visuo-motor coordination in a dose-related manner. The possibility that disruption of performance observed at higher doses may have resulted from non-specific actions of these drugs such as decreases in feeding motivation were not supported by results from ancillary experiments. Changes in performance characteristic of high dose effects were similar in nature to changes observed when the degree of task difficulty was increased. Doses of d-amphetamine up to and including those reported to produce signs of stereotypy failed to influence performance. The potential of the conveyor belt task for measuring visuo-motor coordination in both primate and rodent species is discussed.

Prevention of motor‐vehicle deaths by changing vehicle factors

PubMed Central

Robertson, Leon S

2007-01-01

Objective To estimate the effect of changing vehicle factors to reduce mortality in a comprehensive study. Design/methods Odds of death in the United States during 2000–2005 were analyzed, involving specific makes and models of 1999–2005 model year cars, minivans, and sport utility vehicles using logistic regression after selection of factors to be included by examination of least‐squares correlations of vehicle factors to maximize independence of predictors. Based on the regression coefficients, percentages of deaths preventable by changes in selected factors were calculated. Correlations of vehicle characteristics to environmental and behavioral risk factors were also examined to assess any potential confounding. Results Deaths in the studied vehicles would have been 42% lower had all had electronic stability control (ESC) systems. Improved crashworthiness as measured by offset frontal and side crash tests would have produced an additional 28% reduction, and static stability improvement would have reduced the deaths 11%. Although weight–power that reduces fuel economy is associated with lower risk to drivers, it increases risk of deaths to pedestrians and bicyclists but has an overall minor effect compared to the other factors. Conclusion A large majority of motor‐vehicle‐related fatalities could be avoided by universal adoption of the most effective technologies. PMID:17916886

The role of matched controls in building an evidence base for hospital-avoidance schemes: a retrospective evaluation.

PubMed

Steventon, Adam; Bardsley, Martin; Billings, John; Georghiou, Theo; Lewis, Geraint Hywel

2012-08-01

To test whether two hospital-avoidance interventions altered rates of hospital use: "intermediate care" and "integrated care teams." Linked administrative data for England covering the period 2004 to 2009. This study was commissioned after the interventions had been in place for several years. We developed a method based on retrospective analysis of person-level data comparing health care use of participants with that of prognostically matched controls. Individuals were linked to administrative datasets through a trusted intermediary and a unique patient identifier. Participants who received the intermediate care intervention showed higher rates of unscheduled hospital admission than matched controls, whereas recipients of the integrated care team intervention showed no difference. Both intervention groups showed higher rates of mortality than did their matched controls. These are potentially powerful techniques for assessing impacts on hospital activity. Neither intervention reduced admission rates. Although our analysis of hospital utilization controlled for a wide range of observable characteristics, the difference in mortality rates suggests that some residual confounding is likely. Evaluation is constrained when performed retrospectively, and careful interpretation is needed. © Health Research and Educational Trust.

Effects of caffeine on performance and mood: withdrawal reversal is the most plausible explanation.

PubMed

James, Jack E; Rogers, Peter J

2005-10-01

Although it is widely believed that caffeine can enhance human performance and mood, the validity of this belief has been questioned, giving rise to debate. The central question is whether superior performance and mood after caffeine represent net benefits, or whether differences between caffeine and control conditions are due to reversal of adverse withdrawal effects. To provide a focussed review of relevant experimental studies with the aim of clarifying current understanding regarding the effects of caffeine on human performance and mood. To avoid the shortcomings of standard placebo-controlled studies, which are ambiguous due to failure to control for the confounding influence of withdrawal reversal, three main experimental approaches have been employed: studies that compare consumers and low/non-consumers, pre-treatment and ad lib consumption studies, and long-term withdrawal studies. Of the three approaches, only long-term withdrawal studies are capable of unambiguously revealing the net effects of caffeine. Overall, there is little evidence of caffeine having beneficial effects on performance or mood under conditions of long-term caffeine use vs abstinence. Although modest acute effects may occur following initial use, tolerance to these effects appears to develop in the context of habitual use of the drug. Appropriately controlled studies show that the effects of caffeine on performance and mood, widely perceived to be net beneficial psychostimulant effects, are almost wholly attributable to reversal of adverse withdrawal effects associated with short periods of abstinence from the drug.

The Value of Response Times in Item Response Modeling

ERIC Educational Resources Information Center

Molenaar, Dylan

2015-01-01

A new and very interesting approach to the analysis of responses and response times is proposed by Goldhammer (this issue). In his approach, differences in the speed-ability compromise within respondents are considered to confound the differences in ability between respondents. These confounding effects of speed on the inferences about ability can…

Combating Unmeasured Confounding in Cross-Sectional Studies: Evaluating Instrumental-Variable and Heckman Selection Models

PubMed Central

DeMaris, Alfred

2014-01-01

Unmeasured confounding is the principal threat to unbiased estimation of treatment “effects” (i.e., regression parameters for binary regressors) in nonexperimental research. It refers to unmeasured characteristics of individuals that lead them both to be in a particular “treatment” category and to register higher or lower values than others on a response variable. In this article, I introduce readers to 2 econometric techniques designed to control the problem, with a particular emphasis on the Heckman selection model (HSM). Both techniques can be used with only cross-sectional data. Using a Monte Carlo experiment, I compare the performance of instrumental-variable regression (IVR) and HSM to that of ordinary least squares (OLS) under conditions with treatment and unmeasured confounding both present and absent. I find HSM generally to outperform IVR with respect to mean-square-error of treatment estimates, as well as power for detecting either a treatment effect or unobserved confounding. However, both HSM and IVR require a large sample to be fully effective. The use of HSM and IVR in tandem with OLS to untangle unobserved confounding bias in cross-sectional data is further demonstrated with an empirical application. Using data from the 2006–2010 General Social Survey (National Opinion Research Center, 2014), I examine the association between being married and subjective well-being. PMID:25110904

Who really gets strep sore throat? Confounding and effect modification of a time-varying exposure on recurrent events.

PubMed

Follmann, Dean; Huang, Chiung-Yu; Gabriel, Erin

2016-10-30

Unmeasured confounding is the fundamental obstacle to drawing causal conclusions about the impact of an intervention from observational data. Typically, covariates are measured to eliminate or ameliorate confounding, but they may be insufficient or unavailable. In the special setting where a transient intervention or exposure varies over time within each individual and confounding is time constant, a different tack is possible. The key idea is to condition on either the overall outcome or the proportion of time in the intervention. These measures can eliminate the unmeasured confounding either by conditioning or by use of a proxy covariate. We evaluate existing methods and develop new models from which causal conclusions can be drawn from such observational data even if no baseline covariates are measured. Our motivation for this work was to determine the causal effect of Streptococcus bacteria in the throat on pharyngitis (sore throat) in Indian schoolchildren. Using our models, we show that existing methods can be badly biased and that sick children who are rarely colonized have a high probability that the Streptococcus bacteria are causing their disease. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Comparing a marginal structural model with a Cox proportional hazard model to estimate the effect of time-dependent drug use in observational studies: statin use for primary prevention of cardiovascular disease as an example from the Rotterdam Study.

PubMed

de Keyser, Catherine E; Leening, Maarten J G; Romio, Silvana A; Jukema, J Wouter; Hofman, Albert; Ikram, M Arfan; Franco, Oscar H; Stijnen, Theo; Stricker, Bruno H

2014-11-01

When studying the causal effect of drug use in observational data, marginal structural modeling (MSM) can be used to adjust for time-dependent confounders that are affected by previous treatment. The objective of this study was to compare traditional Cox proportional hazard models (with and without time-dependent covariates) with MSM to study causal effects of time-dependent drug use. The example of primary prevention of cardiovascular disease (CVD) with statins was examined using up to 17.7 years of follow-up from 4,654 participants of the observational prospective population-based Rotterdam Study. In the MSM model, the weight was based on measurements of established cardiovascular risk factors and co-morbidity. In general, we could not demonstrate important differences in results from the Cox models and MSM. Results from analysis on duration of statin use suggested that substantial residual confounding by indication was not accounted for during the period shortly after statin initiation. In conclusion, although on theoretical grounds MSM is an elegant technique, lack of data on the precise time-dependent confounders, such as indication of treatment or other considerations of the prescribing physician jeopardizes the calculation of valid weights. Confounding remains a hurdle in observational effectiveness research on preventive drugs with a multitude of prescription determinants.

Advanced statistical methods to study the effects of gastric tube and non-invasive ventilation on functional decline and survival in amyotrophic lateral sclerosis.

PubMed

Atassi, Nazem; Cudkowicz, Merit E; Schoenfeld, David A

2011-07-01

A few studies suggest that non-invasive ventilation (1) and gastric tube (G-tube) may have a positive impact on survival but the effect on functional decline is unclear. Confounding by indication may have produced biased estimates of the benefit seen in some of these retrospective studies. The objective of this study was to evaluate the effects of G-tube and NIV on survival and functional decline using advanced statistical models that adjust for confounding by indications. A database of 331 subjects enrolled in previous clinical trials in ALS was available for analysis. Marginal structural models (MSM) were used to compare the mortality hazards and ALSFRS-R slopes between treatment and non-treatment groups, after adjusting for confounding by indication. Results showed that the placement of a G-tube was associated with an additional 1.42 units/month decline in the ALSFRS-R slope (p < 0.0001) and increased mortality hazard of 0.28 (p = 0.02). The use of NIV had no significant effect on ALSFRS-R decline or mortality. In conclusion, marginal structural models can be used to adjust for confounding by indication in retrospective ALS studies. G-tube placement could be followed by a faster rate of functional decline and increased mortality. Our results may suffer from some of the limitations of retrospective analyses.

How multiple causes combine: independence constraints on causal inference.

PubMed

Liljeholm, Mimi

2015-01-01

According to the causal power view, two core constraints-that causes occur independently (i.e., no confounding) and influence their effects independently-serve as boundary conditions for causal induction. This study investigated how violations of these constraints modulate uncertainty about the existence and strength of a causal relationship. Participants were presented with pairs of candidate causes that were either confounded or not, and that either interacted or exerted their influences independently. Consistent with the causal power view, uncertainty about the existence and strength of causal relationships was greater when causes were confounded or interacted than when unconfounded and acting independently. An elemental Bayesian causal model captured differences in uncertainty due to confounding but not those due to an interaction. Implications of distinct sources of uncertainty for the selection of contingency information and causal generalization are discussed.

Accounting for context in studies of health inequalities: a review and comparison of analytic approaches.

PubMed

Schempf, Ashley H; Kaufman, Jay S

2012-10-01

A common epidemiologic objective is to evaluate the contribution of residential context to individual-level disparities by race or socioeconomic position. We reviewed analytic strategies to account for the total (observed and unobserved factors) contribution of environmental context to health inequalities, including conventional fixed effects (FE) and hybrid FE implemented within a random effects (RE) or a marginal model. To illustrate results and limitations of the various analytic approaches of accounting for the total contextual component of health disparities, we used data on births nested within neighborhoods as an applied example of evaluating neighborhood confounding of racial disparities in gestational age at birth, including both a continuous and a binary outcome. Ordinary and RE models provided disparity estimates that can be substantially biased in the presence of neighborhood confounding. Both FE and hybrid FE models can account for cluster level confounding and provide disparity estimates unconfounded by neighborhood, with the latter having greater flexibility in allowing estimation of neighborhood-level effects and intercept/slope variability when implemented in a RE specification. Given the range of models that can be implemented in a hybrid approach and the frequent goal of accounting for contextual confounding, this approach should be used more often. Published by Elsevier Inc.

Avoiding stimulus confounds in Implicit Association Tests by using the concepts as stimuli.

PubMed

Steffens, Melanie C; Kirschbaum, Michael; Glados, Petra

2008-06-01

Implicit Association Tests (IATs) are supposed to measure associations between concepts. In order to achieve that aim, participants are required to assign individual stimuli to those concepts under time pressure in two different tasks. Previous research has shown that not only the associations of the concepts with each other, but also the stimuli's cross-category associations influence the observed reaction time difference between these tasks (i.e. the IAT effect). Little is known about adequate stimulus selection. In this article, we introduce a variant of the IAT, the Concept Association Task (CAT) in which the concepts themselves or synonyms of them are used as stimuli. Three experiments on Germans' attitudes towards foreigners yielded evidence for the convergent validity of the CAT: (1) it correlated well with other IAT versions; (2) it correlated higher with spontaneous attitude-related judgements than other IAT versions; and (3) it correlated with response-window priming, another implicit measure based on reaction times. Furthermore, we showed that the CAT yielded reasonable findings when other IAT versions appear to yield distorted ones.

Optimising rigid motion compensation for small animal brain PET imaging

NASA Astrophysics Data System (ADS)

Spangler-Bickell, Matthew G.; Zhou, Lin; Kyme, Andre Z.; De Laat, Bart; Fulton, Roger R.; Nuyts, Johan

2016-10-01

Motion compensation (MC) in PET brain imaging of awake small animals is attracting increased attention in preclinical studies since it avoids the confounding effects of anaesthesia and enables behavioural tests during the scan. A popular MC technique is to use multiple external cameras to track the motion of the animal’s head, which is assumed to be represented by the motion of a marker attached to its forehead. In this study we have explored several methods to improve the experimental setup and the reconstruction procedures of this method: optimising the camera-marker separation; improving the temporal synchronisation between the motion tracker measurements and the list-mode stream; post-acquisition smoothing and interpolation of the motion data; and list-mode reconstruction with appropriately selected subsets. These techniques have been tested and verified on measurements of a moving resolution phantom and brain scans of an awake rat. The proposed techniques improved the reconstructed spatial resolution of the phantom by 27% and of the rat brain by 14%. We suggest a set of optimal parameter values to use for awake animal PET studies and discuss the relative significance of each parameter choice.

Study of radiative heat transfer in Ångström- and nanometre-sized gaps

DOE PAGES

Cui, Longji; Jeong, Wonho; Fernández-Hurtado, Víctor; ...

2017-02-15

Radiative heat transfer in Ångström- and nanometre-sized gaps is of great interest because of both its technological importance and open questions regarding the physics of energy transfer in this regime. Here in this paper we report studies of radiative heat transfer in few Å to 5nm gap sizes, performed under ultrahigh vacuum conditions between a Au-coated probe featuring embedded nanoscale thermocouples and a heated planar Au substrate that were both subjected to various surface-cleaning procedures. By drawing on the apparent tunnelling barrier height as a signature of cleanliness, we found that upon systematically cleaning via a plasma or locally pushingmore » the tip into the substrate by a few nanometres, the observed radiative conductances decreased from unexpectedly large values to extremely small ones—below the detection limit of our probe—as expected from our computational results. Our results show that it is possible to avoid the confounding effects of surface contamination and systematically study thermal radiation in Ångström- and nanometre-sized gaps.« less

Methodological basis for the optimization of a marine sea-urchin embryo test (SET) for the ecological assessment of coastal water quality.

PubMed

Saco-Alvarez, Liliana; Durán, Iria; Ignacio Lorenzo, J; Beiras, Ricardo

2010-05-01

The sea-urchin embryo test (SET) has been frequently used as a rapid, sensitive, and cost-effective biological tool for marine monitoring worldwide, but the selection of a sensitive, objective, and automatically readable endpoint, a stricter quality control to guarantee optimum handling and biological material, and the identification of confounding factors that interfere with the response have hampered its widespread routine use. Size increase in a minimum of n=30 individuals per replicate, either normal larvae or earlier developmental stages, was preferred to observer-dependent, discontinuous responses as test endpoint. Control size increase after 48 h incubation at 20 degrees C must meet an acceptability criterion of 218 microm. In order to avoid false positives minimums of 32 per thousand salinity, 7 pH and 2mg/L oxygen, and a maximum of 40 microg/L NH(3) (NOEC) are required in the incubation media. For in situ testing size increase rates must be corrected on a degree-day basis using 12 degrees C as the developmental threshold. Copyright 2010 Elsevier Inc. All rights reserved.

Prediction versus aetiology: common pitfalls and how to avoid them.

PubMed

van Diepen, Merel; Ramspek, Chava L; Jager, Kitty J; Zoccali, Carmine; Dekker, Friedo W

2017-04-01

Prediction research is a distinct field of epidemiologic research, which should be clearly separated from aetiological research. Both prediction and aetiology make use of multivariable modelling, but the underlying research aim and interpretation of results are very different. Aetiology aims at uncovering the causal effect of a specific risk factor on an outcome, adjusting for confounding factors that are selected based on pre-existing knowledge of causal relations. In contrast, prediction aims at accurately predicting the risk of an outcome using multiple predictors collectively, where the final prediction model is usually based on statistically significant, but not necessarily causal, associations in the data at hand.In both scientific and clinical practice, however, the two are often confused, resulting in poor-quality publications with limited interpretability and applicability. A major problem is the frequently encountered aetiological interpretation of prediction results, where individual variables in a prediction model are attributed causal meaning. This article stresses the differences in use and interpretation of aetiological and prediction studies, and gives examples of common pitfalls. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Tutorial in Biostatistics: Instrumental Variable Methods for Causal Inference*

PubMed Central

Baiocchi, Michael; Cheng, Jing; Small, Dylan S.

2014-01-01

A goal of many health studies is to determine the causal effect of a treatment or intervention on health outcomes. Often, it is not ethically or practically possible to conduct a perfectly randomized experiment and instead an observational study must be used. A major challenge to the validity of observational studies is the possibility of unmeasured confounding (i.e., unmeasured ways in which the treatment and control groups differ before treatment administration which also affect the outcome). Instrumental variables analysis is a method for controlling for unmeasured confounding. This type of analysis requires the measurement of a valid instrumental variable, which is a variable that (i) is independent of the unmeasured confounding; (ii) affects the treatment; and (iii) affects the outcome only indirectly through its effect on the treatment. This tutorial discusses the types of causal effects that can be estimated by instrumental variables analysis; the assumptions needed for instrumental variables analysis to provide valid estimates of causal effects and sensitivity analysis for those assumptions; methods of estimation of causal effects using instrumental variables; and sources of instrumental variables in health studies. PMID:24599889

An assessment of the possible extent of confounding in epidemiological studies of lung cancer risk among roofers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mundt, D.J.; van Wijngaarden, E.; Mundt, K.A.

2007-07-01

We evaluated the likelihood and extent to which the observed increased risk of lung cancer may be due to confounding (a mixing of effects of multiple exposures) by co-exposure to other potential carcinogens present in roofing or to lifestyle variables. We conducted a review of the epidemiological and industrial hygiene literature of asphalt-exposed workers. Peer-reviewed epidemiological studies of asphalt fumes, related occupational exposures, and confounding factors were identified from MEDLINE (1966 early 2004). Industrial hygiene studies of asphalt workers were identified through MEDLINE, publicly available government documents, and asphalt industry documents. Using well established statistical methods, we quantified the extentmore » to which lung cancer relative risk estimates among roofers reflect confounding from other exposures, using different prevalence and risk scenarios. The relative risk of lung cancer varied from 1.2 to 5.0 in 13 epidemiological studies of roofers; most studies reported a relative risk between 1.2 and 1.4. Smoking, asbestos and coal tar were the most likely confounders, but the prevalence of these factors varied over time. The results of the study indicate that much of the observed risk reported in epidemiological studies of cancer among roofers is well within the range of what may have resulted from confounding by reasonable and expected levels of smoking, asbestos or coal tar. This may be particularly true for those studies that did not adjust for these confounders and where the exposure was defined as employment in the roofing industry. In addition to poorly defined asphalt exposure, uncontrolled confounding cannot reliably be ruled out in studies of lung cancer among asphalt-exposed roofers. Therefore, it is not possible to conclude whether roofers are at increased risk of lung cancer due to asphalt exposure.« less

The exploratory behaviour of rats in the hole-board apparatus: Is head-dipping a valid measure of neophilia?

PubMed Central

Brown, Gillian R.; Nemes, Christopher

2008-01-01

The exploratory behaviour of laboratory rodents is of interest within a number of areas of behavioural pharmacology. However, how best to measure exploratory behaviour in rodents remains a contentious issue. Many unconditioned tests, such as the open field, potentially confound general locomotor activity with exploration. The hole-board apparatus appears to avoid this confound, as head-dipping into holes in the floor is assumed to be a valid measure of the subject's attraction towards novelty (neophilia). This study aimed to investigate whether head-dipping should be considered a valid measure of neophilia by comparing performance of adult male and female Lister hooded rats on the hole-board task (a) over repeated sessions and (b) when novel objects were absent or present underneath the holes. The results show that head-dipping initially decreased across repeated exposures, while time spent in the aversive central area increased. No change in head-dipping was seen in response to objects being placed underneath the holes. Rather than being a measure of neophilia, these results support the hypothesis that head-dipping represents an escape response, which declines as the subject becomes less fearful. These results are compared with previous studies of repeated exposure to other novel environments. PMID:18406075

Nutritional Issues in Food Allergy.

PubMed

Skypala, Isabel J; McKenzie, Rebecca

2018-05-15

Diet and nutrition play an important role in the development and management of food allergy. The diet of expectant mothers can have an effect on their offspring in terms of allergic outcomes. A host of confounding factors may influence this, with a maternal diet rich in fruits and vegetables, fish, vitamin D-rich foods associated with a lower risk of allergic disease in their children. More surprisingly, the consumption of milk and butter has also been shown to have a protective effect, especially in a farm environment. Similarly, the diet of the infant can also be important, not only in terms of breast feeding, but also the timing of the introduction of complementary foods, the diversity of the diet and the effect of individual foods on the development of allergy. One factor which has clearly been shown not to influence the development of food allergy is allergen avoidance by expectant mothers. In the infant diet, the manipulation of the gut microbiome to prevent the development of atopic disease is clearly an area which promises much, although studies have yet to provide a breakthrough in the prevention of atopic dermatitis. More concrete evidence of the value of diet in prevention has come from studies evaluating infant eating patterns which may protect gut health, through the consumption of large amounts of home-processed fruits and vegetables. The consumption of fish during the first year of life has also been shown to be protective. The importance of nutritional issues in children and adults who have a food allergy has become much more accepted in recent years. The primary allergenic foods in infancy and childhood, milk, egg, wheat and soy are also ones which are present in many foods and thus their avoidance can be problematic from a nutritional perspective. Thus, children with a food allergy can have their growth compromised through avoidance, especially pre-diagnosis, when foods may be excluded without any expert nutritional input. The management of a food allergy largely remains the exclusion of the offending food(s), but it is now clear that in doing so, children in particular can be at nutritional risk if insufficient attention is paid to the rest of the diet. Adults with food allergy are often thought not to need nutritional counselling; however, many will exclude a wide range of foods due to anxiety about trace exposure, or similar foods causing reactions. The avoidance of staple foods such as milk and wheat are common, but substitute foods very often do not have comparable nutritional profiles. Adults may also be more susceptible to on-line promotion of extreme nutritional regimes which can be extremely harmful. All food allergic individuals, whatever their age, should have a nutrition review to ensure they are consuming a healthy, balanced diet, and are not avoiding food groups unnecessarily.

Weight Loss and Coronary Heart Disease: Sensitivity Analysis for Unmeasured Confounding by Undiagnosed Disease.

PubMed

Danaei, Goodarz; Robins, James M; Young, Jessica G; Hu, Frank B; Manson, JoAnn E; Hernán, Miguel A

2016-03-01

Evidence for the effect of weight loss on coronary heart disease (CHD) or mortality has been mixed. The effect estimates can be confounded due to undiagnosed diseases that may affect weight loss. We used data from the Nurses' Health Study to estimate the 26-year risk of CHD under several hypothetical weight loss strategies. We applied the parametric g-formula and implemented a novel sensitivity analysis for unmeasured confounding due to undiagnosed disease by imposing a lag time for the effect of weight loss on chronic disease. Several sensitivity analyses were conducted. The estimated 26-year risk of CHD did not change under weight loss strategies using lag times from 0 to 18 years. For a 6-year lag time, the risk ratios of CHD for weight loss compared with no weight loss ranged from 1.00 (0.99, 1.02) to 1.02 (0.99, 1.05) for different degrees of weight loss with and without restricting the weight loss strategy to participants with no major chronic disease. Similarly, no protective effect of weight loss was estimated for mortality risk. In contrast, we estimated a protective effect of weight loss on risk of type 2 diabetes. We estimated that maintaining or losing weight after becoming overweight or obese does not reduce the risk of CHD or death in this cohort of middle-age US women. Unmeasured confounding, measurement error, and model misspecification are possible explanations but these did not prevent us from estimating a beneficial effect of weight loss on diabetes.

Leaf litter traits of invasive species slow down decomposition compared to Spanish natives: a broad phylogenetic comparison.

PubMed

Godoy, Oscar; Castro-Díez, Pilar; Van Logtestijn, Richard S P; Cornelissen, Johannes H C; Valladares, Fernando

2010-03-01

Leaf traits related to the performance of invasive alien species can influence nutrient cycling through litter decomposition. However, there is no consensus yet about whether there are consistent differences in functional leaf traits between invasive and native species that also manifest themselves through their "after life" effects on litter decomposition. When addressing this question it is important to avoid confounding effects of other plant traits related to early phylogenetic divergences and to understand the mechanism underlying the observed results to predict which invasive species will exert larger effects on nutrient cycling. We compared initial leaf litter traits, and their effect on decomposability as tested in standardized incubations, in 19 invasive-native pairs of co-familial species from Spain. They included 12 woody and seven herbaceous alien species representative of the Spanish invasive flora. The predictive power of leaf litter decomposition rates followed the order: growth form > family > status (invasive vs. native) > leaf type. Within species pairs litter decomposition tended to be slower and more dependent on N and P in invaders than in natives. This difference was likely driven by the higher lignin content of invader leaves. Although our study has the limitation of not representing the natural conditions from each invaded community, it suggests a potential slowing down of the nutrient cycle at ecosystem scale upon invasion.

Associations of Cannabis and Cigarette Use with Depression and Anxiety at Age 18: Findings from the Avon Longitudinal Study of Parents and Children

PubMed Central

Gage, Suzanne H.; Hickman, Matthew; Heron, Jon; Munafò, Marcus R.; Lewis, Glyn; Macleod, John; Zammit, Stanley

2015-01-01

Introduction Substance use is associated with common mental health disorders, but the causal effect of specific substances is uncertain. We investigate whether adolescent cannabis and cigarette use is associated with incident depression and anxiety, while attempting to account for confounding and reverse causation. Methods We used data from ALSPAC, a UK birth cohort study, to investigate associations between cannabis or cigarettes (measured at age 16) and depression or anxiety (measured at age 18), before and after adjustment for pre-birth, childhood and adolescent confounders. Our imputed sample size was 4561 participants. Results Both cannabis (unadjusted OR 1.50, 95% CI 1.26, 1.80) and cigarette use (OR 1.37, 95% CI 1.16, 1.61) increased the odds of developing depression. Adjustment for pre-birth and childhood confounders partly attenuated these relationships though strong evidence of association persisted for cannabis use. There was weak evidence of association for cannabis (fully adjusted OR 1.30, 95% CI 0.98, 1.72) and insufficient evidence for association for cigarette use (fully adjusted OR = 0.97, 95% CI 0.75, 1.24) after mutually adjusting for each other, or for alcohol or other substance use. Neither cannabis nor cigarette use were associated with anxiety after adjustment for pre-birth and childhood confounders. Conclusions Whilst evidence of association between cannabis use and depression persisted after adjusting for pre-term and childhood confounders, our results highlight the difficulties in trying to estimate and interpret independent effects of cannabis and tobacco on psychopathology. Complementary methods are required to robustly examine effects of cannabis and tobacco on psychopathology. PMID:25875443

Estimating the monetary value of willingness to pay for E-book reader's attributes using partially confounded factorial conjoint choice experiment

NASA Astrophysics Data System (ADS)

Yong, Chin-Khian

2013-09-01

A partially confounded factorial conjoint choice experiments design was used to examine the monetary value of the willingness to pay for E-book Reader's attributes. Conjoint analysis is an efficient, cost-effective, and most widely used quantitative method in marketing research to understand consumer preferences and value trade-off. Value can be interpreted by customer or consumer as the received of multiple benefits from a price that was paid. The monetary value of willingness to pay for battery life, internal memory, external memory, screen size, text to Speech, touch screen, and converting handwriting to digital text of E-book reader were estimated in this study. Due to the significant interaction effect of the attributes with the price, the monetary values for the seven attributes were found to be different at different values of odds of purchasing versus not purchasing. The significant interactions effects were one of the main contribution of the partially confounded factorial conjoint choice experiment.

Modelling affective pain in mice: Effects of inflammatory hypersensitivity on place escape/avoidance behaviour, anxiety and hedonic state.

PubMed

Refsgaard, L K; Hoffmann-Petersen, J; Sahlholt, M; Pickering, D S; Andreasen, J T

2016-03-15

The place escape/avoidance paradigm (PEAP) has been used to assess the affective component of pain in rats. Using the Complete Freund's Adjuvant (CFA) model of inflammatory pain, the current study aimed at developing a mouse version of PEAP and investigating the relation between PEAP and other behavioural responses, namely anxiety-like behaviour, locomotor activity, and hedonic state. A novel paradigm assessing the affective component of pain in mice was developed by modifying the setup known from rat studies: Animals were forced to stay 2 × 5 min in the light and the dark area of a box while being stimulated with a suprathreshold filament on the untreated or treated paw, respectively. This was followed by a 30-min test with unrestricted movement. Anxiety-like behaviour, locomotor activity, and hedonic state were assessed with the elevated zero maze (EZM), an open field setup, and a saccharin preference test, respectively, and correlated with the PEAP behaviour to examine potentially confounding parameters of the novel paradigm. In the PEAP, CFA-treated animals spent more time in the light area. CFA also increased anxiety-like behaviour significantly, whereas locomotor activity was unaffected. A significant, albeit modest, reduction in saccharin preference was observed. PEAP responses showed no significant correlations with any other behavioural measure. The PEAP results suggest that this paradigm might be successfully applied in mice to study affective pain. CFA treatment was associated with increased anxiety-like behaviour and anhedonia; however, this appeared unrelated to the PEAP responses. Copyright © 2016 Elsevier B.V. All rights reserved.

Activity restriction induced by fear of falling and objective and subjective measures of physical function: a prospective cohort study.

PubMed

Deshpande, Nandini; Metter, E Jeffrey; Lauretani, Fulvio; Bandinelli, Stefania; Guralnik, Jack; Ferrucci, Luigi

2008-04-01

To examine whether activity restriction specifically induced by fear of falling (FF) contributes to greater risk of disability and decline in physical function. Prospective cohort study. Population-based older cohort. Six hundred seventy-three community-living elderly (> or = 65) participants in the Invecchiare in Chianti Study who reported FF. FF, fear-induced activity restriction, cognition, depressive symptoms, comorbidities, smoking history, and demographic factors were assessed at baseline. Disability in activities of daily living (ADLs) and instrumental activities of daily living (IADLs) and performance on the Short Performance Physical Battery (SPPB) were evaluated at baseline and at the 3-year follow-up. One-quarter (25.5%) of participants did not report any activity restriction, 59.6% reported moderate activity restriction (restriction or avoidance of < 3 activities), and 14.9% reported severe activity restriction (restriction or avoidance of > or = 3 activities). The severe restriction group reported significantly higher IADL disability and worse SPPB scores than the no restriction and moderate restriction groups. Severe activity restriction was a significant independent predictor of worsening ADL disability and accelerated decline in lower extremity performance on SPPB over the 3-year follow-up. Severe and moderate activity restriction were independent predictors of worsening IADL disability. Results were consistent even after adjusting for multiple potential confounders. In an elderly population, activity restriction associated with FF is an independent predictor of decline in physical function. Future intervention studies in geriatric preventive care should directly address risk factors associated with FF and activity restriction to substantiate long-term effects on physical abilities and autonomy of older persons.

Maternal childhood trauma, postpartum depression, and infant outcomes: Avoidant affective processing as a potential mechanism.

PubMed

Choi, Karmel W; Sikkema, Kathleen J; Vythilingum, Bavi; Geerts, Lut; Faure, Sheila C; Watt, Melissa H; Roos, Annerine; Stein, Dan J

2017-03-15

Women who have experienced childhood trauma may be at risk for postpartum depression, increasing the likelihood of negative outcomes among their children. Predictive pathways from maternal childhood trauma to child outcomes, as mediated by postpartum depression, require investigation. A longitudinal sample of South African women (N=150) was followed through pregnancy and postpartum. Measures included maternal trauma history reported during pregnancy; postpartum depression through six months; and maternal-infant bonding, infant development, and infant physical growth at one year. Structural equation models tested postpartum depression as a mediator between maternal experiences of childhood trauma and children's outcomes. A subset of women (N=33) also participated in a lab-based emotional Stroop paradigm, and their responses to fearful stimuli at six weeks were explored as a potential mechanism linking maternal childhood trauma, postpartum depression, and child outcomes. Women with childhood trauma experienced greater depressive symptoms through six months postpartum, which then predicted negative child outcomes at one year. Mediating effects of postpartum depression were significant, and persisted for maternal-infant bonding and infant growth after controlling for covariates and antenatal distress. Maternal avoidance of fearful stimuli emerged as a potential affective mechanism. Limitations included modest sample size, self-report measures, and unmeasured potential confounders. Findings suggest a mediating role of postpartum depression in the intergenerational transmission of negative outcomes. Perinatal interventions that address maternal trauma histories and depression, as well as underlying affective mechanisms, may help interrupt cycles of disadvantage, particularly in high-trauma settings such as South Africa. Copyright © 2017. Published by Elsevier B.V.

[Symptoms of Celiac disease in childhood].

PubMed

Mouterde, O; Dumant, C; Mallet, E

2013-06-01

The knowledge regarding celiac disease has increased dramatically in recent years, due to the availability of accurate serologic markers. Mass screening studies have shown that the prevalence of sensitization can be as high as 1/80. The range of symptoms is wide, from the classic growth failure, denutrition and diarrhea in infancy to clinically and histologically asymptomatic sensitized subjects. The interest of a routine mass screening is debated. The classical celiac disease in infancy is well known. Atypical symptoms and potentially associated disease are more frequent and potentially confounding. Physicians should be aware of any clue for celiac disease in atypical cases in order to improve the diagnostic yield, and therefore avoiding short or long term consequences. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Stability and change in health behaviours as predictors for disability pension: a prospective cohort study of Swedish twins

PubMed Central

2011-01-01

Background Stability or changes of health behaviours have not been studied in association with incidence of disability pension (DP). The aims were to (1) investigate if stability or changes in health behaviours predict DP due to musculoskeletal diagnosis (MSD), (2) to evaluate if an association exists for DP in general, and (3) after taking familial confounding into account. Methods The study sample was 16,713 like-sexed twin individuals born in Sweden between 1935-1958 (6195 complete twin pairs) who had participated in two surveys 25 years apart, were alive, and not pensioned at the time of the latest survey. Cox proportional hazards analysis was used to assess the associations (hazard ratios (HR) with 95% confidence intervals (CI)) between stability and change in health behaviours (physical activity, tobacco and alcohol use, body mass index (BMI)), and number of pain locations collected at two time points 25 years apart and the incidence of DP until 2008. Results During the follow-up, 1843 (11%) individuals were granted DP with 747 of these due to MSD. A higher proportion of women were granted DP than men. Increase in BMI and stable use of tobacco products were predictors for DP due to MSD (HR 1.21-1.48) and DP in general (HR 1.10-1.41). The stability in the frequency of physical activity and increased frequency of physical activity were protective factors for DP due to MSD only when accounting for familial confounding. However, the number of pain locations (stability, increase, or decrease) was the strongest predictor for future DP due to MSD (HR 3.69, CI 2.99-4.56) and DP in general (HR 2.15, CI 1.92-2.42). In discordant pair analysis, the HRs for pain were lower, indicating potential familial confounding. Conclusions Health behaviours in adulthood, including an increase in pain locations were associated with the incidence of DP. The association between physical activity and DP was especially related to adulthood choices or habits, i.e., the individual decision about frequency of exercising. Thus, it is important to e.g. increase public awareness of the potential beneficial effects of exercise throughout life to avoid permanent exclusion from the labour market for medical reasons. PMID:21880151

Stability and change in health behaviours as predictors for disability pension: a prospective cohort study of Swedish twins.

PubMed

Ropponen, Annina; Narusyte, Jurgita; Alexanderson, Kristina; Svedberg, Pia

2011-08-31

Stability or changes of health behaviours have not been studied in association with incidence of disability pension (DP). The aims were to (1) investigate if stability or changes in health behaviours predict DP due to musculoskeletal diagnosis (MSD), (2) to evaluate if an association exists for DP in general, and (3) after taking familial confounding into account. The study sample was 16,713 like-sexed twin individuals born in Sweden between 1935-1958 (6195 complete twin pairs) who had participated in two surveys 25 years apart, were alive, and not pensioned at the time of the latest survey. Cox proportional hazards analysis was used to assess the associations (hazard ratios (HR) with 95% confidence intervals (CI)) between stability and change in health behaviours (physical activity, tobacco and alcohol use, body mass index (BMI)), and number of pain locations collected at two time points 25 years apart and the incidence of DP until 2008. During the follow-up, 1843 (11%) individuals were granted DP with 747 of these due to MSD. A higher proportion of women were granted DP than men. Increase in BMI and stable use of tobacco products were predictors for DP due to MSD (HR 1.21-1.48) and DP in general (HR 1.10-1.41). The stability in the frequency of physical activity and increased frequency of physical activity were protective factors for DP due to MSD only when accounting for familial confounding. However, the number of pain locations (stability, increase, or decrease) was the strongest predictor for future DP due to MSD (HR 3.69, CI 2.99-4.56) and DP in general (HR 2.15, CI 1.92-2.42). In discordant pair analysis, the HRs for pain were lower, indicating potential familial confounding. Health behaviours in adulthood, including an increase in pain locations were associated with the incidence of DP. The association between physical activity and DP was especially related to adulthood choices or habits, i.e., the individual decision about frequency of exercising. Thus, it is important to e.g. increase public awareness of the potential beneficial effects of exercise throughout life to avoid permanent exclusion from the labour market for medical reasons.

On negative outcome control of unobserved confounding as a generalization of difference-in-differences

PubMed Central

Sofer, Tamar; Richardson, David B.; Colicino, Elena; Schwartz, Joel; Tchetgen Tchetgen, Eric J.

2016-01-01

The difference-in-differences (DID) approach is a well known strategy for estimating the effect of an exposure in the presence of unobserved confounding. The approach is most commonly used when pre-and post-exposure outcome measurements are available, and one can assume that the association of the unobserved confounder with the outcome is equal in the two exposure groups, and constant over time. Then, one recovers the treatment effect by regressing the change in outcome over time on the exposure. In this paper, we interpret the difference-in-differences as a negative outcome control (NOC) approach. We show that the pre-exposure outcome is a negative control outcome, as it cannot be influenced by the subsequent exposure, and it is affected by both observed and unobserved confounders of the exposure-outcome association of interest. The relation between DID and NOC provides simple conditions under which negative control outcomes can be used to detect and correct for confounding bias. However, for general negative control outcomes, the DID-like assumption may be overly restrictive and rarely credible, because it requires that both the outcome of interest and the control outcome are measured on the same scale. Thus, we present a scale-invariant generalization of the DID that may be used in broader NOC contexts. The proposed approach is demonstrated in simulations and on a Normative Aging Study data set, in which Body Mass Index is used for NOC of the relationship between air pollution and inflammatory outcomes. PMID:28239233

Confounder summary scores when comparing the effects of multiple drug exposures.

PubMed

Cadarette, Suzanne M; Gagne, Joshua J; Solomon, Daniel H; Katz, Jeffrey N; Stürmer, Til

2010-01-01

Little information is available comparing methods to adjust for confounding when considering multiple drug exposures. We compared three analytic strategies to control for confounding based on measured variables: conventional multivariable, exposure propensity score (EPS), and disease risk score (DRS). Each method was applied to a dataset (2000-2006) recently used to examine the comparative effectiveness of four drugs. The relative effectiveness of risedronate, nasal calcitonin, and raloxifene in preventing non-vertebral fracture, were each compared to alendronate. EPSs were derived both by using multinomial logistic regression (single model EPS) and by three separate logistic regression models (separate model EPS). DRSs were derived and event rates compared using Cox proportional hazard models. DRSs derived among the entire cohort (full cohort DRS) was compared to DRSs derived only among the referent alendronate (unexposed cohort DRS). Less than 8% deviation from the base estimate (conventional multivariable) was observed applying single model EPS, separate model EPS or full cohort DRS. Applying the unexposed cohort DRS when background risk for fracture differed between comparison drug exposure cohorts resulted in -7 to + 13% deviation from our base estimate. With sufficient numbers of exposed and outcomes, either conventional multivariable, EPS or full cohort DRS may be used to adjust for confounding to compare the effects of multiple drug exposures. However, our data also suggest that unexposed cohort DRS may be problematic when background risks differ between referent and exposed groups. Further empirical and simulation studies will help to clarify the generalizability of our findings.

Correlations between cannabis use and IQ change in the Dunedin cohort are consistent with confounding from socioeconomic status

PubMed Central

Rogeberg, Ole

2013-01-01

Does cannabis use have substantial and permanent effects on neuropsychological functioning? Renewed and intense attention to the issue has followed recent research on the Dunedin cohort, which found a positive association between, on the one hand, adolescent-onset cannabis use and dependence and, on the other hand, a decline in IQ from childhood to adulthood [Meier et al. (2012) Proc Natl Acad Sci USA 109(40):E2657–E2664]. The association is given a causal interpretation by the authors, but existing research suggests an alternative confounding model based on time-varying effects of socioeconomic status on IQ. A simulation of the confounding model reproduces the reported associations from the Dunedin cohort, suggesting that the causal effects estimated in Meier et al. are likely to be overestimates, and that the true effect could be zero. Further analyses of the Dunedin cohort are proposed to distinguish between the competing interpretations. Although it would be too strong to say that the results have been discredited, the methodology is flawed and the causal inference drawn from the results premature. PMID:23319626

Association between wrist ratio and carpal tunnel syndrome: Effect modification by body mass index.

PubMed

Thiese, Matthew S; Merryweather, Andrew; Koric, Alzina; Ott, Ulrike; Wood, Eric M; Kapellusch, Jay; Foster, James; Garg, Arun; Deckow-Schaefer, Gwen; Tomich, Suzanna; Kendall, Richard; Drury, David L; Wertsch, Jacqueline; Hegmann, Kurt T

2017-12-01

Previous studies have reported higher wrist ratios (WR) related to carpal tunnel syndrome (CTS) but have not assessed effect modification by obesity and may have inadequately controlled for confounders. Baseline data of a multicenter prospective cohort study were analyzed. CTS was defined by nerve conduction study (NCS) criteria and symptoms. Among the 1,206 participants, a square-shaped wrist was associated with CTS after controlling for confounders (prevalence ratio = 2.27; 95% confidence interval [95% CI], 1.33-3.86). Body mass index (BMI) was a strong effect modifier on the relationship between WR and both CTS and abnormal NCS results, with normal weight strata of rectangular versus square wrists = 8.18 (95% CI, 1.63-49.96) and 7.12 (95% CI, 2.19-23.16), respectively. A square wrist is significantly associated with CTS after controlling for confounders. Effect modification by high BMI masked the eightfold magnitude adjusted relationship seen between WR and CTS among normal weight participants. Muscle Nerve 56: 1047-1053, 2017. © 2017 Wiley Periodicals, Inc.

The “Dry-Run” Analysis: A Method for Evaluating Risk Scores for Confounding Control

PubMed Central

Wyss, Richard; Hansen, Ben B.; Ellis, Alan R.; Gagne, Joshua J.; Desai, Rishi J.; Glynn, Robert J.; Stürmer, Til

2017-01-01

Abstract A propensity score (PS) model's ability to control confounding can be assessed by evaluating covariate balance across exposure groups after PS adjustment. The optimal strategy for evaluating a disease risk score (DRS) model's ability to control confounding is less clear. DRS models cannot be evaluated through balance checks within the full population, and they are usually assessed through prediction diagnostics and goodness-of-fit tests. A proposed alternative is the “dry-run” analysis, which divides the unexposed population into “pseudo-exposed” and “pseudo-unexposed” groups so that differences on observed covariates resemble differences between the actual exposed and unexposed populations. With no exposure effect separating the pseudo-exposed and pseudo-unexposed groups, a DRS model is evaluated by its ability to retrieve an unconfounded null estimate after adjustment in this pseudo-population. We used simulations and an empirical example to compare traditional DRS performance metrics with the dry-run validation. In simulations, the dry run often improved assessment of confounding control, compared with the C statistic and goodness-of-fit tests. In the empirical example, PS and DRS matching gave similar results and showed good performance in terms of covariate balance (PS matching) and controlling confounding in the dry-run analysis (DRS matching). The dry-run analysis may prove useful in evaluating confounding control through DRS models. PMID:28338910

External adjustment sensitivity analysis for unmeasured confounding: an application to coronary stent outcomes, Pennsylvania 2004-2008.

PubMed

Huesch, Marco D

2013-06-01

Assessing the real-world comparative effectiveness of common interventions is challenged by unmeasured confounding. To determine whether the mortality benefit shown for drug-eluting stents (DES) over bare metal stents (BMS) in observational studies persists after controls for/tests for confounding. Retrospective observational study involving 38,019 patients, 65 years or older admitted for an index percutaneous coronary intervention receiving DES or BMS in Pennsylvania in 2004-2005 followed up for death through 3 years. Analysis was at the patient level. Mortality was analyzed with Cox proportional hazards models allowing for stratification by disease severity or DES use propensity, accounting for clustering of patients. Instrumental variables analysis used lagged physician stent usage to proxy for the focal stent type decision. A method originating in work by Cornfield and others in 1954 and popularized by Greenland in 1996 was used to assess robustness to confounding. DES was associated with a significantly lower adjusted risk of death at 3 years in Cox and in instrumented analyses. An implausibly strong hypothetical unobserved confounder would be required to fully explain these results. Confounding by indication can bias observational studies. No strong evidence of such selection biases was found in the reduced risk of death among elderly patients receiving DES instead of BMS in a Pennsylvanian state-wide population. © Health Research and Educational Trust.

Confounding, causality, and confusion: the role of intermediate variables in interpreting observational studies in obstetrics.

PubMed

Ananth, Cande V; Schisterman, Enrique F

2017-08-01

Prospective and retrospective cohorts and case-control studies are some of the most important study designs in epidemiology because, under certain assumptions, they can mimic a randomized trial when done well. These assumptions include, but are not limited to, properly accounting for 2 important sources of bias: confounding and selection bias. While not adjusting the causal association for an intermediate variable will yield an unbiased estimate of the exposure-outcome's total causal effect, it is often that obstetricians will want to adjust for an intermediate variable to assess if the intermediate is the underlying driver of the association. Such a practice must be weighed in light of the underlying research question and whether such an adjustment is necessary should be carefully considered. Gestational age is, by far, the most commonly encountered variable in obstetrics that is often mislabeled as a confounder when, in fact, it may be an intermediate. If, indeed, gestational age is an intermediate but if mistakenly labeled as a confounding variable and consequently adjusted in an analysis, the conclusions can be unexpected. The implications of this overadjustment of an intermediate as though it were a confounder can render an otherwise persuasive study downright meaningless. This commentary provides an exposition of confounding bias, collider stratification, and selection biases, with applications in obstetrics and perinatal epidemiology. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of parenting in the prediction of criminal involvement: findings from a nationally representative sample of youth and a sample of adopted youth.

PubMed

Beaver, Kevin M; Schwartz, Joseph A; Connolly, Eric J; Al-Ghamdi, Mohammed Said; Kobeisy, Ahmed Nezar

2015-03-01

The role of parenting in the development of criminal behavior has been the source of a vast amount of research, with the majority of studies detecting statistically significant associations between dimensions of parenting and measures of criminal involvement. An emerging group of scholars, however, has drawn attention to the methodological limitations-mainly genetic confounding-of the parental socialization literature. The current study addressed this limitation by analyzing a sample of adoptees to assess the association between 8 parenting measures and 4 criminal justice outcome measures. The results revealed very little evidence of parental socialization effects on criminal behavior before controlling for genetic confounding and no evidence of parental socialization effects on criminal involvement after controlling for genetic confounding. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Syphilis may be a confounding factor, not a causative agent, in syphilitic ALS.

PubMed

Tuk, Bert

2016-01-01

Based upon a review of published clinical observations regarding syphilitic amyotrophic lateral sclerosis (ALS), I hypothesize that syphilis is actually a confounding factor, not a causative factor, in syphilitic ALS. Moreover, I propose that the successful treatment of ALS symptoms in patients with syphilitic ALS using penicillin G and hydrocortisone is an indirect consequence of the treatment regimen and is not due to the treatment of syphilis. Specifically, I propose that the observed effect is due to the various pharmacological activities of penicillin G ( e.g ., a GABA receptor antagonist) and/or the multifaceted pharmacological activity of hydrocortisone. The notion that syphilis may be a confounding factor in syphilitic ALS is highly relevant, as it suggests that treating ALS patients with penicillin G and hydrocortisone-regardless of whether they present with syphilitic ALS or non-syphilitic ALS-may be effective at treating this rapidly progressive, highly devastating disease.

Assessing moderated mediation in linear models requires fewer confounding assumptions than assessing mediation.

PubMed

Loeys, Tom; Talloen, Wouter; Goubert, Liesbet; Moerkerke, Beatrijs; Vansteelandt, Stijn

2016-11-01

It is well known from the mediation analysis literature that the identification of direct and indirect effects relies on strong no unmeasured confounding assumptions of no unmeasured confounding. Even in randomized studies the mediator may still be correlated with unobserved prognostic variables that affect the outcome, in which case the mediator's role in the causal process may not be inferred without bias. In the behavioural and social science literature very little attention has been given so far to the causal assumptions required for moderated mediation analysis. In this paper we focus on the index for moderated mediation, which measures by how much the mediated effect is larger or smaller for varying levels of the moderator. We show that in linear models this index can be estimated without bias in the presence of unmeasured common causes of the moderator, mediator and outcome under certain conditions. Importantly, one can thus use the test for moderated mediation to support evidence for mediation under less stringent confounding conditions. We illustrate our findings with data from a randomized experiment assessing the impact of being primed with social deception upon observer responses to others' pain, and from an observational study of individuals who ended a romantic relationship assessing the effect of attachment anxiety during the relationship on mental distress 2 years after the break-up. © 2016 The British Psychological Society.

What are the causal effects of breastfeeding on IQ, obesity and blood pressure? Evidence from comparing high-income with middle-income cohorts.

PubMed

Brion, Marie-Jo A; Lawlor, Debbie A; Matijasevich, Alicia; Horta, Bernardo; Anselmi, Luciana; Araújo, Cora L; Menezes, Ana Maria B; Victora, Cesar G; Smith, George Davey

2011-06-01

A novel approach is explored for improving causal inference in observational studies by comparing cohorts from high-income with low- or middle-income countries (LMIC), where confounding structures differ. This is applied to assessing causal effects of breastfeeding on child blood pressure (BP), body mass index (BMI) and intelligence quotient (IQ). Standardized approaches for assessing the confounding structure of breastfeeding by socio-economic position were applied to the British Avon Longitudinal Study of Parents and Children (ALSPAC) (N ≃ 5000) and Brazilian Pelotas 1993 cohorts (N ≃ 1000). This was used to improve causal inference regarding associations of breastfeeding with child BP, BMI and IQ. Analyses were extended to include results from a meta-analysis of five LMICs (N ≃ 10 000) and compared with a randomized trial of breastfeeding promotion. Findings Although higher socio-economic position was strongly associated with breastfeeding in ALSPAC, there was little such patterning in Pelotas. In ALSPAC, breastfeeding was associated with lower BP, lower BMI and higher IQ, adjusted for confounders, but in the directions expected if due to socioeconomic patterning. In contrast, in Pelotas, breastfeeding was not strongly associated with BP or BMI but was associated with higher IQ. Differences in associations observed between ALSPAC and the LMIC meta-analysis were in line with those observed between ALSPAC and Pelotas, but with robust evidence of heterogeneity detected between ALSPAC and the LMIC meta-analysis associations. Trial data supported the conclusions inferred by the cross-cohort comparisons, which provided evidence for causal effects on IQ but not for BP or BMI. While reported associations of breastfeeding with child BP and BMI are likely to reflect residual confounding, breastfeeding may have causal effects on IQ. Comparing associations between populations with differing confounding structures can be used to improve causal inference in observational studies.

Control selection and confounding factors: A lesson from a Japanese case-control study to examine acellular pertussis vaccine effectiveness.

PubMed

Ohfuji, Satoko; Okada, Kenji; Nakano, Takashi; Ito, Hiroaki; Hara, Megumi; Kuroki, Haruo; Hirota, Yoshio

2017-08-24

When using a case-control study design to examine vaccine effectiveness, both the selection of control subjects and the consideration of potential confounders must be the important issues to ensure accurate results. In this report, we described our experience from a case-control study conducted to evaluate the effectiveness of acellular pertussis vaccine combined with diphtheria-tetanus toxoids (DTaP vaccine). Newly diagnosed pertussis cases and age- and sex-matched friend-controls were enrolled, and the history of DTaP vaccination was compared between groups. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for development of pertussis. After adjustment for potential confounders, four doses of DTaP vaccination showed a lower OR for pediatrician-diagnosed pertussis (OR=0.11, 95% CI, 0.01-0.99). In addition, the decreasing OR of four doses vaccination was more pronounced for laboratory-confirmed pertussis (OR=0.07, 95%CI, 0.01-0.82). Besides, positive association with pertussis was observed in subjects with a history of steroid treatment (OR=5.67) and those with a recent contact with a lasting cough (OR=4.12). When using a case-control study to evaluate the effectiveness of vaccines, particularly those for uncommon infectious diseases such as pertussis, the use of friend-controls may be optimal due to the fact that they shared a similar experience for exposure to the pathogen as the cases. In addition, to assess vaccine effectiveness as accurately as possible, the effects of confounding should be adequately controlled with a matching or analysis technique. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Causal diagrams and multivariate analysis III: confound it!

PubMed

Jupiter, Daniel C

2015-01-01

This commentary concludes my series concerning inclusion of variables in multivariate analyses. We take up the issues of confounding and effect modification and summarize the work we have thus far done. Finally, we provide a rough algorithm to help guide us through the maze of possibilities that we have outlined. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Effect of Teosinte Cytoplasmic Genomes on Maize Phenotype

PubMed Central

Allen, James O.

2005-01-01

Determining the contribution of organelle genes to plant phenotype is hampered by several factors, including the paucity of variation in the plastid and mitochondrial genomes. To circumvent this problem, evolutionary divergence between maize (Zea mays ssp. mays) and the teosintes, its closest relatives, was utilized as a source of cytoplasmic genetic variation. Maize lines in which the maize organelle genomes were replaced through serial backcrossing by those representing the entire genus, yielding alloplasmic sublines, or cytolines were created. To avoid the confounding effects of segregating nuclear alleles, an inbred maize line was utilized. Cytolines with Z. mays teosinte cytoplasms were generally indistinguishable from maize. However, cytolines with cytoplasm from the more distantly related Z. luxurians, Z. diploperennis, or Z. perennis exhibited a plethora of differences in growth, development, morphology, and function. Significant differences were observed for 56 of the 58 characters studied. Each cytoline was significantly different from the inbred line for most characters. For a given character, variation was often greater among cytolines having cytoplasms from the same species than among those from different species. The characters differed largely independently of each other. These results suggest that the cytoplasm contributes significantly to a large proportion of plant traits and that many of the organelle genes are phenotypically important. PMID:15731518

Evolutionary theory and teleology.

PubMed

O'Grady, R T

1984-04-21

The order within and among living systems can be explained rationally by postulating a process of descent with modification, effected by factors which are extrinsic or intrinsic to the organisms. Because at the time Darwin proposed his theory of evolution there was no concept of intrinsic factors which could evolve, he postulated a process of extrinsic effects--natural selection. Biological order was thus seen as an imposed, rather than an emergent, property. Evolutionary change was seen as being determined by the functional efficiency (adaptedness) of the organism in its environment, rather than by spontaneous changes in intrinsically generated organizing factors. The initial incompleteness of Darwin's explanatory model, and the axiomatization of its postulates in neo-Darwinism, has resulted in a theory of functionalism, rather than structuralism. As such, it introduces an unnecessary teleology which confounds evolutionary studies and reduces the usefulness of the theory. This problem cannot be detected from within the neo-Darwinian paradigm because the different levels of end-directed activity--teleomatic, teleonomic, and teleological--are not recognized. They are, in fact, considered to influence one another. The theory of nonequilibrium evolution avoids these problems by returning to the basic principles of biological order and developing a structuralist explanation of intrinsically generated change. Extrinsic factors may affect the resultant evolutionary pattern, but they are neither necessary nor sufficient for evolution to occur.

The Integrative Effects of Cognitive Reappraisal on Negative Affect: Associated Changes in Secretory Immunoglobulin A, Unpleasantness and ERP Activity

PubMed Central

Zhang, Wencai; Li, Fan; Qin, Shaozheng; Luo, Jing

2012-01-01

Although the regulatory role of cognitive reappraisal in negative emotional responses is widely recognized, this reappraisal's effect on acute saliva secretory immunoglobulin A (SIgA), as well as the relationships among affective, immunological, and event-related potential (ERP) changes, remains unclear. In this study, we selected only people with low positive coping scores (PCSs) as measured by the Trait Coping Style Questionnaire to avoid confounding by intrinsic coping styles. First, we found that the acute stress of viewing unpleasant pictures consistently decreased SIgA concentration and secretion rate, increased perceptions of unpleasantness and amplitude of late positive potentials (LPPs) between 200–300 ms and 400–1000 ms. After participants used cognitive reappraisal, their SIgA concentration and secretion rate significantly increased and their unpleasantness and LPP amplitudes significantly decreased compared with a control condition. Second, we found a significantly positive correlation between the increases in SIgA and the decreases in unpleasantness and a significantly negative correlation between the increases in SIgA and the increases in LPP across the two groups. This study is the first to demonstrate that cognitive reappraisal reverses the decrease of SIgA. In addition, it revealed strong correlations among affective, SIgA and electrophysiological changes with convergent multilevel evidence. PMID:22319586

Altered sensitization patterns to sweet food stimuli in patients recovered from anorexia and bulimia nervosa.

PubMed

Wagner, Angela; Simmons, Alan N; Oberndorfer, Tyson A; Frank, Guido K W; McCurdy-McKinnon, Danyale; Fudge, Julie L; Yang, Tony T; Paulus, Martin P; Kaye, Walter H

2015-12-30

Recent studies show that higher-order appetitive neural circuitry may contribute to restricted eating in anorexia nervosa (AN) and overeating in bulimia nervosa (BN). The purpose of this study was to determine whether sensitization effects might underlie pathologic eating behavior when a taste stimulus is administered repeatedly. Recovered AN (RAN, n=14) and BN (RBN, n=15) subjects were studied in order to avoid the confounding effects of altered nutritional state. Functional magnetic resonance imaging (fMRI) measured higher-order brain response to repeated tastes of sucrose (caloric) and sucralose (non-caloric). To test sensitization, the neuronal response to the first and second administration was compared. RAN patients demonstrated a decreased sensitization to sucrose in contrast to RBN patients who displayed the opposite pattern, increased sensitization to sucrose. However, the latter was not as pronounced as in healthy control women (n=13). While both eating disorder subgroups showed increased sensitization to sucralose, the healthy controls revealed decreased sensitization. These findings could reflect on a neuronal level the high caloric intake of RBN during binges and the low energy intake for RAN. RAN seem to distinguish between high energy and low energy sweet stimuli while RBN do not. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Mediation analysis with time varying exposures and mediators

PubMed Central

VanderWeele, Tyler J.; Tchetgen Tchetgen, Eric J.

2016-01-01

Summary In this paper we consider causal mediation analysis when exposures and mediators vary over time. We give non-parametric identification results, discuss parametric implementation, and also provide a weighting approach to direct and indirect effects based on combining the results of two marginal structural models. We also discuss how our results give rise to a causal interpretation of the effect estimates produced from longitudinal structural equation models. When there are time-varying confounders affected by prior exposure and mediator, natural direct and indirect effects are not identified. However, we define a randomized interventional analogue of natural direct and indirect effects that are identified in this setting. The formula that identifies these effects we refer to as the “mediational g-formula.” When there is no mediation, the mediational g-formula reduces to Robins’ regular g-formula for longitudinal data. When there are no time-varying confounders affected by prior exposure and mediator values, then the mediational g-formula reduces to a longitudinal version of Pearl’s mediation formula. However, the mediational g-formula itself can accommodate both mediation and time-varying confounders and constitutes a general approach to mediation analysis with time-varying exposures and mediators. PMID:28824285

Mediation analysis with time varying exposures and mediators.

PubMed

VanderWeele, Tyler J; Tchetgen Tchetgen, Eric J

2017-06-01

In this paper we consider causal mediation analysis when exposures and mediators vary over time. We give non-parametric identification results, discuss parametric implementation, and also provide a weighting approach to direct and indirect effects based on combining the results of two marginal structural models. We also discuss how our results give rise to a causal interpretation of the effect estimates produced from longitudinal structural equation models. When there are time-varying confounders affected by prior exposure and mediator, natural direct and indirect effects are not identified. However, we define a randomized interventional analogue of natural direct and indirect effects that are identified in this setting. The formula that identifies these effects we refer to as the "mediational g-formula." When there is no mediation, the mediational g-formula reduces to Robins' regular g-formula for longitudinal data. When there are no time-varying confounders affected by prior exposure and mediator values, then the mediational g-formula reduces to a longitudinal version of Pearl's mediation formula. However, the mediational g-formula itself can accommodate both mediation and time-varying confounders and constitutes a general approach to mediation analysis with time-varying exposures and mediators.

Effect of Human Auditory Efferent Feedback on Cochlear Gain and Compression

PubMed Central

Drga, Vit; Plack, Christopher J.

2014-01-01

The mammalian auditory system includes a brainstem-mediated efferent pathway from the superior olivary complex by way of the medial olivocochlear system, which reduces the cochlear response to sound (Warr and Guinan, 1979; Liberman et al., 1996). The human medial olivocochlear response has an onset delay of between 25 and 40 ms and rise and decay constants in the region of 280 and 160 ms, respectively (Backus and Guinan, 2006). Physiological studies with nonhuman mammals indicate that onset and decay characteristics of efferent activation are dependent on the temporal and level characteristics of the auditory stimulus (Bacon and Smith, 1991; Guinan and Stankovic, 1996). This study uses a novel psychoacoustical masking technique using a precursor sound to obtain a measure of the efferent effect in humans. This technique avoids confounds currently associated with other psychoacoustical measures. Both temporal and level dependency of the efferent effect was measured, providing a comprehensive measure of the effect of human auditory efferents on cochlear gain and compression. Results indicate that a precursor (>20 dB SPL) induced efferent activation, resulting in a decrease in both maximum gain and maximum compression, with linearization of the compressive function for input sound levels between 50 and 70 dB SPL. Estimated gain decreased as precursor level increased, and increased as the silent interval between the precursor and combined masker-signal stimulus increased, consistent with a decay of the efferent effect. Human auditory efferent activation linearizes the cochlear response for mid-level sounds while reducing maximum gain. PMID:25392499

Observational studies and the difficult quest for causality: lessons from vaccine effectiveness and impact studies.

PubMed

Lipsitch, Marc; Jha, Ayan; Simonsen, Lone

2016-12-01

Although randomized placebo-controlled trials (RCT) are critical to establish efficacy of vaccines at the time of licensure, important remaining questions about vaccine effectiveness (VE)-used here to include individual-level measures and population-wide impact of vaccine programmes-can only be answered once the vaccine is in use, from observational studies. However, such studies are inherently at risk for bias. Using a causal framework and illustrating with examples, we review newer approaches to detecting and avoiding confounding and selection bias in three major classes of observational study design: cohort, case-control and ecological studies. Studies of influenza VE, especially in seniors, are an excellent demonstration of the challenges of detecting and reducing such bias, and so we use influenza VE as a running example. We take a fresh look at the time-trend studies often dismissed as 'ecological'. Such designs are the only observational study design that can measure the overall effect of a vaccination programme [indirect (herd) as well as direct effects], and are in fact already an important part of the evidence base for several vaccines currently in use. Despite the great strides towards more robust observational study designs, challenges lie ahead for evaluating best practices for achieving robust unbiased results from observational studies. This is critical for evaluation of national and global vaccine programme effectiveness. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Optimizing methods and dodging pitfalls in microbiome research.

PubMed

Kim, Dorothy; Hofstaedter, Casey E; Zhao, Chunyu; Mattei, Lisa; Tanes, Ceylan; Clarke, Erik; Lauder, Abigail; Sherrill-Mix, Scott; Chehoud, Christel; Kelsen, Judith; Conrad, Máire; Collman, Ronald G; Baldassano, Robert; Bushman, Frederic D; Bittinger, Kyle

2017-05-05

Research on the human microbiome has yielded numerous insights into health and disease, but also has resulted in a wealth of experimental artifacts. Here, we present suggestions for optimizing experimental design and avoiding known pitfalls, organized in the typical order in which studies are carried out. We first review best practices in experimental design and introduce common confounders such as age, diet, antibiotic use, pet ownership, longitudinal instability, and microbial sharing during cohousing in animal studies. Typically, samples will need to be stored, so we provide data on best practices for several sample types. We then discuss design and analysis of positive and negative controls, which should always be run with experimental samples. We introduce a convenient set of non-biological DNA sequences that can be useful as positive controls for high-volume analysis. Careful analysis of negative and positive controls is particularly important in studies of samples with low microbial biomass, where contamination can comprise most or all of a sample. Lastly, we summarize approaches to enhancing experimental robustness by careful control of multiple comparisons and to comparing discovery and validation cohorts. We hope the experimental tactics summarized here will help researchers in this exciting field advance their studies efficiently while avoiding errors.

Regulatory principles and experimental approaches to the circadian control of starch turnover

PubMed Central

Seaton, Daniel D.; Ebenhöh, Oliver; Millar, Andrew J.; Pokhilko, Alexandra

2014-01-01

In many plants, starch is synthesized during the day and degraded during the night to avoid carbohydrate starvation in darkness. The circadian clock participates in a dynamic adjustment of starch turnover to changing environmental condition through unknown mechanisms. We used mathematical modelling to explore the possible scenarios for the control of starch turnover by the molecular components of the plant circadian clock. Several classes of plausible models were capable of describing the starch dynamics observed in a range of clock mutant plants and light conditions, including discriminating circadian protocols. Three example models of these classes are studied in detail, differing in several important ways. First, the clock components directly responsible for regulating starch degradation are different in each model. Second, the intermediate species in the pathway may play either an activating or inhibiting role on starch degradation. Third, the system may include a light-dependent interaction between the clock and downstream processes. Finally, the clock may be involved in the regulation of starch synthesis. We discuss the differences among the models’ predictions for diel starch profiles and the properties of the circadian regulators. These suggest additional experiments to elucidate the pathway structure, avoid confounding results and identify the molecular components involved. PMID:24335560

Effect of enhanced biosecurity and selected on-farm factors on Campylobacter colonization of chicken broilers.

PubMed

Georgiev, M; Beauvais, W; Guitian, J

2017-02-01

Human campylobacteriosis is the most commonly reported gastrointestinal bacterial infection in the EU; poultry meat has been identified as the main source of infection. We tested the hypothesis that enhanced biosecurity and other factors such as welfare status, breed, the practice of partial depopulation and number of empty days between flocks may prevent Campylobacter spp. caecal colonization of poultry batches at high levels (>123 000 c.f.u./g in pooled caecal samples). We analysed data from 2314 poultry batches sampled at slaughter in the UK in 2011-2013. We employed random-effects logistic regression to account for clustering of batches within farms and adjust for confounding. We estimated population attributable fractions using adjusted risk ratios. Enhanced biosecurity reduced the odds of colonization at partial depopulation [odds ratio (OR) 0·25, 95% confidence interval (CI) 0·14-0·47] and, to a lesser extent, at final depopulation (OR 0·47, 95% CI 0·25-0·89). An effect of the type of breed was also found. Under our assumptions, approximately 1/3 of highly colonized batches would be avoided if they were all raised under enhanced biosecurity or without partial depopulation. The results of the study indicate that on-farm measures can play an important role in reducing colonization of broiler chickens with Campylobacter spp. and as a result human exposure.

Risk of unintentional injuries in children and adolescents with ADHD and the impact of ADHD medications: A systematic review and meta-analysis.

PubMed

Ruiz-Goikoetxea, Maite; Cortese, Samuele; Aznarez-Sanado, Maite; Magallón, Sara; Alvarez Zallo, Noelia; Luis, Elkin O; de Castro-Manglano, Pilar; Soutullo, Cesar; Arrondo, Gonzalo

2018-01-01

A systematic review with meta-analyses was performed to: 1) quantify the association between ADHD and risk of unintentional physical injuries in children/adolescents ("risk analysis"); 2) assess the effect of ADHD medications on this risk ("medication analysis"). We searched 114 databases through June 2017. For the risk analysis, studies reporting sex-controlled odds ratios (ORs) or hazard ratios (HRs) estimating the association between ADHD and injuries were combined. Pooled ORs (28 studies, 4,055,620 individuals without and 350,938 with ADHD) and HRs (4 studies, 901,891 individuals without and 20,363 with ADHD) were 1.53 (95% CI=1.40,1.67) and 1.39 (95% CI=1.06,1.83), respectively. For the medication analysis, we meta-analysed studies that avoided the confounding-by-indication bias [four studies with a self-controlled methodology and another comparing risk over time and groups (a "difference in differences" methodology)]. The pooled effect size was 0.879 (95% CI=0.838,0.922) (13,254 individuals with ADHD). ADHD is significantly associated with an increased risk of unintentional injuries and ADHD medications have a protective effect, at least in the short term, as indicated by self-controlled studies. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Childhood Medical and Behavioral Consequences of Maternal Cocaine Use1

PubMed Central

Singer, Lynn; Farkas, Kathleen; Kliegman, Robert

2014-01-01

Reviewed available studies of the impact of fetal cocaine exposure on child medical and developmental outcome, as well as the current status of clinical psychological interventions and research strategies. Current studies are inconclusive but suggest that prenatal exposure to crack-cocaine can have significant effects on the growth and neurological development of the infant, with the potential of later learning and behavioral disabilities. Social-environmental correlates of maternal cocaine use are confounding factors with known negative effects on child outcome. Large, population-based studies using multivariate analyses are needed to determine the independent effects of cocaine on child outcome relative to other confounding variables. PMID:1382125

Diagnostics for Confounding of Time-varying and Other Joint Exposures.

PubMed

Jackson, John W

2016-11-01

The effects of joint exposures (or exposure regimes) include those of adhering to assigned treatment versus placebo in a randomized controlled trial, duration of exposure in a cohort study, interactions between exposures, and direct effects of exposure, among others. Unlike the setting of a single point exposure (e.g., propensity score matching), there are few tools to describe confounding for joint exposures or how well a method resolves it. Investigators need tools that describe confounding in ways that are conceptually grounded and intuitive for those who read, review, and use applied research to guide policy. We revisit the implications of exchangeability conditions that hold in sequentially randomized trials, and the bias structure that motivates the use of g-methods, such as marginal structural models. From these, we develop covariate balance diagnostics for joint exposures that can (1) describe time-varying confounding, (2) assess whether covariates are predicted by prior exposures given their past, the indication for g-methods, and (3) describe residual confounding after inverse probability weighting. For each diagnostic, we present time-specific metrics that encompass a wide class of joint exposures, including regimes of multivariate time-varying exposures in censored data, with multivariate point exposures as a special case. We outline how to estimate these directly or with regression and how to average them over person-time. Using a simulated example, we show how these metrics can be presented graphically. This conceptually grounded framework can potentially aid the transparent design, analysis, and reporting of studies that examine joint exposures. We provide easy-to-use tools to implement it.

Statin adherence and risk of acute cardiovascular events among women: a cohort study accounting for time-dependent confounding affected by previous adherence.

PubMed

Lavikainen, Piia; Helin-Salmivaara, Arja; Eerola, Mervi; Fang, Gang; Hartikainen, Juha; Huupponen, Risto; Korhonen, Maarit Jaana

2016-06-03

Previous studies on the effect of statin adherence on cardiovascular events in the primary prevention of cardiovascular disease have adjusted for time-dependent confounding, but potentially introduced bias into their estimates as adherence and confounders were measured simultaneously. We aimed to evaluate the effect when accounting for time-dependent confounding affected by previous adherence as well as time sequence between factors. Retrospective cohort study. Finnish healthcare registers. Women aged 45-64 years initiating statin use for primary prevention of cardiovascular disease in 2001-2004 (n=42 807). Acute cardiovascular event defined as a composite of acute coronary syndrome and acute ischaemic stroke was our primary outcome. Low-energy fractures were used as a negative control outcome to evaluate the healthy-adherer effect. During the 3-year follow-up, 474 women experienced the primary outcome event and 557 suffered a low-energy fracture. The causal HR estimated with marginal structural model for acute cardiovascular events for all the women who remained adherent (proportion of days covered ≥80%) to statin therapy during the previous adherence assessment year was 0.78 (95% CI: 0.65 to 0.94) when compared with everybody remaining non-adherent (proportion of days covered <80%). The result was robust against alternative model specifications. Statin adherers had a potentially reduced risk of experiencing low-energy fractures compared with non-adherers (HR 0.90, 95% CI 0.76 to 1.07). Our study, which took into account the time dependence of adherence and confounders, as well as temporal order between these factors, is support for the concept that adherence to statins in women in primary prevention decreases the risk of acute cardiovascular events by about one-fifth in comparison to non-adherence. However, part of the observed effect of statin adherence on acute cardiovascular events may be due to the healthy-adherer effect. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Effects of aggregation of drug and diagnostic codes on the performance of the high-dimensional propensity score algorithm: an empirical example.

PubMed

Le, Hoa V; Poole, Charles; Brookhart, M Alan; Schoenbach, Victor J; Beach, Kathleen J; Layton, J Bradley; Stürmer, Til

2013-11-19

The High-Dimensional Propensity Score (hd-PS) algorithm can select and adjust for baseline confounders of treatment-outcome associations in pharmacoepidemiologic studies that use healthcare claims data. How hd-PS performance is affected by aggregating medications or medical diagnoses has not been assessed. We evaluated the effects of aggregating medications or diagnoses on hd-PS performance in an empirical example using resampled cohorts with small sample size, rare outcome incidence, or low exposure prevalence. In a cohort study comparing the risk of upper gastrointestinal complications in celecoxib or traditional NSAIDs (diclofenac, ibuprofen) initiators with rheumatoid arthritis and osteoarthritis, we (1) aggregated medications and International Classification of Diseases-9 (ICD-9) diagnoses into hierarchies of the Anatomical Therapeutic Chemical classification (ATC) and the Clinical Classification Software (CCS), respectively, and (2) sampled the full cohort using techniques validated by simulations to create 9,600 samples to compare 16 aggregation scenarios across 50% and 20% samples with varying outcome incidence and exposure prevalence. We applied hd-PS to estimate relative risks (RR) using 5 dimensions, predefined confounders, ≤ 500 hd-PS covariates, and propensity score deciles. For each scenario, we calculated: (1) the geometric mean RR; (2) the difference between the scenario mean ln(RR) and the ln(RR) from published randomized controlled trials (RCT); and (3) the proportional difference in the degree of estimated confounding between that scenario and the base scenario (no aggregation). Compared with the base scenario, aggregations of medications into ATC level 4 alone or in combination with aggregation of diagnoses into CCS level 1 improved the hd-PS confounding adjustment in most scenarios, reducing residual confounding compared with the RCT findings by up to 19%. Aggregation of codes using hierarchical coding systems may improve the performance of the hd-PS to control for confounders. The balance of advantages and disadvantages of aggregation is likely to vary across research settings.

Coping with confounds in multivoxel pattern analysis: what should we do about reaction time differences? A comment on Todd, Nystrom & Cohen 2013.

PubMed

Woolgar, Alexandra; Golland, Polina; Bode, Stefan

2014-09-01

Multivoxel pattern analysis (MVPA) is a sensitive and increasingly popular method for examining differences between neural activation patterns that cannot be detected using classical mass-univariate analysis. Recently, Todd et al. ("Confounds in multivariate pattern analysis: Theory and rule representation case study", 2013, NeuroImage 77: 157-165) highlighted a potential problem for these methods: high sensitivity to confounds at the level of individual participants due to the use of directionless summary statistics. Unlike traditional mass-univariate analyses where confounding activation differences in opposite directions tend to approximately average out at group level, group level MVPA results may be driven by any activation differences that can be discriminated in individual participants. In Todd et al.'s empirical data, factoring out differences in reaction time (RT) reduced a classifier's ability to distinguish patterns of activation pertaining to two task rules. This raises two significant questions for the field: to what extent have previous multivoxel discriminations in the literature been driven by RT differences, and by what methods should future studies take RT and other confounds into account? We build on the work of Todd et al. and compare two different approaches to remove the effect of RT in MVPA. We show that in our empirical data, in contrast to that of Todd et al., the effect of RT on rule decoding is negligible, and results were not affected by the specific details of RT modelling. We discuss the meaning of and sensitivity for confounds in traditional and multivoxel approaches to fMRI analysis. We observe that the increased sensitivity of MVPA comes at a price of reduced specificity, meaning that these methods in particular call for careful consideration of what differs between our conditions of interest. We conclude that the additional complexity of the experimental design, analysis and interpretation needed for MVPA is still not a reason to favour a less sensitive approach. Copyright © 2014 Elsevier Inc. All rights reserved.

Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance.

PubMed

Keogh, Ruth; Frost, Chris; Owen, Gail; Daniel, Rhian M; Langbehn, Doug R; Leavitt, Blair; Durr, Alexandra; Roos, Raymund A C; Landwehrmeyer, G Bernhard; Reilmann, Ralf; Borowsky, Beth; Stout, Julie; Craufurd, David; Tabrizi, Sarah J

2016-01-11

 Insufficient evidence exists to guide the long-term pharmacological management of Huntington's disease (HD) although most current interventions rely on symptomatic management. The effect of many frontline treatments on potential endpoints for HD clinical trials remains unknown. Our objective was to investigate how therapies widely used to manage HD affect the symptom for which they are prescribed and other endpoints using data from TRACK-HD. We used longitudinal models to estimate effects of medication use on performance on tests of motor, cognitive and neuropsychiatric function using data from 123 TRACK-HD stage 1/2 participants across four study visits. Adjustment for confounding by prior medication use, prior clinical performance, concomitant use of other medications, and baseline variables (sex, disease group, age, CAG, study site, education) enabled a closer-to-causal interpretation of the associations. Adjusting for baseline variables only, medication use was typically associated with worse clinical performance, reflecting greater medication use in more advanced patients. After additional adjustment for longitudinal confounders such "inverse" associations were generally eliminated and in the expected directions: participants taking neuroleptics tended to have better motor performance, improved affect and poorer cognitive performance, and those taking SSRI/SNRIs had less apathy, less affect and better total behaviour scores. However, we uncovered few statistically significant associations. Limitations include sample size and unmeasured confounding. In conclusion, adjustment for confounding by prior measurements largely eliminated associations between medication use and poorer clinical performance from simple analyses. However, there was little convincing evidence of causal effects of medication on clinical performance and larger cohorts or trials are needed.

Effects of Age at First Childbirth and Other Factors on Central Obesity in Postmenopausal Women: The 2013–2015 Korean National Health and Nutrition Examination Survey

PubMed Central

Lee, Wang Jin; Lee, Joo Ha; Kwag, Byoung Gyu; Chang, Shin Hae; Choi, Yu Jin

2018-01-01

Background Waist circumference is one of the key components of metabolic syndrome. Recent studies demonstrated that the reproductive profile was associated with metabolic syndrome in postmenopausal women. This study focused on the association between central obesity and age at first childbirth. It also considered other factors associated with central obesity in postmenopausal women. Methods This study was based on the 2013–2015 Korean National Health and Nutrition Examination Survey and involved 3,143 naturally postmenopausal women. These women were divided into three groups according to their age at first childbirth: 19 years or younger (n=252), 20–29 years (n=2,695), and 30 years or older (n=196). Multivariate analysis using logistic regression was performed to evaluate the effects of various reproductive factors, including other confounding factors. Results During adjustment for confounding factors, in the early age at first childbirth group, odds ratios (95% confidence intervals) for central obesity decreased. In the final model, younger age at first childbirth was not significantly related to central obesity (waist circumference more than 85 cm) in naturally postmenopausal women after adjusting for other confounding factors. Conclusion Younger age at first childbirth was not significantly associated with central obesity after adjustment for confounding factors. PMID:29788703

Gene × environment interaction studies have not properly controlled for potential confounders: the problem and the (simple) solution.

PubMed

Keller, Matthew C

2014-01-01

Candidate gene × environment (G × E) interaction research tests the hypothesis that the effects of some environmental variable (e.g., childhood maltreatment) on some outcome measure (e.g., depression) depend on a particular genetic polymorphism. Because this research is inherently nonexperimental, investigators have been rightly concerned that detected interactions could be driven by confounders (e.g., ethnicity, gender, age, socioeconomic status) rather than by the specified genetic or environmental variables per se. In an attempt to eliminate such alternative explanations for detected G × E interactions, investigators routinely enter the potential confounders as covariates in general linear models. However, this practice does not control for the effects these variables might have on the G × E interaction. Rather, to properly control for confounders, researchers need to enter the covariate × environment and the covariate × gene interaction terms in the same model that tests the G × E term. In this manuscript, I demonstrate this point analytically and show that the practice of improperly controlling for covariates is the norm in the G × E interaction literature to date. Thus, many alternative explanations for G × E findings that investigators had thought were eliminated have not been. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

Assessing Hospital Performance After Percutaneous Coronary Intervention Using Big Data.

PubMed

Spertus, Jacob V; T Normand, Sharon-Lise; Wolf, Robert; Cioffi, Matt; Lovett, Ann; Rose, Sherri

2016-11-01

Although risk adjustment remains a cornerstone for comparing outcomes across hospitals, optimal strategies continue to evolve in the presence of many confounders. We compared conventional regression-based model to approaches particularly suited to leveraging big data. We assessed hospital all-cause 30-day excess mortality risk among 8952 adults undergoing percutaneous coronary intervention between October 1, 2011, and September 30, 2012, in 24 Massachusetts hospitals using clinical registry data linked with billing data. We compared conventional logistic regression models with augmented inverse probability weighted estimators and targeted maximum likelihood estimators to generate more efficient and unbiased estimates of hospital effects. We also compared a clinically informed and a machine-learning approach to confounder selection, using elastic net penalized regression in the latter case. Hospital excess risk estimates range from -1.4% to 2.0% across methods and confounder sets. Some hospitals were consistently classified as low or as high excess mortality outliers; others changed classification depending on the method and confounder set used. Switching from the clinically selected list of 11 confounders to a full set of 225 confounders increased the estimation uncertainty by an average of 62% across methods as measured by confidence interval length. Agreement among methods ranged from fair, with a κ statistic of 0.39 (SE: 0.16), to perfect, with a κ of 1 (SE: 0.0). Modern causal inference techniques should be more frequently adopted to leverage big data while minimizing bias in hospital performance assessments. © 2016 American Heart Association, Inc.

Hypothyroidism and carpal tunnel syndrome: a meta-analysis.

PubMed

Shiri, Rahman

2014-12-01

This study aimed to assess the magnitude of the association between hypothyroidism and carpal tunnel syndrome (CTS). Eighteen studies were included in a random-effects meta-analysis. A meta-analysis of the studies that did not control their estimates for any confounder showed an association between a thyroid disease (hypo- or hyperthyroidism) and CTS (N = 9,573, effect size [ES] = 1.32 (95% confidence interval [CI], 1.04-1.68) and between hypothyroidism and CTS (N = 64,531, ES = 2.15 [95% CI, 1.64-2.83]). When a meta-analysis limited to the studies that controlled their estimates for some potential confounders, the association between a thyroid disease and CTS disappeared (N = 4,799, ES = 1.17 [95% CI, 0.71-1.92], I(2) = 0%), and the effect size for hypothyroidism largely attenuated (N = 71,133, ES = 1.44 [95% CI, 1.27-1.63], I(2) = 0%). Moreover, there was evidence of publication bias. This meta-analysis found only a modest association between hypothyroidism and CTS. Confounding and publication bias may still account for part of the remaining excess risk. © 2014 Wiley Periodicals, Inc.

Combined effect of short-term dehydration and sublethal acute oral dicrotophos exposure confounds the diagnosis of anticholinesterase exposure in common quail (Coturnix coturnix) using plasma cholinesterase activity.

PubMed

Heffernan, James; Mineau, Pierre; Falk, Ramona; Wickstrom, Mark

2012-07-01

Common Quail (Coturnix coturnix) were subjected to controlled and replicated experiments in the summer of 2008 to investigate the effects of short-term dehydration on cholinesterase activity in brain and plasma and the interaction between dehydration and exposure to the organophosphorus pesticide dicrotophos in these same tissues. Our objective was to determine if dehydration could confound the diagnosis of anticholinesterase exposure using inhibition of cholinesterase activity in quail tissues. The effect of dehydration was quantified using measures of plasma osmolality and hematocrit. Dicrotophos exposure caused significant inhibition of cholinesterase activity in brain, while the effects of dehydration and interaction were not significant. Dehydration caused significant duration-dependent increases in plasma osmolality and hematocrit. Dehydration also caused a significant increase in plasma cholinesterase activity. Variation in the change in plasma cholinesterase activity in response to dehydration was significantly and positively correlated with dehydration-induced variation in both the change in plasma osmolality and the change in hematocrit. These correlations suggest that plasma cholinesterase activity in quail is not limited to plasma but occupies some larger pool of the extracellular fluid volume, and we suggest lymph is part of that pool. The effects of dehydration on plasma cholinesterase activity masked the inhibitory effects of dicrotophos. Here, the combination of dehydration and dicrotophos exposure produced plasma cholinesterase activity that was not significantly different from reference and pre-exposure values, confounding the diagnosis of anticholinesterase exposure in dehydrated, dicrotophos-exposed quail. A method to adjust plasma cholinesterase activities for the confounding effects of dehydration and enable the diagnosis of anticholinesterase exposure in dehydrated, dicrotophos-exposed quail was developed. Clinicians and practitioners responsible for the diagnosis of anticholinesterase exposure in birds are cautioned that dehydration, commonly observed in sick wildlife, may mask the effect of anticholinesterases on plasma cholinesterase activity.

Coping strategies and quality of life in caregivers of dependent elderly relatives.

PubMed

Rodríguez-Pérez, Margarita; Abreu-Sánchez, Ana; Rojas-Ocaña, María Jesús; Del-Pino-Casado, Rafael

2017-04-14

Despite the importance of coping in caregiving, there are few studies on the relationship between coping and quality of life in caregivers of the frail dependent elderly. Thus, this study aims to analyze the relationship between coping strategies and quality of life dimensions in primary caregivers of dependent elderly relatives. A cross-sectional study was conducted from 86 caregivers. Predictive variables were coping strategies (problem-focused, emotion-focused, socially-supported, and dysfunctional); dependent variables were quality of life dimensions (psychological, physical, relational, and environmental); and potential confounding variables were age, gender, perceived health and burden of caregiver, and functional capacity of care receiver. Correlation coefficients were calculated and multiple linear regression analysis was performed. After controlling for potential confounders, dysfunctional coping was related to worse quality of life in the psychological dimension, while emotion-focused and socially-supported coping were related to superior psychological and environmental dimensions of quality of life. The physical and relational dimensions of quality of life were not related to coping strategies. 1) it is important to consider coping strategies in the assessment of primary caregivers of dependent elderly relatives; 2) the quality of life of caregivers is related to their coping strategies, 3) their quality of life can be worsened by avoidance-type coping, and 4) their quality of life can be improved by active emotion-focused coping and socially-supported coping.

Analysis of Longitudinal Studies With Repeated Outcome Measures: Adjusting for Time-Dependent Confounding Using Conventional Methods.

PubMed

Keogh, Ruth H; Daniel, Rhian M; VanderWeele, Tyler J; Vansteelandt, Stijn

2018-05-01

Estimation of causal effects of time-varying exposures using longitudinal data is a common problem in epidemiology. When there are time-varying confounders, which may include past outcomes, affected by prior exposure, standard regression methods can lead to bias. Methods such as inverse probability weighted estimation of marginal structural models have been developed to address this problem. However, in this paper we show how standard regression methods can be used, even in the presence of time-dependent confounding, to estimate the total effect of an exposure on a subsequent outcome by controlling appropriately for prior exposures, outcomes, and time-varying covariates. We refer to the resulting estimation approach as sequential conditional mean models (SCMMs), which can be fitted using generalized estimating equations. We outline this approach and describe how including propensity score adjustment is advantageous. We compare the causal effects being estimated using SCMMs and marginal structural models, and we compare the two approaches using simulations. SCMMs enable more precise inferences, with greater robustness against model misspecification via propensity score adjustment, and easily accommodate continuous exposures and interactions. A new test for direct effects of past exposures on a subsequent outcome is described.

Suspicious scars: physical child abuse vs Ehlers-Danlos syndrome.

PubMed

Vadysinghe, Amal Nishantha; Wickramashinghe, Chatula Usari; Nanayakkara, Dineshi Nadira; Kaluarachchi, Chandishni Ishara

2018-01-01

Child abuse is a sensitive topic among many medical practitioners and the diagnosis of this entity requires awareness about conditions which can mimic physical child abuse. Here, the authors present a case of a 13-year-old school non-attendee who was referred due to multiple scars, over areas prone to accidental as well as non-accidental injury, who underwent medicolegal examination due to suspicion of physical child abuse. On further inquiry, it was discovered that she had easy bruising and poor wound healing. A diagnosis of Ehlers-Danlos syndrome was established and physical child abuse was excluded. This case emphasizes the importance of identifying conditions which may confound the diagnosis of physical child abuse. This is of utmost importance in avoiding adverse legal and psycho-social implications on the child, family and society.

[Understanding heart failure].

PubMed

Boo, José Fernando Guadalajara

2006-01-01

Heart failure is a disease with several definitions. The term "heart failure" is used by has brougth about confusion in the terminology. For this reason, the value of the ejection fraction (< 0.40 or < 0.35) is used in most meganalyses on the treatment of heart failure, avoiding the term "heart failure" that is a confounding concept. In this paper we carefully analyze the meaning of contractility, ventricular function or performance, preload, afterload, heart failure, compensation mechanisms in heart failure, myocardial oxygen consumption, inadequate, adequate and inappropriate hypertrophy, systole, diastole, compliance, problems of relaxation, and diastolic dysfunction. Their definitions are supported by the original scientific descriptions in an attempt to clarify the concepts about ventricular function and heart failure and, in this way, use the same scientific language about the meaning of ventricular function, heart failure, and diastolic dysfunction.

Amnion as a surrogate tissue reporter of the effects of maternal preeclampsia on the fetus.

PubMed

Suzuki, Masako; Maekawa, Ryo; Patterson, Nicole E; Reynolds, David M; Calder, Brent R; Reznik, Sandra E; Heo, Hye J; Einstein, Francine Hughes; Greally, John M

2016-01-01

Preeclampsia, traditionally characterized by high blood pressure and proteinuria, is a common pregnancy complication, which affects 2-8 % of all pregnancies. Although children born to women with preeclampsia have a higher risk of hypertension in later life, the mechanism of this increased risk is unknown. DNA methylation is an epigenetic modification that has been studied as a mediator of cellular memory of adverse exposures in utero. Since each cell type in the body has a unique DNA profile, cell subtype composition is a major confounding factor in studies of tissues with heterogeneous cell types. The best way to avoid this confounding effect is by using purified cell types. However, using purified cell types in large cohort translational studies is difficult. The amnion, the inner layer of the fetal membranes of the placenta, is derived from the epiblast and consists of two cell types, which are easy to isolate from the delivered placenta. In this study, we demonstrate the value of using amnion samples for DNA methylation studies, revealing distinctive patterns between fetuses exposed to proteinuria or hypertension and fetuses from normal pregnancies. We performed a genome-wide DNA methylation analysis, HpaII tiny fragment Enrichment by Ligation-mediated PCR (HELP)-tagging, on 62 amnion samples from the placentas of uncomplicated, normal pregnancies and from those with complications of preeclampsia or hypertension. Using a regression model approach, we found 123, 85, and 99 loci with high-confidence hypertension-associated, proteinuria-associated, and hypertension- and proteinuria-associated DNA methylation changes, respectively. A gene ontology analysis showed DNA methylation changes to be selecting genes with different biological processes in exposure status. We also found that these differentially methylated regions overlap loci previously reported as differentially methylated regions in preeclampsia. Our findings support prior observations that preeclampsia is associated with changes of DNA methylation near genes that have previously been found to be dysregulated in preeclampsia. We propose that amniotic membranes represent a valuable surrogate fetal tissue on which to perform epigenome-wide association studies of adverse intrauterine conditions.

Risk of adverse birth outcomes in populations living near landfill sites

PubMed Central

Elliott, Paul; Briggs, David; Morris, Sara; de Hoogh, Cornelis; Hurt, Christopher; Jensen, Tina Kold; Maitland, Ian; Richardson, Sylvia; Wakefield, Jon; Jarup, Lars

2001-01-01

Objective To investigate the risk of adverse birth outcomes associated with residence near landfill sites in Great Britain. Design Geographical study of risks of adverse birth outcomes in populations living within 2 km of 9565 landfill sites operational at some time between 1982 and 1997 (from a total of 19 196 sites) compared with those living further away. Setting Great Britain. Subjects Over 8.2 million live births, 43 471 stillbirths, and 124 597 congenital anomalies (including terminations). Main outcome measures All congenital anomalies combined, some specific anomalies, and prevalence of low and very low birth weight (<2500 g and <1500 g). Results For all anomalies combined, relative risk of residence near landfill sites (all waste types) was 0.92 (99% confidence interval 0.907 to 0.923) unadjusted, and 1.01 (1.005 to 1.023) adjusted for confounders. Adjusted risks were 1.05 (1.01 to 1.10) for neural tube defects, 0.96 (0.93 to 0.99) for cardiovascular defects, 1.07 (1.04 to 1.10) for hypospadias and epispadias (with no excess of surgical correction), 1.08 (1.01 to 1.15) for abdominal wall defects, 1.19 (1.05 to 1.34) for surgical correction of gastroschisis and exomphalos, and 1.05 (1.047 to 1.055) and 1.04 (1.03 to 1.05) for low and very low birth weight respectively. There was no excess risk of stillbirth. Findings for special (hazardous) waste sites did not differ systematically from those for non-special sites. For some specific anomalies, higher risks were found in the period before opening compared with after opening of a landfill site, especially hospital admissions for abdominal wall defects. Conclusions We found small excess risks of congenital anomalies and low and very low birth weight in populations living near landfill sites. No causal mechanisms are available to explain these findings, and alternative explanations include data artefacts and residual confounding. Further studies are needed to help differentiate between the various possibilities. What is already known on this topicVarious studies have found excess risks of certain congenital anomalies and low birth weight near landfill sitesRisks up to two to three times higher have been reportedThese studies have been difficult to interpret because of problems of exposure classification, small sample size, confounding, and reporting biasWhat this study addsSome 80% of the British population lives within 2 km of known landfill sites in Great BritainBy including all landfill sites in the country, we avoided the problem of selective reporting, and maximised statistical powerAlthough we found excess risks of congenital anomalies and low birth weight near landfill sites in Great Britain, they were smaller than in some other studiesFurther work is needed to differentiate potential data artefacts and confounding effects from possible causal associations with landfill PMID:11509424

Air pollutants and health outcomes: Assessment of confounding by influenza

NASA Astrophysics Data System (ADS)

Thach, Thuan-Quoc; Wong, Chit-Ming; Chan, King-Pan; Chau, Yuen-Kwan; Neil Thomas, G.; Ou, Chun-Quan; Yang, Lin; Peiris, Joseph S. M.; Lam, Tai-Hing; Hedley, Anthony J.

2010-04-01

We assessed confounding of associations between short-term effects of air pollution and health outcomes by influenza using Hong Kong mortality and hospitalization data for 1996-2002. Three measures of influenza were defined: (i) intensity: weekly proportion of positive influenza viruses, (ii) epidemic: weekly number of positive influenza viruses ≥4% of the annual number for ≥2 consecutive weeks, and (iii) predominance: an epidemic period with co-circulation of respiratory syncytial virus <2% of the annual positive isolates for ≥2 consecutive weeks. We examined effects of influenza on associations between nitrogen dioxide (NO 2), sulfur dioxide (SO 2), particulate matter with aerodynamic diameter ≤10 μm (PM 10) and ozone (O 3) and health outcomes including all natural causes mortality, cardiorespiratory mortality and hospitalization. Generalized additive Poisson regression model with natural cubic splines was fitted to control for time-varying covariates to estimate air pollution health effects. Confounding with influenza was assessed using an absolute difference of >0.1% between unadjusted and adjusted excess risks (ER%). Without adjustment, pollutants were associated with positive ER% for all health outcomes except asthma and stroke hospitalization with SO 2 and stroke hospitalization with O 3. Following adjustment, changes in ER% for all pollutants were <0.1% for all natural causes mortality, but >0.1% for mortality from stroke with NO 2 and SO 2, cardiac or heart disease with NO 2, PM 10 and O 3, lower respiratory infections with NO 2 and O 3 and mortality from chronic obstructive pulmonary disease with all pollutants. Changes >0.1% were seen for acute respiratory disease hospitalization with NO 2, SO 2 and O 3 and acute lower respiratory infections hospitalization with PM 10. Generally, influenza does not confound the observed associations of air pollutants with all natural causes mortality and cardiovascular hospitalization, but for some pollutants and subgroups of cardiorespiratory mortality and respiratory hospitalization there was evidence to suggest confounding by influenza.

Considerations for automated machine learning in clinical metabolic profiling: Altered homocysteine plasma concentration associated with metformin exposure.

PubMed

Orlenko, Alena; Moore, Jason H; Orzechowski, Patryk; Olson, Randal S; Cairns, Junmei; Caraballo, Pedro J; Weinshilboum, Richard M; Wang, Liewei; Breitenstein, Matthew K

2018-01-01

With the maturation of metabolomics science and proliferation of biobanks, clinical metabolic profiling is an increasingly opportunistic frontier for advancing translational clinical research. Automated Machine Learning (AutoML) approaches provide exciting opportunity to guide feature selection in agnostic metabolic profiling endeavors, where potentially thousands of independent data points must be evaluated. In previous research, AutoML using high-dimensional data of varying types has been demonstrably robust, outperforming traditional approaches. However, considerations for application in clinical metabolic profiling remain to be evaluated. Particularly, regarding the robustness of AutoML to identify and adjust for common clinical confounders. In this study, we present a focused case study regarding AutoML considerations for using the Tree-Based Optimization Tool (TPOT) in metabolic profiling of exposure to metformin in a biobank cohort. First, we propose a tandem rank-accuracy measure to guide agnostic feature selection and corresponding threshold determination in clinical metabolic profiling endeavors. Second, while AutoML, using default parameters, demonstrated potential to lack sensitivity to low-effect confounding clinical covariates, we demonstrated residual training and adjustment of metabolite features as an easily applicable approach to ensure AutoML adjustment for potential confounding characteristics. Finally, we present increased homocysteine with long-term exposure to metformin as a potentially novel, non-replicated metabolite association suggested by TPOT; an association not identified in parallel clinical metabolic profiling endeavors. While warranting independent replication, our tandem rank-accuracy measure suggests homocysteine to be the metabolite feature with largest effect, and corresponding priority for further translational clinical research. Residual training and adjustment for a potential confounding effect by BMI only slightly modified the suggested association. Increased homocysteine is thought to be associated with vitamin B12 deficiency - evaluation for potential clinical relevance is suggested. While considerations for clinical metabolic profiling are recommended, including adjustment approaches for clinical confounders, AutoML presents an exciting tool to enhance clinical metabolic profiling and advance translational research endeavors.

Rodent Models of Genetic Contributions to Motivation to Abuse Alcohol

PubMed Central

Crabbe, John C.

2016-01-01

The distinction between alcohol use (normative) and abuse (unfortunately common) implies dysregulation of motivation directed toward the drug. Genetic contributions to abuse risk are mediated through personality differences, other predispositions to drink excessively, and differences in sensitivity to the acute and chronic consequences of the drug. How to assess motivation in laboratory animals is not straightforward but risk factors for and consequences of alcohol abuse can be modeled with reasonable fidelity in laboratory rodents. Remarkably few rodent studies focus on the genetic contributions to alcohol’s reinforcing value: almost all examine preferential drinking of unflavored alcohol over water. Such studies will likely never avoid the confounding role of taste preferences and most often yield intake levels insufficient to yield a pharmacologically significant blood alcohol level. Genotypes that avoid alcohol probably do so based on pre-ingestive sensory cues; however, post-ingestive consequences are also important. Thus, the quest for improved measures of reinforcing value continues. We have genetic differences aplenty, but still lack evidence that any genotype will readily self-administer alcohol to the devastating extent that many alcoholics will. Encouraging results that are emerging include improved behavioral methods for elevating alcohol intake and inferring alcohol reinforcement, as well as new genetic animal models. Several ingenious assays to index alcohol’s motivational effects have been used extensively. Alcoholic drinking that attempts to prevent or to alleviate withdrawal symptoms has been modeled. Another characteristic of alcoholic drinking is its persistence despite abundant evidence to the drinker of the damaging effects of the excessive drinking on work, relationships, and/or health. Modeling such persistence in rodents has been uncommon to date. New genetic animal models include lines of mice selectively bred for chronic high drinking, and other bred for high binge-like drinking. We have a much more clear idea now about some important experiments remaining to be performed. PMID:25306777

Coping and sickness absence

PubMed Central

Schaufeli, Wilmar B.; van Dijk, Frank J. H.; Blonk, Roland W. B.

2007-01-01

Objectives The aim of this study is to examine the role of coping styles in sickness absence. In line with findings that contrast the reactive–passive focused strategies, problem-solving strategies are generally associated with positive results in terms of well-being and overall health outcomes; our hypothesis is that such strategies are positively related to a low frequency of sickness absence and with short lengths (total number of days absent) and durations (mean duration per spell). Methods Using a prospective design, employees’ (N = 3,628) responses on a self-report coping inventory are used to predict future registered sickness absence (i.e. frequency, length, duration, and median time before the onset of a new sick leave period). Results and conclusions In accordance with our hypothesis, and after adjustment for potential confounders, employees with an active problem-solving coping strategy are less likely to drop out because of sickness absence in terms of frequency, length (longer than 14 days), and duration (more than 7 days) of sickness absence. This positive effect is observed in the case of seeking social support only for the duration of sickness absence and in the case of palliative reaction only for the length and frequency of absence. In contrast, an avoidant coping style, representing a reactive–passive strategy, increases the likelihood of frequent absences significantly, as well as the length and duration of sickness absence. Expression of emotions, representing another reactive–passive strategy, has no effect on future sickness absenteeism. The median time before the onset of a new episode of absenteeism is significantly extended for active problem-solving and reduced for avoidance and for a palliative response. The results of the present study support the notion that problem-solving coping and reactive–passive strategies are inextricably connected to frequency, duration, length and onset of sickness absence. Especially, active problem-solving decreases the chance of future sickness absence. PMID:17701200

Coping and sickness absence.

PubMed

van Rhenen, Willem; Schaufeli, Wilmar B; van Dijk, Frank J H; Blonk, Roland W B

2008-02-01

The aim of this study is to examine the role of coping styles in sickness absence. In line with findings that contrast the reactive-passive focused strategies, problem-solving strategies are generally associated with positive results in terms of well-being and overall health outcomes; our hypothesis is that such strategies are positively related to a low frequency of sickness absence and with short lengths (total number of days absent) and durations (mean duration per spell). Using a prospective design, employees' (N = 3,628) responses on a self-report coping inventory are used to predict future registered sickness absence (i.e. frequency, length, duration, and median time before the onset of a new sick leave period). In accordance with our hypothesis, and after adjustment for potential confounders, employees with an active problem-solving coping strategy are less likely to drop out because of sickness absence in terms of frequency, length (longer than 14 days), and duration (more than 7 days) of sickness absence. This positive effect is observed in the case of seeking social support only for the duration of sickness absence and in the case of palliative reaction only for the length and frequency of absence. In contrast, an avoidant coping style, representing a reactive-passive strategy, increases the likelihood of frequent absences significantly, as well as the length and duration of sickness absence. Expression of emotions, representing another reactive-passive strategy, has no effect on future sickness absenteeism. The median time before the onset of a new episode of absenteeism is significantly extended for active problem-solving and reduced for avoidance and for a palliative response. The results of the present study support the notion that problem-solving coping and reactive-passive strategies are inextricably connected to frequency, duration, length and onset of sickness absence. Especially, active problem-solving decreases the chance of future sickness absence.

A flexible, interpretable framework for assessing sensitivity to unmeasured confounding.

PubMed

Dorie, Vincent; Harada, Masataka; Carnegie, Nicole Bohme; Hill, Jennifer

2016-09-10

When estimating causal effects, unmeasured confounding and model misspecification are both potential sources of bias. We propose a method to simultaneously address both issues in the form of a semi-parametric sensitivity analysis. In particular, our approach incorporates Bayesian Additive Regression Trees into a two-parameter sensitivity analysis strategy that assesses sensitivity of posterior distributions of treatment effects to choices of sensitivity parameters. This results in an easily interpretable framework for testing for the impact of an unmeasured confounder that also limits the number of modeling assumptions. We evaluate our approach in a large-scale simulation setting and with high blood pressure data taken from the Third National Health and Nutrition Examination Survey. The model is implemented as open-source software, integrated into the treatSens package for the R statistical programming language. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Bias with respect to socioeconomic status: A closer look at zip code matching in a pneumococcal vaccine effectiveness study.

PubMed

Link-Gelles, Ruth; Westreich, Daniel; Aiello, Allison E; Shang, Nong; Weber, David J; Holtzman, Corinne; Scherzinger, Karen; Reingold, Arthur; Schaffner, William; Harrison, Lee H; Rosen, Jennifer B; Petit, Susan; Farley, Monica; Thomas, Ann; Eason, Jeffrey; Wigen, Christine; Barnes, Meghan; Thomas, Ola; Zansky, Shelley; Beall, Bernard; Whitney, Cynthia G; Moore, Matthew R

2016-12-01

In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the US for prevention of invasive pneumococcal disease in children. Individual-level socioeconomic status (SES) is a potential confounder of the estimated effectiveness of PCV13 and is often controlled for in observational studies using zip code as a proxy. We assessed the utility of zip code matching for control of SES in a post-licensure evaluation of the effectiveness of PCV13 (calculated as [1-matched odds ratio]*100). We used a directed acyclic graph to identify subsets of confounders and collected SES variables from birth certificates, geo-coding, a parent interview, and follow-up with medical providers. Cases tended to be more affluent than eligible controls (for example, 48.3% of cases had private insurance vs. 44.6% of eligible controls), but less affluent than enrolled controls (52.9% of whom had private insurance). Control of confounding subsets, however, did not result in a meaningful change in estimated vaccine effectiveness (original estimate: 85.1%, 95% CI 74.8-91.9%; adjusted estimate: 82.5%, 95% CI 65.6-91.1%). In the context of a post-licensure vaccine effectiveness study, zip code appears to be an adequate, though not perfect, proxy for individual SES.

Postpartum weight loss and infant feeding.

PubMed

Haiek, L N; Kramer, M S; Ciampi, A; Tirado, R

2001-01-01

Women are often advised that lactation accelerates loss of the excess weight gained during pregnancy, but the evidence underlying this advice is sparse and conflicting. To help fill this gap, we assessed differences in the rate of postpartum weight loss in the first 9 months postpartum according to method of infant feeding. Two hundred thirty-six women attending two public health clinics in Montreal were weighed in one to four routine infant immunization visits up to the 9th postpartum month. After each weighing, we administered a telephone questionnaire assessing the method of infant feeding (predominantly breast-feeding, mixed-feeding, or predominantly bottle-feeding) and potential confounders. Data were analyzed using unbalanced multivariate repeated measures linear regression. Infant feeding was not associated with statistically significant differences in the rate of weight loss. Gestational weight gain, postpartum smoking, and maternal birthplace were important predictors of postpartum weight change. Although our results cannot exclude an effect of more exclusive or more prolonged breast-feeding, breast-feeding as commonly practiced does not appear to influence the rate of postpartum weight loss. This information should be useful in counseling new or prospective mothers and in avoiding unrealistic expectations.

Maternal and paternal personality profiles of adolescent suicide attempters.

PubMed

Bolat, Nurullah; Kadak, Tayyib; Eliacik, Kayi; Sargin, Enis; Incekas, Secil; Gunes, Hatice

2017-02-01

Personality features have been correlated with suicidal behaviors in recent decades. Given its neurobiological background, Cloninger's model of personality, the Temperament and Character Inventory (TCI), may help to identify the maternal and paternal personality dimensions associated with adolescent suicide attempts. The present study is the first that specifically compares the temperament and character profiles of both mothers and fathers of the adolescent suicide attempters with a control group, by considering the influence of demographic and clinical factors. The study group comprised 117 parents of 71 adolescent suicide attempters and 119 parents of 71 age- and gender-matched adolescents without a suicide attempt included as a control group. The TCI and Brief Symptom Inventory (BSI) were applied to the parents in both groups. Logistic regression analysis, which was performed to adjust confounding factors, demonstrated significantly higher scores for harm avoidance among the mothers and lower scores of self-directedness among the fathers of the adolescent suicide attempters. New psychotherapeutic modalities considering the high-risk parental personality traits would be beneficial to support parent-adolescent relationships and may have a preventative effect on adolescent suicide. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Association between hormone replacement therapy and dementia: is it time to forget?

PubMed

Almeida, Osvaldo P; Flicker, Leon

2005-06-01

The results of in vitro and animal studies provide a strong rationale for the use of hormone replacement therapy (HRT) to prevent dementia and Alzheimer's disease (AD). In humans, the results of 16 observational studies are consistent with the hypothesis that estrogen use reduces the risk of AD by 10 to 60%. However, women who are prescribed HRT are less likely to have hypertension, diabetes and history of stroke than nonusers. As all of these factors have been associated with increased risk of dementia (including AD), this "prescription bias" may have a significant impact on the results of observational studies. Randomized trials are designed with the aim of avoiding many of the potential biases and confounding (measured or unmeasured) of observational studies. The results of the Women's Health Initiative Memory Study (WHIMS) indicate that HRT (estrogen plus progestin or estrogen alone) increases the risk of dementia (hazard ratio, HR = 1.8, 95% CI = 1.2-2.6). Taking into account the results of the WHIMS and the adverse health events associated with the use of estrogen plus progestin or estrogen alone, we conclude that HRT cannot be recommended as a safe and effective strategy to prevent dementia.

Fraser River sockeye salmon productivity and climate: A re-analysis that avoids an undesirable property of Ricker’s curve

NASA Astrophysics Data System (ADS)

McKinnell, Skip

2008-05-01

In descending order of importance, artificial spawning channels, density-dependent mortality, carryover mortality, and climate have significant influences on the average productivity of Fraser River sockeye salmon ( Oncorhynchus nerka). When factors that are known or have been hypothesized to affect Fraser River sockeye salmon productivity are included in a single analytical framework, no significant change in average productivity occurred in 1976/1977, however, beginning in 1989 average productivity was significantly lower. In the one lake (Chilko) in the Fraser River basin where pre-smolt survival can be distinguished from post-smolt survival, this decline arose from freshwater causes. After accounting for other factors that have a greater influence, Fraser River sockeye salmon productivity tends to be slightly lower in years when the intensity of the Aleutian low pressure region is stormier in winter, although the effect is not strongly expressed in any particular population. A footnote to the study was the realization that estimates of Ricker’s density-dependent mortality parameter, β, are influenced by both the numerical properties of the equation and by population biology; density-dependent and density-independent influences on the estimates of the parameter are confounded.

Rasch Mixture Models for DIF Detection

PubMed Central

Strobl, Carolin; Zeileis, Achim

2014-01-01

Rasch mixture models can be a useful tool when checking the assumption of measurement invariance for a single Rasch model. They provide advantages compared to manifest differential item functioning (DIF) tests when the DIF groups are only weakly correlated with the manifest covariates available. Unlike in single Rasch models, estimation of Rasch mixture models is sensitive to the specification of the ability distribution even when the conditional maximum likelihood approach is used. It is demonstrated in a simulation study how differences in ability can influence the latent classes of a Rasch mixture model. If the aim is only DIF detection, it is not of interest to uncover such ability differences as one is only interested in a latent group structure regarding the item difficulties. To avoid any confounding effect of ability differences (or impact), a new score distribution for the Rasch mixture model is introduced here. It ensures the estimation of the Rasch mixture model to be independent of the ability distribution and thus restricts the mixture to be sensitive to latent structure in the item difficulties only. Its usefulness is demonstrated in a simulation study, and its application is illustrated in a study of verbal aggression. PMID:29795819

Selection bias in rheumatic disease research.

PubMed

Choi, Hyon K; Nguyen, Uyen-Sa; Niu, Jingbo; Danaei, Goodarz; Zhang, Yuqing

2014-07-01

The identification of modifiable risk factors for the development of rheumatic conditions and their sequelae is crucial for reducing the substantial worldwide burden of these diseases. However, the validity of such research can be threatened by sources of bias, including confounding, measurement and selection biases. In this Review, we discuss potentially major issues of selection bias--a type of bias frequently overshadowed by other bias and feasibility issues, despite being equally or more problematic--in key areas of rheumatic disease research. We present index event bias (a type of selection bias) as one of the potentially unifying reasons behind some unexpected findings, such as the 'risk factor paradox'--a phenomenon exemplified by the discrepant effects of certain risk factors on the development versus the progression of osteoarthritis (OA) or rheumatoid arthritis (RA). We also discuss potential selection biases owing to differential loss to follow-up in RA and OA research, as well as those due to the depletion of susceptibles (prevalent user bias) and immortal time bias. The lesson remains that selection bias can be ubiquitous and, therefore, has the potential to lead the field astray. Thus, we conclude with suggestions to help investigators avoid such issues and limit the impact on future rheumatology research.

Establishment of auditory discrimination and detection of tinnitus induced by salicylic acid and intense tone exposure in the rat.

PubMed

Sederholm, Fredrik; Swedberg, Michael D B

2013-05-13

Rats were trained in a two lever food reinforced operant procedure to discriminate a 8000 Hz pure tone stimulus from its absence. Responding on one lever was reinforced in the presence of the tone and responding on the other lever was reinforced when the tone was absent. Frequency generalization testing yielded an inverted U-shaped function, whereas sound pressure level generalization testing yielded a continuous decrease in responding on the tone associated lever with decreasing sound pressure levels. The administration of sodium salicylic acid (150-450 mg/kg) generated responding on the tone associated lever suggesting that salicylic acid induced an experience that had commonalities with the percept of the training tone stimulus. After exposure to intense sound, responding consistent with the presence of tinnitus was achieved and Lidocaine failed to reduce tinnitus behavior. The use of a two choice design helped avoid confounding factors induced by drug induced side effects. Further, since no auditory cues were employed in the test situation the model achieves resistance to potential bias due to hearing impairment and hyperacusis. We propose that this model may be useful in detecting tinnitus. Copyright © 2013 Elsevier B.V. All rights reserved.

Selection bias in rheumatic disease research

PubMed Central

Choi, Hyon K.; Nguyen, Uyen-Sa; Niu, Jingbo; Danaei, Goodarz; Zhang, Yuqing

2014-01-01

The identification of modifiable risk factors for the development of rheumatic conditions and their sequelae is crucial for reducing the substantial worldwide burden of these diseases. However, the validity of such research can be threatened by sources of bias, including confounding, measurement and selection biases. In this Review, we discuss potentially major issues of selection bias—a type of bias frequently overshadowed by other bias and feasibility issues, despite being equally or more problematic—in key areas of rheumatic disease research. We present index event bias (a type of selection bias) as one of the potentially unifying reasons behind some unexpected findings, such as the ‘risk factor paradox’—a phenomenon exemplified by the discrepant effects of certain risk factors on the development versus the progression of osteoarthritis (OA) or rheumatoid arthritis (RA). We also discuss potential selection biases owing to differential loss to follow-up in RA and OA research, as well as those due to the depletion of susceptibles (prevalent user bias) and immortal time bias. The lesson remains that selection bias can be ubiquitous and, therefore, has the potential to lead the field astray. Thus, we conclude with suggestions to help investigators avoid such issues and limit the impact on future rheumatology research. PMID:24686510

Epidemiologic tools to study the influence of environmental factors on fecundity and pregnancy-related outcomes.

PubMed

Slama, Rémy; Ballester, Ferran; Casas, Maribel; Cordier, Sylvaine; Eggesbø, Merete; Iniguez, Carmen; Nieuwenhuijsen, Mark; Philippat, Claire; Rey, Sylvie; Vandentorren, Stéphanie; Vrijheid, Martine

2014-01-01

Adverse pregnancy outcomes entail a large health burden for the mother and offspring; a part of it might be avoided by better understanding the role of environmental factors in their etiology. Our aims were to review the assessment tools to characterize fecundity troubles and pregnancy-related outcomes in human populations and their sensitivity to environmental factors. For each outcome, we reviewed the possible study designs, main sources of bias, and their suggested cures. In terms of study design, for most pregnancy outcomes, cohorts with recruitment early during or even before pregnancy allow efficient characterization of pregnancy-related events, time-varying confounders, and in utero exposures that may impact birth outcomes and child health. Studies on congenital anomalies require specific designs, assessment of anomalies in medical pregnancy terminations, and, for congenital anomalies diagnosed postnatally, follow-up during several months after birth. Statistical analyses should take into account environmental exposures during the relevant time windows; survival models are an appropriate approach for fecundity, fetal loss, and gestational duration/preterm delivery. Analysis of gestational duration could distinguish pregnancies according to delivery induction (and possibly pregnancy-related conditions). In conclusion, careful design and analysis are required to better characterize environmental effects on human reproduction.

Post-traumatic stress disorder dimensions and asthma morbidity in World Trade Center rescue and recovery workers.

PubMed

Mindlis, I; Morales-Raveendran, E; Goodman, E; Xu, K; Vila-Castelar, C; Keller, K; Crawford, G; James, S; Katz, C L; Crowley, L E; de la Hoz, R E; Markowitz, S; Wisnivesky, J P

2017-09-01

Using data from a cohort of World Trade Center (WTC) rescue and recovery workers with asthma, we assessed whether meeting criteria for post-traumatic stress disorder (PTSD), sub-threshold PTSD, and for specific PTSD symptom dimensions are associated with increased asthma morbidity. Participants underwent a Structured Clinical Interview for Diagnostic and Statistical Manual to assess the presence of PTSD following DSM-IV criteria during in-person interviews between December 2013 and April 2015. We defined sub-threshold PTSD as meeting criteria for two of three symptom dimensions: re-experiencing, avoidance, or hyper-arousal. Asthma control, acute asthma-related healthcare utilization, and asthma-related quality of life data were collected using validated scales. Unadjusted and multiple regression analyses were performed to assess the relationship between sub-threshold PTSD and PTSD symptom domains with asthma morbidity measures. Of the 181 WTC workers with asthma recruited into the study, 28% had PTSD and 25% had sub-threshold PTSD. Patients with PTSD showed worse asthma control, higher rates of inpatient healthcare utilization, and poorer asthma quality of life than those with sub-threshold or no PTSD. After adjusting for potential confounders, among patients not meeting the criteria for full PTSD, those presenting symptoms of re-experiencing exhibited poorer quality of life (p = 0.003). Avoidance was associated with increased acute healthcare use (p = 0.05). Sub-threshold PTSD was not associated with asthma morbidity (p > 0.05 for all comparisons). There may be benefit in assessing asthma control in patients with sub-threshold PTSD symptoms as well as those with full PTSD to more effectively identify ongoing asthma symptoms and target management strategies.

Activity Restriction Induced by Fear of Falling and Objective and Subjective Measures of Physical Function: A Prospective Cohort Study

PubMed Central

Deshpande, Nandini; Metter, E. Jeffrey; Lauretani, Fulvio; Bandinelli, Stefania; Guralnik, Jack; Ferrucci, Luigi

2009-01-01

Objectives To examine whether activity restriction specifically induced by fear of falling (FF) contributes to greater risk of disability and decline in physical function. Design Prospective cohort study. Setting Population-based older cohort. Participants Six hundred seventy-three community-living elderly (≥65) participants in the Invecchiare in Chianti Study who reported FF. Measurements FF, fear-induced activity restriction, cognition, depressive symptoms, comorbidities, smoking history, and demographic factors were assessed at baseline. Disability in activities of daily living (ADLs) and instrumental activities of daily living (IADLs) and performance on the Short Performance Physical Battery (SPPB) were evaluated at baseline and at the 3-year follow-up. Results One-quarter (25.5%) of participants did not report any activity restriction, 59.6% reported moderate activity restriction (restriction or avoidance of <3 activities), and 14.9% reported severe activity restriction (restriction or avoidance of ≥3 activities). The severe restriction group reported significantly higher IADL disability and worse SPPB scores than the no restriction and moderate restriction groups. Severe activity restriction was a significant independent predictor of worsening ADL disability and accelerated decline in lower extremity performance on SPPB over the 3-year follow-up. Severe and moderate activity restriction were independent predictors of worsening IADL disability. Results were consistent even after adjusting for multiple potential confounders. Conclusion In an elderly population, activity restriction associated with FF is an independent predictor of decline in physical function. Future intervention studies in geriatric preventive care should directly address risk factors associated with FF and activity restriction to substantiate long-term effects on physical abilities and autonomy of older persons. PMID:18312314

Low-grade inflammation decreases emotion recognition - Evidence from the vaccination model of inflammation.

PubMed

Balter, Leonie J T; Hulsken, Sasha; Aldred, Sarah; Drayson, Mark T; Higgs, Suzanne; Veldhuijzen van Zanten, Jet J C S; Raymond, Jane E; Bosch, Jos A

2018-05-06

The ability to adequately interpret the mental state of another person is key to complex human social interaction. Recent evidence suggests that this ability, considered a hallmark of 'theory of mind' (ToM), becomes impaired by inflammation. However, extant supportive empirical evidence is based on experiments that induce not only inflammation but also induce discomfort and sickness, factors that could also account for temporary social impairment. Hence, an experimental inflammation manipulation was applied that avoided this confound, isolating effects of inflammation and social interaction. Forty healthy male participants (mean age = 25, SD = 5 years) participated in this double-blind placebo-controlled crossover trial. Inflammation was induced using Salmonella Typhi vaccination (0.025 mg; Typhim Vi, Sanofi Pasteur, UK); saline-injection was used as a control. About 6 h 30 m after injection in each condition, participants completed the Reading the Mind in the Eyes Test (RMET), a validated test for assessing how well the mental states of others can be inferred through observation of the eyes region of the face. Vaccination induced systemic inflammation, elevating IL-6 by +419% (p < .001), without fever, sickness symptoms (e.g., nausea, light-headedness), or mood changes (all p's > .21). Importantly, compared to placebo, vaccination significantly reduced RMET accuracy (p < .05). RMET stimuli selected on valence (positive, negative, neutral) provided no evidence of a selective impact of treatment. By utilizing an inflammation-induction procedure that avoided concurrent sicknesses or symptoms in a double-blinded design, the present study provides further support for the hypothesis that immune activation impairs ToM. Such impairment may provide a mechanistic link explaining social-cognitive deficits in psychopathologies that exhibit low-grade inflammation, such as major depression. Copyright © 2018 Elsevier Inc. All rights reserved.

Design and statistical problems in prevention.

PubMed

Gullberg, B

1996-01-01

Clinical and epidemiological research in osteoporosis can benefit from using the methods and techniques established in the area of chronic disease epidemiology. However, attention has to be given to the special characteristics such as the multifactorial nature and the fact that the subjects usually are of high ages. In order to evaluate prevention it is of course first necessary to detect and confirm reversible risk factors. The advantage and disadvantage of different design (cross-sectional, cohort and case-control) are well known. The effects of avoidable biases, e.g. selection, observation and confounding have to be balanced against practical conveniences like time, expenses, recruitment etc. The translation of relative risks into population attributable risks (etiologic fractions, prevented fractions) are complex and are usually performed under unrealistic, simplified assumptions. The consequences of interactions (synergy) between risk factors are often neglected. The multifactorial structure requires application of more advanced multi-level statistical techniques. The common strategy in prevention to target a cluster of risk factors in order to avoid the multifactorial nature implies that in the end it is impossible to separate each unique factor. Experimental designs for evaluating prevention like clinical trials and intervention have to take into account the distinction between explanatory and pragmatic studies. An explanatory approach is similar to an idealized laboratory trial while the pragmatic design is more realistic, practical and has a general public health perspective. The statistical techniques to be used in osteoporosis research are implemented in easy available computer-packages like SAS, SPSS, BMDP and GLIM. In addition to the traditional logistic regression methods like Cox analysis and Poisson regression also analysis of repeated measurement and cluster analysis are relevant.

Using instrumental variables to disentangle treatment and placebo effects in blinded and unblinded randomized clinical trials influenced by unmeasured confounders

NASA Astrophysics Data System (ADS)

Chaibub Neto, Elias

2016-11-01

Clinical trials traditionally employ blinding as a design mechanism to reduce the influence of placebo effects. In practice, however, it can be difficult or impossible to blind study participants and unblinded trials are common in medical research. Here we show how instrumental variables can be used to quantify and disentangle treatment and placebo effects in randomized clinical trials comparing control and active treatments in the presence of confounders. The key idea is to use randomization to separately manipulate treatment assignment and psychological encouragement conversations/interactions that increase the participants’ desire for improved symptoms. The proposed approach is able to improve the estimation of treatment effects in blinded studies and, most importantly, opens the doors to account for placebo effects in unblinded trials.

Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis

PubMed Central

Yang, Fan; Wang, Jiebiao; Pierce, Brandon L.; Chen, Lin S.

2017-01-01

The impact of inherited genetic variation on gene expression in humans is well-established. The majority of known expression quantitative trait loci (eQTLs) impact expression of local genes (cis-eQTLs). More research is needed to identify effects of genetic variation on distant genes (trans-eQTLs) and understand their biological mechanisms. One common trans-eQTLs mechanism is “mediation” by a local (cis) transcript. Thus, mediation analysis can be applied to genome-wide SNP and expression data in order to identify transcripts that are “cis-mediators” of trans-eQTLs, including those “cis-hubs” involved in regulation of many trans-genes. Identifying such mediators helps us understand regulatory networks and suggests biological mechanisms underlying trans-eQTLs, both of which are relevant for understanding susceptibility to complex diseases. The multitissue expression data from the Genotype-Tissue Expression (GTEx) program provides a unique opportunity to study cis-mediation across human tissue types. However, the presence of complex hidden confounding effects in biological systems can make mediation analyses challenging and prone to confounding bias, particularly when conducted among diverse samples. To address this problem, we propose a new method: Genomic Mediation analysis with Adaptive Confounding adjustment (GMAC). It enables the search of a very large pool of variables, and adaptively selects potential confounding variables for each mediation test. Analyses of simulated data and GTEx data demonstrate that the adaptive selection of confounders by GMAC improves the power and precision of mediation analysis. Application of GMAC to GTEx data provides new insights into the observed patterns of cis-hubs and trans-eQTL regulation across tissue types. PMID:29021290

Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis.

PubMed

Yang, Fan; Wang, Jiebiao; Pierce, Brandon L; Chen, Lin S

2017-11-01

The impact of inherited genetic variation on gene expression in humans is well-established. The majority of known expression quantitative trait loci (eQTLs) impact expression of local genes ( cis -eQTLs). More research is needed to identify effects of genetic variation on distant genes ( trans -eQTLs) and understand their biological mechanisms. One common trans -eQTLs mechanism is "mediation" by a local ( cis ) transcript. Thus, mediation analysis can be applied to genome-wide SNP and expression data in order to identify transcripts that are " cis -mediators" of trans -eQTLs, including those " cis -hubs" involved in regulation of many trans -genes. Identifying such mediators helps us understand regulatory networks and suggests biological mechanisms underlying trans -eQTLs, both of which are relevant for understanding susceptibility to complex diseases. The multitissue expression data from the Genotype-Tissue Expression (GTEx) program provides a unique opportunity to study cis -mediation across human tissue types. However, the presence of complex hidden confounding effects in biological systems can make mediation analyses challenging and prone to confounding bias, particularly when conducted among diverse samples. To address this problem, we propose a new method: Genomic Mediation analysis with Adaptive Confounding adjustment (GMAC). It enables the search of a very large pool of variables, and adaptively selects potential confounding variables for each mediation test. Analyses of simulated data and GTEx data demonstrate that the adaptive selection of confounders by GMAC improves the power and precision of mediation analysis. Application of GMAC to GTEx data provides new insights into the observed patterns of cis -hubs and trans -eQTL regulation across tissue types. © 2017 Yang et al.; Published by Cold Spring Harbor Laboratory Press.

Association of Body Mass Index with Depression, Anxiety and Suicide—An Instrumental Variable Analysis of the HUNT Study

PubMed Central

Bjørngaard, Johan Håkon; Carslake, David; Lund Nilsen, Tom Ivar; Linthorst, Astrid C. E.; Davey Smith, George; Gunnell, David; Romundstad, Pål Richard

2015-01-01

Objective While high body mass index is associated with an increased risk of depression and anxiety, cumulative evidence indicates that it is a protective factor for suicide. The associations from conventional observational studies of body mass index with mental health outcomes are likely to be influenced by reverse causality or confounding by ill-health. In the present study, we investigated the associations between offspring body mass index and parental anxiety, depression and suicide in order to avoid problems with reverse causality and confounding by ill-health. Methods We used data from 32,457 mother-offspring and 27,753 father-offspring pairs from the Norwegian HUNT-study. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale and suicide death from national registers. Associations between offspring and own body mass index and symptoms of anxiety and depression and suicide mortality were estimated using logistic and Cox regression. Causal effect estimates were estimated with a two sample instrument variable approach using offspring body mass index as an instrument for parental body mass index. Results Both own and offspring body mass index were positively associated with depression, while the results did not indicate any substantial association between body mass index and anxiety. Although precision was low, suicide mortality was inversely associated with own body mass index and the results from the analysis using offspring body mass index supported these results. Adjusted odds ratios per standard deviation body mass index from the instrumental variable analysis were 1.22 (95% CI: 1.05, 1.43) for depression, 1.10 (95% CI: 0.95, 1.27) for anxiety, and the instrumental variable estimated hazard ratios for suicide was 0.69 (95% CI: 0.30, 1.63). Conclusion The present study’s results indicate that suicide mortality is inversely associated with body mass index. We also found support for a positive association between body mass index and depression, but not for anxiety. PMID:26167892

Association of Body Mass Index with Depression, Anxiety and Suicide-An Instrumental Variable Analysis of the HUNT Study.

PubMed

Bjørngaard, Johan Håkon; Carslake, David; Lund Nilsen, Tom Ivar; Linthorst, Astrid C E; Davey Smith, George; Gunnell, David; Romundstad, Pål Richard

2015-01-01

While high body mass index is associated with an increased risk of depression and anxiety, cumulative evidence indicates that it is a protective factor for suicide. The associations from conventional observational studies of body mass index with mental health outcomes are likely to be influenced by reverse causality or confounding by ill-health. In the present study, we investigated the associations between offspring body mass index and parental anxiety, depression and suicide in order to avoid problems with reverse causality and confounding by ill-health. We used data from 32,457 mother-offspring and 27,753 father-offspring pairs from the Norwegian HUNT-study. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale and suicide death from national registers. Associations between offspring and own body mass index and symptoms of anxiety and depression and suicide mortality were estimated using logistic and Cox regression. Causal effect estimates were estimated with a two sample instrument variable approach using offspring body mass index as an instrument for parental body mass index. Both own and offspring body mass index were positively associated with depression, while the results did not indicate any substantial association between body mass index and anxiety. Although precision was low, suicide mortality was inversely associated with own body mass index and the results from the analysis using offspring body mass index supported these results. Adjusted odds ratios per standard deviation body mass index from the instrumental variable analysis were 1.22 (95% CI: 1.05, 1.43) for depression, 1.10 (95% CI: 0.95, 1.27) for anxiety, and the instrumental variable estimated hazard ratios for suicide was 0.69 (95% CI: 0.30, 1.63). The present study's results indicate that suicide mortality is inversely associated with body mass index. We also found support for a positive association between body mass index and depression, but not for anxiety.

Recognized spontaneous abortion in mid-pregnancy and patterns of pregnancy alcohol use.

PubMed

Chiodo, Lisa M; Bailey, Beth A; Sokol, Robert J; Janisse, James; Delaney-Black, Virginia; Hannigan, John H

2012-05-01

Alcohol consumption during pregnancy is one potential risk factor for spontaneous abortion (SAb). Prior research suggested that heavy drinking during pregnancy was associated with significantly increased rates of SAb, but results for lower levels of drinking have been inconsistent. We examined the association between different levels and patterns of prenatal alcohol consumption and SAb in a high-risk inner-city sample. We hypothesized that higher levels, binge patterns, and more frequent drinking would be associated with increased rates of SAb. The quantity and frequency of self-reported peri-conceptional and repeated in-pregnancy maternal drinking volumes per beverage type were assessed with semi-structured interviews in a prospective subsample of 302 African-American mothers. Relations between various measures of prenatal alcohol exposure and SAb were assessed using logistic regression. After controlling for various potential confounders, there was a significant positive relation between average absolute alcohol use per day across pregnancy and SAb. Greater frequency of drinking episodes also predicted SAb: an average of even one day of drinking per week across pregnancy was associated with an increase in the incidence of SAb. However, contrary to our hypothesis, neither the amount of alcohol drunk per drinking day nor a measure of binge drinking was significantly related to SAb after controlling for confounders. Differences in when women who drank at risk levels initiated antenatal care may have under-estimated the impact of alcohol on SAb in this low-SES urban African-American sample. Some drinking measures averaged across pregnancy may have under-estimated consumption and overestimated risk of SAb, but other risk drinking measures that avoid this limitation show similar relations to SAb. Identifying fetal risk drinking in pregnant women is critical to increasing the effectiveness of interventions that reduce risk level alcohol consumption and protect from pregnancy loss. Copyright © 2012 Elsevier Inc. All rights reserved.

A sequential Cox approach for estimating the causal effect of treatment in the presence of time-dependent confounding applied to data from the Swiss HIV Cohort Study.

PubMed

Gran, Jon Michael; Røysland, Kjetil; Wolbers, Marcel; Didelez, Vanessa; Sterne, Jonathan A C; Ledergerber, Bruno; Furrer, Hansjakob; von Wyl, Viktor; Aalen, Odd O

2010-11-20

When estimating the effect of treatment on HIV using data from observational studies, standard methods may produce biased estimates due to the presence of time-dependent confounders. Such confounding can be present when a covariate, affected by past exposure, is both a predictor of the future exposure and the outcome. One example is the CD4 cell count, being a marker for disease progression for HIV patients, but also a marker for treatment initiation and influenced by treatment. Fitting a marginal structural model (MSM) using inverse probability weights is one way to give appropriate adjustment for this type of confounding. In this paper we study a simple and intuitive approach to estimate similar treatment effects, using observational data to mimic several randomized controlled trials. Each 'trial' is constructed based on individuals starting treatment in a certain time interval. An overall effect estimate for all such trials is found using composite likelihood inference. The method offers an alternative to the use of inverse probability of treatment weights, which is unstable in certain situations. The estimated parameter is not identical to the one of an MSM, it is conditioned on covariate values at the start of each mimicked trial. This allows the study of questions that are not that easily addressed fitting an MSM. The analysis can be performed as a stratified weighted Cox analysis on the joint data set of all the constructed trials, where each trial is one stratum. The model is applied to data from the Swiss HIV cohort study. Copyright © 2010 John Wiley & Sons, Ltd.

Understanding Confounding Effects in Linguistic Coordination: An Information-Theoretic Approach

PubMed Central

Gao, Shuyang; Ver Steeg, Greg; Galstyan, Aram

2015-01-01

We suggest an information-theoretic approach for measuring stylistic coordination in dialogues. The proposed measure has a simple predictive interpretation and can account for various confounding factors through proper conditioning. We revisit some of the previous studies that reported strong signatures of stylistic accommodation, and find that a significant part of the observed coordination can be attributed to a simple confounding effect—length coordination. Specifically, longer utterances tend to be followed by longer responses, which gives rise to spurious correlations in the other stylistic features. We propose a test to distinguish correlations in length due to contextual factors (topic of conversation, user verbosity, etc.) and turn-by-turn coordination. We also suggest a test to identify whether stylistic coordination persists even after accounting for length coordination and contextual factors. PMID:26115446

Gang membership and substance use: guilt as a gendered causal pathway

PubMed Central

Coffman, Donna L.; Melde, Chris; Esbensen, Finn-Aage

2014-01-01

Objectives We examine whether anticipated guilt for substance use is a gendered mechanism underlying the noted enhancement effect of gang membership on illegal drug use. We also demonstrate a method for making stronger causal inferences when assessing mediation in the presence of moderation and time-varying confounding. Methods We estimate a series of inverse propensity weighted models to obtain unbiased estimates of mediation in the presence of confounding of the exposure (i.e., gang membership) and mediator (i.e., anticipated guilt) using three waves of data from a multi-site panel study of a law-related education program for youth (N=1,113). Results The onset of gang membership significantly decreased anticipated substance use guilt among both male and female respondents. This reduction was significantly associated with increased frequency of substance use only for female respondents, however, suggesting that gender moderates the mechanism through which gang membership influences substance use. Conclusions Criminologists are often concerned with identifying causal pathways for antisocial and/or delinquent behavior, but confounders of the exposure, mediator, and outcome often interfere with efforts to assess mediation. Many new approaches have been proposed for strengthening causal inference for mediation effects. After controlling for confounding using inverse propensity weighting, our results suggest that interventions aimed at reducing substance use by current and former female gang members should focus on the normative aspects of these behaviors. PMID:26190954

Gang membership and substance use: guilt as a gendered causal pathway.

PubMed

Coffman, Donna L; Melde, Chris; Esbensen, Finn-Aage

2015-03-01

We examine whether anticipated guilt for substance use is a gendered mechanism underlying the noted enhancement effect of gang membership on illegal drug use. We also demonstrate a method for making stronger causal inferences when assessing mediation in the presence of moderation and time-varying confounding. We estimate a series of inverse propensity weighted models to obtain unbiased estimates of mediation in the presence of confounding of the exposure (i.e., gang membership) and mediator (i.e., anticipated guilt) using three waves of data from a multi-site panel study of a law-related education program for youth ( N =1,113). The onset of gang membership significantly decreased anticipated substance use guilt among both male and female respondents. This reduction was significantly associated with increased frequency of substance use only for female respondents, however, suggesting that gender moderates the mechanism through which gang membership influences substance use. Criminologists are often concerned with identifying causal pathways for antisocial and/or delinquent behavior, but confounders of the exposure, mediator, and outcome often interfere with efforts to assess mediation. Many new approaches have been proposed for strengthening causal inference for mediation effects. After controlling for confounding using inverse propensity weighting, our results suggest that interventions aimed at reducing substance use by current and former female gang members should focus on the normative aspects of these behaviors.

Estimating influenza vaccine effectiveness: Evolution of methods to better understand effects of confounding in older adults.

PubMed

McElhaney, Janet E; Andrew, Melissa K; McNeil, Shelly A

2017-11-01

Older adults are at high risk for serious complications of influenza illness and loss of vaccine-mediated protection. It is increasingly recognized that in addition to age, multiple chronic conditions and associated frailty contribute to the decline in vaccine effectiveness in this population. However, observational studies have been fraught with issues of confounding related to the degree of frailty and functional decline, measures of which are not included in standard administrative health care databases that are used to calculate vaccine effectiveness. This issue has led to the identification of confounding by indication or from "healthy vaccinee" bias, which respectively lead to underestimates or overestimates of influenza vaccine effectiveness. In addition, the sensitivity and specificity of the criteria used to define influenza-like illness declines with increasing age due to atypical presentations of illness and the inability to distinguish between influenza and other respiratory viruses. The test-negative case:control design has emerged as a method to estimate influenza vaccine effectiveness by comparing vaccination rates in those with laboratory-confirmed influenza to those with other acute viral respiratory illnesses. This review provides a perspective on how test-negative case:control study designs and new insights into mechanisms of protection have considerably strengthened influenza vaccination policy decisions for older adults that have historically been undermined by the conclusions of observational studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Psychotic experiences and risk of self-injurious behaviour in the general population: a systematic review and meta-analysis.

PubMed

Honings, S; Drukker, M; Groen, R; van Os, J

2016-01-01

Recent studies suggest that psychotic experiences (PE) in the general population are associated with an increased risk of self-injurious behaviour. Both the magnitude of this association and the level of adjustment for confounders vary among studies. A meta-analysis was performed to integrate the available evidence. The influence of possible confounders, including variably defined depression, was assessed. A systematic review and meta-analysis was conducted including general population studies reporting on the risk of self-injurious behaviour in individuals with PE. Studies were identified by a systematic search strategy in Pubmed, PsycINFO and Embase. Reported effect sizes were extracted and meta-analytically pooled. The risk of self-injurious behaviour was 3.20 times higher in individuals with PE compared with those without. Subanalyses showed that PE were associated with self-harm, suicidal ideation as well as suicidal attempts. All studies had scope for considerable residual confounding; effect sizes adjusted for depression were significantly smaller than effect sizes unadjusted for depression. In the longitudinal studies, adjustment for psychopathology resulted in a 74% reduction in excess risk. PE are associated with self-injurious behaviour, suggesting they have potential as passive markers of suicidality. However, the association is confounded and several methodological issues remain, particularly how to separate PE from the full range of connected psychopathology in determining any specific association with self-injurious behaviour. Given evidence that PE represent an indicator of severity of non-psychotic psychopathology, the association between PE and self-injurious behaviour probably reflects a greater likelihood of self-injurious behaviour in more severe states of mental distress.

Pre-study feasibility and identifying sensitivity analyses for protocol pre-specification in comparative effectiveness research.

PubMed

Girman, Cynthia J; Faries, Douglas; Ryan, Patrick; Rotelli, Matt; Belger, Mark; Binkowitz, Bruce; O'Neill, Robert

2014-05-01

The use of healthcare databases for comparative effectiveness research (CER) is increasing exponentially despite its challenges. Researchers must understand their data source and whether outcomes, exposures and confounding factors are captured sufficiently to address the research question. They must also assess whether bias and confounding can be adequately minimized. Many study design characteristics may impact on the results; however, minimal if any sensitivity analyses are typically conducted, and those performed are post hoc. We propose pre-study steps for CER feasibility assessment and to identify sensitivity analyses that might be most important to pre-specify to help ensure that CER produces valid interpretable results.

Testing for gene-environment interaction under exposure misspecification.

PubMed

Sun, Ryan; Carroll, Raymond J; Christiani, David C; Lin, Xihong

2017-11-09

Complex interplay between genetic and environmental factors characterizes the etiology of many diseases. Modeling gene-environment (GxE) interactions is often challenged by the unknown functional form of the environment term in the true data-generating mechanism. We study the impact of misspecification of the environmental exposure effect on inference for the GxE interaction term in linear and logistic regression models. We first examine the asymptotic bias of the GxE interaction regression coefficient, allowing for confounders as well as arbitrary misspecification of the exposure and confounder effects. For linear regression, we show that under gene-environment independence and some confounder-dependent conditions, when the environment effect is misspecified, the regression coefficient of the GxE interaction can be unbiased. However, inference on the GxE interaction is still often incorrect. In logistic regression, we show that the regression coefficient is generally biased if the genetic factor is associated with the outcome directly or indirectly. Further, we show that the standard robust sandwich variance estimator for the GxE interaction does not perform well in practical GxE studies, and we provide an alternative testing procedure that has better finite sample properties. © 2017, The International Biometric Society.

An Improved Framework for Confound Regression and Filtering for Control of Motion Artifact in the Preprocessing of Resting-State Functional Connectivity Data

PubMed Central

Satterthwaite, Theodore D.; Elliott, Mark A.; Gerraty, Raphael T.; Ruparel, Kosha; Loughead, James; Calkins, Monica E.; Eickhoff, Simon B.; Hakonarson, Hakon; Gur, Ruben C.; Gur, Raquel E.; Wolf, Daniel H.

2013-01-01

Several recent reports in large, independent samples have demonstrated the influence of motion artifact on resting-state functional connectivity MRI (rsfc-MRI). Standard rsfc-MRI preprocessing typically includes regression of confounding signals and band-pass filtering. However, substantial heterogeneity exists in how these techniques are implemented across studies, and no prior study has examined the effect of differing approaches for the control of motion-induced artifacts. To better understand how in-scanner head motion affects rsfc-MRI data, we describe the spatial, temporal, and spectral characteristics of motion artifacts in a sample of 348 adolescents. Analyses utilize a novel approach for describing head motion on a voxelwise basis. Next, we systematically evaluate the efficacy of a range of confound regression and filtering techniques for the control of motion-induced artifacts. Results reveal that the effectiveness of preprocessing procedures on the control of motion is heterogeneous, and that improved preprocessing provides a substantial benefit beyond typical procedures. These results demonstrate that the effect of motion on rsfc-MRI can be substantially attenuated through improved preprocessing procedures, but not completely removed. PMID:22926292

The statistical pitfalls of the partially randomized preference design in non-blinded trials of psychological interventions.

PubMed

Gemmell, Isla; Dunn, Graham

2011-03-01

In a partially randomized preference trial (PRPT) patients with no treatment preference are allocated to groups at random, but those who express a preference receive the treatment of their choice. It has been suggested that the design can improve the external and internal validity of trials. We used computer simulation to illustrate the impact that an unmeasured confounder could have on the results and conclusions drawn from a PRPT. We generated 4000 observations ("patients") that reflected the distribution of the Beck Depression Index (DBI) in trials of depression. Half were randomly assigned to a randomized controlled trial (RCT) design and half were assigned to a PRPT design. In the RCT, "patients" were evenly split between treatment and control groups; whereas in the preference arm, to reflect patient choice, 87.5% of patients were allocated to the experimental treatment and 12.5% to the control. Unadjusted analyses of the PRPT data consistently overestimated the treatment effect and its standard error. This lead to Type I errors when the true treatment effect was small and Type II errors when the confounder effect was large. The PRPT design is not recommended as a method of establishing an unbiased estimate of treatment effect due to the potential influence of unmeasured confounders. Copyright © 2011 John Wiley & Sons, Ltd.

Confounding by dietary patterns of the inverse association between alcohol consumption and type 2 diabetes risk.

PubMed

Imamura, Fumiaki; Lichtenstein, Alice H; Dallal, Gerard E; Meigs, James B; Jacques, Paul F

2009-07-01

The ability to interpret epidemiologic observations is limited because of potential residual confounding by correlated dietary components. Dietary pattern analyses by factor analysis or partial least squares may overcome the limitation. To examine confounding by dietary pattern as well as standard risk factors and selected nutrients, the authors modeled the longitudinal association between alcohol consumption and 7-year risk of type 2 diabetes mellitus in 2,879 healthy adults enrolled in the Framingham Offspring Study (1991-2001) by Cox proportional hazard models. After adjustment for standard risk factors, consumers of > or =9.0 drinks/week had a significantly lower risk of type 2 diabetes mellitus compared with abstainers (hazard ratio = 0.47, 95% confidence interval (CI): 0.27, 0.81). Adjustment for selected nutrients had little effect on the hazard ratio, whereas adjustment for dietary pattern variables by factor analysis significantly shifted the hazard ratio away from null (hazard ratio = 0.33, 95% CI: 0.17, 0.64) by 40.0% (95% CI: 16.8, 57.0; P = 0.002). Dietary pattern variables by partial least squares showed similar results. Therefore, the observed inverse association, consistent with past studies, was confounded by dietary patterns, and this confounding was not captured by individual nutrient adjustment. The data suggest that alcohol intake, not dietary patterns associated with alcohol intake, is responsible for the observed inverse association with type 2 diabetes mellitus risk.

Estimating the Effect of Targeted Screening Strategies: An Application to Colonoscopy and Colorectal Cancer.

PubMed

Thomas, Duncan C

2017-07-01

Screening behavior depends on previous screening history and family members' behaviors, which can act as both confounders and intermediate variables on a causal pathway from screening to disease risk. Conventional analyses that adjust for these variables can lead to incorrect inferences about the causal effect of screening if high-risk individuals are more likely to be screened. Analyzing the data in a manner that treats screening as randomized conditional on covariates allows causal parameters to be estimated; inverse probability weighting based on propensity of exposure scores is one such method considered here. I simulated family data under plausible models for the underlying disease process and for screening behavior to assess the performance of alternative methods of analysis and whether a targeted screening approach based on individuals' risk factors would lead to a greater reduction in cancer incidence in the population than a uniform screening policy. Simulation results indicate that there can be a substantial underestimation of the effect of screening on subsequent cancer risk when using conventional analysis approaches, which is avoided by using inverse probability weighting. A large case-control study of colonoscopy and colorectal cancer from Germany shows a strong protective effect of screening, but inverse probability weighting makes this effect even stronger. Targeted screening approaches based on either fixed risk factors or family history yield somewhat greater reductions in cancer incidence with fewer screens needed to prevent one cancer than population-wide approaches, but the differences may not be large enough to justify the additional effort required. See video abstract at, http://links.lww.com/EDE/B207.

Directed acyclic graphs (DAGs): an aid to assess confounding in dental research.

PubMed

Merchant, Anwar T; Pitiphat, Waranuch

2002-12-01

Confounding, a special type of bias, occurs when an extraneous factor is associated with the exposure and independently affects the outcome. In order to get an unbiased estimate of the exposure-outcome relationship, we need to identify potential confounders, collect information on them, design appropriate studies, and adjust for confounding in data analysis. However, it is not always clear which variables to collect information on and adjust for in the analyses. Inappropriate adjustment for confounding can even introduce bias where none existed. Directed acyclic graphs (DAGs) provide a method to select potential confounders and minimize bias in the design and analysis of epidemiological studies. DAGs have been used extensively in expert systems and robotics. Robins (1987) introduced the application of DAGs in epidemiology to overcome shortcomings of traditional methods to control for confounding, especially as they related to unmeasured confounding. DAGs provide a quick and visual way to assess confounding without making parametric assumptions. We introduce DAGs, starting with definitions and rules for basic manipulation, stressing more on applications than theory. We then demonstrate their application in the control of confounding through examples of observational and cross-sectional epidemiological studies.

Interference from related actions in spoken word production: Behavioural and fMRI evidence.

PubMed

de Zubicaray, Greig; Fraser, Douglas; Ramajoo, Kori; McMahon, Katie

2017-02-01

Few investigations of lexical access in spoken word production have investigated the cognitive and neural mechanisms involved in action naming. These are likely to be more complex than the mechanisms involved in object naming, due to the ways in which conceptual features of action words are represented. The present study employed a blocked cyclic naming paradigm to examine whether related action contexts elicit a semantic interference effect akin to that observed with categorically related objects. Participants named pictures of intransitive actions to avoid a confound with object processing. In Experiment 1, body-part related actions (e.g., running, walking, skating, hopping) were named significantly slower compared to unrelated actions (e.g., laughing, running, waving, hiding). Experiment 2 employed perfusion functional Magnetic Resonance Imaging (fMRI) to investigate the neural mechanisms involved in this semantic interference effect. Compared to unrelated actions, naming related actions elicited significant perfusion signal increases in frontotemporal cortex, including bilateral inferior frontal gyrus (IFG) and hippocampus, and decreases in bilateral posterior temporal, occipital and parietal cortices, including intraparietal sulcus (IPS). The findings demonstrate a role for temporoparietal cortex in conceptual-lexical processing of intransitive action knowledge during spoken word production, and support the proposed involvement of interference resolution and incremental learning mechanisms in the blocked cyclic naming paradigm. Copyright © 2017 Elsevier Ltd. All rights reserved.

An analysis of the impact of pre-analytical factors on the urine proteome: Sample processing time, temperature, and proteolysis.

PubMed

Hepburn, Sophie; Cairns, David A; Jackson, David; Craven, Rachel A; Riley, Beverley; Hutchinson, Michelle; Wood, Steven; Smith, Matthew Welberry; Thompson, Douglas; Banks, Rosamonde E

2015-06-01

We have examined the impact of sample processing time delay, temperature, and the addition of protease inhibitors (PIs) on the urinary proteome and peptidome, an important aspect of biomarker studies. Ten urine samples from patients with varying pathologies were each divided and PIs added to one-half, with aliquots of each then processed and frozen immediately, or after a delay of 6 h at 4°C or room temperature (20-22°C), effectively yielding 60 samples in total. Samples were then analyzed by 2D-PAGE, SELDI-TOF-MS, and immunoassay. Interindividual variability in profiles was the dominant feature in all analyses. Minimal changes were observed by 2D-PAGE as a result of delay in processing, temperature, or PIs and no changes were seen in IgG, albumin, β2 -microglobulin, or α1 -microglobulin measured by immunoassay. Analysis of peptides showed clustering of some samples by presence/absence of PIs but the extent was very patient-dependent with most samples showing minimal effects. The extent of processing-induced changes and the benefit of PI addition are patient- and sample-dependent. A consistent processing methodology is essential within a study to avoid any confounding of the results. © 2014 The Authors PROTEOMICS Clinical Applications Published by Wiley-VCH Verlag GmbH & Co. KGaA.

An analysis of the impact of pre‐analytical factors on the urine proteome: Sample processing time, temperature, and proteolysis

PubMed Central

Hepburn, Sophie; Cairns, David A.; Jackson, David; Craven, Rachel A.; Riley, Beverley; Hutchinson, Michelle; Wood, Steven; Smith, Matthew Welberry; Thompson, Douglas

2015-01-01

Purpose We have examined the impact of sample processing time delay, temperature, and the addition of protease inhibitors (PIs) on the urinary proteome and peptidome, an important aspect of biomarker studies. Experimental design Ten urine samples from patients with varying pathologies were each divided and PIs added to one‐half, with aliquots of each then processed and frozen immediately, or after a delay of 6 h at 4°C or room temperature (20–22°C), effectively yielding 60 samples in total. Samples were then analyzed by 2D‐PAGE, SELDI‐TOF‐MS, and immunoassay. Results Interindividual variability in profiles was the dominant feature in all analyses. Minimal changes were observed by 2D‐PAGE as a result of delay in processing, temperature, or PIs and no changes were seen in IgG, albumin, β2‐microglobulin, or α1‐microglobulin measured by immunoassay. Analysis of peptides showed clustering of some samples by presence/absence of PIs but the extent was very patient‐dependent with most samples showing minimal effects. Conclusions and clinical relevance The extent of processing‐induced changes and the benefit of PI addition are patient‐ and sample‐dependent. A consistent processing methodology is essential within a study to avoid any confounding of the results. PMID:25400092

Surrogate measures and consistent surrogates

PubMed Central

VanderWeele, Tyler J.

2014-01-01

Summary Surrogates which allow one to predict the effect of the treatment on the outcome of interest from the effect of the treatment on the surrogate are of importance when it is difficult or expensive to measure the primary outcome. Unfortunately, the use of such surrogates can give rise to paradoxical situations in which the effect of the treatment on the surrogate is positive, the surrogate and outcome are strongly positively correlated, but the effect of the treatment on the outcome is negative, a phenomenon sometimes referred to as the "surrogate paradox." New results are given for consistent surrogates that extend the existing literature on sufficient conditions that ensure the surrogate paradox is not manifest. Specifically, it is shown that for the surrogate paradox to beman.est it must be the case that either there is (i) a direct effect of treatment on the outcome not through the surrogate and in the opposite direction as that through the surrogate or (ii) confounding for the effect of the surrogate on the outcome, or (iii) a lack of transitivity so that treatment does not positively affect the surrogate for all the same individuals for which the surrogate positively affects the outcome. The conditions for consistent surrogates and the results of the paper are important because they allow investigators to predict the direction of the effect of the treatment on the outcome simply from the direction of the effect of the treatment on the surrogate. These results on consistent surrogates are then related to the four approaches to surrogate outcomes described by Joffe and Greene (2009, Biometrics 65, 530–538) to assess whether the standard criterion used by these approaches to assess whether a surrogate is "good" suffices to avoid the surrogate paradox. PMID:24073861

Clinical uses of brain natriuretic peptide in diagnosing and managing heart failure.

PubMed

Anderson, Kelley M

2008-06-01

To review current issues in the diagnosis, prognosis, and management of heart failure (HF), focusing on the clinical use of brain natriuretic peptide (BNP) as a diagnostic marker. Selective review of scientific literature and clinical practice guidelines. BNP is a useful clinical tool for the diagnosis, prognosis, and management of HF patients. Studies have consistently demonstrated high sensitivity, specificity, and negative predictive value of BNP levels in diagnostic situations. BNP cannot differentiate between systolic and diastolic HF. BNP can be used to assist in diagnosing HF in emergency and outpatient situations, particularly when the presenting symptom is dyspnea; determining HF prognosis, including predicting death and cardiac events; and potentially managing individuals with HF by determining safe discharge levels from acute care to avoid readmissions. BNP levels can vary depending on multiple confounders; therefore, clinical interpretation can be difficult.

Cardiac surgery report cards: comprehensive review and statistical critique.

PubMed

Shahian, D M; Normand, S L; Torchiana, D F; Lewis, S M; Pastore, J O; Kuntz, R E; Dreyer, P I

2001-12-01

Public report cards and confidential, collaborative peer education represent distinctly different approaches to cardiac surgery quality assessment and improvement. This review discusses the controversies regarding their methodology and relative effectiveness. Report cards have been the more commonly used approach, typically as a result of state legislation. They are based on the presumption that publication of outcomes effectively motivates providers, and that market forces will reward higher quality. Numerous studies have challenged the validity of these hypotheses. Furthermore, although states with report cards have reported significant decreases in risk-adjusted mortality, it is unclear whether this improvement resulted from public disclosure or, rather, from the development of internal quality programs by hospitals. An additional confounding factor is the nationwide decline in heart surgery mortality, including states without quality monitoring. Finally, report cards may engender negative behaviors such as high-risk case avoidance and "gaming" of the reporting system, especially if individual surgeon results are published. The alternative approach, continuous quality improvement, may provide an opportunity to enhance performance and reduce interprovider variability while avoiding the unintended negative consequences of report cards. This collaborative method, which uses exchange visits between programs and determination of best practice, has been highly effective in northern New England and in the Veterans Affairs Administration. However, despite their potential advantages, quality programs based solely on confidential continuous quality improvement do not address the issue of public accountability. For this reason, some states may continue to mandate report cards. In such instances, it is imperative that appropriate statistical techniques and report formats are used, and that professional organizations simultaneously implement continuous quality improvement programs. The statistical methodology underlying current report cards is flawed, and does not justify the degree of accuracy presented to the public. All existing risk-adjustment methods have substantial inherent imprecision, and this is compounded when the results of such patient-level models are aggregated and used inappropriately to assess provider performance. Specific problems include sample size differences, clustering of observations, multiple comparisons, and failure to account for the random component of interprovider variability. We advocate the use of hierarchical or multilevel statistical models to address these concerns, as well as report formats that emphasize the statistical uncertainty of the results.

Mismatch of Posttraumatic Stress Disorder (PTSD) Symptoms and DSM-IV Symptom Clusters in a Cancer Sample: Exploratory Factor Analysis of the PTSD Checklist-Civilian Version

PubMed Central

Shelby, Rebecca A.; Golden-Kreutz, Deanna M.; Andersen, Barbara L.

2007-01-01

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; American Psychiatric Association, 1994a) conceptualization of posttraumatic stress disorder (PTSD) includes three symptom clusters: reexperiencing, avoidance/numbing, and arousal. The PTSD Checklist-Civilian Version (PCL-C) corresponds to the DSM-IV PTSD symptoms. In the current study, we conducted exploratory factor analysis (EFA) of the PCL-C with two aims: (a) to examine whether the PCL-C evidenced the three-factor solution implied by the DSM-IV symptom clusters, and (b) to identify a factor solution for the PCL-C in a cancer sample. Women (N = 148) with Stage II or III breast cancer completed the PCL-C after completion of cancer treatment. We extracted two-, three-, four-, and five-factor solutions using EFA. Our data did not support the DSM-IV PTSD symptom clusters. Instead, EFA identified a four-factor solution including reexperiencing, avoidance, numbing, and arousal factors. Four symptom items, which may be confounded with illness and cancer treatment-related symptoms, exhibited poor factor loadings. Using these symptom items in cancer samples may lead to overdiagnosis of PTSD and inflated rates of PTSD symptoms. PMID:16281232

Data-Driven Significance Estimation for Precise Spike Correlation

PubMed Central

Grün, Sonja

2009-01-01

The mechanisms underlying neuronal coding and, in particular, the role of temporal spike coordination are hotly debated. However, this debate is often confounded by an implicit discussion about the use of appropriate analysis methods. To avoid incorrect interpretation of data, the analysis of simultaneous spike trains for precise spike correlation needs to be properly adjusted to the features of the experimental spike trains. In particular, nonstationarity of the firing of individual neurons in time or across trials, a spike train structure deviating from Poisson, or a co-occurrence of such features in parallel spike trains are potent generators of false positives. Problems can be avoided by including these features in the null hypothesis of the significance test. In this context, the use of surrogate data becomes increasingly important, because the complexity of the data typically prevents analytical solutions. This review provides an overview of the potential obstacles in the correlation analysis of parallel spike data and possible routes to overcome them. The discussion is illustrated at every stage of the argument by referring to a specific analysis tool (the Unitary Events method). The conclusions, however, are of a general nature and hold for other analysis techniques. Thorough testing and calibration of analysis tools and the impact of potentially erroneous preprocessing stages are emphasized. PMID:19129298

Use of an eight-arm radial water maze to assess working and reference memory following neonatal brain injury.

PubMed

Penley, Stephanie C; Gaudet, Cynthia M; Threlkeld, Steven W

2013-12-04

Working and reference memory are commonly assessed using the land based radial arm maze. However, this paradigm requires pretraining, food deprivation, and may introduce scent cue confounds. The eight-arm radial water maze is designed to evaluate reference and working memory performance simultaneously by requiring subjects to use extra-maze cues to locate escape platforms and remedies the limitations observed in land based radial arm maze designs. Specifically, subjects are required to avoid the arms previously used for escape during each testing day (working memory) as well as avoid the fixed arms, which never contain escape platforms (reference memory). Re-entries into arms that have already been used for escape during a testing session (and thus the escape platform has been removed) and re-entries into reference memory arms are indicative of working memory deficits. Alternatively, first entries into reference memory arms are indicative of reference memory deficits. We used this maze to compare performance of rats with neonatal brain injury and sham controls following induction of hypoxia-ischemia and show significant deficits in both working and reference memory after eleven days of testing. This protocol could be easily modified to examine many other models of learning impairment.

Recreational Drug Use and T Lymphocyte Subpopulations in HIV-uninfected and HIV-infected Men

PubMed Central

Chao, Chun; Jacobson, Lisa P; Tashkin, Donald; Martínez-Maza, Otoniel; Roth, Michael D; Margolick, Joseph B; Chmiel, Joan S; Rinaldo, Charles; Zhang, Zuo-Feng; Detels, Roger

2009-01-01

The effects of recreational drugs on CD4 and CD8 T cells in humans are not well understood. We conducted a longitudinal analysis of men who have sex with men (MSM) enrolled in the Multicenter AIDS Cohort Study to define associations between self-reported use of marijuana, cocaine, poppers and amphetamines, and CD4 and CD8 T cell parameters in both HIV-uninfected and HIV-infected MSM. For the HIV-infected MSM, we used clinical and laboratory data collected semiannually before 1996 to avoid potential effects of antiretroviral treatment. A regression model that allowed random intercepts and slopes as well as autoregressive covariance structure for within subject errors was used. Potential confounders adjusted for included length of follow-up, demographics, tobacco smoking, alcohol use, risky sexual behaviors, history of sexually transmitted infections, and antiviral therapy. We found no clinically meaningful associations between use of marijuana, cocaine, poppers, or amphetamines and CD4 and CD8 T cell counts, percentages, or rates of change in either HIV-uninfected or -infected men. The regression coefficients were of minimum magnitude despite some reaching statistical significance. No threshold effect was detected for frequent (at least weekly) or continuous substance use in the previous year. These results indicate that use of these substances does not adversely affect the numbers and percentages of circulating CD4 or CD8 T cells in either HIV-uninfected or -infected MSM. PMID:18180115

A new approach to hierarchical data analysis: Targeted maximum likelihood estimation for the causal effect of a cluster-level exposure.

PubMed

Balzer, Laura B; Zheng, Wenjing; van der Laan, Mark J; Petersen, Maya L

2018-01-01

We often seek to estimate the impact of an exposure naturally occurring or randomly assigned at the cluster-level. For example, the literature on neighborhood determinants of health continues to grow. Likewise, community randomized trials are applied to learn about real-world implementation, sustainability, and population effects of interventions with proven individual-level efficacy. In these settings, individual-level outcomes are correlated due to shared cluster-level factors, including the exposure, as well as social or biological interactions between individuals. To flexibly and efficiently estimate the effect of a cluster-level exposure, we present two targeted maximum likelihood estimators (TMLEs). The first TMLE is developed under a non-parametric causal model, which allows for arbitrary interactions between individuals within a cluster. These interactions include direct transmission of the outcome (i.e. contagion) and influence of one individual's covariates on another's outcome (i.e. covariate interference). The second TMLE is developed under a causal sub-model assuming the cluster-level and individual-specific covariates are sufficient to control for confounding. Simulations compare the alternative estimators and illustrate the potential gains from pairing individual-level risk factors and outcomes during estimation, while avoiding unwarranted assumptions. Our results suggest that estimation under the sub-model can result in bias and misleading inference in an observational setting. Incorporating working assumptions during estimation is more robust than assuming they hold in the underlying causal model. We illustrate our approach with an application to HIV prevention and treatment.

Breast-feeding reduces the risk for childhood eczema.

PubMed

Kull, Inger; Böhme, Maria; Wahlgren, Carl-Fredrik; Nordvall, Lennart; Pershagen, Göran; Wickman, Magnus

2005-09-01

The evidence for a preventive effect of breast-feeding on the development of eczema in childhood remains controversial. To investigate the effect of breast-feeding in various phenotypes of eczema to 4 years. A birth cohort of 4089 children made up the study base. Data on breast-feeding, allergic symptoms, and potential confounders were obtained from questionnaires when the children were 2 months and 1, 2, and 4 years old. At 4 years, blood specific IgE was analyzed. Children with symptoms of eczema and asthma during the period of breast-feeding were excluded in most analyses on risk assessment of eczema and asthma, respectively, to avoid disease-related modification of exposure. Exclusive breast-feeding for >or=4 months reduced the risk for eczema at the age of 4 years (odds ratio [OR], 0.78; 95% CI, 0.63--0.96) irrespective of combination with asthma, sensitization to common allergens, or parental allergic disease. This decreased risk was most evident for children with onset of eczema during the first 2 years persisting to 4 years (OR, 0.59; 95% CI, 0.45--0.77). Among children with early-onset eczema, irrespective of persistency, followed by late onset of asthma or early-onset asthma irrespective of persistency, followed by late-onset eczema to 4 years, a protective effect of breast-feeding was also seen (OR, 0.48; 95% CI, 0.30--0.76). Breast-feeding 4 months or more reduces the risk for eczema and onset of the allergy march to age 4.

Patent Ductus Arteriosus in the Preterm Infant: Diagnostic and Treatment Options.

PubMed

Prescott, Stephanie; Keim-Malpass, Jessica

2017-02-01

The incidence of hemodynamically significant patent ductus arteriosus (hsPDA) increases with decreasing gestational age and is associated with many common morbidities of extreme prematurity. Controversies remain surrounding the definition of hsPDA, the population of infants requiring treatment, the appropriate timing and method of treatment, and the outcomes associated with PDA and its therapies. This integrative literature review focuses on diagnostic and treatment recommendations derived from the highest levels of evidence. PubMed and CINAHL were searched using key words "neonatal" and "patent ductus arteriosus" to discover the highest levels of evidence surrounding diagnosis, treatment methods, and outcomes. The lack of consensus surrounding the diagnosis and clinical significance of PDA hinders meta-analysis across studies and confounds understanding of appropriate management strategies. Novel biomarkers, pharmaceutical choices, and transcatheter closure methods are expanding diagnostic and treatment options. Infants weighing less than 1000 g are at highest risk. Prophylactic closure is no longer recommended, although early asymptomatic therapy is still preferred by some to avoid prolonged pulmonary overcirculation or decreased renal and gut perfusion. Conservative treatment measures such as fluid restriction and diuretic administration have not consistently proven effective and are in some instances detrimental. Cyclooxygenase inhibitors are effective but have adverse renal and mesenteric effects. Oral ibuprofen is associated with lower instance of necrotizing enterocolitis. Well-defined staging criteria would aid in comparison and meta-analysis. Trials that include a control group that receives no therapy may help separate the outcomes associated with prematurity from those associated with PDA.

Emotional Numbness Modifies the Effect of End-of-Life Discussions on End-of-Life Care

PubMed Central

Maciejewski, Paul K.; Prigerson, Holly G.

2012-01-01

Context Overall, end-of-life (EOL) discussions are unrelated to psychological distress and associated with lower rates of aggressive care near death. Nevertheless, patients who report they feel emotionally numb about their illness might encounter difficulties cognitively processing an EOL discussion. Objectives We hypothesized that emotional numbness would modify the influence of EOL discussions on the receipt of less aggressive EOL care. Methods Data were derived from structured interviews with 290 participants in the federally-funded Coping with Cancer Study, a multisite, prospective cohort study of advanced cancer patients followed through their death. Patients’ reports of EOL discussions with their physician and emotional numbness were assessed a median of 4.6 months before death. Information about aggressive EOL care (i.e., ventilation, resuscitation in the last week of life, death in the Intensive Care Unit) was obtained from postmortem caregiver interviews and medical charts. Main and interactive effects of EOL discussions and emotional numbness on aggressive EOL care, adjusting for potential confounds, were evaluated using multiple logistic regression. Results The likelihood of aggressive EOL care associated with having EOL discussions increased by a factor of nine (adjusted odds ratio=9.02, 95% confidence interval 1.37, 59.6, P=0.022) for every unit increase in a patient’s emotional numbness score. Conclusion Emotional numbness diminishes a patient’s capacity to benefit from EOL discussions. EOL decision making may be more effective if clinical communications with emotionally numb patients are avoided. PMID:22926093

Effect of tuberculosis on the survival of HIV-infected men in a country with low TB incidence

PubMed Central

López-Gatell, H; Cole, SR; Margolick, JB; Witt, MD; Martinson, J; Phair, JP; Jacobson, LP

2010-01-01

Evidence regarding the effect of tuberculosis disease (TB) on HIV disease progression at the population level remains inconclusive. We estimated the effect of incident TB on time to acquired immunodeficiency syndrome (AIDS)-related death, using a marginal structural Cox model. Between 1984 and 2005, 2,882 HIV-infected men in the Multicenter AIDS Cohort Study contributed 21,914 person-years while followed for a median of 5.4 years. At study entry, the median CD4 cell count and HIV-1 RNA viral load were 533 cells/mm3 (interquartile range [IQR], 365 – 737) and 12,953 copies/ml (IQR, 2,453 – 48,540), respectively. This study was performed in a setting with a modest exposure to HAART; 8,295 of 23,801 (35%) person-years were followed during the HAART era. Fifteen men incurred incident TB, yielding a TB incidence of 7 (95% confidence interval [CI]: 4, 14) per 10,000 person-years, and 1,072 died of AIDS-related causes. Accounting for potential confounders, including CD4 cell count and viral load, the hazard of AIDS-related death was 2.4 times larger for the person-time with TB, compared to the person-time without TB (95% CI: 1.2, 4.7). Results underscore the importance of avoiding TB by using preventive interventions, such as treatment of latent TB infection, particularly in populations with a large prevalence of HIV/TB co-infected individuals. PMID:18753866

Probabilistic bias analysis in pharmacoepidemiology and comparative effectiveness research: a systematic review.

PubMed

Hunnicutt, Jacob N; Ulbricht, Christine M; Chrysanthopoulou, Stavroula A; Lapane, Kate L

2016-12-01

We systematically reviewed pharmacoepidemiologic and comparative effectiveness studies that use probabilistic bias analysis to quantify the effects of systematic error including confounding, misclassification, and selection bias on study results. We found articles published between 2010 and October 2015 through a citation search using Web of Science and Google Scholar and a keyword search using PubMed and Scopus. Eligibility of studies was assessed by one reviewer. Three reviewers independently abstracted data from eligible studies. Fifteen studies used probabilistic bias analysis and were eligible for data abstraction-nine simulated an unmeasured confounder and six simulated misclassification. The majority of studies simulating an unmeasured confounder did not specify the range of plausible estimates for the bias parameters. Studies simulating misclassification were in general clearer when reporting the plausible distribution of bias parameters. Regardless of the bias simulated, the probability distributions assigned to bias parameters, number of simulated iterations, sensitivity analyses, and diagnostics were not discussed in the majority of studies. Despite the prevalence and concern of bias in pharmacoepidemiologic and comparative effectiveness studies, probabilistic bias analysis to quantitatively model the effect of bias was not widely used. The quality of reporting and use of this technique varied and was often unclear. Further discussion and dissemination of the technique are warranted. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Drug safety analyses in a rheumatoid arthritis registry: application of different approaches regarding timing of exposure and confounder measurement.

PubMed

Solomon, Daniel H; Shadick, Nancy A; Weinblatt, Michael E; Zak, Agnes; Frits, Michelle; Franklin, Jessica M

2017-06-13

Patient registry data serves an increasing role in drug safety and comparative effectiveness research, but registry databases often do not contain confounder information measured at the same time that treatments begin. This study evaluated a set of approaches for estimating confounder values at treatment initiation using actual data from a rheumatoid arthritis (RA) registry to examine the risk of infection associated with different biologic DMARDs (bDMARDs). We examined the risk of infection associated with starting a TNF inhibitor (TNFi) versus any of the other non-TNFi bDMARDs. Different confounder assessment approaches were tested. All approaches were tested in Cox proportional hazard regression models that used a propensity score (PS). The confounder of interest was the disease activity score (DAS28-CRP). The confounder assessment approaches utilized different temporal relationships between the DAS28-CRP measurement and the start of the treatments of interest. We included 219 subjects with RA with 269 initiations of either a TNFi or a different bDMARD or both. Among this group, 305 infections were reported and confirmed through chart review. The hazard ratio (HR) for the risk of infection associated with use of a non-TNFi bDMARD ranged from 1.17 to 3.03 using 13 different approaches; only the approach with the highest HR produced results significantly different than one, but this approach included the fewest subjects and infections. The relative risk of infection for TNFi and other non-TNFi bDMARDs was similar using various approaches regarding which DAS28-CRP score should be used as the baseline measure in adjusted analyses.

The psychological costs and benefits of being highly persistent: personality profiles distinguish mood disorders from anxiety disorders.

PubMed

Cloninger, C Robert; Zohar, Ada H; Hirschmann, Schmuel; Dahan, Dana

2012-02-01

The personality trait of Persistence is highly valued by conscientious overachievers, but it has both psychological costs and benefits. The interactions among multiple personality factors influencing the development of mood and anxiety disorders have been confounded in prior clinical samples, but can be disentangled in terms of their underlying brain circuitry and influence on perception of emotional stimuli. 285 individuals who represented the full range of personality variation in a large sample of adult volunteers from the general community of Israel were selected for follow-up by psychiatric interviews, cognitive testing, and medical examinations. The Temperament and Character Inventory (TCI) measured profiles of traits that distinguished individuals with diagnoses of mood and/or anxiety disorders using linear discriminant analysis and non-linear profile analysis. High Harm Avoidance and low Self-directedness strongly distinguished people with mood and/or anxiety disorders from those with neither. High Persistence distinguished people with only anxiety disorders from those with mood disorders. High Persistence was associated with greater health and happiness overall, but also led to more negative emotions than in people with low Persistence unless they were both unusually tolerant of frustration (i.e., low in Harm Avoidance) and self-accepting of personal limitations (i.e. high in Self-directedness). Subjects were volunteers over 40 years of age at assessment. People who are highly persistent (i.e., persevering, ambitious, perfectionistic) are more likely to have anxiety disorders than mood disorders, even when they have other traits increasing risk for both (i.e., high Harm Avoidance and low Self-directedness). High Persistence increases both positive and negative emotions in most people. However, high Persistence reduces negative emotions and increases positive emotions if a person is easy-going (i.e., "happy-go-lucky" when low in both Harm Avoidance and Self-directedness). Copyright © 2011 Elsevier B.V. All rights reserved.

Lesser prairie-chicken avoidance of trees in a grassland landscape

USGS Publications Warehouse

Lautenbach, Joseph M.; Plumb, Reid T.; Robinson, Samantha G.; Hagen, Christian A.; Haukos, David A.; Pitman, James C.

2016-01-01

Grasslands are among the most imperiled ecosystems in North America. Reasons that grasslands are threatened include conversion to row-crop agriculture, fragmentation, and changes in fire regimes. The reduction of fire processes in remaining prairies has resulted in tree encroachment and establishment in grasslands, further reducing grassland quantity and quality. Grassland birds have been experiencing precipitous population declines in recent decades, commensurate with landscape changes to grasslands. The lesser prairie-chicken (Tympanuchus pallidicinctus Ridgway) is a declining species of prairie grouse of conservation concern. We used second- and third-order habitat selection metrics to test if female lesser prairie-chickens avoid grasslands where trees were present. Our results indicated that female lesser prairie-chickens selected habitats avoiding the nearest trees by 283 m on average, nearly twice as far as would be expected at random. Lesser prairie-chickens were 40 times more likely to use habitats with tree densities of 0 trees ∙ ha− 1 than habitats with 5 trees ∙ ha− 1. Probability of use indicated that lesser prairie-chickens were 19 times more likely to use habitats 1000 m from the nearest tree when compared with using habitats 0 m from the nearest tree. Nest survival was not affected at densities < 2 trees ∙ ha− 1; however, we could not test if nest survival was affected at greater tree densities as no nests were detected at densities > 2 trees ∙ ha− 1. Avoidance of trees could be due to perceived increased predation risk, reduced habitat quality, or a combination of these potentially confounding factors. Preventing further establishment and expansion of trees in landscapes occupied by lesser prairie-chickens could contribute to the continued persistence of the species. Additionally, restoring grasslands through tree removal may facilitate conservation efforts for grassland species such as the lesser prairie-chicken by improving habitat quality and promoting expansion of occupied range.

The Effects of Constraints and Mastery on Mental and Physical Health: Conceptual and Methodological Considerations

PubMed Central

Infurna, Frank J.; Mayer, Axel

2015-01-01

Perceived control and health are closely interrelated in adulthood and old age. However, less is known regarding the differential implications of two facets of perceived control, constraints and mastery, for mental and physical health. Furthermore, a limitation of previous research testing the pathways linking perceived control to mental and physical health is that mediation was tested with cross-sectional designs and not in a longitudinal mediation design that accounts for temporal ordering and prior confounds. Using data from the Health and Retirement Study (HRS; n = 7,612, M age = 68, SD = 10.66; 59% women) we examined the effect of constraints and mastery on 4-year changes in mental and physical health and whether physical activity mediated such effects in a longitudinal mediation design. Using confirmatory factor analysis, we modeled the two-factor structure of perceived control that consisted of constraints and mastery. In our longitudinal mediation model, where we accounted for possible confounders (e.g., age, gender, education, neuroticism, conscientiousness, memory, and health conditions), constraints showed a stronger total effect on mental and physical health, than mastery, such that more constraints were associated with 4-year declines in mental and physical health. Physical activity did not mediate the effect of constraints and mastery on mental and physical health (indirect effect). In order to demonstrate the importance of a longitudinal mediation model that accounts for confounders, we also estimated the mediated effect using two models commonly used in the literature: cross-sectional mediation model and longitudinal mediation model without accounting for confounders. These mediation models indicated a spurious indirect effect that cannot be causally interpreted. Our results showcase that constraints and mastery have differential implications for mental and physical health, as well as how a longitudinal mediation design can illustrate (or not) pathways in developmental processes. Our discussion focuses on the conceptual and methodological implications of a two facet model of perceived control and the strengths of longitudinal mediation designs for testing conceptual models of human development. PMID:25938243

The effects of constraints and mastery on mental and physical health: Conceptual and methodological considerations.

PubMed

Infurna, Frank J; Mayer, Axel

2015-06-01

Perceived control and health are closely interrelated in adulthood and old age. However, less is known regarding the differential implications of 2 facets of perceived control, constraints and mastery, for mental and physical health. Furthermore, a limitation of previous research testing the pathways linking perceived control to mental and physical health is that mediation was tested with cross-sectional designs and not in a longitudinal mediation design that accounts for temporal ordering and prior confounds. Using data from the Health and Retirement Study (HRS; n = 7,612, M age = 68, SD = 10.66; 59% women) we examined the effect of constraints and mastery on 4-year changes in mental and physical health and whether physical activity mediated such effects in a longitudinal mediation design. Using confirmatory factor analysis, we modeled the 2-factor structure of perceived control that consisted of constraints and mastery. In our longitudinal mediation model, where we accounted for possible confounders (e.g., age, gender, education, neuroticism, conscientiousness, memory, and health conditions), constraints showed a stronger total effect on mental and physical health, than mastery, such that more constraints were associated with 4-year declines in mental and physical health. Physical activity did not mediate the effect of constraints and mastery on mental and physical health (indirect effect). To demonstrate the importance of a longitudinal mediation model that accounts for confounders, we also estimated the mediated effect using 2 models commonly used in the literature: cross-sectional mediation model and longitudinal mediation model without accounting for confounders. These mediation models indicated a spurious indirect effect that cannot be causally interpreted. Our results showcase that constraints and mastery have differential implications for mental and physical health, as well as how a longitudinal mediation design can illustrate (or not) pathways in developmental processes. Our discussion focuses on the conceptual and methodological implications of a 2 facet model of perceived control and the strengths of longitudinal mediation designs for testing conceptual models of human development. (c) 2015 APA, all rights reserved.

Molecular reclassification of Crohn's disease: a cautionary note on population stratification.

PubMed

Maus, Bärbel; Jung, Camille; Mahachie John, Jestinah M; Hugot, Jean-Pierre; Génin, Emmanuelle; Van Steen, Kristel

2013-01-01

Complex human diseases commonly differ in their phenotypic characteristics, e.g., Crohn's disease (CD) patients are heterogeneous with regard to disease location and disease extent. The genetic susceptibility to Crohn's disease is widely acknowledged and has been demonstrated by identification of over 100 CD associated genetic loci. However, relating CD subphenotypes to disease susceptible loci has proven to be a difficult task. In this paper we discuss the use of cluster analysis on genetic markers to identify genetic-based subgroups while taking into account possible confounding by population stratification. We show that it is highly relevant to consider the confounding nature of population stratification in order to avoid that detected clusters are strongly related to population groups instead of disease-specific groups. Therefore, we explain the use of principal components to correct for population stratification while clustering affected individuals into genetic-based subgroups. The principal components are obtained using 30 ancestry informative markers (AIM), and the first two PCs are determined to discriminate between continental origins of the affected individuals. Genotypes on 51 CD associated single nucleotide polymorphisms (SNPs) are used to perform latent class analysis, hierarchical and Partitioning Around Medoids (PAM) cluster analysis within a sample of affected individuals with and without the use of principal components to adjust for population stratification. It is seen that without correction for population stratification clusters seem to be influenced by population stratification while with correction clusters are unrelated to continental origin of individuals.

Molecular Reclassification of Crohn’s Disease: A Cautionary Note on Population Stratification

PubMed Central

Maus, Bärbel; Jung, Camille; Mahachie John, Jestinah M.; Hugot, Jean-Pierre; Génin, Emmanuelle; Van Steen, Kristel

2013-01-01

Complex human diseases commonly differ in their phenotypic characteristics, e.g., Crohn’s disease (CD) patients are heterogeneous with regard to disease location and disease extent. The genetic susceptibility to Crohn’s disease is widely acknowledged and has been demonstrated by identification of over 100 CD associated genetic loci. However, relating CD subphenotypes to disease susceptible loci has proven to be a difficult task. In this paper we discuss the use of cluster analysis on genetic markers to identify genetic-based subgroups while taking into account possible confounding by population stratification. We show that it is highly relevant to consider the confounding nature of population stratification in order to avoid that detected clusters are strongly related to population groups instead of disease-specific groups. Therefore, we explain the use of principal components to correct for population stratification while clustering affected individuals into genetic-based subgroups. The principal components are obtained using 30 ancestry informative markers (AIM), and the first two PCs are determined to discriminate between continental origins of the affected individuals. Genotypes on 51 CD associated single nucleotide polymorphisms (SNPs) are used to perform latent class analysis, hierarchical and Partitioning Around Medoids (PAM) cluster analysis within a sample of affected individuals with and without the use of principal components to adjust for population stratification. It is seen that without correction for population stratification clusters seem to be influenced by population stratification while with correction clusters are unrelated to continental origin of individuals. PMID:24147066

Relative preservation of the recognition of positive facial expression "happiness" in Alzheimer disease.

PubMed

Maki, Yohko; Yoshida, Hiroshi; Yamaguchi, Tomoharu; Yamaguchi, Haruyasu

2013-01-01

Positivity recognition bias has been reported for facial expression as well as memory and visual stimuli in aged individuals, whereas emotional facial recognition in Alzheimer disease (AD) patients is controversial, with possible involvement of confounding factors such as deficits in spatial processing of non-emotional facial features and in verbal processing to express emotions. Thus, we examined whether recognition of positive facial expressions was preserved in AD patients, by adapting a new method that eliminated the influences of these confounding factors. Sensitivity of six basic facial expressions (happiness, sadness, surprise, anger, disgust, and fear) was evaluated in 12 outpatients with mild AD, 17 aged normal controls (ANC), and 25 young normal controls (YNC). To eliminate the factors related to non-emotional facial features, averaged faces were prepared as stimuli. To eliminate the factors related to verbal processing, the participants were required to match the images of stimulus and answer, avoiding the use of verbal labels. In recognition of happiness, there was no difference in sensitivity between YNC and ANC, and between ANC and AD patients. AD patients were less sensitive than ANC in recognition of sadness, surprise, and anger. ANC were less sensitive than YNC in recognition of surprise, anger, and disgust. Within the AD patient group, sensitivity of happiness was significantly higher than those of the other five expressions. In AD patient, recognition of happiness was relatively preserved; recognition of happiness was most sensitive and was preserved against the influences of age and disease.

Appraisal of neurobehavioral methods in environmental health research: the developing brain as a target for neurotoxic chemicals.

PubMed

Winneke, Gerhard

2007-10-01

Psychological tests as developed and validated in the field of differential psychology have a longstanding tradition as tools to study individual differences. In clinical neuropsychology, global or more specific tests are used as neuropsychological tools in the differential diagnosis of various forms of brain damage or neurobehavioral dysfunction following chemical insults, such as mental sequelae of prenatal alcohol consumption by pregnant mothers (fetal alcohol syndrome) or of maternal thyroid deficiency during pregnancy. Psychometric tests are constructed to fulfill basic quality criteria, namely objectivity, reliability and validity. For strictly diagnostic purposes in individual cases they must also possess normative values based on representative reference groups. Intelligence tests or their developmental variants are often used as endpoints in environmental health research for studying neurodevelopmental adversity due to early exposure to neurotoxic chemicals in the environment. Intelligence as treated in psychology is a complex construct made up of specific cognitive functions which usually cover verbal, numerical and spatial skills, as well as perceptual speed, memory and reasoning. In this paper, case studies covering neurodevelopmental adversity of inorganic lead, of methylmercury and of polychlorinated biphenyls (PCBs) are reviewed, and the issue of postnatal behavioral sequelae of prenatal exposure is covered. In such observational studies precautions must be taken in order to avoid pitfalls of causative interpretation of associations between exposure and neurobehavioral outcome. This requires consideration of co-exposure and confounding. Important confounders considered in most modern developmental cohort studies are maternal intelligence and quality of the home environment.

Neurophysiological mechanism of possibly confounding peripheral activation of the facial nerve during corticobulbar tract monitoring.

PubMed

Téllez, Maria J; Ulkatan, Sedat; Urriza, Javier; Arranz-Arranz, Beatriz; Deletis, Vedran

2016-02-01

To improve the recognition and possibly prevent confounding peripheral activation of the facial nerve caused by leaking transcranial electrical stimulation (TES) current during corticobulbar tract monitoring. We applied a single stimulus and a short train of electrical stimuli directly to the extracranial portion of the facial nerve. We compared the peripherally elicited compound muscle action potential (CMAP) of the facial nerve with the responses elicited by TES during intraoperative monitoring of the corticobulbar tract. A single stimulus applied directly to the facial nerve at subthreshold intensities did not evoke a CMAP, whereas short trains of subthreshold stimuli repeatedly evoked CMAPs. This is due to the phenomenon of sub- or near-threshold super excitability of the cranial nerve. Therefore, the facial responses evoked by short trains TES, when the leaked current reaches the facial nerve at sub- or near-threshold intensity, could lead to false interpretation. Our results revealed a potential pitfall in the current methodology for facial corticobulbar tract monitoring that is due to the activation of the facial nerve by subthreshold trains of stimuli. This study proposes a new criterion to exclude peripheral activation during corticobulbar tract monitoring. The failure to recognize and avoid facial nerve activation due to leaking current in the peripheral portion of the facial nerve during TES decreases the reliability of corticobulbar tract monitoring by increasing the possibility of false interpretation. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Ocular side effects following intravitreal injection therapy for retinoblastoma: a systematic review.

PubMed

Smith, Stephen J; Smith, Brian D; Mohney, Brian G

2014-03-01

To describe the ocular side effects in patients receiving intravitreal injection therapy (IViT) for retinoblastoma. PubMed (1946-present), Scopus (all years), Science Citation Index (1900-present) and Conference Proceedings Citation Index-Science (1990-present) electronic databases were searched to identify all published reports of therapeutic intravitreal injections for retinoblastoma in humans. Ten studies with original IViT ocular side effect data were included in this systematic review. In these combined reports, a total of 1287 intravitreal injections were given to 306 eyes of 295 patients, with a mean follow-up of 74.1 months. Two hundred sixty-one (88.5%) patients received comparatively standard melphalan IViT doses (8-30 mcg). Ocular side effects occurred in 38 patients (17 significant, 21 minor). The proportion of patients experiencing potentially significant ocular side effects following standard melphalan IViT regimens was 0.031 (8/261; 95% CI 0.013 to 0.06). The side effects of these eight included iris atrophy in three, two each with chorioretinal atrophy and vitreous haemorrhage and one with retinal detachment. Of the other nine patients with significant complications, five experienced sight-threatening complications following dramatic dose escalations (four with melphalan, one with thiotepa), three experienced complications that are commonly associated with concurrent therapies given to these patients and one had a retinal detachment. Of the 61 patients receiving IViT via safety-enhancing injection techniques, all six significant side effects were either attributed to the therapeutic dose or confounded by concurrent treatments. Significant ocular complications following IViT for retinoblastoma are uncommon, and this risk may be reduced further by the use of careful injection technique and standard dosing regimens. Care must be taken in the dosing of intravitreal treatments to avoid potentially irreversible vision loss.

Evaluation of the effects of plant-derived essential oils on central nervous system function using discrete shuttle-type conditioned avoidance response in mice.

PubMed

Umezu, Toyoshi

2012-06-01

Although plant-derived essential oils (EOs) have been used to treat various mental disorders, their central nervous system (CNS) acting effects have not been clarified. The present study compared the effects of 20 kinds of EOs with the effects of already-known CNS acting drugs to examine whether the EOs exhibited CNS stimulant-like effects, CNS depressant-like effects, or neither. All agents were tested using a discrete shuttle-type conditioned avoidance task in mice. Essential oils of peppermint and chamomile exhibited CNS stimulant-like effects; that is, they increased the response rate (number of shuttlings/min) of the avoidance response. Linden also increased the response rate, however, the effect was not dose-dependent. In contrast, EOs of orange, grapefruit, and cypress exhibited CNS depressant-like effects; that is, they decreased the response rate of the avoidance response. Essential oils of eucalyptus and rose decreased the avoidance rate (number of avoidance responses/number of avoidance trials) without affecting the response rate, indicating that they may exhibit some CNS acting effects. Essential oils of 12 other plants, including juniper, patchouli, geranium, jasmine, clary sage, neroli, lavender, lemon, ylang-ylang, niaouli, vetivert and frankincense had no effect on the avoidance response in mice. Copyright © 2011 John Wiley & Sons, Ltd.

A propensity scoring approach to characterizing the effects of maternal smoking during pregnancy on offspring's initial responses to cigarettes and alcohol

PubMed Central

Bidwell, L. Cinnamon; Palmer, Rohan H.C.; Brick, Leslie; Madden, Pamela A.F.; Heath, Andrew C.; Knopik, Valerie S.

2016-01-01

When examining the effects of prenatal exposure to maternal smoking during pregnancy (MSDP) on later offspring substance use, it is critical to consider familial environments confounded with MSDP. The purpose of this study was to examine the effect of MSDP on offspring's initial reactions to cigarettes and alcohol, which are indicators of future substance-use related problems. We tested these effects using two propensity score approaches (1) by controlling for confounding using the MSDP propensity score and 2) examining effects of MSDP across the MSDP risk distribution by grouping individuals into quantiles based on their MSDP propensity score. This study used data from 829 unrelated mothers with a reported lifetime history of smoking to determine the propensity for smoking only during their first trimester (MSDP-E) or throughout their entire pregnancy (MSDP-T). Propensity score analyses focused on the offspring (N=1616 female twins) of a large subset of these mothers. We examined the effects of levels of MSDP-E/T on offspring initial reactions to their first experiences with alcohol and cigarettes, across the distribution of liability for MSDP-E/T. MSDP-E/T emerged as significant predictors of offspring reactions to alcohol and cigarettes, but the effects were confounded by the familial liability for MSDP. Further, the unique MSDP effects that emerged were not uniform across the MSDP familial risk distribution. Our findings underscore the importance of properly accounting for correlated familial risk factors when examining the effects of MSDP on substance related outcomes. PMID:27098899

WHAT TO DO IF THERE IS NO REFERENCE SYSTEM

EPA Science Inventory

Efficient management and regulation of anthropogenic point source inputs requires a demonstrated and measurable ecological effect. In all ecosystems, the evaluation of anthropogenic effects is confounded by the effects of naturally existing environmental factors and river nonpoin...

Hepatic fat quantification: a prospective comparison of magnetic resonance spectroscopy and analysis methods for chemical-shift gradient echo magnetic resonance imaging with histologic assessment as the reference standard.

PubMed

Kang, Bo-Kyeong; Yu, Eun Sil; Lee, Seung Soo; Lee, Youngjoo; Kim, Namkug; Sirlin, Claude B; Cho, Eun Yoon; Yeom, Suk Keu; Byun, Jae Ho; Park, Seong Ho; Lee, Moon-Gyu

2012-06-01

The aims of this study were to assess the confounding effects of hepatic iron deposition, inflammation, and fibrosis on hepatic steatosis (HS) evaluation by magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) and to assess the accuracies of MRI and MRS for HS evaluation, using histology as the reference standard. In this institutional review board-approved prospective study, 56 patients gave informed consents and underwent chemical-shift MRI and MRS of the liver on a 1.5-T magnetic resonance scanner. To estimate MRI fat fraction (FF), 4 analysis methods were used (dual-echo, triple-echo, multiecho, and multi-interference), and MRS FF was calculated with T2 correction. Degrees of HS, iron deposition, inflammation, and fibrosis were analyzed in liver resection (n = 37) and biopsy (n = 19) specimens. The confounding effects of histology on fat quantification were assessed by multiple linear regression analysis. Using the histologic degree of HS as the reference standard, the accuracies of each method in estimating HS and diagnosing an HS of 5% or greater were determined by linear regression and receiver operating characteristic analyses. Iron deposition significantly confounded estimations of FF by the dual-echo (P < 0.001) and triple-echo (P = 0.033) methods, whereas no histologic feature confounded the multiecho and multi-interference methods or MRS. The MRS (r = 0.95) showed the strongest correlation with histologic degree of HS, followed by the multiecho (r = 0.92), multi-interference (r = 0.91), triple-echo (r = 0.90), and dual-echo (r = 0.85) methods. For diagnosing HS, the areas under the curve tended to be higher for MRS (0.96) and the multiecho (0.95), multi-interference (0.95), and triple-echo (0.95) methods than for the dual-echo method (0.88) (P ≥ 0.13). The multiecho and multi-interference MRI methods and MRS can accurately quantify hepatic fat, with coexisting histologic abnormalities having no confounding effects.

Title: Studies on drug switchability showed heterogeneity in methodological approaches: a scoping review.

PubMed

Belleudi, Valeria; Trotta, Francesco; Vecchi, Simona; Amato, Laura; Addis, Antonio; Davoli, Marina

2018-05-16

Several drugs share the same therapeutic indication, including those undergoing patent expiration. Concerns on the interchangeability are frequent in clinical practice, challenging the evaluation of switchability through observational research. To conduct a scoping review of observational studies on drug switchability to identify methodological strategies adopted to deal with bias and confounding. We searched PubMed, EMBASE, and Web of Science (updated 1/31/2017) to identify studies evaluating switchability in terms of effectiveness/safety outcomes or compliance. Three reviewers independently screened studies extracting all characteristics. Strategies to address confounding, particularly, previous drug use and switching reasons were considered. All findings were summarized in descriptive analyses. Thirty-two studies, published in the last 10 years, met the inclusion criteria. Epilepsy, cardiovascular and rheumatology were the most frequently represented clinical areas. 75% of the studies reported data on effectiveness/safety outcomes. The most frequent study design was cohort (65.6%) followed by case-control (21.9%) and self-controlled (12.5%). Case-control and case-crossover studies showed homogeneous methodological strategies to deal with bias and confounding. Among cohort studies, the confounding associated with previous drug use was addressed introducing variables in multivariate model (47.3%) or selecting only adherent patients (14.3%). Around 30% of cohort studies did not report reasons for switching. In the remaining 70%, clinical parameters or previous occurrence of outcomes were measured to identify switching connected with lack of effectiveness or adverse events. This study represents a starting point for researchers and administrators who are approaching the investigation and assessment of issues related to interchangeability of drugs. Copyright © 2018. Published by Elsevier Inc.

A comparison of propensity score-based approaches to health service evaluation: a case study of a preoperative physician-led clinic for high-risk surgical patients.

PubMed

Pham, Clarabelle T; Gibb, Catherine L; Mittinty, Murthy N; Fitridge, Robert A; Marshall, Villis R; Karnon, Jonathan D

2016-10-01

A physician-led clinic for the preoperative optimization and management of high-risk surgical patients was implemented in a South Australian public hospital in 2008. This study aimed to estimate the costs and effects of the clinic using a mixed retrospective and prospective observational study design. Alternative propensity score estimation methods were applied to retrospective routinely collected administrative and clinical data, using weighted and matched cohorts. Supplementary survey-based prospective data were collected to inform the analysis of the retrospective data and reduce potential unmeasured confounding. Using weighted cohorts, clinic patients had a significantly longer mean length of stay and higher mean cost. With the matched cohorts, reducing the calliper width resulted in a shorter mean length of stay in the clinic group, but the costs remained significantly higher. The prospective data indicated potential unmeasured confounding in all analyses other than in the most tightly matched cohorts. The application of alternative propensity-based approaches to a large sample of retrospective data, supplemented with a smaller sample of prospective data, informed a pragmatic approach to reducing potential observed and unmeasured confounding in an evaluation of a physician-led preoperative clinic. The need to generate tightly matched cohorts to reduce the potential for unmeasured confounding indicates that significant uncertainty remains around the effects of the clinic. This study illustrates the value of mixed retrospective and prospective observational study designs but also underlines the need to prospectively plan for the evaluation of costs and effects alongside the implementation of significant service innovations. © 2016 John Wiley & Sons, Ltd.

Influence of GSTM1 and GSTT1 genotypes and confounding factors on the frequency of sister chromatid exchange and micronucleus among road construction workers.

PubMed

Kumar, Anil; Yadav, Anita; Giri, Shiv Kumar; Dev, Kapil; Gautam, Sanjeev Kumar; Gupta, Ranjan; Aggarwal, Neeraj

2011-07-01

In the present study, we have investigated the influence of polymorphism of GSTM1 and GSTT1 genes and confounding factors such as age, sex, exposure duration and consumption habits on cytogenetic biomarkers. Frequency of sister chromatid exchanges (SCEs), high frequency cell (HFC) and cytokinesis blocked micronuclei (CBMN) were evaluated in peripheral blood lymphocytes of 115 occupationally exposed road construction workers and 105 unexposed individuals. The distribution of null and positive genotypes of glutathione-S transferase gene was evaluated by multiplex PCR among control and exposed subjects. An increased frequency of CBMN (7.03±2.08); SCE (6.95±1.76) and HFC (6.28±1.69) were found in exposed subjects when compared to referent (CBMN - 3.35±1.10; SCE - 4.13±1.30 and HFC - 3.98±1.56). These results were found statistically significant at p<0.05. When the effect of confounding factors on the frequency of studied biomarkers was evaluated, a strong positive interaction was found. The individuals having GSTM1 and GSTT1 null genotypes had higher frequency of CBMN, SCE and HFC. The association between GSTM1 and GSTT1 genotypes and studied biomarkers was found statistically significant at p<0.05. Our findings suggest that individuals having null type of GST are more susceptible to cytogenetic damage by occupational exposure regardless of confounding factors. There is a significant effect of polymorphism of these genes on cytogenetic biomarkers which are considered as early effects of genotoxic carcinogens. Copyright © 2011 Elsevier Ltd. All rights reserved.

Improving observational study estimates of treatment effects using joint modeling of selection effects and outcomes: the case of AAA repair.

PubMed

O'Malley, A James; Cotterill, Philip; Schermerhorn, Marc L; Landon, Bruce E

2011-12-01

When 2 treatment approaches are available, there are likely to be unmeasured confounders that influence choice of procedure, which complicates estimation of the causal effect of treatment on outcomes using observational data. To estimate the effect of endovascular (endo) versus open surgical (open) repair, including possible modification by institutional volume, on survival after treatment for abdominal aortic aneurysm, accounting for observed and unobserved confounding variables. Observational study of data from the Medicare program using a joint model of treatment selection and survival given treatment to estimate the effects of type of surgery and institutional volume on survival. We studied 61,414 eligible repairs of intact abdominal aortic aneurysms during 2001 to 2004. The outcome, perioperative death, is defined as in-hospital death or death within 30 days of operation. The key predictors are use of endo, transformed endo and open volume, and endo-volume interactions. There is strong evidence of nonrandom selection of treatment with potential confounding variables including institutional volume and procedure date, variables not typically adjusted for in clinical trials. The best fitting model included heterogeneous transformations of endo volume for endo cases and open volume for open cases as predictors. Consistent with our hypothesis, accounting for unmeasured selection reduced the mortality benefit of endo. The effect of endo versus open surgery varies nonlinearly with endo and open volume. Accounting for institutional experience and unmeasured selection enables better decision-making by physicians making treatment referrals, investigators evaluating treatments, and policy makers.

Effects of optimism on creativity under approach and avoidance motivation

PubMed Central

Icekson, Tamar; Roskes, Marieke; Moran, Simone

2014-01-01

Focusing on avoiding failure or negative outcomes (avoidance motivation) can undermine creativity, due to cognitive (e.g., threat appraisals), affective (e.g., anxiety), and volitional processes (e.g., low intrinsic motivation). This can be problematic for people who are avoidance motivated by nature and in situations in which threats or potential losses are salient. Here, we review the relation between avoidance motivation and creativity, and the processes underlying this relation. We highlight the role of optimism as a potential remedy for the creativity undermining effects of avoidance motivation, due to its impact on the underlying processes. Optimism, expecting to succeed in achieving success or avoiding failure, may reduce negative effects of avoidance motivation, as it eases threat appraisals, anxiety, and disengagement—barriers playing a key role in undermining creativity. People experience these barriers more under avoidance than under approach motivation, and beneficial effects of optimism should therefore be more pronounced under avoidance than approach motivation. Moreover, due to their eagerness, approach motivated people may even be more prone to unrealistic over-optimism and its negative consequences. PMID:24616690

The prompted optional randomization trial: a new design for comparative effectiveness research.

PubMed

Flory, James; Karlawish, Jason

2012-12-01

Randomized controlled trials are the gold standard for medical evidence because randomization provides the best-known protection against confounding of results. Randomization has practical and ethical problems that limit the number of trials that can be conducted, however. A different method for collecting clinical data retains the statistically useful properties of randomization without incurring its practical and ethical challenges. A computerized prompt introduces a random element into clinical decision-making that can be instantly overridden if it conflicts with optimal patient care. This creates a weak form of randomization that still eliminates the effect of all confounders, can be carried out without disturbing routine clinical care, and arguably will not require research-grade informed consent.

Impact of Vaccination on 14 High-Risk HPV Type Infections: A Mathematical Modelling Approach

PubMed Central

Vänskä, Simopekka; Auranen, Kari; Leino, Tuija; Salo, Heini; Nieminen, Pekka; Kilpi, Terhi; Tiihonen, Petri; Apter, Dan; Lehtinen, Matti

2013-01-01

The development of high-risk human papillomavirus (hrHPV) infection to cervical cancer is a complicated process. We considered solely hrHPV infections, thus avoiding the confounding effects of disease progression, screening, and treatments. To analyse hrHPV epidemiology and to estimate the overall impact of vaccination against infections with hrHPVs, we developed a dynamic compartmental transmission model for single and multiple infections with 14 hrHPV types. The infection-related parameters were estimated using population-based sexual behaviour and hrHPV prevalence data from Finland. The analysis disclosed the important role of persistent infections in hrHPV epidemiology, provided further evidence for a significant natural immunity, and demonstrated the dependence of transmission probability estimates on the model structure. The model predicted that vaccinating girls at 80% coverage will result in a 55% reduction in the overall hrHPV prevalence and a higher 65% reduction in the prevalence of persistent hrHPV infections in females. In males, the reduction will be 42% in the hrHPV prevalence solely by the herd effect from the 80% coverage in girls. If such high coverage among girls is not reached, it is still possible to reduce the female hrHPV prevalence indirectly by the herd effect if also boys are included in the vaccination program. On the other hand, any herd effects in older unvaccinated cohorts were minor. Limiting the epidemiological model to infection yielded improved understanding of the hrHPV epidemiology and of mechanisms with which vaccination impacts on hrHPV infections. PMID:24009669

Instrumental variables as bias amplifiers with general outcome and confounding.

PubMed

Ding, P; VanderWeele, T J; Robins, J M

2017-06-01

Drawing causal inference with observational studies is the central pillar of many disciplines. One sufficient condition for identifying the causal effect is that the treatment-outcome relationship is unconfounded conditional on the observed covariates. It is often believed that the more covariates we condition on, the more plausible this unconfoundedness assumption is. This belief has had a huge impact on practical causal inference, suggesting that we should adjust for all pretreatment covariates. However, when there is unmeasured confounding between the treatment and outcome, estimators adjusting for some pretreatment covariate might have greater bias than estimators without adjusting for this covariate. This kind of covariate is called a bias amplifier, and includes instrumental variables that are independent of the confounder, and affect the outcome only through the treatment. Previously, theoretical results for this phenomenon have been established only for linear models. We fill in this gap in the literature by providing a general theory, showing that this phenomenon happens under a wide class of models satisfying certain monotonicity assumptions. We further show that when the treatment follows an additive or multiplicative model conditional on the instrumental variable and the confounder, these monotonicity assumptions can be interpreted as the signs of the arrows of the causal diagrams.

The relationship between urinary tract infection during pregnancy and preeclampsia: causal, confounded or spurious?

PubMed

Karmon, Anatte; Sheiner, Eyal

2008-06-01

Preeclampsia is a major cause of maternal morbidity, although its precise etiology remains elusive. A number of studies suggest that urinary tract infection (UTI) during the course of gestation is associated with elevated risk for preeclampsia, while others have failed to prove such an association. In our medical center, pregnant women who were exposed to at least one UTI episode during pregnancy were 1.3 times more likely to have mild preeclampsia and 1.8 times more likely to have severe preeclampsia as compared to unexposed women. Our results are based on univariate analyses and are not adjusted for potential confounders. This editorial aims to discuss the relationship between urinary tract infection and preeclampsia, as well as examine the current problems regarding the interpretation of this association. Although the relationship between UTI and preeclampsia has been demonstrated in studies with various designs, carried-out in a variety of settings, the nature of this association is unclear. By taking into account timeline, dose-response effects, treatment influences, and potential confounders, as well as by neutralizing potential biases, future studies may be able to clarify the relationship between UTI and preeclampsia by determining if it is causal, confounded, or spurious.

Confounding and Statistical Significance of Indirect Effects: Childhood Adversity, Education, Smoking, and Anxious and Depressive Symptomatology.

PubMed

Sheikh, Mashhood Ahmed

2017-01-01

The life course perspective, the risky families model, and stress-and-coping models provide the rationale for assessing the role of smoking as a mediator in the association between childhood adversity and anxious and depressive symptomatology (ADS) in adulthood. However, no previous study has assessed the independent mediating role of smoking in the association between childhood adversity and ADS in adulthood. Moreover, the importance of mediator-response confounding variables has rarely been demonstrated empirically in social and psychiatric epidemiology. The aim of this paper was to (i) assess the mediating role of smoking in adulthood in the association between childhood adversity and ADS in adulthood, and (ii) assess the change in estimates due to different mediator-response confounding factors (education, alcohol intake, and social support). The present analysis used data collected from 1994 to 2008 within the framework of the Tromsø Study ( N = 4,530), a representative prospective cohort study of men and women. Seven childhood adversities (low mother's education, low father's education, low financial conditions, exposure to passive smoke, psychological abuse, physical abuse, and substance abuse distress) were used to create a childhood adversity score. Smoking status was measured at a mean age of 54.7 years (Tromsø IV), and ADS in adulthood was measured at a mean age of 61.7 years (Tromsø V). Mediation analysis was used to assess the indirect effect and the proportion of mediated effect (%) of childhood adversity on ADS in adulthood via smoking in adulthood. The test-retest reliability of smoking was good (Kappa: 0.67, 95% CI: 0.63; 0.71) in this sample. Childhood adversity was associated with a 10% increased risk of smoking in adulthood (Relative risk: 1.10, 95% CI: 1.03; 1.18), and both childhood adversity and smoking in adulthood were associated with greater levels of ADS in adulthood ( p < 0.001). Smoking in adulthood did not significantly mediate the association between childhood adversity and ADS in adulthood. However, when education was excluded as a mediator-response confounding variable, the indirect effect of childhood adversity on ADS in adulthood was statistically significant ( p < 0.05). This study shows that a careful inclusion of potential confounding variables is important when assessing mediation.

Confounding and Statistical Significance of Indirect Effects: Childhood Adversity, Education, Smoking, and Anxious and Depressive Symptomatology

PubMed Central

Sheikh, Mashhood Ahmed

2017-01-01

The life course perspective, the risky families model, and stress-and-coping models provide the rationale for assessing the role of smoking as a mediator in the association between childhood adversity and anxious and depressive symptomatology (ADS) in adulthood. However, no previous study has assessed the independent mediating role of smoking in the association between childhood adversity and ADS in adulthood. Moreover, the importance of mediator-response confounding variables has rarely been demonstrated empirically in social and psychiatric epidemiology. The aim of this paper was to (i) assess the mediating role of smoking in adulthood in the association between childhood adversity and ADS in adulthood, and (ii) assess the change in estimates due to different mediator-response confounding factors (education, alcohol intake, and social support). The present analysis used data collected from 1994 to 2008 within the framework of the Tromsø Study (N = 4,530), a representative prospective cohort study of men and women. Seven childhood adversities (low mother's education, low father's education, low financial conditions, exposure to passive smoke, psychological abuse, physical abuse, and substance abuse distress) were used to create a childhood adversity score. Smoking status was measured at a mean age of 54.7 years (Tromsø IV), and ADS in adulthood was measured at a mean age of 61.7 years (Tromsø V). Mediation analysis was used to assess the indirect effect and the proportion of mediated effect (%) of childhood adversity on ADS in adulthood via smoking in adulthood. The test-retest reliability of smoking was good (Kappa: 0.67, 95% CI: 0.63; 0.71) in this sample. Childhood adversity was associated with a 10% increased risk of smoking in adulthood (Relative risk: 1.10, 95% CI: 1.03; 1.18), and both childhood adversity and smoking in adulthood were associated with greater levels of ADS in adulthood (p < 0.001). Smoking in adulthood did not significantly mediate the association between childhood adversity and ADS in adulthood. However, when education was excluded as a mediator-response confounding variable, the indirect effect of childhood adversity on ADS in adulthood was statistically significant (p < 0.05). This study shows that a careful inclusion of potential confounding variables is important when assessing mediation. PMID:28824498

The effects of verbal information and approach-avoidance training on children's fear-related responses

PubMed Central

Lester, Kathryn J.; Lisk, Stephen C.; Mikita, Nina; Mitchell, Sophie; Huijding, Jorg; Rinck, Mike; Field, Andy P.

2015-01-01

Background and objectives This study examined the effects of verbal information and approach-avoidance training on fear-related cognitive and behavioural responses about novel animals. Methods One hundred and sixty children (7–11 years) were randomly allocated to receive: a) positive verbal information about one novel animal and threat information about a second novel animal (verbal information condition); b) approach-avoidance training in which they repeatedly pushed away (avoid) or pulled closer (approach) pictures of the animals (approach-avoidance training), c) a combined condition in which verbal information was given prior to approach-avoidance training (verbal information + approach-avoidance training) and d) a combined condition in which approach-avoidance training was given prior to verbal information (approach-avoidance training + verbal information). Results Threat and positive information significantly increased and decreased fear beliefs and avoidance behaviour respectively. Approach-avoidance training was successful in training the desired behavioural responses but had limited effects on fear-related responses. Verbal information and both combined conditions resulted in significantly larger effects than approach-avoidance training. We found no evidence for an additive effect of these pathways. Limitations This study used a non-clinical sample and focused on novel animals rather than animals about which children already had experience or established fears. The study also compared positive information/approach with threat information/avoid training, limiting specific conclusions regarding the independent effects of these conditions. Conclusions The present study finds little evidence in support of a possible causal role for behavioural response training in the aetiology of childhood fear. However, the provision of verbal information appears to be an important pathway involved in the aetiology of childhood fear. PMID:25698069

The effects of verbal information and approach-avoidance training on children's fear-related responses.

PubMed

Lester, Kathryn J; Lisk, Stephen C; Mikita, Nina; Mitchell, Sophie; Huijding, Jorg; Rinck, Mike; Field, Andy P

2015-09-01

This study examined the effects of verbal information and approach-avoidance training on fear-related cognitive and behavioural responses about novel animals. One hundred and sixty children (7-11 years) were randomly allocated to receive: a) positive verbal information about one novel animal and threat information about a second novel animal (verbal information condition); b) approach-avoidance training in which they repeatedly pushed away (avoid) or pulled closer (approach) pictures of the animals (approach-avoidance training), c) a combined condition in which verbal information was given prior to approach-avoidance training (verbal information + approach-avoidance training) and d) a combined condition in which approach-avoidance training was given prior to verbal information (approach-avoidance training + verbal information). Threat and positive information significantly increased and decreased fear beliefs and avoidance behaviour respectively. Approach-avoidance training was successful in training the desired behavioural responses but had limited effects on fear-related responses. Verbal information and both combined conditions resulted in significantly larger effects than approach-avoidance training. We found no evidence for an additive effect of these pathways. This study used a non-clinical sample and focused on novel animals rather than animals about which children already had experience or established fears. The study also compared positive information/approach with threat information/avoid training, limiting specific conclusions regarding the independent effects of these conditions. The present study finds little evidence in support of a possible causal role for behavioural response training in the aetiology of childhood fear. However, the provision of verbal information appears to be an important pathway involved in the aetiology of childhood fear. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Anesthesia in Experimental Stroke Research

PubMed Central

Hoffmann, Ulrike; Sheng, Huaxin; Ayata, Cenk; Warner, David S.

2016-01-01

Anesthetics have enabled major advances in development of experimental models of human stroke. Yet their profound pharmacologic effects on neural function can confound the interpretation of experimental stroke research. Anesthetics have drug and dose-specific effects on cerebral blood flow and metabolism, neurovascular coupling, autoregulation, ischemic depolarizations, excitotoxicity, inflammation, neural networks, and numerous molecular pathways relevant for stroke outcome. Both pre- and post-conditioning properties have been described. Anesthetics also modulate systemic arterial blood pressure, lung ventilation, and thermoregulation, all of which may interact with the ischemic insult as well as the therapeutic interventions. These confounds present a dilemma. Here, we provide an overview of the anesthetic mechanisms of action and molecular and physiologic effects on factors relevant to stroke outcomes that can guide the choice and optimization of the anesthetic regimen in experimental stroke. PMID:27534542

Conditional Random Fields for Fast, Large-Scale Genome-Wide Association Studies

PubMed Central

Huang, Jim C.; Meek, Christopher; Kadie, Carl; Heckerman, David

2011-01-01

Understanding the role of genetic variation in human diseases remains an important problem to be solved in genomics. An important component of such variation consist of variations at single sites in DNA, or single nucleotide polymorphisms (SNPs). Typically, the problem of associating particular SNPs to phenotypes has been confounded by hidden factors such as the presence of population structure, family structure or cryptic relatedness in the sample of individuals being analyzed. Such confounding factors lead to a large number of spurious associations and missed associations. Various statistical methods have been proposed to account for such confounding factors such as linear mixed-effect models (LMMs) or methods that adjust data based on a principal components analysis (PCA), but these methods either suffer from low power or cease to be tractable for larger numbers of individuals in the sample. Here we present a statistical model for conducting genome-wide association studies (GWAS) that accounts for such confounding factors. Our method scales in runtime quadratic in the number of individuals being studied with only a modest loss in statistical power as compared to LMM-based and PCA-based methods when testing on synthetic data that was generated from a generalized LMM. Applying our method to both real and synthetic human genotype/phenotype data, we demonstrate the ability of our model to correct for confounding factors while requiring significantly less runtime relative to LMMs. We have implemented methods for fitting these models, which are available at http://www.microsoft.com/science. PMID:21765897

A stratification approach using logit-based models for confounder adjustment in the study of continuous outcomes.

PubMed

Tan, Chuen Seng; Støer, Nathalie C; Chen, Ying; Andersson, Marielle; Ning, Yilin; Wee, Hwee-Lin; Khoo, Eric Yin Hao; Tai, E-Shyong; Kao, Shih Ling; Reilly, Marie

2017-01-01

The control of confounding is an area of extensive epidemiological research, especially in the field of causal inference for observational studies. Matched cohort and case-control study designs are commonly implemented to control for confounding effects without specifying the functional form of the relationship between the outcome and confounders. This paper extends the commonly used regression models in matched designs for binary and survival outcomes (i.e. conditional logistic and stratified Cox proportional hazards) to studies of continuous outcomes through a novel interpretation and application of logit-based regression models from the econometrics and marketing research literature. We compare the performance of the maximum likelihood estimators using simulated data and propose a heuristic argument for obtaining the residuals for model diagnostics. We illustrate our proposed approach with two real data applications. Our simulation studies demonstrate that our stratification approach is robust to model misspecification and that the distribution of the estimated residuals provides a useful diagnostic when the strata are of moderate size. In our applications to real data, we demonstrate that parity and menopausal status are associated with percent mammographic density, and that the mean level and variability of inpatient blood glucose readings vary between medical and surgical wards within a national tertiary hospital. Our work highlights how the same class of regression models, available in most statistical software, can be used to adjust for confounding in the study of binary, time-to-event and continuous outcomes.

Is the Relation Between Ozone and Mortality Confounded by Chemical Components of Particulate Matter? Analysis of 7 Components in 57 US Communities

PubMed Central

Anderson, G. Brooke; Krall, Jenna R.; Peng, Roger D.; Bell, Michelle L.

2012-01-01

Epidemiologic studies have linked tropospheric ozone pollution and human mortality. Although research has shown that this relation is not confounded by particulate matter when measured by mass, little scientific evidence exists on whether confounding exists by chemical components of the particle mixture. Using mortality and particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5) component data from 57 US communities (2000–2005), the authors investigate whether the ozone-mortality relation is confounded by 7 components of PM2.5: sulfate, nitrate, silicon, elemental carbon, organic carbon matter, sodium ion, and ammonium. Together, these components constitute most PM2.5 mass in the United States. Estimates of the effect of ozone on mortality were almost identical before and after controlling for the 7 components of PM2.5 considered (mortality increase/10-ppb ozone increase, before and after controlling: ammonium, 0.34% vs. 0.35%; elemental carbon, 0.36% vs. 0.37%; nitrate, 0.27% vs. 0.26%; organic carbon matter, 0.34% vs. 0.31%; silicon, 0.36% vs. 0.37%; sodium ion, 0.21% vs. 0.18%; and sulfate, 0.35% vs. 0.38%). Additionally, correlations were weak between ozone and each particulate component across all communities. Previous research found that the ozone-mortality relation is not confounded by particulate matter measured by mass; this national study indicates that the relation is also robust to control for specific components of PM2.5. PMID:23043133

Mismeasurement and the resonance of strong confounders: correlated errors.

PubMed

Marshall, J R; Hastrup, J L; Ross, J S

1999-07-01

Confounding in epidemiology, and the limits of standard methods of control for an imperfectly measured confounder, have been understood for some time. However, most treatments of this problem are based on the assumption that errors of measurement in confounding and confounded variables are independent. This paper considers the situation in which a strong risk factor (confounder) and an inconsequential but suspected risk factor (confounded) are each measured with errors that are correlated; the situation appears especially likely to occur in the field of nutritional epidemiology. Error correlation appears to add little to measurement error as a source of bias in estimating the impact of a strong risk factor: it can add to, diminish, or reverse the bias induced by measurement error in estimating the impact of the inconsequential risk factor. Correlation of measurement errors can add to the difficulty involved in evaluating structures in which confounding and measurement error are present. In its presence, observed correlations among risk factors can be greater than, less than, or even opposite to the true correlations. Interpretation of multivariate epidemiologic structures in which confounding is likely requires evaluation of measurement error structures, including correlations among measurement errors.

Biomechanical and psychosocial exposures are independent risk factors for carpal tunnel syndrome: assessment of confounding using causal diagrams.

PubMed

Harris-Adamson, Carisa; Eisen, Ellen A; Neophytou, Andreas; Kapellusch, Jay; Garg, Arun; Hegmann, Kurt T; Thiese, Matthew S; Dale, Ann Marie; Evanoff, Bradley; Bao, Stephen; Silverstein, Barbara; Gerr, Fred; Burt, Susan; Rempel, David

2016-11-01

Between 2001 and 2010, six research groups conducted coordinated prospective studies of carpal tunnel syndrome (CTS) incidence among US workers from various industries to estimate exposure-response relationships. This analysis examined the presence and magnitude of confounding between biomechanical and workplace psychosocial factors and incidence of dominant-hand CTS. 1605 participants, without CTS at enrolment, were followed for up to 3.5 years (2471 person-years). Demographic information, medical history and workplace psychosocial stress measures were collected at baseline. Individual workplace biomechanical exposures were collected for each task and combined across the workweek using time-weighted averaging (TWA). CTS case criteria were based on symptoms and results of electrophysiological testing. HRs were estimated with Cox proportional hazard models. Confounding was assessed using causal diagrams and an empirical criterion of 10% or greater change in effect estimate magnitude. There were 109 incident CTS cases (IR=4.41/100 person-years; 6.7% cumulative incidence). The relationships between CTS and forceful repetition rate, % time forceful hand exertion and the Threshold Limit Value for Hand Activity Level (TLV-HAL) were slightly confounded by decision latitude with effect estimates being attenuated towards the null (10-14% change) after adjustment. The risk of CTS among participants reporting high job strain was attenuated towards the null by 14% after adjusting for the HAL Scale or the % time forceful hand exertions. Although attenuation of the relationships between CTS and some biomechanical and work psychosocial exposures was observed after adjusting for confounding, the magnitudes were small and confirmed biomechanical and work psychosocial exposures as independent risk factors for incident CTS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

On causal interpretation of race in regressions adjusting for confounding and mediating variables

PubMed Central

VanderWeele, Tyler J.; Robinson, Whitney R.

2014-01-01

We consider several possible interpretations of the “effect of race” when regressions are run with race as an exposure variable, controlling also for various confounding and mediating variables. When adjustment is made for socioeconomic status early in a person’s life, we discuss under what contexts the regression coefficients for race can be interpreted as corresponding to the extent to which a racial inequality would remain if various socioeconomic distributions early in life across racial groups could be equalized. When adjustment is also made for adult socioeconomic status, we note how the overall racial inequality can be decomposed into the portion that would be eliminated by equalizing adult socioeconomic status across racial groups and the portion of the inequality that would remain even if adult socioeconomic status across racial groups were equalized. We also discuss a stronger interpretation of the “effect of race” (stronger in terms of assumptions) involving the joint effects of race-associated physical phenotype (e.g. skin color), parental physical phenotype, genetic background and cultural context when such variables are thought to be hypothetically manipulable and if adequate control for confounding were possible. We discuss some of the challenges with such an interpretation. Further discussion is given as to how the use of selected populations in examining racial disparities can additionally complicate the interpretation of the effects. PMID:24887159

Neuropsychological functioning in older people with type 2 diabetes: the effect of controlling for confounding factors.

PubMed

Asimakopoulou, K G; Hampson, S E; Morrish, N J

2002-04-01

Neuropsychological functioning was examined in a group of 33 older (mean age 62.40 +/- 9.62 years) people with Type 2 diabetes (Group 1) and 33 non-diabetic participants matched with Group 1 on age, sex, premorbid intelligence and presence of hypertension and cardio/cerebrovascular conditions (Group 2). Data statistically corrected for confounding factors obtained from the diabetic group were compared with the matched control group. The results suggested small cognitive deficits in diabetic people's verbal memory and mental flexibility (Logical Memory A and SS7). No differences were seen between the two samples in simple and complex visuomotor attention, sustained complex visual attention, attention efficiency, mental double tracking, implicit memory, and self-reported memory problems. These findings indicate minimal cognitive impairment in relatively uncomplicated Type 2 diabetes and demonstrate the importance of control and matching for confounding factors.

If it is published in the peer-reviewed literature, it must be true?

PubMed

Wagner, Louis K

2014-10-01

Epidemiological research correlating cancer rates in a population of patients with radiation doses from medical X-rays is fraught with confounding factors that obfuscate the likelihood that any positive relationship is causal. This is a review of four studies involving some of those confounding factors. Comparisons of findings with other studies not encumbered by similar confounding factors can enhance assertions of causation between medical X-rays and cancer rates. Even so, such assertions rest significantly on opinions of researchers regarding the degree of consistency between findings among various studies. The question as to what degree any findings truly represent cause and effect will likely still meet with controversy. The importance of these findings to medicine should therefore not lie in any controversy regarding causation, but in what the findings potentially mean with regard to benefit and risk for patients and the professional practice of medicine.

Maternal smoking during pregnancy and children's cognitive and physical development: a causal risk factor?

PubMed

Gilman, Stephen E; Gardener, Hannah; Buka, Stephen L

2008-09-01

There remains considerable debate regarding the effects of maternal smoking during pregnancy on children's growth and development. Evidence that exposure to maternal smoking during pregnancy is associated with numerous adverse outcomes is contradicted by research suggesting that these associations are spurious. The authors investigated the relation between maternal smoking during pregnancy and 14 developmental outcomes of children from birth through age 7 years, using data from the Collaborative Perinatal Project (1959-1974; n = 52,919). In addition to adjusting for potential confounders measured contemporaneously with maternal smoking, the authors fitted conditional fixed-effects models among siblings that controlled for unmeasured confounders. Results from the conditional analyses indicated a birth weight difference of -85.63 g associated with smoking of >or=20 cigarettes daily during pregnancy (95% confidence interval: -131.91, -39.34) and 2.73 times' higher odds of being overweight at age 7 years (95% confidence interval: 1.30, 5.71). However, the associations between maternal smoking and 12 other outcomes studied (including Apgar score, intelligence, academic achievement, conduct problems, and asthma) were entirely eliminated after adjustment for measured and unmeasured confounders. The authors conclude that the hypothesized effects of maternal smoking during pregnancy on these outcomes either are not present or are not distinguishable from a broader range of familial factors associated with maternal smoking.

African ancestry, lung function and the effect of genetics

PubMed Central

Wehrmeister, Fernando C.; Hartwig, Fernando P.; Perez-Padilla, Rogelio; Gigante, Denise P.; Barros, Fernando C.; Oliveira, Isabel O.; Ferreira, Gustavo D.; Horta, Bernardo L.

2015-01-01

African-Americans have smaller lung function compared with European-Americans. The aim of this study was to disentangle the contribution of genetics from other variables on lung function. A cohort was followed from birth to 30 years of age in Brazil. Several variables were collected: genomic analysis based on DNA; forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) obtained by spirometry; height measured by anthropometrists; and thorax circumference evaluated by photonic scanner. Crude and adjusted linear regression models were calculated according to African ancestry. The sample comprised 2869 participants out of 3701 members of the cohort. Males with higher African ancestry by DNA analysis had a smaller FEV1 (−0.13 L, 95% CI −0.23– −0.03 L) and FVC (−0.21 L, 95% CI −0.32– −0.09 L) compared with those with less African ancestry, having accounted for height, sitting to standing height ratio and other confounders. Similar effects were seen in females. After adjustment, ancestry remained significantly associated with lung function, but the large effect of adjustment for confounding among males (but not females) does not allow us to exclude the possibility that residual confounding may still account for these findings. PMID:25700383

Breath biomarkers for lung cancer detection and assessment of smoking related effects--confounding variables, influence of normalization and statistical algorithms.

PubMed

Kischkel, Sabine; Miekisch, Wolfram; Sawacki, Annika; Straker, Eva M; Trefz, Phillip; Amann, Anton; Schubert, Jochen K

2010-11-11

Up to now, none of the breath biomarkers or marker sets proposed for cancer recognition has reached clinical relevance. Possible reasons are the lack of standardized methods of sampling, analysis and data processing and effects of environmental contaminants. Concentration profiles of endogenous and exogenous breath markers were determined in exhaled breath of 31 lung cancer patients, 31 smokers and 31 healthy controls by means of SPME-GC-MS. Different correcting and normalization algorithms and a principal component analysis were applied to the data. Differences of exhalation profiles in cancer and non-cancer patients did not persist if physiology and confounding variables were taken into account. Smoking history, inspired substance concentrations, age and gender were recognized as the most important confounding variables. Normalization onto PCO2 or BSA or correction for inspired concentrations only partially solved the problem. In contrast, previous smoking behaviour could be recognized unequivocally. Exhaled substance concentrations may depend on a variety of parameters other than the disease under investigation. Normalization and correcting parameters have to be chosen with care as compensating effects may be different from one substance to the other. Only well-founded biomarker identification, normalization and data processing will provide clinically relevant information from breath analysis. 2010 Elsevier B.V. All rights reserved.

Reporting of research quality characteristics of studies published in 6 major clinical dental specialty journals.

PubMed

Pandis, Nikolaos; Polychronopoulou, Argy; Madianos, Phoebus; Makou, Margarita; Eliades, Theodore

2011-06-01

The objective of this article was to record reporting characteristics related to study quality of research published in major specialty dental journals with the highest impact factor (Journal of Endodontics, Journal of Oral and Maxillofacial Surgery, American Journal of Orthodontics and Dentofacial Orthopedics; Pediatric Dentistry, Journal of Clinical Periodontology, and International Journal of Prosthetic Dentistry). The included articles were classified into the following 3 broad subject categories: (1) cross-sectional (snap-shot), (2) observational, and (3) interventional. Multinomial logistic regression was conducted for effect estimation using the journal as the response and randomization, sample calculation, confounding discussed, multivariate analysis, effect measurement, and confidence intervals as the explanatory variables. The results showed that cross-sectional studies were the dominant design (55%), whereas observational investigations accounted for 13%, and interventions/clinical trials for 32%. Reporting on quality characteristics was low for all variables: random allocation (15%), sample size calculation (7%), confounding issues/possible confounders (38%), effect measurements (16%), and multivariate analysis (21%). Eighty-four percent of the published articles reported a statistically significant main finding and only 13% presented confidence intervals. The Journal of Clinical Periodontology showed the highest probability of including quality characteristics in reporting results among all dental journals. Copyright © 2011 Elsevier Inc. All rights reserved.

Stratification for the propensity score compared with linear regression techniques to assess the effect of treatment or exposure.

PubMed

Senn, Stephen; Graf, Erika; Caputo, Angelika

2007-12-30

Stratifying and matching by the propensity score are increasingly popular approaches to deal with confounding in medical studies investigating effects of a treatment or exposure. A more traditional alternative technique is the direct adjustment for confounding in regression models. This paper discusses fundamental differences between the two approaches, with a focus on linear regression and propensity score stratification, and identifies points to be considered for an adequate comparison. The treatment estimators are examined for unbiasedness and efficiency. This is illustrated in an application to real data and supplemented by an investigation on properties of the estimators for a range of underlying linear models. We demonstrate that in specific circumstances the propensity score estimator is identical to the effect estimated from a full linear model, even if it is built on coarser covariate strata than the linear model. As a consequence the coarsening property of the propensity score-adjustment for a one-dimensional confounder instead of a high-dimensional covariate-may be viewed as a way to implement a pre-specified, richly parametrized linear model. We conclude that the propensity score estimator inherits the potential for overfitting and that care should be taken to restrict covariates to those relevant for outcome. Copyright (c) 2007 John Wiley & Sons, Ltd.

Sex-specific role of education on the associations of socioeconomic status indicators with obesity risk: A population-based study in South Korea

PubMed Central

Chung, Woojin; Lim, Seung-ji; Lee, Sunmi

2018-01-01

Background No study of obesity risk for people in developed countries has conducted a multi-dimensional analysis of the association of socioeconomic status with obesity. In this paper, we investigated if education functions as either a confounder or an effect modifier in the association of another socioeconomic status indicator with obesity. Methods This cross-sectional study analyzed data of an adult population sample (10,905 men and 14,580 women) from the Korea National Health and Nutrition Examination Survey (2010–2014). The study performed multivariate logistic regression analyses for three education levels and four indicators of socioeconomic status (i.e., marital status, residential area, occupation, and income). Results The overall prevalence of obesity was 38.1% in men and 29.1% in women (p < 0.001). In men, while education functioned as an effect modifier in the association between marital status and obesity (p for interaction = 0.006), it functioned as both a confounder (p < 0.001) and an effect modifier (p for interaction < 0.001) in the association between residential area and obesity. In contrast, in women, education functioned as a confounder in the association of residential area with obesity (p = 0.010). However, it functioned as both a confounder (p < 0.001) and an effect modifier (p for interaction = 0.012) in the association between income and obesity. A prediction showed that unlike in women, education was positively associated with obesity risk for some socioeconomic indicator groups in men; for example, in a rural resident group, a higher level of education increased the probability of being obese by 19.7%. Conclusions The present study suggests the need to examine sex-specific studies regarding the role of education on the association between other socioeconomic status indicators and obesity. This should be considered in planning education policies to reduce the risk of obesity. PMID:29298319

High birth weight and perinatal mortality among siblings: A register based study in Norway, 1967-2011.

PubMed

Kristensen, Petter; Keyes, Katherine M; Susser, Ezra; Corbett, Karina; Mehlum, Ingrid Sivesind; Irgens, Lorentz M

2017-01-01

Perinatal mortality according to birth weight has an inverse J-pattern. Our aim was to estimate the influence of familial factors on this pattern, applying a cohort sibling design. We focused on excess mortality among macrosomic infants (>2 SD above the mean) and hypothesized that the birth weight-mortality association could be explained by confounding shared family factors. We also estimated how the participant's deviation from mean sibling birth weight influenced the association. We included 1 925 929 singletons, born term or post-term to mothers with more than one delivery 1967-2011 registered in the Medical Birth Registry of Norway. We examined z-score birth weight and perinatal mortality in random-effects and sibling fixed-effects logistic regression models including measured confounders (e.g. maternal diabetes) as well as unmeasured shared family confounders (through fixed effects models). Birth weight-specific mortality showed an inverse J-pattern, being lowest (2.0 per 1000) at reference weight (z-score +1 to +2) and increasing for higher weights. Mortality in the highest weight category was 15-fold higher than reference. This pattern changed little in multivariable models. Deviance from mean sibling birth weight modified the mortality pattern across the birth weight spectrum: small and medium-sized infants had increased mortality when being smaller than their siblings, and large-sized infants had an increased risk when outweighing their siblings. Maternal diabetes and birth weight acted in a synergistic fashion with mortality among macrosomic infants in diabetic pregnancies in excess of what would be expected for additive effects. The inverse J-pattern between birth weight and mortality is not explained by measured confounders or unmeasured shared family factors. Infants are at particularly high mortality risk when their birth weight deviates substantially from their siblings. Sensitivity analysis suggests that characteristics related to maternal diabetes could be important in explaining the increased mortality among macrosomic infants.

Sex-specific role of education on the associations of socioeconomic status indicators with obesity risk: A population-based study in South Korea.

PubMed

Chung, Woojin; Kim, Jaeyeun; Lim, Seung-Ji; Lee, Sunmi

2018-01-01

No study of obesity risk for people in developed countries has conducted a multi-dimensional analysis of the association of socioeconomic status with obesity. In this paper, we investigated if education functions as either a confounder or an effect modifier in the association of another socioeconomic status indicator with obesity. This cross-sectional study analyzed data of an adult population sample (10,905 men and 14,580 women) from the Korea National Health and Nutrition Examination Survey (2010-2014). The study performed multivariate logistic regression analyses for three education levels and four indicators of socioeconomic status (i.e., marital status, residential area, occupation, and income). The overall prevalence of obesity was 38.1% in men and 29.1% in women (p < 0.001). In men, while education functioned as an effect modifier in the association between marital status and obesity (p for interaction = 0.006), it functioned as both a confounder (p < 0.001) and an effect modifier (p for interaction < 0.001) in the association between residential area and obesity. In contrast, in women, education functioned as a confounder in the association of residential area with obesity (p = 0.010). However, it functioned as both a confounder (p < 0.001) and an effect modifier (p for interaction = 0.012) in the association between income and obesity. A prediction showed that unlike in women, education was positively associated with obesity risk for some socioeconomic indicator groups in men; for example, in a rural resident group, a higher level of education increased the probability of being obese by 19.7%. The present study suggests the need to examine sex-specific studies regarding the role of education on the association between other socioeconomic status indicators and obesity. This should be considered in planning education policies to reduce the risk of obesity.

Negative control exposure studies in the presence of measurement error: implications for attempted effect estimate calibration

PubMed Central

Sanderson, Eleanor; Macdonald-Wallis, Corrie; Davey Smith, George

2018-01-01

Abstract Background Negative control exposure studies are increasingly being used in epidemiological studies to strengthen causal inference regarding an exposure-outcome association when unobserved confounding is thought to be present. Negative control exposure studies contrast the magnitude of association of the negative control, which has no causal effect on the outcome but is associated with the unmeasured confounders in the same way as the exposure, with the magnitude of the association of the exposure with the outcome. A markedly larger effect of the exposure on the outcome than the negative control on the outcome strengthens inference that the exposure has a causal effect on the outcome. Methods We investigate the effect of measurement error in the exposure and negative control variables on the results obtained from a negative control exposure study. We do this in models with continuous and binary exposure and negative control variables using analysis of the bias of the estimated coefficients and Monte Carlo simulations. Results Our results show that measurement error in either the exposure or negative control variables can bias the estimated results from the negative control exposure study. Conclusions Measurement error is common in the variables used in epidemiological studies; these results show that negative control exposure studies cannot be used to precisely determine the size of the effect of the exposure variable, or adequately adjust for unobserved confounding; however, they can be used as part of a body of evidence to aid inference as to whether a causal effect of the exposure on the outcome is present. PMID:29088358

Negative control exposure studies in the presence of measurement error: implications for attempted effect estimate calibration.

PubMed

Sanderson, Eleanor; Macdonald-Wallis, Corrie; Davey Smith, George

2018-04-01

Negative control exposure studies are increasingly being used in epidemiological studies to strengthen causal inference regarding an exposure-outcome association when unobserved confounding is thought to be present. Negative control exposure studies contrast the magnitude of association of the negative control, which has no causal effect on the outcome but is associated with the unmeasured confounders in the same way as the exposure, with the magnitude of the association of the exposure with the outcome. A markedly larger effect of the exposure on the outcome than the negative control on the outcome strengthens inference that the exposure has a causal effect on the outcome. We investigate the effect of measurement error in the exposure and negative control variables on the results obtained from a negative control exposure study. We do this in models with continuous and binary exposure and negative control variables using analysis of the bias of the estimated coefficients and Monte Carlo simulations. Our results show that measurement error in either the exposure or negative control variables can bias the estimated results from the negative control exposure study. Measurement error is common in the variables used in epidemiological studies; these results show that negative control exposure studies cannot be used to precisely determine the size of the effect of the exposure variable, or adequately adjust for unobserved confounding; however, they can be used as part of a body of evidence to aid inference as to whether a causal effect of the exposure on the outcome is present.

An independent component analysis confounding factor correction framework for identifying broad impact expression quantitative trait loci

PubMed Central

Ju, Jin Hyun; Crystal, Ronald G.

2017-01-01

Genome-wide expression Quantitative Trait Loci (eQTL) studies in humans have provided numerous insights into the genetics of both gene expression and complex diseases. While the majority of eQTL identified in genome-wide analyses impact a single gene, eQTL that impact many genes are particularly valuable for network modeling and disease analysis. To enable the identification of such broad impact eQTL, we introduce CONFETI: Confounding Factor Estimation Through Independent component analysis. CONFETI is designed to address two conflicting issues when searching for broad impact eQTL: the need to account for non-genetic confounding factors that can lower the power of the analysis or produce broad impact eQTL false positives, and the tendency of methods that account for confounding factors to model broad impact eQTL as non-genetic variation. The key advance of the CONFETI framework is the use of Independent Component Analysis (ICA) to identify variation likely caused by broad impact eQTL when constructing the sample covariance matrix used for the random effect in a mixed model. We show that CONFETI has better performance than other mixed model confounding factor methods when considering broad impact eQTL recovery from synthetic data. We also used the CONFETI framework and these same confounding factor methods to identify eQTL that replicate between matched twin pair datasets in the Multiple Tissue Human Expression Resource (MuTHER), the Depression Genes Networks study (DGN), the Netherlands Study of Depression and Anxiety (NESDA), and multiple tissue types in the Genotype-Tissue Expression (GTEx) consortium. These analyses identified both cis-eQTL and trans-eQTL impacting individual genes, and CONFETI had better or comparable performance to other mixed model confounding factor analysis methods when identifying such eQTL. In these analyses, we were able to identify and replicate a few broad impact eQTL although the overall number was small even when applying CONFETI. In light of these results, we discuss the broad impact eQTL that have been previously reported from the analysis of human data and suggest that considerable caution should be exercised when making biological inferences based on these reported eQTL. PMID:28505156

An independent component analysis confounding factor correction framework for identifying broad impact expression quantitative trait loci.

PubMed

Ju, Jin Hyun; Shenoy, Sushila A; Crystal, Ronald G; Mezey, Jason G

2017-05-01

Genome-wide expression Quantitative Trait Loci (eQTL) studies in humans have provided numerous insights into the genetics of both gene expression and complex diseases. While the majority of eQTL identified in genome-wide analyses impact a single gene, eQTL that impact many genes are particularly valuable for network modeling and disease analysis. To enable the identification of such broad impact eQTL, we introduce CONFETI: Confounding Factor Estimation Through Independent component analysis. CONFETI is designed to address two conflicting issues when searching for broad impact eQTL: the need to account for non-genetic confounding factors that can lower the power of the analysis or produce broad impact eQTL false positives, and the tendency of methods that account for confounding factors to model broad impact eQTL as non-genetic variation. The key advance of the CONFETI framework is the use of Independent Component Analysis (ICA) to identify variation likely caused by broad impact eQTL when constructing the sample covariance matrix used for the random effect in a mixed model. We show that CONFETI has better performance than other mixed model confounding factor methods when considering broad impact eQTL recovery from synthetic data. We also used the CONFETI framework and these same confounding factor methods to identify eQTL that replicate between matched twin pair datasets in the Multiple Tissue Human Expression Resource (MuTHER), the Depression Genes Networks study (DGN), the Netherlands Study of Depression and Anxiety (NESDA), and multiple tissue types in the Genotype-Tissue Expression (GTEx) consortium. These analyses identified both cis-eQTL and trans-eQTL impacting individual genes, and CONFETI had better or comparable performance to other mixed model confounding factor analysis methods when identifying such eQTL. In these analyses, we were able to identify and replicate a few broad impact eQTL although the overall number was small even when applying CONFETI. In light of these results, we discuss the broad impact eQTL that have been previously reported from the analysis of human data and suggest that considerable caution should be exercised when making biological inferences based on these reported eQTL.

Employment effects of the Danish rehabilitation benefit.

PubMed

Pallesen, Palle B; Lynge, Elsebeth

2012-06-01

Social benefits aim to bring marginalised citizens back into the labour force. As benefits constitute a burden for tax payers, attention has been given to measure the effect. We used register data to assess the employment effect of rehabilitation benefit; the most liberal social benefit in Denmark. We used data on rehabilitation benefits paid during 1994-2004. In the study design, special care was given to overcome selection bias. We identified municipalities with most frequent (generous) and least frequent (stingy) use of rehabilitation benefit, controlling for confounders (step 1). From the generous municipalities, population subgroups where ≥10% received rehabilitation benefit (vulnerable group) were identified based on age, sex, education, cohabitation, children, and health (step 2). Outcome measure was employment rate in 2005 for vulnerable groups in generous municipalities compared with vulnerable groups in stingy municipalities, controlled for municipality employment rate, i.e. a ratio of ratios (step 3). Use of rehabilitation benefit varied 10-fold across the 271 Danish municipalities. The employment rate in 2005 for vulnerable groups was lower in generous than in stingy municipalities. The ratio of ratios was 0.915 (95% CI 0.888-0.945) for men and 0.919 (95% CI 0.896-0.942) for women. No positive employment effect of generous use of rehabilitation benefit was found. Although residual confounding cannot be excluded, it is nevertheless remarkable that the possibly positive effect of rehabilitation benefit was not sufficiently large to become visible, even in a study particularly designed to eliminate selection biases and to control for confounding.

How Confounder Strength Can Affect Allocation of Resources in Electronic Health Records.

PubMed

Lynch, Kristine E; Whitcomb, Brian W; DuVall, Scott L

2018-01-01

When electronic health record (EHR) data are used, multiple approaches may be available for measuring the same variable, introducing potentially confounding factors. While additional information may be gleaned and residual confounding reduced through resource-intensive assessment methods such as natural language processing (NLP), whether the added benefits offset the added cost of the additional resources is not straightforward. We evaluated the implications of misclassification of a confounder when using EHRs. Using a combination of simulations and real data surrounding hospital readmission, we considered smoking as a potential confounder. We compared ICD-9 diagnostic code assignment, which is an easily available measure but has the possibility of substantial misclassification of smoking status, with NLP, a method of determining smoking status that more expensive and time-consuming than ICD-9 code assignment but has less potential for misclassification. Classification of smoking status with NLP consistently produced less residual confounding than the use of ICD-9 codes; however, when minimal confounding was present, differences between the approaches were small. When considerable confounding is present, investing in a superior measurement tool becomes advantageous.

Febuxostat in the management of gout: a cost-effectiveness analysis.

PubMed

Smolen, Lee J; Gahn, James C; Mitri, Ghaith; Shiozawa, Aki

2016-01-01

To determine the cost-effectiveness of febuxostat vs allopurinol for the management of gout. A stochastic microsimulation cost-effectiveness model with a US private-payer perspective and 5-year time horizon was developed. Model flow based on guideline and real-world treatment paradigms incorporated gout flare, serum uric acid (sUA) testing, treatment titration, discontinuation, and adverse events, chronic kidney disease (CKD) incidence and progression, and type 2 diabetes mellitus (T2DM) incidence. Outcomes were estimated for the general gout population and for gout patients with CKD stages 3/4. Modeled treatment interventions were daily oral febuxostat 40-80 mg and allopurinol 100-300 mg. Baseline patient characteristics were taken from epidemiologic studies, efficacy data from randomized controlled trials, adverse event rates from package inserts, and costs from the literature, government sources, and expert opinion. Eight clinically-relevant incremental cost-effectiveness ratios were estimated: per patient reaching target sUA, per flare avoided, per CKD incidence, progression, stages 3/4 progression, and stage 5 progression avoided, per incident T2DM avoided, and per death avoided. Five-year incremental cost-effectiveness ratios for the general gout population were $5377 per patient reaching target sUA, $1773 per flare avoided, $221,795 per incident CKD avoided, $29,063 per CKD progression avoided, $36,018 per progression to CKD 3/4 avoided, $71,426 per progression to CKD 5 avoided, $214,277 per incident T2DM avoided, and $217,971 per death avoided. In patients with CKD 3/4, febuxostat dominated allopurinol for all cost-effectiveness outcome measures. Febuxostat may be a cost-effective alternative to allopurinol, especially for patients with CKD stages 3 or 4.

Avoiding hypothermia, an intervention to prevent morbidity and mortality from pneumonia in young children.

PubMed

Pio, Antonio; Kirkwood, Betty R; Gove, Sandy

2010-02-01

Observations and experiments in animals and human beings grant plausibility to the hypothesis that hypothermia is a risk factor for pneumonia. Exposure of body to cold stress causes alterations in the systemic and local defenses against respiratory infections, favoring the infection by inhalation of pathogens normally present in the oropharynx. Neonates and young infants with hypothermia have an increased risk of death; however, there is no strong demonstration that hypothermia leads to pneumonia in these children. Studies that properly addressed the problem of confounding variables have shown an association between cold weather and pneumonia incidence. Probably the strongest evidence that supports the plausibility of the hypothesis is provided by the controlled comparison between patients with traumatic brain injury treated with hypothermia and those treated under normal body temperature. The association between exposure to cold and pneumonia is strong enough to warrant further research focused in young children in developing countries.

Commercial Hype Versus Reality: Our Current Scientific Understanding of Gluten and Athletic Performance.

PubMed

Lis, Dana M; Fell, James W; Ahuja, Kiran D K; Kitic, Cecilia M; Stellingwerff, Trent

2016-01-01

Recent explosion in the prevalence of gluten-free athletes, exacerbated by unsubstantiated commercial health claims, has led to some professional athletes touting gluten-free diet as the secret to their success. Forty-one percent of athletes report adhering to a gluten-free diet (GFD), which is four-fold higher than the population-based clinical requirements. Many nonceliac athletes believe that gluten avoidance improves gastrointestinal well-being, reduces inflammation, and provides an ergogenic edge, despite the fact that limited data yet exist to support any of these benefits. There are several plausible associations between endurance-based exercise and gastrointestinal permeability whereby a GFD may be beneficial. However, the implications of confounding factors, including the risks of unnecessary dietary restriction, financial burden, food availability, psychosocial implications, alterations in short-chain carbohydrates (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols), and other wheat constituents emphasize the need for further evaluation.

Measurement of H2S in vivo and in vitro by the monobromobimane method

PubMed Central

Shen, Xinggui; Kolluru, Gopi K.; Yuan, Shuai; Kevil, Christopher

2015-01-01

The gasotransmitter hydrogen sulfide (H2S) is known as an important regulator in several physiological and pathological responses. Among the challenges facing the field is the accurate and reliable measurement of hydrogen sulfide bioavailability. We have reported an approach to discretely measure sulfide and sulfide pools using the monobromobimane (MBB) method coupled with RP-HPLC. The method involves the derivatization of sulfide with excess MBB under precise reaction conditions at room temperature to form sulfide-dibimane. The resultant fluorescent sulfide-dibimane (SDB) is analyzed by RP-HPLC using fluorescence detection with the limit of detection for SDB (2 nM). Care must be taken to avoid conditions that may confound H2S measurement with this method. Overall, RP-HPLC with fluorescence detection of SDB is a useful and powerful tool to measure biological sulfide levels. PMID:25725514

Measurement of H2S in vivo and in vitro by the monobromobimane method.

PubMed

Shen, Xinggui; Kolluru, Gopi K; Yuan, Shuai; Kevil, Christopher G

2015-01-01

The gasotransmitter hydrogen sulfide (H2S) is known as an important regulator in several physiological and pathological responses. Among the challenges facing the field is the accurate and reliable measurement of hydrogen sulfide bioavailability. We have reported an approach to discretely measure sulfide and sulfide pools using the monobromobimane (MBB) method coupled with reversed phase high-performance liquid chromatography (RP-HPLC). The method involves the derivatization of sulfide with excess MBB under precise reaction conditions at room temperature to form sulfide dibimane (SDB). The resultant fluorescent SDB is analyzed by RP-HPLC using fluorescence detection with the limit of detection for SDB (2 nM). Care must be taken to avoid conditions that may confound H2S measurement with this method. Overall, RP-HPLC with fluorescence detection of SDB is a useful and powerful tool to measure biological sulfide levels. © 2015 Elsevier Inc. All rights reserved.

Photobiological implications of melanin photoprotection after UVB-induced tanning of human skin but not UVA-induced tanning.

PubMed

Coelho, Sergio G; Yin, Lanlan; Smuda, Christoph; Mahns, Andre; Kolbe, Ludger; Hearing, Vincent J

2015-03-01

Repetitive suberythemal UVA and/or UVB exposures were used to generate comparable UV-induced tans in human skin over the course of 2 weeks. To evaluate the potential photoprotective values of those UVA- and/or UVB- induced tans and to avoid the confounding issue of residual UV-induced DNA damage, we waited 1 week before challenging those areas with a 1.5 MED of UVA+UVB after which we measure DNA damage. The results show that the type of UV used to induce skin pigmentation affects the redistribution of melanin in the skin and/or de novo melanin synthesis. The UVA-induced tans failed to even provide a minimal SPF of 1.5, which suggests that producing a tan with UVA-rich sunlamps prior to a holiday or vacation is completely counterproductive. Published 2014. This article is a US Government work and is in the public domain in the USA.

The currency and tempo of extinction.

PubMed

Regan, H M; Lupia, R; Drinnan, A N; Burgman, M A

2001-01-01

This study examines estimates of extinction rates for the current purported biotic crisis and from the fossil record. Studies that compare current and geological extinctions sometimes use metrics that confound different sources of error and reflect different features of extinction processes. The per taxon extinction rate is a standard measure in paleontology that avoids some of the pitfalls of alternative approaches. Extinction rates reported in the conservation literature are rarely accompanied by measures of uncertainty, despite many elements of the calculations being subject to considerable error. We quantify some of the most important sources of uncertainty and carry them through the arithmetic of extinction rate calculations using fuzzy numbers. The results emphasize that estimates of current and future rates rely heavily on assumptions about the tempo of extinction and on extrapolations among taxa. Available data are unlikely to be useful in measuring magnitudes or trends in current extinction rates.

A review of environmental contributions to childhood motor skills

PubMed Central

Golding, Jean; Emmett, Pauline; Iles-Caven, Yasmin; Steer, Colin; Lingam, Raghu

2013-01-01

Although much of children’s motor skills have a heredity component, at least half of the variance is likely to be influenced by the environment It is important to ascertain features of the environment that are responsible so that toxins can be avoided, children at risk can be identified and beneficial interventions initiated. This review outlines the results of published studies and recommends the areas where further research is required. We found much confusion with little comparability concerning the ages or measures used. Few studies had sufficient power and few allowed for confounders. We found that research to date implicates associations with prenatal drinking ≥4 drinks of alcohol per day; diabetes; taking antidepressant drugs; being deficient in iodine or iron; dietary fish; and postnatal depression. The child appearing to be most at risk was born of low birth weight (but not due to preterm delivery); or with neonatal problems. PMID:24170258

Use of medicines by older people in a large British national survey, and their relation to vitamin status indices.

PubMed

Bates, C J; Walmsley, C M; Prentice, A; Finch, S

1999-03-01

To describe the extent of use of medicines by older people living in Britain, and to explore relationships with vitamin status indices. The National Diet and Nutrition Survey of people aged 65 years and over collected data from a British sample during 1994-95. The present study has made novel use of it, to relate medicine use with biochemical indices of vitamin status. Eighty postcode areas, selected randomly from mainland Britain. 1506 people, 65 years and over gave information about use of medication, and a 4-day weighed food record. Three-quarters gave blood for status indices. 78% of those living in the community and 93% of those in institutions were using medication. Certain vitamin status indices: plasma retinol, erythrocyte folate and riboflavin, paradoxically suggested better status in users than in non-users of antihypertensive, gastrointestinal, central nervous system, corticosteroid or diabetic drugs. There was evidence of a link with renal insufficiency, especially for plasma retinol, but neither this nor increased nutrient intake, acute phase effects or haemoconcentration could explain the paradoxical associations. Caution is needed in interpreting certain vitamin status indices, especially in older people who are extensively using medicines. New vitamin indices are needed, to avoid confounding interferences.

Epidemiologic Tools to Study the Influence of Environmental Factors on Fecundity and Pregnancy-related Outcomes

PubMed Central

Slama, Rémy; Ballester, Ferran; Casas, Maribel; Cordier, Sylvaine; Eggesbø, Merete; Iniguez, Carmen; Nieuwenhuijsen, Mark; Philippat, Claire; Rey, Sylvie; Vandentorren, Stéphanie; Vrijheid, Martine

2014-01-01

Adverse pregnancy outcomes entail a large health burden for the mother and offspring; a part of it might be avoided by better understanding the role of environmental factors in their etiology. Our aims were to review the assessment tools to characterize fecundity troubles and pregnancy-related outcomes in human populations and their sensitivity to environmental factors. For each outcome, we reviewed the possible study designs, main sources of bias, and their suggested cures. In terms of study design, for most pregnancy outcomes, cohorts with recruitment early during or even before pregnancy allow efficient characterization of pregnancy-related events, time-varying confounders, and in utero exposures that may impact birth outcomes and child health. Studies on congenital anomalies require specific designs, assessment of anomalies in medical pregnancy terminations, and, for congenital anomalies diagnosed postnatally, follow-up during several months after birth. Statistical analyses should take into account environmental exposures during the relevant time windows; survival models are an appropriate approach for fecundity, fetal loss, and gestational duration/preterm delivery. Analysis of gestational duration could distinguish pregnancies according to delivery induction (and possibly pregnancy-related conditions). In conclusion, careful design and analysis are required to better characterize environmental effects on human reproduction. PMID:24363355

Restrictive educational placements increase adolescent risks for students with early-starting conduct problems.

PubMed

Powers, Christopher J; Bierman, Karen L; Coffman, Donna L

2016-08-01

Students with early-starting conduct problems often do poorly in school; they are disproportionately placed in restrictive educational placements outside of mainstream classrooms. Although intended to benefit students, research suggests that restrictive placements may exacerbate the maladjustment of youth with conduct problems. Mixed findings, small samples, and flawed designs limit the utility of existing research. This study examined the impact of restrictive educational placements on three adolescent outcomes (high school noncompletion, conduct disorder, depressive symptoms) in a sample of 861 students with early-starting conduct problems followed longitudinally from kindergarten (age 5-6). Causal modeling with propensity scores was used to adjust for confounding factors associated with restrictive placements. Analyses explored the timing of placement (elementary vs. secondary school) and moderation of impact by initial problem severity. Restrictive educational placement in secondary school (but not in elementary school) was iatrogenic, increasing the risk of high school noncompletion and the severity of adolescent conduct disorder. Negative effects were amplified for students with conduct problem behavior with less cognitive impairment. To avoid harm to students and to society, schools must find alternatives to restrictive placements for students with conduct problems in secondary school, particularly when these students do not have cognitive impairments that might warrant specialized educational supports. © 2015 Association for Child and Adolescent Mental Health.

Selective Attention to Semantic and Syntactic Features Modulates Sentence Processing Networks in Anterior Temporal Cortex

PubMed Central

Rogalsky, Corianne

2009-01-01

Numerous studies have identified an anterior temporal lobe (ATL) region that responds preferentially to sentence-level stimuli. It is unclear, however, whether this activity reflects a response to syntactic computations or some form of semantic integration. This distinction is difficult to investigate with the stimulus manipulations and anomaly detection paradigms traditionally implemented. The present functional magnetic resonance imaging study addresses this question via a selective attention paradigm. Subjects monitored for occasional semantic anomalies or occasional syntactic errors, thus directing their attention to semantic integration, or syntactic properties of the sentences. The hemodynamic response in the sentence-selective ATL region (defined with a localizer scan) was examined during anomaly/error-free sentences only, to avoid confounds due to error detection. The majority of the sentence-specific region of interest was equally modulated by attention to syntactic or compositional semantic features, whereas a smaller subregion was only modulated by the semantic task. We suggest that the sentence-specific ATL region is sensitive to both syntactic and integrative semantic functions during sentence processing, with a smaller portion of this area preferentially involved in the later. This study also suggests that selective attention paradigms may be effective tools to investigate the functional diversity of networks involved in sentence processing. PMID:18669589

Rifamycin action on RNA polymerase in antibiotic-tolerant Mycobacterium tuberculosis results in differentially detectable populations.

PubMed

Saito, Kohta; Warrier, Thulasi; Somersan-Karakaya, Selin; Kaminski, Lina; Mi, Jianjie; Jiang, Xiuju; Park, Suna; Shigyo, Kristi; Gold, Ben; Roberts, Julia; Weber, Elaina; Jacobs, William R; Nathan, Carl F

2017-06-13

Mycobacterium tuberculosis (Mtb) encounters stresses during the pathogenesis and treatment of tuberculosis (TB) that can suppress replication of the bacteria and render them phenotypically tolerant to most available drugs. Where studied, the majority of Mtb in the sputum of most untreated subjects with active TB have been found to be nonreplicating by the criterion that they do not grow as colony-forming units (cfus) when plated on agar. However, these cells are viable because they grow when diluted in liquid media. A method for generating such "differentially detectable" (DD) Mtb in vitro would aid studies of the biology and drug susceptibility of this population, but lack of independent confirmation of reported methods has contributed to skepticism about their existence. Here, we identified confounding artifacts that, when avoided, allowed development of a reliable method of producing cultures of ≥90% DD Mtb in starved cells. We then characterized several drugs according to whether they contribute to the generation of DD Mtb or kill them. Of the agents tested, rifamycins led to DD Mtb generation, an effect lacking in a rifampin-resistant strain with a mutation in rpoB , which encodes the canonical rifampin target, the β subunit of RNA polymerase. In contrast, thioridazine did not generate DD Mtb from starved cells but killed those generated by rifampin.

Instrumental variable methods in comparative safety and effectiveness research.

PubMed

Brookhart, M Alan; Rassen, Jeremy A; Schneeweiss, Sebastian

2010-06-01

Instrumental variable (IV) methods have been proposed as a potential approach to the common problem of uncontrolled confounding in comparative studies of medical interventions, but IV methods are unfamiliar to many researchers. The goal of this article is to provide a non-technical, practical introduction to IV methods for comparative safety and effectiveness research. We outline the principles and basic assumptions necessary for valid IV estimation, discuss how to interpret the results of an IV study, provide a review of instruments that have been used in comparative effectiveness research, and suggest some minimal reporting standards for an IV analysis. Finally, we offer our perspective of the role of IV estimation vis-à-vis more traditional approaches based on statistical modeling of the exposure or outcome. We anticipate that IV methods will be often underpowered for drug safety studies of very rare outcomes, but may be potentially useful in studies of intended effects where uncontrolled confounding may be substantial.

Instruction-Based Approach-Avoidance Effects: Changing Stimulus Evaluation via the Mere Instruction to Approach or Avoid Stimuli.

PubMed

Van Dessel, Pieter; De Houwer, Jan; Gast, Anne; Tucker Smith, Colin

2015-01-01

Prior research suggests that repeatedly approaching or avoiding a certain stimulus changes the liking of this stimulus. We investigated whether these effects of approach and avoidance training occur also when participants do not perform these actions but are merely instructed about the stimulus-action contingencies. Stimulus evaluations were registered using both implicit (Implicit Association Test and evaluative priming) and explicit measures (valence ratings). Instruction-based approach-avoidance effects were observed for relatively neutral fictitious social groups (i.e., Niffites and Luupites), but not for clearly valenced well-known social groups (i.e., Blacks and Whites). We conclude that instructions to approach or avoid stimuli can provide sufficient bases for establishing both implicit and explicit evaluations of novel stimuli and discuss several possible reasons for why similar instruction-based approach-avoidance effects were not found for valenced well-known stimuli.

Perceived fairness of pay among people with and without disabilities: a propensity score matched analysis of working Australians.

PubMed

Milner, Allison; Aitken, Zoe; Krnjacki, Lauren; Bentley, Rebecca; Blakely, Tony; LaMontagne, Anthony D; Kavanagh, Anne M

2015-09-01

Equity and fairness at work are associated with a range of organizational and health outcomes. Past research suggests that workers with disabilities experience inequity in the workplace. It is difficult to conclude whether the presence of disability is the reason for perceived unfair treatment due to the possible confounding of effect estimates by other demographic or socioeconomic factors. The data source was the Household, Income, and Labor Dynamics in Australia (HILDA) survey (2001-2012). Propensity for disability was calculated from logistic models including gender, age, education, country of birth, and father's occupational skill level as predictors. We then used nearest neighbor (on propensity score) matched analysis to match workers with disabilities to workers without disability. Results suggest that disability is independently associated with lower fairness of pay after controlling for confounding factors in the propensity score matched analysis; although results do suggest less than half a standard deviation difference, indicating small effects. Similar results were apparent in standard multivariable regression models and alternative propensity score analyses (stratification, covariate adjustment using the propensity score, and inverse probability of treatment weighting). Whilst neither multivariable regression nor propensity scores adjust for unmeasured confounding, and there remains the potential for other biases, similar results for the two methodological approaches to confounder adjustment provide some confidence of an independent association of disability with perceived unfairness of pay. Based on this, we suggest that the disparity in the perceived fairness of pay between people with and without disabilities may be explained by worse treatment of people with disabilities in the workplace.

The impact of in-work tax credit for families on self-rated health in adults: a cohort study of 6900 New Zealanders.

PubMed

Pega, Frank; Carter, Kristie; Kawachi, Ichiro; Davis, Peter; Gunasekara, Fiona Imlach; Lundberg, Olle; Blakely, Tony

2013-08-01

In-work tax credit (IWTC) for families, a welfare-to-work policy intervention, may impact health status by improving income and employment. Most studies estimate that IWTCs in the USA and the UK have no effect on self-rated health (SRH) and several other health outcomes, but these estimates may be biased by confounding. The current study estimates the impact of one such IWTC intervention (called In-Work Tax Credit) on SRH in adults in New Zealand, controlling more fully for confounding. We used data from seven waves (2002-2009) of the Survey of Family, Income and Employment, restricted to a balanced panel of adults in families. The exposures, eligibility for IWTC and the amount of IWTC a family was eligible for, were derived for each wave by applying government eligibility and entitlement criteria. The outcome, SRH, was collected annually. We used fixed effects regression analyses to eliminate time-invariant confounding and adjusted for measured time-varying confounders. Becoming eligible for IWTC was associated with no detectable change in SRH over the past year (β=0.001, 95% CI -0.022 to 0.023). A $1000 increase in the IWTC amount a family was eligible for increased SRH by 0.003 units (95% CI -0.005 to 0.011). This study found that becoming eligible for IWTC or a substantial increase in the IWTC amount was not associated with any detectable difference in SRH over the short term. Future research should investigate the impact of IWTC on health over the longer term.

The Effect of Positive and Negative Feedback on Risk-Taking across Different Contexts.

PubMed

Losecaat Vermeer, Annabel B; Sanfey, Alan G

2015-01-01

Preferences for risky choices have often been shown to be unstable and context-dependent. Though people generally avoid gambles with mixed outcomes, a phenomenon often attributed to loss aversion, contextual factors can impact this dramatically. For example, people typically prefer risky options after a financial loss, while generally choosing safer options after a monetary gain. However, it is unclear what exactly contributes to these preference shifts as a function of prior outcomes, as these gain/loss outcomes are usually confounded with participant performance, and therefore it is unclear whether these effects are driven purely by the monetary gains or losses, or rather by success or failure at the actual task. Here, we experimentally separated the effects of monetary gains/losses from performance success/failure prior to a standard risky choice. Participants performed a task in which they experienced contextual effects: 1) monetary gain or loss based directly on performance, 2) monetary gain or loss that was randomly awarded and was, crucially, independent from performance, and 3) success or failure feedback based on performance, but without any monetary incentive. Immediately following these positive/negative contexts, participants were presented with a gain-loss gamble that they had to decide to either play or pass. We found that risk preferences for identical sets of gambles were biased by positive and negative contexts containing monetary gains and losses, but not by contexts containing performance feedback. This data suggests that the observed framing effects are driven by aversion for monetary losses and not simply by the positive or negative valence of the context, or by potential moods resulting from positive or negative contexts. These results highlight the specific context dependence of risk preferences.

Birth order has no effect on intelligence: a reply and extension of previous findings.

PubMed

Wichman, Aaron L; Rodgers, Joseph Lee; Maccallum, Robert C

2007-09-01

We address points raised by Zajonc and Sulloway, who reject findings showing that birth order has no effect on intelligence. Many objections to findings of null birth-order results seem to stem from a misunderstanding of the difference between study designs where birth order is confounded with true causal influences on intelligence across families and designs that control for some of these influences. We discuss some of the consequences of not appreciating the nature of this difference. When between-family confounds are controlled using appropriate study designs and techniques such as multilevel modeling, birth order is shown not to influence intelligence. We conclude with an empirical investigation of the replicability and generalizability of this approach.

Adult Lifespan Cognitive Variability in the Cross-Sectional Cam-CAN Cohort

PubMed Central

Green, Emma; Shafto, Meredith A.; Matthews, Fiona E.; White, Simon R.

2015-01-01

This study examines variability across the age span in cognitive performance in a cross-sectional, population-based, adult lifespan cohort from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) study (n = 2680). A key question we highlight is whether using measures that are designed to detect age-related cognitive pathology may not be sensitive to, or reflective of, individual variability among younger adults. We present three issues that contribute to the debate for and against age-related increases in variability. Firstly, the need to formally define measures of central tendency and measures of variability. Secondly, in addition to the commonly addressed location-confounding (adjusting for covariates) there may exist changes in measures of variability due to confounder sub-groups. Finally, that increases in spread may be a result of floor or ceiling effects; where the measure is not sensitive enough at all ages. From the Cam-CAN study, a large population-based dataset, we demonstrate the existence of variability-confounding for the immediate episodic memory task; and show that increasing variance with age in our general cognitive measures is driven by a ceiling effect in younger age groups. PMID:26690191

Adult Lifespan Cognitive Variability in the Cross-Sectional Cam-CAN Cohort.

PubMed

Green, Emma; Shafto, Meredith A; Matthews, Fiona E; White, Simon R

2015-12-07

This study examines variability across the age span in cognitive performance in a cross-sectional, population-based, adult lifespan cohort from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) study (n = 2680). A key question we highlight is whether using measures that are designed to detect age-related cognitive pathology may not be sensitive to, or reflective of, individual variability among younger adults. We present three issues that contribute to the debate for and against age-related increases in variability. Firstly, the need to formally define measures of central tendency and measures of variability. Secondly, in addition to the commonly addressed location-confounding (adjusting for covariates) there may exist changes in measures of variability due to confounder sub-groups. Finally, that increases in spread may be a result of floor or ceiling effects; where the measure is not sensitive enough at all ages. From the Cam-CAN study, a large population-based dataset, we demonstrate the existence of variability-confounding for the immediate episodic memory task; and show that increasing variance with age in our general cognitive measures is driven by a ceiling effect in younger age groups.

Education and smoking: confounding or effect modification by phenotypic personality traits?

PubMed

Chapman, Benjamin; Fiscella, Kevin; Duberstein, Paul; Kawachi, Ichiro

2009-12-01

Little is known about whether educational gradients in smoking patterns can be explained by financial measures of socioeconomic status (SES) and/or personality traits. To assess whether the relationship of education to (1) never smoking and (2) having quit smoking would be confounded by financial measures of SES or by personality; whether lower Neuroticism and higher Conscientiousness would be associated with having abstained from or quit smoking; and whether education effects were modified by personality. Using data from the Midlife Development in the US National Survey, 2,429 individuals were classified as current (n = 695), former (n = 999), or never (n = 735) smokers. Multinomial logistic regressions examined study questions. Greater education was strongly associated with both never and former smoking, with no confounding by financial status and personality. Never smoking was associated with lower Openness and higher Conscientiousness, while have quit was associated with higher Neuroticism. Education interacted additively with Conscientiousness to increase and with Openness to decrease the probability of never smoking. Education and personality should be considered unconfounded smoking risks in epidemiologic and clinical studies. Educational associations with smoking may vary by personality dispositions, and prevention and intervention programs should consider both sets of factors.

Effect of breast feeding on intelligence in children: prospective study, sibling pairs analysis, and meta-analysis.

PubMed

Der, Geoff; Batty, G David; Deary, Ian J

2006-11-04

To assess the importance of maternal intelligence, and the effect of controlling for it and other important confounders, in the link between breast feeding and children's intelligence. Examination of the effect of breast feeding on cognitive ability and the impact of a range of potential confounders, in particular maternal IQ, within a national database. Additional analyses compared pairs of siblings from the sample who were and were not breast fed. The results are considered in the context of other studies that have also controlled for parental intelligence via meta-analysis. 1979 US national longitudinal survey of youth. Data on 5475 children, the offspring of 3161 mothers in the longitudinal survey. IQ in children measured by Peabody individual achievement test. The mother's IQ was more highly predictive of breastfeeding status than were her race, education, age, poverty status, smoking, the home environment, or the child's birth weight or birth order. One standard deviation advantage in maternal IQ more than doubled the odds of breast feeding. Before adjustment, breast feeding was associated with an increase of around 4 points in mental ability. Adjustment for maternal intelligence accounted for most of this effect. When fully adjusted for a range of relevant confounders, the effect was small (0.52) and non-significant (95% confidence interval -0.19 to 1.23). The results of the sibling comparisons and meta-analysis corroborated these findings. Breast feeding has little or no effect on intelligence in children. While breast feeding has many advantages for the child and mother, enhancement of the child's intelligence is unlikely to be among them.

Using ecological propensity score to adjust for missing confounders in small area studies.

PubMed

Wang, Yingbo; Pirani, Monica; Hansell, Anna L; Richardson, Sylvia; Blangiardo, Marta

2017-11-09

Small area ecological studies are commonly used in epidemiology to assess the impact of area level risk factors on health outcomes when data are only available in an aggregated form. However, the resulting estimates are often biased due to unmeasured confounders, which typically are not available from the standard administrative registries used for these studies. Extra information on confounders can be provided through external data sets such as surveys or cohorts, where the data are available at the individual level rather than at the area level; however, such data typically lack the geographical coverage of administrative registries. We develop a framework of analysis which combines ecological and individual level data from different sources to provide an adjusted estimate of area level risk factors which is less biased. Our method (i) summarizes all available individual level confounders into an area level scalar variable, which we call ecological propensity score (EPS), (ii) implements a hierarchical structured approach to impute the values of EPS whenever they are missing, and (iii) includes the estimated and imputed EPS into the ecological regression linking the risk factors to the health outcome. Through a simulation study, we show that integrating individual level data into small area analyses via EPS is a promising method to reduce the bias intrinsic in ecological studies due to unmeasured confounders; we also apply the method to a real case study to evaluate the effect of air pollution on coronary heart disease hospital admissions in Greater London. © The Author 2017. Published by Oxford University Press.

The ethics of hastening death during terminal weaning.

PubMed

Walton, Laura; Bell, Dominic

2013-12-01

Withdrawal of life-sustaining medical treatment (LSMT) is under scrutiny as next-of-kin challenge medical decision-making in the courts and established end-of-life pathways are withdrawn in the face of public criticism. With persistent lobbying for medically assisted dying as the other side of the coin, and professional advice that doctors distance themselves from this activity, the fine line between defensible palliative care and hastening a death needs to be unambiguously defined, particularly with additional confounders such as transplantation initiatives. The medical literature in this domain is dominated by ethical debate on euthanasia and medically assisted dying rather than defensibility within intensive care at the point of withdrawal of LSMT. The process and, therefore, the timing of dying is open to manipulation by intensivists, families, other hospital physicians, courts of law and extraneous influences such as organ donation. Intensivists faced with these challenging processes need to consider some key principles to help them navigate the management of dying. They need to demonstrate transparency in order to engender trust, be responsive to the dynamically evolving needs of patient and family, avoid ambiguity, show consistency and predictability and, finally, they need to conform with society's expectations and professional standards to achieve defensibility for their actions. Adherence to these principles is likely to minimize conflict, maximize patient benefit, maintain public confidence and avoid professional jeopardy.

Exploring or Avoiding Novel Food Resources? The Novelty Conflict in an Invasive Bird

PubMed Central

Sol, Daniel; Griffin, Andrea S.; Bartomeus, Ignasi; Boyce, Hayley

2011-01-01

For an animal invading a novel region, the ability to develop new behaviors should facilitate the use of novel food resources and hence increase its survival in the new environment. However, the need to explore new resources may entail costs such as exposing the animal to unfamiliar predators. These two opposing forces result in an exploration-avoidance conflict, which can be expected to interfere with the acquisition of new resources. However, its consequences should be less dramatic in highly urbanized environments where new food opportunities are common and predation risk is low. We tested this hypothesis experimentally by presenting three foraging tasks to introduced common mynas (Acridotheres tristis) from environments with low and high urbanization levels from Australia. Individuals from the highly urbanized environments, where mynas are both more opportunistic when foraging and less fearful to predators, resolved a technical task faster than those from less urbanized environments. These differences did not reflect innovative ‘personalities’ and were not confounded by sex, morphology or motivational state. Rather, the principal factors underlying differences in mynas' problem-solving ability were neophobic-neophilic responses, which varied across habitats. Thus, mynas seem to modulate their problem-solving ability according to the benefits and costs of innovating in their particular habitat, which may help us understand the great success of the species in highly urbanized environments. PMID:21611168

Late pregnancy reversal from excessive gestational weight gain lowers risk of childhood overweight--a cohort study.

PubMed

von Kries, Rüdiger; Chmitorz, Andrea; Rasmussen, Kathleen M; Bayer, Otmar; Ensenauer, Regina

2013-06-01

Whether reversal to adequate gestational weight gain (GWG) in the third trimester reverses the risk for childhood overweight associated with excessive GWG is assessed. In a retrospective cohort study in 6,665 mother-child pairs, pre-pregnancy weight and the temporal course of GWG were collected from medical records. Overweight as defined by International Obesity Task Force was assessed at a mean age of 5.8 years. Main exposures were exceeding week-specific cut-off values for GWG in the third trimester or any previous trimester. Logistic regression models, adjusted for possible confounding factors, were used to predict the risk of childhood overweight from excessive GWG in the third trimester with stratification by excessive GWG in previous trimesters. In the final model, women who avoided excessive GWG in the third trimester had children with a 31% (odds ratio [OR]: 0.69, 95% confidence interval [CI]: 0.59, 0.82) lower probability being overweight. A similar association was observed for reversing from excessive GWG in the first or second trimester to normal GWG in the third trimester: 27% (OR: 0.73, 95% CI: 0.53, 0.99). Avoidance of excessive GWG in the third trimester is associated with lower risk of childhood overweight even in case of excessive GWG in the first or second trimester. Copyright © 2013 The Obesity Society.

Meta-analyses on intra-aortic balloon pump in cardiogenic shock complicating acute myocardial infarction may provide biased results.

PubMed

Acconcia, M C; Caretta, Q; Romeo, F; Borzi, M; Perrone, M A; Sergi, D; Chiarotti, F; Calabrese, C M; Sili Scavalli, A; Gaudio, C

2018-04-01

Intra-aortic balloon pump (IABP) is the device most commonly investigated in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI). Recently meta-analyses on this topic showed opposite results: some complied with the actual guideline recommendations, while others did not, due to the presence of bias. We investigated the reasons for the discrepancy among meta-analyses and strategies employed to avoid the potential source of bias. Scientific databases were searched for meta-analyses of IABP support in AMI complicated by CS. The presence of clinical diversity, methodological diversity and statistical heterogeneity were analyzed. When we found clinical or methodological diversity, we reanalyzed the data by comparing the patients selected for homogeneous groups. When the fixed effect model was employed despite the presence of statistical heterogeneity, the meta-analysis was repeated adopting the random effect model, with the same estimator used in the original meta-analysis. Twelve meta-analysis were selected. Six meta-analyses of randomized controlled trials (RCTs) were inconclusive because underpowered to detect the IABP effect. Five included RCTs and observational studies (Obs) and one only Obs. Some meta-analyses on RCTs and Obs had biased results due to presence of clinical and/or methodological diversity. The reanalysis of data reallocated for homogeneous groups was no more in contrast with guidelines recommendations. Meta-analyses performed without controlling for clinical and/or methodological diversity, represent a confounding message against a good clinical practice. The reanalysis of data demonstrates the validity of the current guidelines recommendations in addressing clinical decision making in providing IABP support in AMI complicated by CS.

Using spaced retrieval and Montessori-based activities in improving eating ability for residents with dementia.

PubMed

Lin, Li-Chan; Huang, Ya-Ju; Su, Su-Gen; Watson, Roger; Tsai, Belina W-J; Wu, Shiao-Chi

2010-10-01

To construct a training protocol for spaced retrieval (SR) and to investigate the effectiveness of SR and Montessori-based activities in decreasing eating difficulty in older residents with dementia. A single evaluator, blind, and randomized control trial was used. Eighty-five residents with dementia were chosen from three special care units for residents with dementia in long-term care facilities in Taiwan. To avoid any confounding of subjects, the three institutions were randomized into three groups: spaced retrieval, Montessori-based activities, and a control group. The invention consisted of three 30-40 min sessions per week, for 8 weeks. After receiving the intervention, the Edinburgh Feeding Evaluation in Dementia (EdFED) scores and assisted feeding scores for the SR and Montessori-based activity groups were significantly lower than that of the control group. However, the frequencies of physical assistance and verbal assistance for the Montessori-based activity group after intervention were significantly higher than that of the control group, which suggests that residents who received Montessori-based activity need more physical and verbal assistance during mealtimes. In terms of the effects of nutritional status after intervention, Mini-Nutritional Assessment (MNA) in the SR group was significantly higher than that of the control group. This study confirms the efficacy of SR and Montessori-based activities for eating difficulty and eating ability. A longitudinal study to follow the long-term effects of SR and Montessori-based activities on eating ability and nutritional status is recommended. Copyright © 2010 John Wiley & Sons, Ltd.

Burrowing as a novel voluntary strength training method for mice: A comparison of various voluntary strength or resistance exercise methods.

PubMed

Roemers, P; Mazzola, P N; De Deyn, P P; Bossers, W J; van Heuvelen, M J G; van der Zee, E A

2018-04-15

Voluntary strength training methods for rodents are necessary to investigate the effects of strength training on cognition and the brain. However, few voluntary methods are available. The current study tested functional and muscular effects of two novel voluntary strength training methods, burrowing (digging a substrate out of a tube) and unloaded tower climbing, in male C57Bl6 mice. To compare these two novel methods with existing exercise methods, resistance running and (non-resistance) running were included. Motor coordination, grip strength and muscle fatigue were measured at baseline, halfway through and near the end of a fourteen week exercise intervention. Endurance was measured by an incremental treadmill test after twelve weeks. Both burrowing and resistance running improved forelimb grip strength as compared to controls. Running and resistance running increased endurance in the treadmill test and improved motor skills as measured by the balance beam test. Post-mortem tissue analyses revealed that running and resistance running induced Soleus muscle hypertrophy and reduced epididymal fat mass. Tower climbing elicited no functional or muscular changes. As a voluntary strength exercise method, burrowing avoids the confounding effects of stress and positive reinforcers elicited in forced strength exercise methods. Compared to voluntary resistance running, burrowing likely reduces the contribution of aerobic exercise components. Burrowing qualifies as a suitable voluntary strength training method in mice. Furthermore, resistance running shares features of strength training and endurance (aerobic) exercise and should be considered a multi-modal aerobic-strength exercise method in mice. Copyright © 2017 Elsevier B.V. All rights reserved.

The Great Recession worsened blood pressure and blood glucose levels in American adults.

PubMed

Seeman, Teresa; Thomas, Duncan; Merkin, Sharon Stein; Moore, Kari; Watson, Karol; Karlamangla, Arun

2018-03-27

Longitudinal, individual-specific data from the Multi-Ethnic Study of Atherosclerosis (MESA) provide support for the hypothesis that the 2008 to 2010 Great Recession (GR) negatively impacted the health of US adults. Results further advance understanding of the relationship by ( i ) illuminating hypothesized greater negative impacts in population subgroups exposed to more severe impacts of the GR and ( ii ) explicitly controlling for confounding by individual differences in age-related changes in health over time. Analyses overcome limitations of prior work by ( i ) employing individual-level data that avoid concerns about ecological fallacy associated with prior reliance on group-level data, ( ii ) using four waves of data before the GR to estimate and control for underlying individual-level age-related trends, ( iii ) focusing on objective, temporally appropriate health outcomes rather than mortality, and ( iv ) leveraging a diverse cohort to investigate subgroup differences in the GR's impact. Innovative individual fixed-effects modeling controlling for individual-level age-related trajectories yielded substantively important insights: ( i ) significant elevations post-GR for blood pressure and fasting glucose, especially among those on medication pre-GR, and ( ii ) reductions in prevalence and intensity of medication use post-GR. Important differences in the effects of the GR are seen across subgroups, with larger effects among younger adults (who are likely still in the labor force) and older homeowners (whose declining home wealth likely reduced financial security, with less scope for recouping losses during their lifetime); least affected were older adults without a college degree (whose greater reliance on Medicare and Social Security likely provided more protection from the recession).

Current challenges for clinical trials of cardiovascular medical devices.

PubMed

Zannad, Faiez; Stough, Wendy Gattis; Piña, Ileana L; Mehran, Roxana; Abraham, William T; Anker, Stefan D; De Ferrari, Gaetano M; Farb, Andrew; Geller, Nancy L; Kieval, Robert S; Linde, Cecilia; Redberg, Rita F; Stein, Kenneth; Vincent, Alphons; Woehrle, Holger; Pocock, Stuart J

2014-07-15

Several features of cardiovascular devices raise considerations for clinical trial conduct. Prospective, randomized, controlled trials remain the highest quality evidence for safety and effectiveness assessments, but, for instance, blinding may be challenging. In order to avoid bias and not confound data interpretation, the use of objective endpoints and blinding patients, study staff, core labs, and clinical endpoint committees to treatment assignment are helpful approaches. Anticipation of potential bias should be considered and planned for prospectively in a cardiovascular device trial. Prospective, single-arm studies (often referred to as registry studies) can provide additional data in some cases. They are subject to selection bias even when carefully designed; thus, they are generally not acceptable as the sole basis for pre-market approval of high risk cardiovascular devices. However, they complement the evidence base and fill the gaps unanswered by randomized trials. Registry studies present device safety and effectiveness in day-to-day clinical practice settings and detect rare adverse events in the post-market period. No single research design will be appropriate for every cardiovascular device or target patient population. The type of trial, appropriate control group, and optimal length of follow-up will depend on the specific device, its potential clinical benefits, the target patient population and the existence (or lack) of effective therapies, and its anticipated risks. Continued efforts on the part of investigators, the device industry, and government regulators are needed to reach the optimal approach for evaluating the safety and performance of innovative devices for the treatment of cardiovascular disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Genetic distortion of the balance between punishment and relief learning in Drosophila.

PubMed

Yarali, Ayse; Krischke, Markus; Michels, Birgit; Saumweber, Timo; Mueller, Martin J; Gerber, Bertram

2009-01-01

An experience with electric shock can support two opposing kinds of behavioral effects: Stimuli that precede shock during training are subsequently avoided as predictors for punishment, whereas stimuli that follow shock during training are later on approached, as they predict relief. We show here, for the fruit fly Drosophila, that upon the loss of white-function, the balance between these two kinds of learning is distorted in favor of punishment learning: white1118 mutants show stronger punishment learning and weaker relief learning, as compared to wild type flies. Thus, white1118 mutants establish, overall, more "negative" memories for the shock experience. This only concerns the mnemonic effects of the shock; the immediate, reflexive responsiveness to shock remains unaltered. Also, learning about reward is apparently unaffected, both in adult and larval Drosophila. Prompted by the proposed function of the White protein as the transporter for biogenic amine precursors, we probed the brains of white1118 mutants for the amounts of biogenic amines (octopamine, tyramine, dopamine, and serotonin) by using high-pressure liquid chromatography coupled to mass spectrometry. Using this method, we found, however, no difference between white1118 and wild type files for any of the probed amines. In any event, analyses of how the white1118 mutation affects the balance between punishment and relief learning should provide a study case of how heritable distortions of such balance can come about. Finally, the effects of the white1118 mutation should be considered as a source of confound when using white as the "marker gene" in behavior-genetic analyses of any sort.

House Dust Mite Respiratory Allergy: An Overview of Current Therapeutic Strategies.

PubMed

Calderón, Moisés A; Kleine-Tebbe, Jörg; Linneberg, Allan; De Blay, Frédéric; Hernandez Fernandez de Rojas, Dolores; Virchow, Johann Christian; Demoly, Pascal

2015-01-01

Although house dust mite (HDM) allergy is a major cause of respiratory allergic disease, specific diagnosis and effective treatment both present unresolved challenges. Guidelines for the treatment of allergic rhinitis and asthma are well supported in the literature, but specific evidence on the efficacy of pharmacotherapy treatment for known HDM-allergic patients is weaker. The standard diagnostic techniques--skin prick test and specific IgE testing--can be confounded by cross-reactivity. However, component-resolved diagnosis using purified and recombinant allergens can improve the accuracy of specific IgE testing, but availability is limited. Treatment options for HDM allergy are limited and include HDM avoidance, which is widely recommended as a strategy, although evidence for its efficacy is variable. Clinical efficacy of pharmacotherapy is well documented; however, symptom relief does not extend beyond the end of treatment. Finally, allergen immunotherapy has a poor but improving evidence base (notably on sublingual tablets) and its benefits last after treatment ends. This review identifies needs for deeper physician knowledge on the extent and impact of HDM allergy in respiratory disease, as well as further development and improved access to molecular allergy diagnosis. Furthermore, there is a need for the development of better-designed clinical trials to explore the utility of allergen-specific approaches, and uptake of data into guidance for physicians on more effective diagnosis and therapy of HDM respiratory allergy in practice. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Omasal sampling technique for assessing fermentative digestion in the forestomach of dairy cows.

PubMed

Huhtanen, P; Brotz, P G; Satter, L D

1997-05-01

A procedure allowing digesta sampling from the omasum via a ruminal cannula without repeated entry into the omasum was developed. The sampling system consisted of a device inserted into the omasum via the ruminal cannula, a tube connecting the device to the ruminal cannula, and a single compressor/vacuum pump. Eight cows given ad libitum access to a total mixed diet were used in a crossover design to evaluate the effects of the sampling system on digestive activity, animal performance, and animal behavior. Results indicated that the omasal sampling system has minimal effect on normal digestive and productive functions of high-producing dairy cows. Dry matter intake was reduced (24.0 vs 21.8 kg/d; P < .02) and seemed related more to the sampling procedures than to the device in the omasum. Observations of animal behavior indicated that cows with the sampling device were similar to control cows, although rumination and total chewing times were reduced slightly. The composition of digesta samples was biased toward an over-abundance of the liquid phase, but using a double-marker system to calculate digesta flow resulted in fairly small coefficients of variation for measurements of ruminal digestion variables. This technique may prove useful for partitioning digestion between the fermentative portion of the forestomach and the lower gastrointestinal tract. The omasal sampling procedure requires less surgical intervention than the traditional methods using abomasal or duodenal cannulas as sampling sites to study forestomach digestion and avoids potentially confounding endogenous secretions of the abomasum.

Compounding Effects of Agricultural Land Use and Water Use in Free-Flowing Rivers: Confounding Issues for Environmental Flows

NASA Astrophysics Data System (ADS)

Hardie, Scott A.; Bobbi, Chris J.

2018-03-01

Defining the ecological impacts of water extraction from free-flowing river systems in altered landscapes is challenging as multiple stressors (e.g., flow regime alteration, increased sedimentation) may have simultaneous effects and attributing causality is problematic. This multiple-stressor context has been acknowledged in environmental flows science, but is often neglected when it comes to examining flow-ecology relationships, and setting and implementing environmental flows. We examined the impacts of land and water use on rivers in the upper Ringarooma River catchment in Tasmania (south-east Australia), which contains intensively irrigated agriculture, to support implementation of a water management plan. Temporal and spatial and trends in river condition were assessed using benthic macroinvertebrates as bioindicators. Relationships between macroinvertebrate community structure and environmental variables were examined using univariate and multivariate analyses, focusing on the impacts of agricultural land use and water use. Structural changes in macroinvertebrate communities in rivers in the catchment indicated temporal and spatial declines in the ecological condition of some stretches of river associated with agricultural land and water use. Moreover, water extraction appeared to exacerbate impairment associated with agricultural land use (e.g., reduced macroinvertebrate density, more flow-avoiding taxa). The findings of our catchment-specific bioassessments will underpin decision-making during the implementation of the Ringarooma water management plan, and highlight the need to consider compounding impacts of land and water use in environmental flows and water planning in agricultural landscapes.

Compounding Effects of Agricultural Land Use and Water Use in Free-Flowing Rivers: Confounding Issues for Environmental Flows.

PubMed

Hardie, Scott A; Bobbi, Chris J

2018-03-01

Defining the ecological impacts of water extraction from free-flowing river systems in altered landscapes is challenging as multiple stressors (e.g., flow regime alteration, increased sedimentation) may have simultaneous effects and attributing causality is problematic. This multiple-stressor context has been acknowledged in environmental flows science, but is often neglected when it comes to examining flow-ecology relationships, and setting and implementing environmental flows. We examined the impacts of land and water use on rivers in the upper Ringarooma River catchment in Tasmania (south-east Australia), which contains intensively irrigated agriculture, to support implementation of a water management plan. Temporal and spatial and trends in river condition were assessed using benthic macroinvertebrates as bioindicators. Relationships between macroinvertebrate community structure and environmental variables were examined using univariate and multivariate analyses, focusing on the impacts of agricultural land use and water use. Structural changes in macroinvertebrate communities in rivers in the catchment indicated temporal and spatial declines in the ecological condition of some stretches of river associated with agricultural land and water use. Moreover, water extraction appeared to exacerbate impairment associated with agricultural land use (e.g., reduced macroinvertebrate density, more flow-avoiding taxa). The findings of our catchment-specific bioassessments will underpin decision-making during the implementation of the Ringarooma water management plan, and highlight the need to consider compounding impacts of land and water use in environmental flows and water planning in agricultural landscapes.

Respiratory carcinogenicity assessment of soluble nickel compounds.

PubMed Central

Oller, Adriana R

2002-01-01

The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear because of limitations of the exposure data, inconsistent results across cohorts, and the presence of mixed exposures to water-insoluble nickel compounds and other confounders that are known or suspected carcinogens. Moreover, well-conducted animal inhalation studies, where exposures were solely to soluble nickel, failed to demonstrate a carcinogenic potential. Similar negative results were seen in animal oral studies. A model exists that relates respiratory carcinogenic potential to the bioavailability of nickel ion at nuclear sites within respiratory target cells. This model helps reconcile human, animal, and mechanistic data for soluble nickel compounds. For inhalation exposures, the predicted lack of bioavailability of nickel ion at target sites suggests that water-soluble nickel compounds, by themselves, will not be complete human carcinogens. However, if inhaled at concentrations high enough to induce chronic lung inflammation, these compounds may enhance carcinogenic risks associated with inhalation exposure to other substances. Overall, the weight of evidence indicates that inhalation exposure to soluble nickel alone will not cause cancer; moreover, if exposures are kept below levels that cause chronic respiratory toxicity, any possible tumor-enhancing effects (particularly in smokers) would be avoided. PMID:12426143

Complacency and Automation Bias in the Use of Imperfect Automation.

PubMed

Wickens, Christopher D; Clegg, Benjamin A; Vieane, Alex Z; Sebok, Angelia L

2015-08-01

We examine the effects of two different kinds of decision-aiding automation errors on human-automation interaction (HAI), occurring at the first failure following repeated exposure to correctly functioning automation. The two errors are incorrect advice, triggering the automation bias, and missing advice, reflecting complacency. Contrasts between analogous automation errors in alerting systems, rather than decision aiding, have revealed that alerting false alarms are more problematic to HAI than alerting misses are. Prior research in decision aiding, although contrasting the two aiding errors (incorrect vs. missing), has confounded error expectancy. Participants performed an environmental process control simulation with and without decision aiding. For those with the aid, automation dependence was created through several trials of perfect aiding performance, and an unexpected automation error was then imposed in which automation was either gone (one group) or wrong (a second group). A control group received no automation support. The correct aid supported faster and more accurate diagnosis and lower workload. The aid failure degraded all three variables, but "automation wrong" had a much greater effect on accuracy, reflecting the automation bias, than did "automation gone," reflecting the impact of complacency. Some complacency was manifested for automation gone, by a longer latency and more modest reduction in accuracy. Automation wrong, creating the automation bias, appears to be a more problematic form of automation error than automation gone, reflecting complacency. Decision-aiding automation should indicate its lower degree of confidence in uncertain environments to avoid the automation bias. © 2015, Human Factors and Ergonomics Society.

Visual context processing deficits in schizophrenia: effects of deafness and disorganization.

PubMed

Horton, Heather K; Silverstein, Steven M

2011-07-01

Visual illusions allow for strong tests of perceptual functioning. Perceptual impairments can produce superior task performance on certain tasks (i.e., more veridical perception), thereby avoiding generalized deficit confounds while tapping mechanisms that are largely outside of conscious control. Using a task based on the Ebbinghaus illusion, a perceptual phenomenon where the perceived size of a central target object is affected by the size of surrounding inducers, we tested hypotheses related to visual integration in deaf (n = 31) and hearing (n = 34) patients with schizophrenia. In past studies, psychiatrically healthy samples displayed increased visual integration relative to schizophrenia samples and thus were less able to correctly judge target sizes. Deafness, and especially the use of sign language, leads to heightened sensitivity to peripheral visual cues and increased sensitivity to visual context. Therefore, relative to hearing subjects, deaf subjects were expected to display increased context sensitivity (ie, a more normal illusion effect as evidenced by a decreased ability to correctly judge central target sizes). Confirming the hypothesis, deaf signers were significantly more sensitive to the illusion than nonsigning hearing patients. Moreover, an earlier age of sign language acquisition, higher levels of linguistic ability, and shorter illness duration were significantly related to increased context sensitivity. As predicted, disorganization was associated with reduced context sensitivity for all subjects. The primary implications of these data are that perceptual organization impairment in schizophrenia is plastic and that it is related to a broader failure in coordinating cognitive activity.

"Watch out!": Effects of instructed threat and avoidance on human free-operant approach-avoidance behavior.

PubMed

Schlund, Michael W; Treacher, Kay; Preston, Oli; Magee, Sandy K; Richman, David M; Brewer, Adam T; Cameron, Gemma; Dymond, Simon

2017-01-01

Approach-avoidance paradigms create a competition between appetitive and aversive contingencies and are widely used in nonhuman research on anxiety. Here, we examined how instructions about threat and avoidance impact control by competing contingencies over human approach-avoidance behavior. Additionally, Experiment 1 examined the effects of threat magnitude (money loss amount) and avoidance cost (fixed ratio requirements), whereas Experiment 2 examined the effects of threat information (available, unavailable and inaccurate) on approach-avoidance. During the task, approach responding was modeled by reinforcing responding with money on a FR schedule. By performing an observing response, participants produced an escalating "threat meter". Instructions stated that the threat meter levels displayed the current probability of losing money, when in fact loss only occurred when the level reached the maximum. Instructions also stated pressing an avoidance button lowered the threat level. Overall, instructions produced cycles of approach and avoidance responding with transitions from approach to avoidance when threat was high and transitions back to approach after avoidance reduced threat. Experiment 1 revealed increasing avoidance cost, but not threat magnitude, shifted approach-avoidance transitions to higher threat levels and increased anxiety ratings, but did not influence the frequency of approach-avoidance cycles. Experiment 2 revealed when threat level information was available or absent earnings were high, but earnings decreased when inaccurate threat information was incompatible with contingencies. Our findings build on prior nonhuman and human approach-avoidance research by highlighting how instructed threat and avoidance can impact human AA behavior and self-reported anxiety. © 2017 Society for the Experimental Analysis of Behavior.

Is incremental hemodialysis ready to return on the scene? From empiricism to kinetic modelling.

PubMed

Basile, Carlo; Casino, Francesco Gaetano; Kalantar-Zadeh, Kamyar

2017-08-01

Most people who make the transition to maintenance dialysis therapy are treated with a fixed dose thrice-weekly hemodialysis regimen without considering their residual kidney function (RKF). The RKF provides effective and naturally continuous clearance of both small and middle molecules, plays a major role in metabolic homeostasis, nutritional status, and cardiovascular health, and aids in fluid management. The RKF is associated with better patient survival and greater health-related quality of life, although these effects may be confounded by patient comorbidities. Preservation of the RKF requires a careful approach, including regular monitoring, avoidance of nephrotoxins, gentle control of blood pressure to avoid intradialytic hypotension, and an individualized dialysis prescription including the consideration of incremental hemodialysis. There is currently no standardized method for applying incremental hemodialysis in practice. Infrequent (once- to twice-weekly) hemodialysis regimens are often used arbitrarily, without knowing which patients would benefit the most from them or how to escalate the dialysis dose as RKF declines over time. The recently heightened interest in incremental hemodialysis has been hindered by the current limitations of the urea kinetic models (UKM) which tend to overestimate the dialysis dose required in the presence of substantial RKF. This is due to an erroneous extrapolation of the equivalence between renal urea clearance (Kru) and dialyser urea clearance (Kd), correctly assumed by the UKM, to the clinical domain. In this context, each ml/min of Kd clears the urea from the blood just as 1 ml/min of Kru does. By no means should such kinetic equivalence imply that 1 ml/min of Kd is clinically equivalent to 1 ml/min of urea clearance provided by the native kidneys. A recent paper by Casino and Basile suggested a variable target model (VTM) as opposed to the fixed model, because the VTM gives more clinical weight to the RKF and allows less frequent hemodialysis treatments at lower RKF. The potentially important clinical and financial implications of incremental hemodialysis render it highly promising and warrant randomized controlled trials.

Management of late-preterm and term infants with hyperbilirubinaemia in resource-constrained settings.

PubMed

Olusanya, Bolajoko O; Ogunlesi, Tinuade A; Kumar, Praveen; Boo, Nem-Yun; Iskander, Iman F; de Almeida, Maria Fernanda B; Vaucher, Yvonne E; Slusher, Tina M

2015-04-12

Hyperbilirubinaemia is a ubiquitous transitional morbidity in the vast majority of newborns and a leading cause of hospitalisation in the first week of life worldwide. While timely and effective phototherapy and exchange transfusion are well proven treatments for severe neonatal hyperbilirubinaemia, inappropriate or ineffective treatment of hyperbilirubinaemia, at secondary and tertiary hospitals, still prevails in many poorly-resourced countries accounting for a disproportionately high burden of bilirubin-induced mortality and long-term morbidity. As part of the efforts to curtail the widely reported risks of frequent but avoidable bilirubin-induced neurologic dysfunction (acute bilirubin encephalopathy (ABE) and kernicterus) in low and middle-income countries (LMICs) with significant resource constraints, this article presents a practical framework for the management of late-preterm and term infants (≥ 35 weeks of gestation) with clinically significant hyperbilirubinaemia in these countries particularly where local practice guidelines are lacking. Standard and validated protocols were followed in adapting available evidence-based national guidelines on the management of hyperbilirubinaemia through a collaboration among clinicians and experts on newborn jaundice from different world regions. Tasks and resources required for the comprehensive management of infants with or at risk of severe hyperbilirubinaemia at all levels of healthcare delivery are proposed, covering primary prevention, early detection, diagnosis, monitoring, treatment, and follow-up. Additionally, actionable treatment or referral levels for phototherapy and exchange transfusion are proposed within the context of several confounding factors such as widespread exclusive breastfeeding, infections, blood group incompatibilities and G6PD deficiency, which place infants at high risk of severe hyperbilirubinaemia and bilirubin-induced neurologic dysfunction in LMICs, as well as the limited facilities for clinical investigations and inconsistent functionality of available phototherapy devices. The need to adjust these levels as appropriate depending on the available facilities in each clinical setting and the risk profile of the infant is emphasised with a view to avoiding over-treatment or under-treatment. These recommendations should serve as a valuable reference material for health workers, guide the development of contextually-relevant national guidelines in each LMIC, as well as facilitate effective advocacy and mobilisation of requisite resources for the optimal care of infants with hyperbilirubinaemia at all levels.

Valence, arousal, familiarity, concreteness, and imageability ratings for 292 two-character Chinese nouns in Cantonese speakers in Hong Kong.

PubMed

Yee, Lydia T S

2017-01-01

Words are frequently used as stimuli in cognitive psychology experiments, for example, in recognition memory studies. In these experiments, it is often desirable to control for the words' psycholinguistic properties because differences in such properties across experimental conditions might introduce undesirable confounds. In order to avoid confounds, studies typically check to see if various affective and lexico-semantic properties are matched across experimental conditions, and so databases that contain values for these properties are needed. While word ratings for these variables exist in English and other European languages, ratings for Chinese words are not comprehensive. In particular, while ratings for single characters exist, ratings for two-character words-which often have different meanings than their constituent characters, are scarce. In this study, ratings for 292 two-character Chinese nouns were obtained from Cantonese speakers in Hong Kong. Affective variables, including valence and arousal, and lexico-semantic variables, including familiarity, concreteness, and imageability, were rated in the study. The words were selected from a film subtitle database containing word frequency information that could be extracted and listed alongside the resulting ratings. Overall, the subjective ratings showed good reliability across all rated dimensions, as well as good reliability within and between the different groups of participants who each rated a subset of the words. Moreover, several well-established relationships between the variables found consistently in other languages were also observed in this study, demonstrating that the ratings are valid. The resulting word database can be used in studies where control for the above psycholinguistic variables is critical to the research design.

Re-examining Definitions of Spirituality in Nursing Research

PubMed Central

Garcia, Katia; KOENIG, Harold G.

2013-01-01

Aim This article presents a discussion of the definition of spirituality and its limitations for nursing research. It proposes a definition that will capture more accurately the role of spirituality in health outcomes. Background Studies have increasingly examined spirituality in nursing research as a coping mechanism attenuating the negative impact of traumatic stress on mental health. Existing definitions of spirituality in nursing research include elements of positive emotional states (meaning, purpose, general well-being) which confound mental health outcomes. Data sources Medline and CINAHL databases were searched from 2007–2011 for research articles examining spirituality definitions and measures used by nurse researchers. Discussion An analysis of the definitions of spirituality in nursing research reveals inconsistencies and confounding mental health concepts. The authors propose defining spirituality in the context of religious involvement when conducting research, while using a broader definition of spirituality when providing spiritual care. They argue such definition provides a more appropriate method of measuring this concept in research aimed at evaluating mental health outcomes while preserving the currently used patient- defined definition of spirituality when providing spiritual care. Nursing Implications A consistent definition of spirituality in nursing research evaluating mental health outcomes, distinct from ‘spiritual care’ in a clinical setting, is essential to avoid tautological results that are meaningless. Appropriate definitions will enable nursing researchers to more clearly identify resilience mechanisms and improved health outcomes in those exposed to traumatic stress. Conclusion A definition of spirituality that focuses on religious involvement provides a more uniform and consistent measure for evaluating mental health outcomes in nursing research. PMID:23600849

Association between depression and glycemic control among type 2 diabetes patients in Lima, Peru.

PubMed

Crispín-Trebejo, Brenda; Robles-Cuadros, María Cristina; Bernabé-Ortiz, Antonio

2015-12-01

There is limited and controversial information regarding the potential impact of depression on glycemic control. This study aims to evaluate the association between depression and poor glycemic control. In addition, the prevalence of depression and rates of poor glycemic control were determined. Cross-sectional study performed in the endocrinology unit of two hospitals of ESSALUD in Peru. The outcome of interest was poor glycemic control, evaluated by glycated hemoglobin (HbA1c: <7% versus ≥7%), whereas the exposure of interest was depression defined as 15 or more points in the Patient Health Questionnaire-9 tool. The association of interest was evaluated using Poisson regression models with robust standard errors reporting prevalence ratios (PR) and 95% confidence intervals (95% CI) adjusting for potential confounders. A total of 277 participants, 184 (66.4%) males, mean age 59.0 (SD: 4.8), and 7.1 (SD: 6.8) years of disease were analyzed. Only 31 participants (11.2%; 95% CI: 7.5%-14.9%) had moderately severe or severe depression, whereas 70 (25.3%; 95% CI 20.3%-30.8%) had good glycemic control. Depression increased the probability of having poor glycemic control (PR=1.32; 95% CI 1.15-1.51) after adjusting for several potential confounders. There is an association between depression and poor glycemic control among type 2 diabetes patients. Our results suggest that early detection of depression might be important to facilitate appropriate glycemic control and avoid further metabolic complications. © 2015 Wiley Publishing Asia Pty Ltd.

Association between depression and glycemic control among type 2 diabetes patients in Lima, Peru

PubMed Central

Crispín‐Trebejo, Brenda; Bernabé‐Ortiz, Antonio

2015-01-01

Abstract Introduction There is limited and controversial information regarding the potential impact of depression on glycemic control. This study aims to evaluate the association between depression and poor glycemic control. In addition, the prevalence of depression and rates of poor glycemic control were determined. Methods Cross‐sectional study performed in the endocrinology unit of two hospitals of ESSALUD in Peru. The outcome of interest was poor glycemic control, evaluated by glycated hemoglobin (HbA1c: < 7% versus ≥ 7%), whereas the exposure of interest was depression defined as 15 or more points in the Patient Health Questionnaire‐9 tool. The association of interest was evaluated using Poisson regression models with robust standard errors reporting prevalence ratios (PR) and 95% confidence intervals (95% CI) adjusting for potential confounders. Results A total of 277 participants, 184 (66.4%) males, mean age 59.0 (SD: 4.8), and 7.1 (SD: 6.8) years of disease were analyzed. Only 31 participants (11.2%; 95% CI: 7.5%–14.9%) had moderately severe or severe depression, whereas 70 (25.3%; 95% CI 20.3%–30.8%) had good glycemic control. Depression increased the probability of having poor glycemic control (PR = 1.32; 95% CI 1.15–1.51) after adjusting for several potential confounders. Conclusions There is an association between depression and poor glycemic control among type 2 diabetes patients. Our results suggest that early detection of depression might be important to facilitate appropriate glycemic control and avoid further metabolic complications. PMID:26037488

Untangling the relative contribution of maltreatment severity and frequency to type of behavioral outcome in foster youth

PubMed Central

Jackson, Yo; Gabrielli, Joy; Fleming, Kandace; Makanui, P. Kalani; Tunno, Angela M.

2014-01-01

Within maltreatment research, type, frequency, and severity of abuse are often confounded and not always specifically documented. The result is that samples are often heterogeneous, and the role of components of maltreatment in predicting outcome is unclear. The purpose of the present study was to identify and test the potential unique role of type, frequency, and severity of maltreatment to elucidate each variable’s role in predicting outcome behavior. Data from 309 youth in foster care (ages 8–22) and their caregivers were collected using the Modified Maltreatment Classification System and the Behavioral Assessment System for Children, 2nd Edition (BASC2), to measure maltreatment exposure and behavioral outcome respectively. A measurement model of the BASC2 was completed to determine model fit within the sample data. A second confirmatory factor analysis (CFA) was completed to determine the unique contributions of frequency and severity of maltreatment across four types of abuse to externalizing, internalizing, and adaptive behavior. The result of the CFA determined good fit of the BASC2 to the sample data after a few modifications. The result of the second CFA indicated that the paths from severity to externalizing behavior and adaptive behavior (reverse loading) were significant. Paths from frequency of abuse were not predictive of behavioral outcome. Maltreatment is a complex construct and researchers are encouraged to avoid confounding components of abuse that may be differentially related to outcome behavior for youth. Untangling the multifaceted nature of abuse is important and may have implications for identifying specific outcomes for youth exposed to maltreatment. PMID:24612908

Risk Factors in Adolescent Hypertension

PubMed Central

Ewald, D. Rose; Haldeman, Lauren A.

2016-01-01

Hypertension is a complex and multifaceted disease, with many contributing factors. While diet and nutrition are important influences, the confounding effects of overweight and obesity, metabolic and genetic factors, racial and ethnic predispositions, socioeconomic status, cultural influences, growth rate, and pubertal stage have even more influence and make diagnosis quite challenging. The prevalence of hypertension in adolescents far exceeds the numbers who have been diagnosed; studies have found that 75% or more go undiagnosed. This literature review summarizes the challenges of blood pressure classification in adolescents, discusses the impact of these confounding influences, and identifies actions that will improve diagnosis and treatment outcomes. PMID:27335997

Testing Maternal Depression and Attachment Style as Moderators of Early Head Start's Effects on Parenting

PubMed Central

Berlin, Lisa J.; Whiteside-Mansell, Leanne; Roggman, Lori A.; Green, Beth L.; Robinson, JoAnn; Spieker, Susan

2010-01-01

This study examined maternal depression, attachment avoidance, and attachment anxiety as moderators of Early Head Start's effects on four parenting outcomes assessed at age 3. Participants (N = 947) were drawn from six sites of the Early Head Start National Research and Evaluation Project, a multi-site randomized trial. Findings suggest more positive program effects for mothers with less initial attachment avoidance or attachment anxiety. First, baseline attachment avoidance moderated EHS program effects on observed maternal supportiveness, such that program mothers with lower baseline attachment avoidance were rated as more supportive of their 3-year-olds than program mothers with higher baseline attachment avoidance. Second, program effects on spanking varied depending on mothers’ baseline attachment anxiety. PMID:21240694

Testing maternal depression and attachment style as moderators of Early Head Start's effects on parenting.

PubMed

Berlin, Lisa J; Whiteside-Mansell, Leanne; Roggman, Lori A; Green, Beth L; Robinson, JoAnn; Spieker, Susan

2011-01-01

This study examined maternal depression, attachment avoidance, and attachment anxiety as moderators of Early Head Start's effects on four parenting outcomes assessed at age three. Participants (N = 947) were drawn from six sites of the Early Head Start National Research and Evaluation Project, a multi-site randomized trial. Findings suggest more positive program effects for mothers with less initial attachment avoidance or attachment anxiety. First, baseline attachment avoidance moderated Early Head Start program effects on observed maternal supportiveness, such that program mothers with lower baseline attachment avoidance were rated as more supportive of their three-year-olds than program mothers with higher baseline attachment avoidance. Second, program effects on spanking varied depending on mothers' baseline attachment anxiety.

Task-independent effects are potential confounders in longitudinal imaging studies of learning in schizophrenia.

PubMed

Korostil, Michele; Fatima, Zainab; Kovacevic, Natasha; Menon, Mahesh; McIntosh, Anthony Randal

2016-01-01

Learning impairment is a core deficit in schizophrenia that impacts on real-world functioning and yet, elucidating its underlying neural basis remains a challenge. A key issue when interpreting learning-task experiments is that task-independent changes may confound interpretation of task-related signal changes in neuroimaging studies. The nature of these task-independent changes in schizophrenia is unknown. Therefore, we examined task-independent "time effects" in a group of participants with schizophrenia contrasted with healthy participants in a longitudinal fMRI learning-experiment designed to allow for examination of non-specific effects of time. Flanking the learning portions of the experiment with a task-of-no-interest allowed us to extract task-independent BOLD changes. Task-independent effects occurred in both groups, but were more robust in the schizophrenia group. There was a significant interaction effect between group and time in a distributed activity pattern that included inferior and superior temporal regions, frontal areas (left anterior insula and superior medial gyri), and parietal areas (posterior cingulate cortices and precuneus). This pattern showed task-independent linear decrease in BOLD amplitude over the two scanning sessions for the schizophrenia group, but showed either opposite effect or no activity changes for the control group. There was a trend towards a correlation between task-independent effects and the presence of more negative symptoms in the schizophrenia group. The strong interaction between group and time suggests that both the scanning experience as a whole and the transition between task-types evokes a different response in persons with schizophrenia and may confound interpretation of learning-related longitudinal imaging experiments if not explicitly considered.

An epidemiological and toxicological evaluation of the carcinogenicity of man-made vitreous fiber, with a consideration of coexposures.

PubMed

Wong, O; Musselman, R P

1994-01-01

Exposure to man-made mineral (or vitreous) fiber (MMMF or MMVF) is a potential health concern in both occupational and environmental settings. Previous epidemiologic studies have reported a small increase of lung cancer among workers exposed to MMVF. Most of these studies were cohort studies and lacked information on fiber concentration, occupational coexposures, and cigarette smoking. Some of the coexposures were known human lung carcinogens and could have accounted for the small lung cancer excess. In a recently completed epidemiologic case-control study of lung cancer in MMVF workers exposed to slag wool fibers, we analyzed lung cancer risk in relation to cumulative fiber exposure (concentration and duration) and smoking history and controlled for other coexposures such as asbestos contamination. No increased lung cancer risk with exposure to slag wool fibers was found. As expected, however, we detected a strong confounding effect of smoking. The findings from this epidemiologic study were consistent with the results of recently completed toxicologic studies, which found that slag wool fibers of dimension classically associated with tumor induction ("Stanton" fibers) do not stay in the lung in sufficient quantity or time to induce tumors in animals. In this paper we emphasize the importance of confounding effects due to coexposures and provide guidelines to estimate the magnitude of potential confounding effects of coexposures such as smoking.

Maternal Smoking during Pregnancy and Children's Cognitive and Physical Development: A Causal Risk Factor?

PubMed Central

Gardener, Hannah; Buka, Stephen L.

2008-01-01

There remains considerable debate regarding the effects of maternal smoking during pregnancy on children's growth and development. Evidence that exposure to maternal smoking during pregnancy is associated with numerous adverse outcomes is contradicted by research suggesting that these associations are spurious. The authors investigated the relation between maternal smoking during pregnancy and 14 developmental outcomes of children from birth through age 7 years, using data from the Collaborative Perinatal Project (1959–1974; n = 52,919). In addition to adjusting for potential confounders measured contemporaneously with maternal smoking, the authors fitted conditional fixed-effects models among siblings that controlled for unmeasured confounders. Results from the conditional analyses indicated a birth weight difference of −85.63 g associated with smoking of ≥20 cigarettes daily during pregnancy (95% confidence interval: −131.91, −39.34) and 2.73 times' higher odds of being overweight at age 7 years (95% confidence interval: 1.30, 5.71). However, the associations between maternal smoking and 12 other outcomes studied (including Apgar score, intelligence, academic achievement, conduct problems, and asthma) were entirely eliminated after adjustment for measured and unmeasured confounders. The authors conclude that the hypothesized effects of maternal smoking during pregnancy on these outcomes either are not present or are not distinguishable from a broader range of familial factors associated with maternal smoking. PMID:18653646

Instrumental variable applications using nursing home prescribing preferences in comparative effectiveness research.

PubMed

Huybrechts, Krista F; Gerhard, Tobias; Franklin, Jessica M; Levin, Raisa; Crystal, Stephen; Schneeweiss, Sebastian

2014-08-01

Nursing home residents are of particular interest for comparative effectiveness research given their susceptibility to adverse treatment effects and systematic exclusion from trials. However, the risk of residual confounding because of unmeasured markers of declining health using conventional analytic methods is high. We evaluated the validity of instrumental variable (IV) methods based on nursing home prescribing preference to mitigate such confounding, using psychotropic medications to manage behavioral problems in dementia as a case study. A cohort using linked data from Medicaid, Medicare, Minimum Data Set, and Online Survey, Certification and Reporting for 2001-2004 was established. Dual-eligible patients ≥65 years who initiated psychotropic medication use after admission were selected. Nursing home prescribing preference was characterized using mixed-effects logistic regression models. The plausibility of IV assumptions was explored, and the association between psychotropic medication class and 180-day mortality was estimated. High-prescribing and low-prescribing nursing homes differed by a factor of 2. Each preference-based IV measure described a substantial proportion of variation in psychotropic medication choice (β(IV → treatment): 0.22-0.36). Measured patient characteristics were well balanced across patient groups based on instrument status (52% average reduction in Mahalanobis distance). There was no evidence that instrument status was associated with markers of nursing home quality of care. Findings indicate that IV analyses using nursing home prescribing preference may be a useful approach in comparative effectiveness studies, and should extend naturally to analyses including untreated comparison groups, which are of great scientific interest but subject to even stronger confounding. Copyright © 2014 John Wiley & Sons, Ltd.

Concurrent and Sustained Cumulative Effects of Adolescent Marijuana Use on Subclinical Psychotic Symptoms.

PubMed

Bechtold, Jordan; Hipwell, Alison; Lewis, David A; Loeber, Rolf; Pardini, Dustin

2016-08-01

Adolescents who regularly use marijuana may be at heightened risk of developing subclinical and clinical psychotic symptoms. However, this association could be explained by reverse causation or other factors. To address these limitations, the current study examined whether adolescents who engage in regular marijuana use exhibit a systematic increase in subclinical psychotic symptoms that persists during periods of sustained abstinence. The sample comprised 1,009 boys who were recruited in 1st and 7th grades. Self-reported frequency of marijuana use, subclinical psychotic symptoms, and several time-varying confounds (e.g., other substance use, internalizing/externalizing problems) were recorded annually from age 13 to 18. Fixed-effects (within-individual change) models examined whether adolescents exhibited an increase in their subclinical psychotic symptoms as a function of their recent and/or cumulative history of regular marijuana use and whether these effects were sustained following abstinence. Models controlled for all time-stable factors (default) and several time-varying covariates as potential confounds. For each year adolescent boys engaged in regular marijuana use, their expected level of subsequent subclinical psychotic symptoms rose by 21% and their expected odds of experiencing subsequent subclinical paranoia or hallucinations rose by 133% and 92%, respectively. The effect of prior regular marijuana use on subsequent subclinical psychotic symptoms persisted even when adolescents stopped using marijuana for a year. These effects were after controlling for all time-stable and several time-varying confounds. No support was found for reverse causation. These results suggest that regular marijuana use may significantly increase the risk that an adolescent will experience persistent subclinical psychotic symptoms.

Refining adverse drug reaction signals by incorporating interaction variables identified using emergent pattern mining.

PubMed

Reps, Jenna M; Aickelin, Uwe; Hubbard, Richard B

2016-02-01

To develop a framework for identifying and incorporating candidate confounding interaction terms into a regularised cox regression analysis to refine adverse drug reaction signals obtained via longitudinal observational data. We considered six drug families that are commonly associated with myocardial infarction in observational healthcare data, but where the causal relationship ground truth is known (adverse drug reaction or not). We applied emergent pattern mining to find itemsets of drugs and medical events that are associated with the development of myocardial infarction. These are the candidate confounding interaction terms. We then implemented a cohort study design using regularised cox regression that incorporated and accounted for the candidate confounding interaction terms. The methodology was able to account for signals generated due to confounding and a cox regression with elastic net regularisation correctly ranking the drug families known to be true adverse drug reactions above those that are not. This was not the case without the inclusion of the candidate confounding interaction terms, where confounding leads to a non-adverse drug reaction being ranked highest. The methodology is efficient, can identify high-order confounding interactions and does not require expert input to specify outcome specific confounders, so it can be applied for any outcome of interest to quickly refine its signals. The proposed method shows excellent potential to overcome some forms of confounding and therefore reduce the false positive rate for signal analysis using longitudinal data. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of Alternative Difference-in-Differences Methods

ERIC Educational Resources Information Center

Yu, Bing

2013-01-01

Difference-in-differences (DID) strategies are particularly useful for evaluating policy effects in natural experiments in which, for example, a policy affects some schools and students but not others. However, the standard DID method may produce biased estimation of the policy effect if the confounding effect of concurrent events varies by…

Intuitive Logic Revisited: New Data and a Bayesian Mixed Model Meta-Analysis

PubMed Central

Singmann, Henrik; Klauer, Karl Christoph; Kellen, David

2014-01-01

Recent research on syllogistic reasoning suggests that the logical status (valid vs. invalid) of even difficult syllogisms can be intuitively detected via differences in conceptual fluency between logically valid and invalid syllogisms when participants are asked to rate how much they like a conclusion following from a syllogism (Morsanyi & Handley, 2012). These claims of an intuitive logic are at odds with most theories on syllogistic reasoning which posit that detecting the logical status of difficult syllogisms requires effortful and deliberate cognitive processes. We present new data replicating the effects reported by Morsanyi and Handley, but show that this effect is eliminated when controlling for a possible confound in terms of conclusion content. Additionally, we reanalyze three studies () without this confound with a Bayesian mixed model meta-analysis (i.e., controlling for participant and item effects) which provides evidence for the null-hypothesis and against Morsanyi and Handley's claim. PMID:24755777

Peer influence as a potential magnifier of ADHD diagnosis.

PubMed

Aronson, Brian

2016-11-01

The prevalence of Attention Deficit and Hyperactivity Disorder (ADHD) is growing in America, but its cause is unclear. Scholars have identified many environmental factors that can cause or confound ADHD diagnosis, but epidemiological studies that try to control for confounding factors still find evidence that rates of ADHD diagnosis are increasing. As a preliminary explanation to ADHD's increasing prevalence, this article examines whether core ADHD diagnostic traits are subject to peer influence. If ADHD diagnosis can be confounded by peer influence, there are several mechanisms that could have caused increased rates of diagnosis. With data drawn from two schools across three waves in the National Longitudinal Survey of Adolescent Health (n = 2193), the author uses a stochastic actor oriented model to estimate the effect of peer influence on inattention, controlling for alternative network and behavioral causes. Results indicate that respondents have a strong likelihood to modify their self-reports of inattention, a core ADHD trait, to resemble that of their friends. Copyright © 2016 Elsevier Ltd. All rights reserved.

Desire thinking as a confounder in the relationship between mindfulness and craving: Evidence from a cross-cultural validation of the Desire Thinking Questionnaire.

PubMed

Chakroun-Baggioni, Nadia; Corman, Maya; Spada, Marcantonio M; Caselli, Gabriele; Gierski, Fabien

2017-10-01

Desire thinking and mindfulness have been associated with craving. The aim of the present study was to validate the French version of the Desire Thinking Questionnaire (DTQ) and to investigate the relationship between mindfulness, desire thinking and craving among a sample of university students. Four hundred and ninety six university students completed the DTQ and measures of mindfulness, craving and alcohol use. Results from confirmatory factor analyses showed that the two-factor structure proposed in the original DTQ exhibited suitable goodness-of-fit statistics. The DTQ also demonstrated good internal reliability, temporal stability and predictive validity. A set of linear regressions revealed that desire thinking had a confounding effect in the relationship between mindfulness and craving. The confounding role of desire thinking in the relationship between mindfulness and craving suggests that interrupting desire thinking may be a viable clinical option aimed at reducing craving. Copyright © 2017 Elsevier B.V. All rights reserved.

Adjustment of ionized calcium concentration for serum pH is not a valid marker of calcium homeostasis: implications for identifying individuals at risk of calcium metabolic disorders.

PubMed

Lam, Virginie; Dhaliwal, Satvinder S; Mamo, John C

2013-05-01

Ionized calcium (iCa) is the biologically active form of this micronutrient. Serum determination of iCa is measured via ion-electrode potentiometry (IEP) and reporting iCa relative to pH 7.4 is normally utilized to avoid the potential confounding effects of ex vivo changes to serum pH. Adjustment of iCa for pH has not been adequately justified. In this study, utilizing carefully standardized protocols for blood collection, the preparation of serum and controlling time of collection-to-analysis, we determined serum iCa and pH utilizing an IEP-analyser hosted at an accredited diagnostic laboratory. Regression analysis of unadjusted-iCa (iCa(raw)) concentration versus pH was described by linear regression and accounted for 37% of serum iCa(raw) variability. iCa(raw) was then expressed at pH 7.4 by either adjusting iCa(raw) based on the linear regression equation describing the association of iCa with serum pH (iCa(regr)) or using IEP coded published normative equations (iCa(pub)). iCa(regr) was comparable to iCa(raw), indicating that blood collection and processing methodologies were sound. However, iCa(pub) yielded values that were significantly lower than iCa(raw). iCa(pub) did not identify 15% subjects who had greater than desirable serum concentration of iCa based on iCa(raw). Sixty percent of subjects with low levels of iCa(raw) were also not detected by iCa(pub). Determination of the kappa value measure of agreement for iCa(raw) versus iCa(pub) showed relatively poor concordance (κ = 0.42). With simple protocols that avoid sampling artefacts, expressing iCa(raw) is likely to be a more valid and physiologically relevant marker of calcium homeostasis than is iCa(pub).

Frequent Use of Paracetamol and Risk of Allergic Disease Among Women in an Ethiopian Population

PubMed Central

Amberbir, Alemayehu; Medhin, Girmay; Hanlon, Charlotte; Britton, John; Venn, Andrea; Davey, Gail

2011-01-01

Introduction The hypothesis that paracetamol might increase the risk of asthma and other allergic diseases have gained support from a range of independent studies. However, in studies based in developed countries, the possibility that paracetamol and asthma are associated through aspirin avoidance is difficult to exclude. Objectives To explore this hypothesis among women in a developing country, where we have previously reported aspirin avoidance to be rare. Methods In 2005/6 a population based cohort of 1065 pregnant women was established in Butajira, Ethiopia and baseline demographic data collected. At 3 years post birth, an interview-based questionnaire administered to 945 (94%) of these women collected data on asthma, eczema, and hay fever in the past 12 month, frequency of paracetamol use and potential confounders. Allergen skin tests to Dermatophagoides pteronyssinus and cockroach were also performed. The independent effects of paracetamol use on allergic outcomes were determined using multiple logistic regression analysis. Findings The prevalence of asthma, eczema and hay fever was 1.7%, 0.9% and 3.8% respectively; of any one of these conditions 5.5%, and of allergen sensitization 7.8%. Paracetamol use in the past month was reported by 29%, and associations of borderline significance were seen for eczema (adjusted OR (95% CI) = 8.51 (1.68 to 43.19) for 1–3 tablets and 2.19 (0.36 to 13.38) for ≥4 tablets, compared to no tablets in the past month; overall p = 0.055) and for ‘any allergic condition’ (adjusted OR (95% CI) = 2.73 (1.22 to 6.11) for 1–3 tablets and 1.35 (0.67 to 2.70) for ≥4 tablets compared to 0 in the past month; overall p = 0.071). Conclusions This study provides further cross-sectional evidence that paracetamol use increases the risk of allergic disease. PMID:21811632

Effects of psychosocial work factors on lifestyle changes: a cohort study.

PubMed

Allard, Karin Olofsson; Thomsen, Jane Frølund; Mikkelsen, Sigurd; Rugulies, Reiner; Mors, Ole; Kærgaard, Anette; Kolstad, Henrik A; Kaerlev, Linda; Andersen, Johan Hviid; Hansen, Ase Marie; Bonde, Jens Peter

2011-12-01

To evaluate the effect of the demand-control-support model, the effort-reward imbalance model, and emotional demands on smoking, alcohol consumption, physical activity, and body mass index. This is a 2-year prospective cohort study of 3224 public sector employees. Measures were assessed with questionnaires. Multiple regression analyses were used to predict changes in lifestyle factors. Low reward predicted smoking, low-decision latitude predicted being inactive, and high demands predicted high-alcohol consumption but only for men at follow-up even after controlling for potential confounders. There were no other significant findings in the expected direction except for some of the confounders. We found only limited and inconsistent support for the hypothesis that a poor psychosocial work environment is associated with an adverse lifestyle.

Exchangeability in the case-crossover design

PubMed Central

Mittleman, Murray A; Mostofsky, Elizabeth

2014-01-01

In cohort and case-control studies, confounding that arises as a result of differences in the distribution of determinants of the outcome between exposure groups leading to non-exchangeability are addressed by restriction, matching or with statistical models. In case-only studies, this issue is addressed by comparing each individual with his/herself. Although case-only designs use self-matching and only include individuals who develop the outcome of interest, issues of non-exchangeability are identical to those that arise in traditional case-control and cohort studies. In this review, we describe one type of case-only design, the case-crossover design, and discuss how the concept of exchangeability can be used to understand issues of confounding, carryover effects, period effects and selection bias in case-crossover studies. PMID:24756878

The Influence of Fuelbed Physical Properties on Biomass Burning Emissions

NASA Astrophysics Data System (ADS)

Urbanski, S. P.; Lincoln, E.; Baker, S. P.; Richardson, M.

2014-12-01

Emissions from biomass fires can significantly degrade regional air quality and therefore are of major concern to air regulators and land managers in the U.S. and Canada. Accurately estimating emissions from different fire types in various ecosystems is crucial to predicting and mitigating the impact of fires on air quality. The physical properties of ecosystems' fuelbeds can heavily influence the combustion processes (e.g. flaming or smoldering) and the resultant emissions. However, despite recent progress in characterizing the composition of biomass smoke, significant knowledge gaps remain regarding the linkage between basic fuelbed physical properties and emissions. In laboratory experiments we examined the effects of fuelbed properties on combustion efficiency (CE) and emissions for an important fuel component of temperate and boreal forests - conifer needles. The bulk density (BD), depth (DZ), and moisture content (MC) of Ponderosa Pine needle fuelbeds were manipulated in 75 burns for which gas and particle emissions were measured. We found CE was negatively correlated with BD, DZ and MC and that the emission factors of species associated with smoldering combustion processes (CO, CH4, particles) were positively correlated with these fuelbed properties. The study indicates the physical properties of conifer needle fuelbeds have a significant effect on CE and hence emissions. However, many of the emission models used to predict and manage smoke impacts on air quality assume conifer litter burns by flaming combustion with a high CE and correspondingly low emissions of CO, CH4, particles, and organic compounds. Our results suggest emission models underestimate emissions from fires involving a large component of conifer needles. Additionally, our findings indicate that laboratory studies of emissions should carefully control fuelbed physical properties to avoid confounding effects that may obscure the effects being tested and lead to erroneous interpretations.

Progressive statistics for studies in sports medicine and exercise science.

PubMed

Hopkins, William G; Marshall, Stephen W; Batterham, Alan M; Hanin, Juri

2009-01-01

Statistical guidelines and expert statements are now available to assist in the analysis and reporting of studies in some biomedical disciplines. We present here a more progressive resource for sample-based studies, meta-analyses, and case studies in sports medicine and exercise science. We offer forthright advice on the following controversial or novel issues: using precision of estimation for inferences about population effects in preference to null-hypothesis testing, which is inadequate for assessing clinical or practical importance; justifying sample size via acceptable precision or confidence for clinical decisions rather than via adequate power for statistical significance; showing SD rather than SEM, to better communicate the magnitude of differences in means and nonuniformity of error; avoiding purely nonparametric analyses, which cannot provide inferences about magnitude and are unnecessary; using regression statistics in validity studies, in preference to the impractical and biased limits of agreement; making greater use of qualitative methods to enrich sample-based quantitative projects; and seeking ethics approval for public access to the depersonalized raw data of a study, to address the need for more scrutiny of research and better meta-analyses. Advice on less contentious issues includes the following: using covariates in linear models to adjust for confounders, to account for individual differences, and to identify potential mechanisms of an effect; using log transformation to deal with nonuniformity of effects and error; identifying and deleting outliers; presenting descriptive, effect, and inferential statistics in appropriate formats; and contending with bias arising from problems with sampling, assignment, blinding, measurement error, and researchers' prejudices. This article should advance the field by stimulating debate, promoting innovative approaches, and serving as a useful checklist for authors, reviewers, and editors.

Global Transcriptional Analysis Reveals the Complex Relationship between Tea Quality, Leaf Senescence and the Responses to Cold-Drought Combined Stress in Camellia sinensis

PubMed Central

Zheng, Chao; Wang, Yu; Ding, Zhaotang; Zhao, Lei

2016-01-01

In field conditions, especially in arid and semi-arid areas, tea plants are often simultaneously exposed to various abiotic stresses such as cold and drought, which have profound effects on leaf senescence process and tea quality. However, most studies of gene expression in stress responses focus on a single inciting agent, and the confounding effect of multiple stresses on crop quality and leaf senescence remain unearthed. Here, global transcriptome profiles of tea leaves under separately cold and drought stress were compared with their combination using RNA-Seq technology. This revealed that tea plants shared a large overlap in unigenes displayed “similar” (26%) expression pattern and avoid antagonistic responses (lowest level of “prioritized” mode: 0%) to exhibit very congruent responses to co-occurring cold and drought stress; 31.5% differential expressed genes and 38% of the transcriptome changes in response to combined stresses were unpredictable from cold or drought single-case studies. We also identified 319 candidate genes for enhancing plant resistance to combined stress. We then investigated the combined effect of cold and drought on tea quality and leaf senescence. Our results showed that drought-induced leaf senescence were severely delayed by (i) modulation of a number of senescence-associated genes and cold responsive genes, (ii) enhancement of antioxidant capacity, (iii) attenuation of lipid degradation, (iv) maintenance of cell wall and photosynthetic system, (v) alteration of senescence-induced sugar effect/sensitivity, as well as (vi) regulation of secondary metabolism pathways that significantly influence the quality of tea during combined stress. Therefore, care should be taken when utilizing a set of stresses to try and maximize leaf longevity and tea quality. PMID:28018394

Verbal short-term memory as an articulatory system: evidence from an alternative paradigm.

PubMed

Cheung, Him; Wooltorton, Lana

2002-01-01

In a series of experiments, the role of articulatory rehearsal in verbal [corrected] short-term memory was examined via a shadowing-plus-recall paradigm. In this paradigm, subjects shadowed a word target presented closely after an auditory memory list before they recalled the list. The phonological relationship between the shadowing target and the final item on the memory list was manipulated. Experiments 1 and 2 demonstrated that targets sounding similar to the list-final memory item generally took longer to shadow than unrelated targets. This inhibitory effect of phonological relatedness was more pronounced with tense- than lax-vowel pseudoword recall lists. The interaction between vowel tenseness and phonological relatedness was replicated in Experiment 3 using shorter lists of real words. In Experiment 4, concurrent articulation was applied during list learning to block rehearsal; consequently, neither the phonological relatedness effect nor its interaction with vowel tenseness emerged. Experiments 5 and 6 manipulated the occurrence frequencies and lexicality of the recall items, respectively, instead of vowel tenseness. Unlike vowel tenseness, these non-articulatory memory factors failed to interact with the phonological relatedness effect. Experiment 7 orthogonally manipulated the vowel tenseness and frequencies of the recall items; slowing in shadowing times due to phonological relatedness was modulated by vowel tenseness but not frequency. Taken together, these results suggest that under the present paradigm, the modifying effect of vowel tenseness on the magnitude of slowing in shadowing due to phonological relatedness is indicative of a prominent articulatory component in verbal short-term retention. The shadowing-plus-recall approach avoids confounding overt recall into internal memory processing, which is an inherent problem of the traditional immediate serial recall and span tasks.

Maternal iron levels early in pregnancy are not associated with offspring IQ score at age 8, findings from a Mendelian randomization study

PubMed Central

Lewis, S J; Bonilla, C; Brion, M-J; Lawlor, D A; Gunnell, D; Ben-Shlomo, Y; Ness, A; Smith, G D

2014-01-01

Background/Objectives: Iron is fundamental to many basic biological functions, and animal studies suggest that iron deficiency early in life can have a lasting impact on the developing brain. Subjects/Methods: We used a population-based cohort of mothers and their children to assess the effect of iron status among pregnant women on the cognitive ability of their offspring. But to avoid the inherent confounding that occurs within observational epidemiology studies we examined the association of maternal genotype at single-nucleotide polymorphisms in the genes HFE (rs1799945) and (rs1800562), TF (rs3811647) and TMPRSS6 (rs1800562), which are related to iron, haemoglobin or transferrin levels, on their child's cognitive test scores at age 8. Results: We found strong associations between HFE and TMPRSS6 genotypes and mother's haemoglobin levels early in pregnancy (P-values are all ⩽4.1 × 10−5) and a genetic score comprised of alleles at these loci was even more strongly associated with haemoglobin levels (P=3.0 × 10−18), suggesting that this was a good instrument to use to look at the effect of prenatal iron levels on offspring cognition. However, mother's genotype at the above loci was not associated with offspring IQ at age 8. Conclusions: We therefore concluded that there is no evidence of an effect of exposure to low levels of iron (within the normal range) in pregnancy on offspring cognition at age 8. However, pregnant women in the UK with low haemoglobin levels are prescribed iron supplements and so we were unable to look at the effect of iron deficiency in our study. PMID:24398642

Use of Self-Matching to Control for Stable Patient Characteristics While Addressing Time-Varying Confounding on Treatment Effect: A Case Study of Older Intensive Care Patients.

PubMed

Han, Ling; Pisani, M A; Araujo, K L B; Allore, Heather G

Exposure-crossover design offers a non-experimental option to control for stable baseline confounding through self-matching while examining causal effect of an exposure on an acute outcome. This study extends this approach to longitudinal data with repeated measures of exposure and outcome using data from a cohort of 340 older medical patients in an intensive care unit (ICU). The analytic sample included 92 patients who received ≥1 dose of haloperidol, an antipsychotic medication often used for patients with delirium. Exposure-crossover design was implemented by sampling the 3-day time segments prior ( Induction) and posterior ( Subsequent) to each treatment episode of receiving haloperidol. In the full cohort, there was a trend of increasing delirium severity scores (Mean±SD: 4.4±1.7) over the course of the ICU stay. After exposure-crossover sampling, the delirium severity score decreased from the Induction (4.9) to the Subsequent (4.1) intervals, with the treatment episode falling in-between (4.5). Based on a GEE Poisson model accounting for self-matching and within-subject correlation, the unadjusted mean delirium severity scores was -0.55 (95% CI: -1.10, -0.01) points lower for the Subsequent than the Induction intervals. The association diminished by 32% (-0.38, 95%CI: -0.99, 0.24) after adjusting only for ICU confounding, while being slightly increased by 7% (-0.60, 95%CI: -1.15, -0.04) when adjusting only for baseline characteristics. These results suggest that longitudinal exposure-crossover design is feasible and capable of partially removing stable baseline confounding through self-matching. Loss of power due to eliminating treatment-irrelevant person-time and uncertainty around allocating person-time to comparison intervals remain methodological challenges.

Gardening and age-related weight gain: Results from a cross-sectional survey of Denver residents.

PubMed

Litt, Jill S; Lambert, Jeffrey Richard; Glueck, Deborah H

2017-12-01

This study examined whether gardening modifies the association between age and body mass index (BMI). We used data from the Neighborhood Environments and Health Survey, which was conducted in Denver (N = 469) between 2006 and 2007. We fit two general linear mixed models. The base model had BMI in kg/m 2 as the outcome, and age, an indicator variable for non-gardening status and the age-by-non-gardening status interaction as predictors. The adjusted model included as covariates the potential confounders of education, ethnicity and self-reported health. We assessed self-selection bias and confounding. BMI was 27.18 kg/m 2 for non-gardeners, 25.62 kg/m 2 for home gardeners, and 24.17 kg/m 2 for community gardeners. In the base model, a statistically significant association was observed between age and BMI for non-gardeners but not for the combined community and home gardening group (F = 9.27, ndf = 1, ddf = 441, p = 0.0025). In the adjusted model, the association between age and BMI in non-gardeners was not statistically significant (F = 1.72, ndf = 1, ddf = 431, p = 0.1908). Gardeners differed on social and demographic factors when compared to non-gardeners. The results from the base model are consistent with the hypothesis that gardening might offset age-related weight gain. However, the cross-sectional design does not permit differentiation of true causal effects from the possible effects of bias and confounding. As a follow-up study, to remove bias and confounding, we are conducting a randomized clinical trial of community gardening in Denver.

Normality of upper and lower peripheral pulse transit time of normotensive and hypertensive children.

PubMed

Foo, Jong Yong Abdiel

2007-08-01

The ankle-brachial index (ABI) is known to be indicative of sub-clinical peripheral arterial diseases that are correlated with cardiovascular disease risk factors like atherosclerosis or ischemic extremity. Due to its occluding measurement nature, this may not be appealing to less cooperative patients when multiple prolonged screening is required. A simple and non-intrusive approach termed pulse transit time ratio (PTTR) has recently shown to be potential surrogate marker for the prolonged ABI measurement. Other studies have also suggested that subjects with hypertension have stiffer arterial wall and thereby can confound transit time related parameters. Thus, it becomes important to understand the PTTR normality and difference of hypertensive children when compared to those measured from normotensive children. About 55 normotensive (39 male; aged 8.4 +/- 2.3 yr) and 4 hypertensive (4 male; aged 5-10 yr) Caucasian children were recruited from the same geographical location. A customized device was used to compute pulse transit time related measurements. Since the PTTR approach produced a delta value that was similar to that of ABI, possible inter-subject physiologic differences had limited confounding effects on the derived PTTR parameter. The obtained transit time measurements from the hypertensive children had lower pulse transit time value when compared to their normotensive counterparts. However, the statistical analysis indicated that they had insignificant PTTR difference (p > 0.01) from those seen in the normotensive children. The findings herein suggest that stiffer arterial wall may have confounding effects on the derived transit time related measurements but it is limited on the PTTR parameter. Similar to the ABI approach, PTTR may be only confounded by abnormal local changes in either of the measured peripheral arterial wall. Hence, the PTTR technique shows promise to be an ABI marker from this perspective.

The influence of approach-avoidance motivational orientation on conflict adaptation.

PubMed

Hengstler, Maikel; Holland, Rob W; van Steenbergen, Henk; van Knippenberg, Ad

2014-06-01

To deal effectively with a continuously changing environment, our cognitive system adaptively regulates resource allocation. Earlier findings showed that an avoidance orientation (induced by arm extension), relative to an approach orientation (induced by arm flexion), enhanced sustained cognitive control. In avoidance conditions, performance on a cognitive control task was enhanced, as indicated by a reduced congruency effect, relative to approach conditions. Extending these findings, in the present behavioral studies we investigated dynamic adaptations in cognitive control-that is, conflict adaptation. We proposed that an avoidance state recruits more resources in response to conflicting signals, and thereby increases conflict adaptation. Conversely, in an approach state, conflict processing diminishes, which consequently weakens conflict adaptation. As predicted, approach versus avoidance arm movements affected both behavioral congruency effects and conflict adaptation: As compared to approach, avoidance movements elicited reduced congruency effects and increased conflict adaptation. These results are discussed in line with a possible underlying neuropsychological model.

Methodological comparison of marginal structural model, time-varying Cox regression, and propensity score methods: the example of antidepressant use and the risk of hip fracture.

PubMed

Ali, M Sanni; Groenwold, Rolf H H; Belitser, Svetlana V; Souverein, Patrick C; Martín, Elisa; Gatto, Nicolle M; Huerta, Consuelo; Gardarsdottir, Helga; Roes, Kit C B; Hoes, Arno W; de Boer, Antonius; Klungel, Olaf H

2016-03-01

Observational studies including time-varying treatments are prone to confounding. We compared time-varying Cox regression analysis, propensity score (PS) methods, and marginal structural models (MSMs) in a study of antidepressant [selective serotonin reuptake inhibitors (SSRIs)] use and the risk of hip fracture. A cohort of patients with a first prescription for antidepressants (SSRI or tricyclic antidepressants) was extracted from the Dutch Mondriaan and Spanish Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) general practice databases for the period 2001-2009. The net (total) effect of SSRI versus no SSRI on the risk of hip fracture was estimated using time-varying Cox regression, stratification and covariate adjustment using the PS, and MSM. In MSM, censoring was accounted for by inverse probability of censoring weights. The crude hazard ratio (HR) of SSRI use versus no SSRI use on hip fracture was 1.75 (95%CI: 1.12, 2.72) in Mondriaan and 2.09 (1.89, 2.32) in BIFAP. After confounding adjustment using time-varying Cox regression, stratification, and covariate adjustment using the PS, HRs increased in Mondriaan [2.59 (1.63, 4.12), 2.64 (1.63, 4.25), and 2.82 (1.63, 4.25), respectively] and decreased in BIFAP [1.56 (1.40, 1.73), 1.54 (1.39, 1.71), and 1.61 (1.45, 1.78), respectively]. MSMs with stabilized weights yielded HR 2.15 (1.30, 3.55) in Mondriaan and 1.63 (1.28, 2.07) in BIFAP when accounting for censoring and 2.13 (1.32, 3.45) in Mondriaan and 1.66 (1.30, 2.12) in BIFAP without accounting for censoring. In this empirical study, differences between the different methods to control for time-dependent confounding were small. The observed differences in treatment effect estimates between the databases are likely attributable to different confounding information in the datasets, illustrating that adequate information on (time-varying) confounding is crucial to prevent bias. Copyright © 2016 John Wiley & Sons, Ltd.

Brief Communication: Latent toxoplasmosis and salivary testosterone concentration--important confounding factors in second to fourth digit ratio studies.

PubMed

Flegr, Jaroslav; Lindová, Jitka; Pivoñková, Vera; Havlícek, Jan

2008-12-01

A sexually dimorphic characteristic, the second to fourth digit ratio (2D:4D ratio), has been shown to reflect the prenatal concentration of sex steroid hormones and to correlate with many personality, physiological, and life history traits. The correlations are usually stronger for the right than the left hand. Most studies have shown that the 2D:4D ratio does not vary with age or postnatal concentration of sex steroid hormones. Recently, a strong association between left hand 2D:4D ratio and infection with a common human parasite Toxoplasma has been reported. We hypothesized that the confounding effect of Toxoplasma infection on left hand 2D:4D ratio could be responsible for the stronger association between different traits and right hand rather than left hand 2D:4D ratio. This confounding effect of toxoplasmosis could also be responsible for the difficulty in finding an association between 2D:4D ratio and age or postnatal steroid hormone concentration. To test this hypothesis, we analyzed the association between sex and age and 2D:4D ratio in a population of 194 female and 106 male students with and without controlling for the confounding variables of Toxoplasma infection and testosterone concentration. Our results showed that the relationship between age and sex and 2D:4D ratio increased sharply when Toxoplasma infection and testosterone concentration were controlled. These results suggest that left hand 2D:4D ratio is more susceptible to postnatal influences and that the confounding factors of Toxoplasma infection, testosterone concentration and possibly also age, should be controlled in future 2D:4D ratio studies. Because of a stronger 2D:4D dimorphism in Toxoplasma-infected than Toxoplasma-free subjects, we predict that 2D:4D ratio dimorphism as well as right hand/left hand 2D:4D ratio dimorphism will be higher in countries with a high prevalence of Toxoplasma infection than in those with a low prevalence. (c) 2008 Wiley-Liss, Inc.

Functional Anatomy of Recognition of Chinese Multi-Character Words: Convergent Evidence from Effects of Transposable Nonwords, Lexicality, and Word Frequency.

PubMed

Lin, Nan; Yu, Xi; Zhao, Ying; Zhang, Mingxia

2016-01-01

This fMRI study aimed to identify the neural mechanisms underlying the recognition of Chinese multi-character words by partialling out the confounding effect of reaction time (RT). For this purpose, a special type of nonword-transposable nonword-was created by reversing the character orders of real words. These nonwords were included in a lexical decision task along with regular (non-transposable) nonwords and real words. Through conjunction analysis on the contrasts of transposable nonwords versus regular nonwords and words versus regular nonwords, the confounding effect of RT was eliminated, and the regions involved in word recognition were reliably identified. The word-frequency effect was also examined in emerged regions to further assess their functional roles in word processing. Results showed significant conjunctional effect and positive word-frequency effect in the bilateral inferior parietal lobules and posterior cingulate cortex, whereas only conjunctional effect was found in the anterior cingulate cortex. The roles of these brain regions in recognition of Chinese multi-character words were discussed.

Functional Anatomy of Recognition of Chinese Multi-Character Words: Convergent Evidence from Effects of Transposable Nonwords, Lexicality, and Word Frequency

PubMed Central

Lin, Nan; Yu, Xi; Zhao, Ying; Zhang, Mingxia

2016-01-01

This fMRI study aimed to identify the neural mechanisms underlying the recognition of Chinese multi-character words by partialling out the confounding effect of reaction time (RT). For this purpose, a special type of nonword—transposable nonword—was created by reversing the character orders of real words. These nonwords were included in a lexical decision task along with regular (non-transposable) nonwords and real words. Through conjunction analysis on the contrasts of transposable nonwords versus regular nonwords and words versus regular nonwords, the confounding effect of RT was eliminated, and the regions involved in word recognition were reliably identified. The word-frequency effect was also examined in emerged regions to further assess their functional roles in word processing. Results showed significant conjunctional effect and positive word-frequency effect in the bilateral inferior parietal lobules and posterior cingulate cortex, whereas only conjunctional effect was found in the anterior cingulate cortex. The roles of these brain regions in recognition of Chinese multi-character words were discussed. PMID:26901644

Task-independent effects are potential confounders in longitudinal imaging studies of learning in schizophrenia

PubMed Central

Korostil, Michele; Fatima, Zainab; Kovacevic, Natasha; Menon, Mahesh; McIntosh, Anthony Randal

2015-01-01

Learning impairment is a core deficit in schizophrenia that impacts on real-world functioning and yet, elucidating its underlying neural basis remains a challenge. A key issue when interpreting learning-task experiments is that task-independent changes may confound interpretation of task-related signal changes in neuroimaging studies. The nature of these task-independent changes in schizophrenia is unknown. Therefore, we examined task-independent “time effects” in a group of participants with schizophrenia contrasted with healthy participants in a longitudinal fMRI learning-experiment designed to allow for examination of non-specific effects of time. Flanking the learning portions of the experiment with a task-of-no-interest allowed us to extract task-independent BOLD changes. Task-independent effects occurred in both groups, but were more robust in the schizophrenia group. There was a significant interaction effect between group and time in a distributed activity pattern that included inferior and superior temporal regions, frontal areas (left anterior insula and superior medial gyri), and parietal areas (posterior cingulate cortices and precuneus). This pattern showed task-independent linear decrease in BOLD amplitude over the two scanning sessions for the schizophrenia group, but showed either opposite effect or no activity changes for the control group. There was a trend towards a correlation between task-independent effects and the presence of more negative symptoms in the schizophrenia group. The strong interaction between group and time suggests that both the scanning experience as a whole and the transition between task-types evokes a different response in persons with schizophrenia and may confound interpretation of learning-related longitudinal imaging experiments if not explicitly considered. PMID:26759790

Wind turbines and idiopathic symptoms: The confounding effect of concurrent environmental exposures.

PubMed

Blanes-Vidal, Victoria; Schwartz, Joel

2016-01-01

Whether or not wind turbines pose a risk to human health is a matter of heated debate. Personal reactions to other environmental exposures occurring in the same settings as wind turbines may be responsible of the reported symptoms. However, these have not been accounted for in previous studies. We investigated whether there is an association between residential proximity to wind turbines and idiopathic symptoms, after controlling for personal reactions to other environmental co-exposures. We assessed wind turbine exposures in 454 residences as the distance to the closest wind turbine (Dw) and number of wind turbines <1000m (Nw1000). Information on symptoms, demographics and personal reactions to exposures was obtained by a blind questionnaire. We identified confounders using confounders' selection criteria and used adjusted logistic regression models to estimate associations. When controlling only for socio-demographic characteristics, log10Dw was associated with "unnatural fatigue" (ORadj=0.38, 95%CI=0.15-1.00) and "difficulty concentrating" (ORadj=0.26, 95%CI=0.08-0.83) and Nw1000 was associated with "unnatural fatigue" (ORadj=1.35, 95%CI=1.07-1.70) and "headache" (ORadj=1.26, 95%CI=1.00-1.58). After controlling for personal reactions to noise from sources different from wind turbines and agricultural odor exposure, we did not observe a significant relationship between residential proximity to wind turbines and symptoms and the parameter estimates were attenuated toward zero. Wind turbines-health associations can be confounded by personal reactions to other environmental co-exposures. Isolated associations reported in the literature may be due to confounding bias. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of oxotremorine and physostigmine on the inhibitory avoidance impairment produced by amitriptyline in male and female mice.

PubMed

Monleón, Santiago; Urquiza, Adoración; Vinader-Caerols, Concepción; Parra, Andrés

2009-12-28

We have previously observed that amitriptyline and other antidepressants produce impairing effects on inhibitory avoidance (also called passive avoidance) in mice of both sexes. In the present study we investigated the involvement of the cholinergic system in the inhibitory avoidance impairment produced by acute amitriptyline in male and female CD1 mice. For this purpose, the effects on said task of acute i.p. administration of several doses of amitriptyline, either alone or in combination with the cholinergic agonists oxotremorine and physostigmine, were evaluated. Pre-training administration of 5, 7.5, 10 or 15 mg/kg of amitriptyline produced a significant impairment of inhibitory avoidance in both males and females. When oxotremorine (0.05 or 0.1 mg/kg) was co-administered with amitriptyline, the antidepressant's impairing effect was partially counteracted, although inhibitory avoidance learning was not significant. Physostigmine (0.15, 0.3 or 0.6 mg/kg) counteracted the impairment produced by amitriptyline, as mice treated with both drugs exhibited inhibitory avoidance learning. These results show that the inhibitory avoidance impairment produced by amitriptyline in male and female mice is mediated, at least partially, by the cholinergic system.

Frequent baked egg ingestion was not associated with change in rate of decline in egg skin prick test in children with challenge confirmed egg allergy.

PubMed

Tey, D; Dharmage, S C; Robinson, M N; Allen, K J; Gurrin, L C; Tang, M L K

2012-12-01

It is controversial whether egg-allergic children should strictly avoid all forms of egg, or if regular ingestion of baked egg will either delay or hasten the resolution of egg allergy. This is the first study to examine the relationship between frequency of baked egg ingestion and rate of decline in egg skin prick test size in egg-allergic children. This was a retrospective clinical cohort study. All children with challenge-proven egg allergy who attended the Royal Children's Hospital Allergy Department 1996-2005 and had at least two egg skin prick tests performed in this period were included (n = 125). Frequency of baked egg ingestion was assessed by telephone questionnaire as follows: (a) frequent (> once per week), (b) regular (> once every 3 months, up to ≤ once per week) or (c) strict avoidance (≤ once every 3 months). The relationship between frequency of baked egg ingestion and rate of decline in egg skin prick test size was examined by multiple linear regression, adjusting for potential confounders. Mean rate of decline in egg skin prick test size in all children was 0.7 mm/year (95% CI 0.5-1.0 mm/year). There was no evidence (P = 0.57) that the rate of decline in egg skin prick test size differed between children who undertook frequent ingestion (n = 21, mean 0.4 mm/year, 95% CI -0.3-1.2 mm/year), regular ingestion (n = 37, mean 0.9 mm/year, 95% CI 0.4-1.4 mm/year) or strict avoidance (n = 67, mean 0.7 mm/year, 95% CI 0.4-1.1 mm/year) of baked egg. Compared with strict dietary avoidance, frequent consumption of baked egg was not associated with a different rate of decline in egg skin prick test size in egg-allergic children. Given that dietary restrictions can adversely impact on the family, it is reasonable to consider liberalizing baked egg in the diet of egg-allergic children. © 2012 Blackwell Publishing Ltd.

Cognitive Impairment in Non-Dialysis-Dependent CKD and the Transition to Dialysis: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

PubMed

Harhay, Meera N; Xie, Dawei; Zhang, Xiaoming; Hsu, Chi-Yuan; Vittinghoff, Eric; Go, Alan S; Sozio, Stephen M; Blumenthal, Jacob; Seliger, Stephen; Chen, Jing; Deo, Rajat; Dobre, Mirela; Akkina, Sanjeev; Reese, Peter P; Lash, James P; Yaffe, Kristine; Tamura, Manjula Kurella

2018-05-02

Advanced chronic kidney disease is associated with elevated risk for cognitive impairment. However, it is not known whether and how cognitive impairment is associated with planning and preparation for end-stage renal disease. Retrospective observational study. 630 adults participating in the CRIC (Chronic Renal Insufficiency Cohort) Study who had cognitive assessments in late-stage CKD, defined as estimated glome-rular filtration rate ≤ 20mL/min/1.73m 2 , and subsequently initiated maintenance dialysis therapy. Predialysis cognitive impairment, defined as a score on the Modified Mini-Mental State Examination lower than previously derived age-based threshold scores. Covariates included age, race/ethnicity, educational attainment, comorbid conditions, and health literacy. Peritoneal dialysis (PD) as first dialysis modality, preemptive permanent access placement, venous catheter avoidance at dialysis therapy initiation, and preemptive wait-listing for a kidney transplant. Multivariable-adjusted logistic regression. Predialysis cognitive impairment was present in 117 (19%) participants. PD was the first dialysis modality among 16% of participants (n=100), 75% had preemptive access placed (n=473), 45% avoided using a venous catheter at dialysis therapy initiation (n=279), and 20% were preemptively wait-listed (n=126). Predialysis cognitive impairment was independently associated with 78% lower odds of PD as the first dialysis modality (adjusted OR [aOR], 0.22; 95% CI, 0.06-0.74; P=0.02) and 42% lower odds of venous catheter avoidance at dialysis therapy initiation (aOR, 0.58; 95% CI, 0.34-0.98; P=0.04). Predialysis cognitive impairment was not independently associated with preemptive permanent access placement or wait-listing. Potential unmeasured confounders; single measure of cognitive function. Predialysis cognitive impairment is associated with a lower likelihood of PD as a first dialysis modality and of venous catheter avoidance at dialysis therapy initiation. Future studies may consider addressing cognitive function when testing strategies to improve patient transitions to dialysis therapy. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

The role of sex and body weight on the metabolic effects of high-fat diet in C57BL/6N mice.

PubMed

Ingvorsen, C; Karp, N A; Lelliott, C J

2017-04-10

Metabolic disorders are commonly investigated using knockout and transgenic mouse models on the C57BL/6N genetic background due to its genetic susceptibility to the deleterious metabolic effects of high-fat diet (HFD). There is growing awareness of the need to consider sex in disease progression, but limited attention has been paid to sexual dimorphism in mouse models and its impact in metabolic phenotypes. We assessed the effect of HFD and the impact of sex on metabolic variables in this strain. We generated a reference data set encompassing glucose tolerance, body composition and plasma chemistry data from 586 C57BL/6N mice fed a standard chow and 733 fed a HFD collected as part of a high-throughput phenotyping pipeline. Linear mixed model regression analysis was used in a dual analysis to assess the effect of HFD as an absolute change in phenotype, but also as a relative change accounting for the potential confounding effect of body weight. HFD had a significant impact on all variables tested with an average absolute effect size of 29%. For the majority of variables (78%), the treatment effect was modified by sex and this was dominated by male-specific or a male stronger effect. On average, there was a 13.2% difference in the effect size between the male and female mice for sexually dimorphic variables. HFD led to a significant body weight phenotype (24% increase), which acts as a confounding effect on the other analysed variables. For 79% of the variables, body weight was found to be a significant source of variation, but even after accounting for this confounding effect, similar HFD-induced phenotypic changes were found to when not accounting for weight. HFD and sex are powerful modifiers of metabolic parameters in C57BL/6N mice. We also demonstrate the value of considering body size as a covariate to obtain a richer understanding of metabolic phenotypes.

Three estimates of the association between linear growth failure and cognitive ability.

PubMed

Cheung, Y B; Lam, K F

2009-09-01

To compare three estimators of association between growth stunting as measured by height-for-age Z-score and cognitive ability in children, and to examine the extent statistical adjustment for covariates is useful for removing confounding due to socio-economic status. Three estimators, namely random-effects, within- and between-cluster estimators, for panel data were used to estimate the association in a survey of 1105 pairs of siblings who were assessed for anthropometry and cognition. Furthermore, a 'combined' model was formulated to simultaneously provide the within- and between-cluster estimates. Random-effects and between-cluster estimators showed strong association between linear growth and cognitive ability, even after adjustment for a range of socio-economic variables. In contrast, the within-cluster estimator showed a much more modest association: For every increase of one Z-score in linear growth, cognitive ability increased by about 0.08 standard deviation (P < 0.001). The combined model verified that the between-cluster estimate was significantly larger than the within-cluster estimate (P = 0.004). Residual confounding by socio-economic situations may explain a substantial proportion of the observed association between linear growth and cognition in studies that attempt to control the confounding by means of multivariable regression analysis. The within-cluster estimator provides more convincing and modest results about the strength of association.

Fresh fruit intake and asthma symptoms in young British adults: confounding or effect modification by smoking?

PubMed

Butland, B K; Strachan, D P; Anderson, H R

1999-04-01

Antioxidant vitamins have been postulated as a protective factor in asthma. The associations between the frequency of fresh fruit consumption in summer, and the prevalence of self-reported asthma symptoms were investigated. The analysis was based on 5,582 males and 5,770 females, born in England, Wales and Scotland between March 3-9, 1958 and aged 33 yrs at the time of survey. The 12-month period prevalence of wheeze and frequent wheeze were inversely associated with frequent intakes of fresh fruit and salad/raw vegetables and positively associated with smoking and lower social class. After adjustment for mutual confounding and sex, associations with smoking persisted, but those with social class and salad/raw vegetable consumption lost significance. The frequency of fresh fruit intake was no longer associated with wheeze after adjustment, but was inversely associated with frequent wheeze and speech-limiting attacks. The association with frequent wheeze differed significantly between smoking groups (never, former, current) and appeared to be confined to exsmokers and current smokers. These findings support postulated associations between infrequent fresh fruit consumption and the prevalence of frequent or severe asthma symptoms in adults. Associations appeared to be restricted to smokers, with effect modification as a more likely explanation of this pattern than residual confounding by smoking.

Measurement error, time lag, unmeasured confounding: Considerations for longitudinal estimation of the effect of a mediator in randomised clinical trials.

PubMed

Goldsmith, K A; Chalder, T; White, P D; Sharpe, M; Pickles, A

2018-06-01

Clinical trials are expensive and time-consuming and so should also be used to study how treatments work, allowing for the evaluation of theoretical treatment models and refinement and improvement of treatments. These treatment processes can be studied using mediation analysis. Randomised treatment makes some of the assumptions of mediation models plausible, but the mediator-outcome relationship could remain subject to bias. In addition, mediation is assumed to be a temporally ordered longitudinal process, but estimation in most mediation studies to date has been cross-sectional and unable to explore this assumption. This study used longitudinal structural equation modelling of mediator and outcome measurements from the PACE trial of rehabilitative treatments for chronic fatigue syndrome (ISRCTN 54285094) to address these issues. In particular, autoregressive and simplex models were used to study measurement error in the mediator, different time lags in the mediator-outcome relationship, unmeasured confounding of the mediator and outcome, and the assumption of a constant mediator-outcome relationship over time. Results showed that allowing for measurement error and unmeasured confounding were important. Contemporaneous rather than lagged mediator-outcome effects were more consistent with the data, possibly due to the wide spacing of measurements. Assuming a constant mediator-outcome relationship over time increased precision.

Measurement error, time lag, unmeasured confounding: Considerations for longitudinal estimation of the effect of a mediator in randomised clinical trials

PubMed Central

Goldsmith, KA; Chalder, T; White, PD; Sharpe, M; Pickles, A

2016-01-01

Clinical trials are expensive and time-consuming and so should also be used to study how treatments work, allowing for the evaluation of theoretical treatment models and refinement and improvement of treatments. These treatment processes can be studied using mediation analysis. Randomised treatment makes some of the assumptions of mediation models plausible, but the mediator–outcome relationship could remain subject to bias. In addition, mediation is assumed to be a temporally ordered longitudinal process, but estimation in most mediation studies to date has been cross-sectional and unable to explore this assumption. This study used longitudinal structural equation modelling of mediator and outcome measurements from the PACE trial of rehabilitative treatments for chronic fatigue syndrome (ISRCTN 54285094) to address these issues. In particular, autoregressive and simplex models were used to study measurement error in the mediator, different time lags in the mediator–outcome relationship, unmeasured confounding of the mediator and outcome, and the assumption of a constant mediator–outcome relationship over time. Results showed that allowing for measurement error and unmeasured confounding were important. Contemporaneous rather than lagged mediator–outcome effects were more consistent with the data, possibly due to the wide spacing of measurements. Assuming a constant mediator–outcome relationship over time increased precision. PMID:27647810

On the Etiology of Sexual Dysfunction

ERIC Educational Resources Information Center

Apfelbaum, Bernard

1977-01-01

Lack of consideration of the sexually functional population has led to misconceptions about causes of sexual dysfunction functioning. Automatic functioning can mask effects of pathogenic influences on sexuality, making these effects appear random, confounding etiological issues and creating the belief that causes of sexual dysfunction and disorder…

Instrumental variable methods in comparative safety and effectiveness research†

PubMed Central

Brookhart, M. Alan; Rassen, Jeremy A.; Schneeweiss, Sebastian

2010-01-01

Summary Instrumental variable (IV) methods have been proposed as a potential approach to the common problem of uncontrolled confounding in comparative studies of medical interventions, but IV methods are unfamiliar to many researchers. The goal of this article is to provide a non-technical, practical introduction to IV methods for comparative safety and effectiveness research. We outline the principles and basic assumptions necessary for valid IV estimation, discuss how to interpret the results of an IV study, provide a review of instruments that have been used in comparative effectiveness research, and suggest some minimal reporting standards for an IV analysis. Finally, we offer our perspective of the role of IV estimation vis-à-vis more traditional approaches based on statistical modeling of the exposure or outcome. We anticipate that IV methods will be often underpowered for drug safety studies of very rare outcomes, but may be potentially useful in studies of intended effects where uncontrolled confounding may be substantial. PMID:20354968

The intention interference effect.

PubMed

Cohen, Anna-Lisa; Kantner, Justin; Dixon, Roger A; Lindsay, D Stephen

2011-01-01

Intentions have been shown to be more accessible (e.g., more quickly and accurately recalled) compared to other sorts of to-be-remembered information; a result termed an intention superiority effect (Goschke & Kuhl, 1993). In the current study, we demonstrate an intention interference effect (IIE) in which color-naming performance in a Stroop task was slower for words belonging to an intention that participants had to remember to carry out (Do-the-Task condition) versus an intention that did not have to be executed (Ignore-the-Task condition). In previous work (e.g., Cohen et al., 2005), having a prospective intention in mind was confounded with carrying a memory load. In Experiment 1, we added a digit-retention task to control for effects of cognitive load. In Experiment 2, we eliminated the memory confound in a new way, by comparing intention-related and control words within each trial. Results from both Experiments 1 and 2 revealed an IIE suggesting that interference is very specific to the intention, not just to a memory load.

Effect of Norbinaltorphimine on Δ9-Tetrahydrocannabinol (THC)-Induced Taste Avoidance in Adolescent and Adult Sprague-Dawley Rats

PubMed Central

Flax, Shaun M.; Wakeford, Alison G.P.; Cheng, Kejun; Rice, Kenner C.; Riley, Anthony L.

2017-01-01

Rationale The aversive effects of Δ9-tetrahydrocannabinol (THC) are mediated by activity at the kappa opioid receptor (KOR) as assessed in adult animals; however, no studies have assessed KOR involvement in the aversive effects of THC in adolescents. Given that adolescents have been reported to be insensitive to the aversive effects induced by KOR agonists, a different mechanism might mediate the aversive effects of THC in this age group. Objectives The present study was designed to assess the impact of KOR antagonism on the aversive effects of THC in adolescent and adult rats using the conditioned taste avoidance (CTA) procedure. Methods Following a single pretreatment injection of norbinaltorphimine (norBNI; 15 mg/kg), CTAs induced by THC (0, 0.56, 1.0, 1.8 and 3.2 mg/kg) were assessed in adolescent (n = 84) and adult (n = 83) Sprague Dawley rats. Results The KOR antagonist, norBNI, had weak and inconsistent effects on THC-induced taste avoidance in adolescent rats in that norBNI both attenuated and strengthened taste avoidance dependent on dose and trial. norBNI had limited impact on the final one-bottle avoidance and no effects on the two-bottle preference test. Interestingly, norBNI had no effect on THC-induced taste avoidance in adult rats as well. Conclusions That norBNI had no significant effect on THC-induced avoidance in adults and a minor and inconsistent effect in adolescents demonstrates that the aversive effects of THC are not mediated by KOR activity as assessed by the CTA design in Sprague Dawley rats. PMID:26025420

Effect of norbinaltorphimine on ∆⁹-tetrahydrocannabinol (THC)-induced taste avoidance in adolescent and adult Sprague-Dawley rats.

PubMed

Flax, Shaun M; Wakeford, Alison G P; Cheng, Kejun; Rice, Kenner C; Riley, Anthony L

2015-09-01

The aversive effects of ∆(9)-tetrahydrocannabinol (THC) are mediated by activity at the kappa opioid receptor (KOR) as assessed in adult animals; however, no studies have assessed KOR involvement in the aversive effects of THC in adolescents. Given that adolescents have been reported to be insensitive to the aversive effects induced by KOR agonists, a different mechanism might mediate the aversive effects of THC in this age group. The present study was designed to assess the impact of KOR antagonism on the aversive effects of THC in adolescent and adult rats using the conditioned taste avoidance (CTA) procedure. Following a single pretreatment injection of norbinaltorphimine (norBNI; 15 mg/kg), CTAs induced by THC (0, 0.56, 1.0, 1.8, and 3.2 mg/kg) were assessed in adolescent (n = 84) and adult (n = 83) Sprague-Dawley rats. The KOR antagonist, norBNI, had weak and inconsistent effects on THC-induced taste avoidance in adolescent rats in that norBNI both attenuated and strengthened taste avoidance dependent on dose and trial. norBNI had limited impact on the final one-bottle avoidance and no effects on the two-bottle preference test. Interestingly, norBNI had no effect on THC-induced taste avoidance in adult rats as well. That norBNI had no significant effect on THC-induced avoidance in adults, and a minor and inconsistent effect in adolescents demonstrates that the aversive effects of THC are not mediated by KOR activity as assessed by the CTA design in Sprague-Dawley rats.

Flaws in Flynn Effect Research with the Wechsler Scales

ERIC Educational Resources Information Center

Weiss, Lawrence G.; Gregoire, Jacques; Zhu, Jianjun

2016-01-01

Many Flynn effect (FE) studies compare scores across different editions of Wechsler's IQ tests. When construct changes are introduced by the test developers in the new edition, however, the presumed generational effects are difficult to untangle from changes due to test content. To remove this confound, we use the same edition of Wechsler…

Partial reinforcement of avoidance and resistance to extinction in humans.

PubMed

Xia, Weike; Dymond, Simon; Lloyd, Keith; Vervliet, Bram

2017-09-01

In anxiety, maladaptive avoidance behavior provides for near-perfect controllability of potential threat. There has been little laboratory-based treatment research conducted on controllability as a contributing factor in the transition from adaptive to maladaptive avoidance. Here, we investigated for the first time whether partial reinforcement rate, or the reliability of avoidance at controlling or preventing contact with an aversive event, influences subsequent extinction of avoidance in humans. Five groups of participants were exposed to different partial reinforcement rates where avoidance cancelled upcoming shock on 100%, 75%, 50%, 25% or 0% of trials. During extinction, all shocks were withheld. Avoidance behavior, online shock expectancy ratings and skin conductance responses (SCRs) were measured throughout. We found that avoidance was a function of relative controllability: higher reinforcement rate groups engaged in significantly more extinction-resistant avoidance than lower reinforcement groups, and shock expectancy was inversely related with reinforcement rate during avoidance acquisition. Partial reinforcement effects were not evident in SCRs. Overall, the current study highlights the clinical relevance of laboratory-based treatment research on partial reinforcement or controllability effects on extinction of avoidance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact Evaluation of a System-Wide Chronic Disease Management Program on Health Service Utilisation: A Propensity-Matched Cohort Study.

PubMed

Billot, Laurent; Corcoran, Kate; McDonald, Alina; Powell-Davies, Gawaine; Feyer, Anne-Marie

2016-06-01

The New South Wales Health (NSW Health) Chronic Disease Management Program (CDMP) delivers interventions to adults at risk of hospitalisation for five target chronic conditions that respond well to ambulatory care: diabetes, hypertension, chronic obstructive pulmonary disease, congestive heart failure, and coronary artery disease. The intervention consists of two main components: (1) care coordination across sectors (acute, ambulatory, and community care from both public and private sectors) and clinical specialties, facilitated by program care coordinators, and (2) health coaching including management of lifestyle risk factors and medications and self-management. These components were broadly prescribed by the head office of NSW Health, which funded the program, and were implemented by regional health services (local health districts) in ways that best suited their own history, environment, workforce, and patient need. We used a propensity-matched cohort study to evaluate health service utilisation after enrolment in the CDMP. The evaluation cohort included 41,303 CDMP participants enrolled between 1 January 2011 and 31 December 2013 who experienced at least one hospital admission or emergency department (ED) presentation for a target condition in the 12 mo preceding enrolment. Potential controls were selected from patients not enrolled in the CDMP but experiencing at least one hospital admission or ED presentation over the same period. Each CDMP patient in the evaluation cohort was matched to one control using 1:1 propensity score matching. The primary outcome was avoidable hospitalisations. Secondary outcomes included avoidable readmissions, avoidable bed days, unplanned hospitalisations, unplanned readmissions, unplanned bed days, ED presentations, and all-cause death. The primary analysis consisted of 30,057 CDMP participants and 30,057 matched controls with a median follow-up of 15 mo. Of those, 25,638 (85.3%) and 25,597 (85.2%) were alive by the end of follow-up in the CDMP and control groups, respectively. Baseline characteristics (including history of health service utilisation) were well balanced between the matched groups. In both groups, utilisation peaked just before the time of enrolment/matching, declined sharply immediately following enrolment, and then continued to decrease more gradually; however, after enrolment, avoidable and unplanned health service utilisation remained higher for CDMP participants compared to controls. The adjusted yearly rate of avoidable hospital admissions was 0.57 (95% CI 0.52 to 0.62) in the CDMP group versus 0.33 (95% CI 0.31 to 0.37) in the control group (adjusted rate ratio 1.70, 95% CI 1.62 to 1.79, p < 0.001). Significant increases in service utilisation were also observed for unplanned hospitalisations (1.42, 95% CI 1.37 to 1.47, p < 0.001) and ED presentations (1.37, 95% CI 1.32 to 1.42, p < 0.001) as well as avoidable (2.00, 95% CI 1.80 to 2.22, p < 0.001) and unplanned (1.51, 95% CI 1.40 to 1.62, p < 0.001) readmissions and avoidable (1.70, 95% CI 1.59 to 1.82, p < 0.001) and unplanned (1.43, 95% CI 1.36 to 1.49, p < 0.001) bed days. No evidence of a difference was seen for all-cause death (adjusted risk ratio 0.96, 95% CI 0.96 to 1.01, p = 0.10) or non-avoidable hospitalisations (all hospitalisations minus avoidable hospitalisations; adjusted rate ratio 1.03, 95% CI 0.97 to 1.10, p = 0.26). Despite the robustness of these results to sensitivity analyses, in the absence of a randomised control group, one cannot exclude the possibility of residual or unmeasured confounding that was not controlled for by the matching process and multivariable analyses. Participation in the CDMP was associated with an increase in avoidable hospital admissions compared to matched controls but no difference in the rate of other types of hospitalisation or death. A possible explanation is that the program identified conditions that required participants to be hospitalised. Service utilisation decreased sharply following its peak for both groups. This finding reflects the natural tendency for high-risk patients to show reductions in use following intense phases of service utilisation and highlights that, despite the additional complexity, a carefully selected control group is essential when assessing the effectiveness of interventions on hospital use.

The effectiveness of health systems in influencing avoidable mortality: a study in Valencia, Spain, 1975-90.

PubMed Central

Albert, X; Bayo, A; Alfonso, J L; Cortina, P; Corella, D

1996-01-01

OBJECTIVES: To measure variations in the Holland and Charlton classifications of avoidable death causes and to estimate the effect of the Spanish national health system on avoidable mortality. DESIGN: Mortality in the Valencian Community was assessed between 1975 and 1990. The classifications of Holland and Charlton, used to assess avoidable causes of death, were compared. Holland's classification was then used to divide avoidable mortality into two groups--medical care indicators (MCI), which show the effectiveness of health care, and national health policy indicators (NHPI), which show the status of primary prevention. Comparisons were made with rates, group rates, and population rates. Trends and indices were also studied. SETTING: Valencia, Spain, 1975-90. RESULTS: During the study period, avoidable morality (only assessed by MCI) fell 63%, whereas the remainder of the mortality (non-MCI causes, that is all the non-avoidable causes together with the NHPI group) fell by 17%. If it is assumed that the mortality due to non-MCI causes indicates the overall effect of the environmental, social, nutritional, and genetic influences, then the difference between this and the MCI group would take us nearer the actual effect of the intervention of the health system. CONCLUSIONS: It is concluded that in this community, the health system has been responsible for approximately 47% of the total reduction in mortality from avoidable causes in the period studied. PMID:8935465

Methods to control for unmeasured confounding in pharmacoepidemiology: an overview.

PubMed

Uddin, Md Jamal; Groenwold, Rolf H H; Ali, Mohammed Sanni; de Boer, Anthonius; Roes, Kit C B; Chowdhury, Muhammad A B; Klungel, Olaf H

2016-06-01

Background Unmeasured confounding is one of the principal problems in pharmacoepidemiologic studies. Several methods have been proposed to detect or control for unmeasured confounding either at the study design phase or the data analysis phase. Aim of the Review To provide an overview of commonly used methods to detect or control for unmeasured confounding and to provide recommendations for proper application in pharmacoepidemiology. Methods/Results Methods to control for unmeasured confounding in the design phase of a study are case only designs (e.g., case-crossover, case-time control, self-controlled case series) and the prior event rate ratio adjustment method. Methods that can be applied in the data analysis phase include, negative control method, perturbation variable method, instrumental variable methods, sensitivity analysis, and ecological analysis. A separate group of methods are those in which additional information on confounders is collected from a substudy. The latter group includes external adjustment, propensity score calibration, two-stage sampling, and multiple imputation. Conclusion As the performance and application of the methods to handle unmeasured confounding may differ across studies and across databases, we stress the importance of using both statistical evidence and substantial clinical knowledge for interpretation of the study results.

Effectiveness of electronic stability control on single-vehicle accidents.

PubMed

Lyckegaard, Allan; Hels, Tove; Bernhoft, Inger Marie

2015-01-01

This study aims at evaluating the effectiveness of electronic stability control (ESC) on single-vehicle injury accidents while controlling for a number of confounders influencing the accident risk. Using police-registered injury accidents from 2004 to 2011 in Denmark with cars manufactured in the period 1998 to 2011 and the principle of induced exposure, 2 measures of the effectiveness of ESC were calculated: The crude odds ratio and the adjusted odds ratio, the latter by means of logistic regression. The logistic regression controlled for a number of confounding factors, of which the following were significant. For the driver: Age, gender, driving experience, valid driving license, and seat belt use. For the vehicle: Year of registration, weight, and ESC. For the accident surroundings: Visibility, light, and location. Finally, for the road: Speed limit, surface, and section characteristics. The present study calculated the crude odds ratio for ESC-equipped cars of getting in a single-vehicle injury accident as 0.40 (95% confidence interval [CI], 0.34-0.47) and the adjusted odds ratio as 0.69 (95% CI, 0.54-0.88). No difference was found in the effectiveness of ESC across the injury severity categories (slight, severe, and fatal). In line with previous results, this study concludes that ESC reduces the risk for single-vehicle injury accidents by 31% when controlling for various confounding factors related to the driver, the car, and the accident surroundings. Furthermore, it is concluded that it is important to control for human factors (at a minimum age and gender) in analyses where evaluations of this type are performed.

Effectiveness of a coordinated and tailored return-to-work intervention for sickness absence beneficiaries with mental health problems.

PubMed

Martin, Marie H T; Nielsen, Maj Britt D; Madsen, Ida E H; Petersen, Signe M A; Lange, Theis; Rugulies, Reiner

2013-12-01

Sickness absence and exclusion from the labour market due to mental health problems (MHPs) is a growing concern in many countries. Knowledge about effective return-to-work (RTW) intervention models is still limited, but a multidisciplinary, coordinated and tailored approach has shown promising results in the context of musculoskeletal disorders. The purpose of this study was to assess the effectiveness of this approach as implemented among sickness absence beneficiaries with MHPs. In a quasi-randomised, controlled trial, we assessed the intervention's effect in terms of time to RTW and labour market status after 1 year. We used two different analytical strategies to compare time to RTW between participants receiving the intervention (n = 88) and those receiving conventional case management (n = 80): (1) a traditional multivariable regression analysis controlling for measured confounding, and (2) an instrumental variable (IV) analysis controlling for unmeasured confounding. The two analytical approaches provided similar results in terms of a longer time to RTW among recipients of the intervention (HR = 0.50; 95 % CI 0.34-0.75), although the estimate provided by the IV-analysis was non-significant (HR = 0.70; 95 % CI 0.23-2.12). After 1 year, more recipients of the intervention than of conventional case management were receiving sickness absence benefits (p = 0.031). The intervention delayed RTW compared to conventional case management, after accounting for measured confounding. The delayed RTW may be due to either implementation or program failure, or both. It may also reflect the complexity of retaining employees with mental health problems in the workplace.

Does Peer Ability Affect Student Achievement?

ERIC Educational Resources Information Center

Hanushek, Eric A.; Kain, John F.; Markman, Jacob M.; Rivkin, Steven G.

Empirical analysis of peer effects on student achievement has been open to question because of the difficulties of separating peer effects from other confounding influences. While most econometric attention has been directed at issues of simultaneous determination of peer interactions, this paper argues that issues of omitted and mismeasured…

Propensity Score Estimation With Boosted Regression for Evaluating Causal Effects in Observational Studies

ERIC Educational Resources Information Center

McCaffrey, Daniel F.; Ridgeway, Greg; Morral, Andrew R.

2004-01-01

Causal effect modeling with naturalistic rather than experimental data is challenging. In observational studies participants in different treatment conditions may also differ on pretreatment characteristics that influence outcomes. Propensity score methods can theoretically eliminate these confounds for all observed covariates, but accurate…

Effects of Disturbance-induced trauma on foraging by subterranean termites (Isoptera: Rhinotermitidae)

Treesearch

R. J. Woodrow; T. G. Shelton; R. J. Oshiro; J. K. Grace; T. L. Wagner

2008-01-01

Toxicant baiting systems are effective at population suppression against both the Formosan subterranean termite, Coptotermes formosanus Shiraki, and the Eastern subterranean termite, Reticulitermes flavipes (Kollar). However, trap shyness (i.e., station abandonment) is often quoted as a confounding factor affecting their success....

IDENTIFICATION AND INTERPRETATION OF DEVELOPMENTAL NEUROTOXICITY EFFECTS: A REPORT FROM THE ILSI RESEARCH FOUNDATION/RISK SCIENCE INSTITUTE EXPERT WORKING GROUP ON NEURODEVELOPMENTAL ENDPOINTS

EPA Science Inventory

The reliable detection, measurement, and interpretation of treatment-related developmental neurotoxicity (DNT) effects depend on appropriate study design and execution, using scientifically established methodologies, with appropriate controls to minimize confounding factors. App...

A systematic literature review on the efficacy–effectiveness gap: comparison of randomized controlled trials and observational studies of glucose-lowering drugs

PubMed Central

Ankarfeldt, Mikkel Z; Adalsteinsson, Erpur; Groenwold, Rolf HH; Ali, M Sanni; Klungel, Olaf H

2017-01-01

Aim To identify a potential efficacy–effectiveness gap and possible explanations (drivers of effectiveness) for differences between results of randomized controlled trials (RCTs) and observational studies investigating glucose-lowering drugs. Methods A systematic literature review was conducted in English language articles published between 1 January, 2000 and 31 January, 2015 describing either RCTs or observational studies comparing glucagon-like peptide-1 analogs (GLP-1) with insulin or comparing dipeptidyl peptidase-4 inhibitors (DPP-4i) with sulfonylurea, all with change in glycated hemoglobin (HbA1c) as outcome. Medline, Embase, Current Content, and Biosis were searched. Information on effect estimates, baseline characteristics of the study population, publication year, study duration, and number of patients, and for observational studies, characteristics related to confounding adjustment and selection- and information bias were extracted. Results From 312 hits, 11 RCTs and 7 observational studies comparing GLP-1 with insulin, and from 474 hits, 16 RCTs and 4 observational studies comparing DPP-4i with sulfonylurea were finally included. No differences were observed in baseline characteristics of the study populations (age, sex, body mass index, time since diagnosis of type 2 diabetes mellitus, and HbA1c) or effect sizes across study designs. Mean effect sizes ranged from −0.43 to 0.91 and from −0.80 to 1.13 in RCTs and observational studies, respectively, comparing GLP-1 with insulin, and from −0.13 to 2.70 and −0.20 to 0.30 in RCTs and observational studies, respectively, comparing DPP-4i and sulfonylurea. Generally, the identified observational studies held potential flaws with regard to confounding adjustment and selection- and information bias. Conclusions Neither potential drivers of effectiveness nor an efficacy–effectiveness gap were identified. However, the limited number of studies and potential problems with confounding adjustment, selection- and information bias in the observational studies, may have hidden a true efficacy-effectiveness gap. PMID:28176959

Differentiating Challenge Reactivity from Psychomotor Activity in Studies of Children’s Psychophysiology: Considerations for Theory and Measurement

PubMed Central

Bush, Nicole R.; Alkon, Abbey; Obradović, Jelena; Stamperdahl, Juliet; Boyce, W. Thomas

2014-01-01

Current methods of assessing children’s physiologic “stress reactivity” may be confounded by psychomotor activity, biasing estimates of the relation between reactivity and health. We examine the joint and independent contributions of psychomotor activity and challenge reactivity during a protocol for children ages 5–6 (N=338). Measures of parasympathetic (RSA) and sympathetic (PEP) reactivity were calculated for social, cognitive, sensory, and emotional challenge tasks. Reactivity was calculated relative to both resting and a paired comparison task that accounted for psychomotor activity effects during each challenge. Results indicated that comparison tasks themselves elicited RSA and PEP responses, and reactivity adjusted for psychomotor activity was incongruent with reactivity calculated using rest. Findings demonstrate the importance of accounting for confounding psychomotor activity effects on physiologic reactivity. PMID:21524757

Comparison between treatment effects in a randomised controlled trial and an observational study using propensity scores in primary care.

PubMed

Stuart, Beth L; Grebel, Louise En; Butler, Christopher C; Hood, Kerenza; Verheij, Theo J M; Little, Paul

2017-09-01

Although randomised controlled trials (RCTs) are considered 'gold standard' evidence, they are not always feasible or appropriate, and may represent a select population. Observational studies provide a useful alternative to enhance applicability, but results can be biased due to confounding. To explore the utility of propensity scores for causal inference in an observational study. Comparison of the effect of amoxicillin on key outcomes in an international RCT and observational study of lower respiratory tract infections. Propensity scores were calculated and applied as probability weights in the analyses. The adjusted results were compared with the effects reported in the RCT. Groups were well balanced in the RCT but significantly imbalanced in the observational study, with evidence of confounding by indication: patients receiving antibiotics tended to be older and more unwell at baseline consultation. In the trial duration of symptoms (hazard ratio 1.06, 95% CI = 0.96 to 1.18) and symptom severity (-0.07, 95% CI = -0.15 to 0.007) did not differ between groups. Weighting by propensity score in the observational study resulted in very similar estimates of effect: duration of symptoms (hazard ratio 1.06, 95% CI = 0.80 to 1.40) and difference for symptom severity (-0.07, 95% CI = -0.34 to 0.20). The observational study, after conditioning on propensity score, echoed the trial results. Provided that detailed information is available on potential sources of confounding, effects of interventions can probably be assessed reasonably well in observational datasets, allowing them to be more directly compared with the results of RCTs. © British Journal of General Practice 2017.

Combining fixed effects and instrumental variable approaches for estimating the effect of psychosocial job quality on mental health: evidence from 13 waves of a nationally representative cohort study.

PubMed

Milner, Allison; Aitken, Zoe; Kavanagh, Anne; LaMontagne, Anthony D; Pega, Frank; Petrie, Dennis

2017-06-23

Previous studies suggest that poor psychosocial job quality is a risk factor for mental health problems, but they use conventional regression analytic methods that cannot rule out reverse causation, unmeasured time-invariant confounding and reporting bias. This study combines two quasi-experimental approaches to improve causal inference by better accounting for these biases: (i) linear fixed effects regression analysis and (ii) linear instrumental variable analysis. We extract 13 annual waves of national cohort data including 13 260 working-age (18-64 years) employees. The exposure variable is self-reported level of psychosocial job quality. The instruments used are two common workplace entitlements. The outcome variable is the Mental Health Inventory (MHI-5). We adjust for measured time-varying confounders. In the fixed effects regression analysis adjusted for time-varying confounders, a 1-point increase in psychosocial job quality is associated with a 1.28-point improvement in mental health on the MHI-5 scale (95% CI: 1.17, 1.40; P < 0.001). When the fixed effects was combined with the instrumental variable analysis, a 1-point increase psychosocial job quality is related to 1.62-point improvement on the MHI-5 scale (95% CI: -0.24, 3.48; P = 0.088). Our quasi-experimental results provide evidence to confirm job stressors as risk factors for mental ill health using methods that improve causal inference. © The Author 2017. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Case-control vaccine effectiveness studies: Preparation, design, and enrollment of cases and controls.

PubMed

Verani, Jennifer R; Baqui, Abdullah H; Broome, Claire V; Cherian, Thomas; Cohen, Cheryl; Farrar, Jennifer L; Feikin, Daniel R; Groome, Michelle J; Hajjeh, Rana A; Johnson, Hope L; Madhi, Shabir A; Mulholland, Kim; O'Brien, Katherine L; Parashar, Umesh D; Patel, Manish M; Rodrigues, Laura C; Santosham, Mathuram; Scott, J Anthony; Smith, Peter G; Sommerfelt, Halvor; Tate, Jacqueline E; Victor, J Chris; Whitney, Cynthia G; Zaidi, Anita K; Zell, Elizabeth R

2017-06-05

Case-control studies are commonly used to evaluate effectiveness of licensed vaccines after deployment in public health programs. Such studies can provide policy-relevant data on vaccine performance under 'real world' conditions, contributing to the evidence base to support and sustain introduction of new vaccines. However, case-control studies do not measure the impact of vaccine introduction on disease at a population level, and are subject to bias and confounding, which may lead to inaccurate results that can misinform policy decisions. In 2012, a group of experts met to review recent experience with case-control studies evaluating the effectiveness of several vaccines; here we summarize the recommendations of that group regarding best practices for planning, design and enrollment of cases and controls. Rigorous planning and preparation should focus on understanding the study context including healthcare-seeking and vaccination practices. Case-control vaccine effectiveness studies are best carried out soon after vaccine introduction because high coverage creates strong potential for confounding. Endpoints specific to the vaccine target are preferable to non-specific clinical syndromes since the proportion of non-specific outcomes preventable through vaccination may vary over time and place, leading to potentially confusing results. Controls should be representative of the source population from which cases arise, and are generally recruited from the community or health facilities where cases are enrolled. Matching of controls to cases for potential confounding factors is commonly used, although should be reserved for a limited number of key variables believed to be linked to both vaccination and disease. Case-control vaccine effectiveness studies can provide information useful to guide policy decisions and vaccine development, however rigorous preparation and design is essential. Published by Elsevier Ltd.

Treatment effect heterogeneity for univariate subgroups in clinical trials: Shrinkage, standardization, or else

PubMed Central

Varadhan, Ravi; Wang, Sue-Jane

2016-01-01

Treatment effect heterogeneity is a well-recognized phenomenon in randomized controlled clinical trials. In this paper, we discuss subgroup analyses with prespecified subgroups of clinical or biological importance. We explore various alternatives to the naive (the traditional univariate) subgroup analyses to address the issues of multiplicity and confounding. Specifically, we consider a model-based Bayesian shrinkage (Bayes-DS) and a nonparametric, empirical Bayes shrinkage approach (Emp-Bayes) to temper the optimism of traditional univariate subgroup analyses; a standardization approach (standardization) that accounts for correlation between baseline covariates; and a model-based maximum likelihood estimation (MLE) approach. The Bayes-DS and Emp-Bayes methods model the variation in subgroup-specific treatment effect rather than testing the null hypothesis of no difference between subgroups. The standardization approach addresses the issue of confounding in subgroup analyses. The MLE approach is considered only for comparison in simulation studies as the “truth” since the data were generated from the same model. Using the characteristics of a hypothetical large outcome trial, we perform simulation studies and articulate the utilities and potential limitations of these estimators. Simulation results indicate that Bayes-DS and Emp-Bayes can protect against optimism present in the naïve approach. Due to its simplicity, the naïve approach should be the reference for reporting univariate subgroup-specific treatment effect estimates from exploratory subgroup analyses. Standardization, although it tends to have a larger variance, is suggested when it is important to address the confounding of univariate subgroup effects due to correlation between baseline covariates. The Bayes-DS approach is available as an R package (DSBayes). PMID:26485117

A Framework for Estimating Causal Effects in Latent Class Analysis: Is There a Causal Link Between Early Sex and Subsequent Profiles of Delinquency?

PubMed Central

Lanza, Stephanie T.; Coffman, Donna L.

2013-01-01

Prevention scientists use latent class analysis (LCA) with increasing frequency to characterize complex behavior patterns and profiles of risk. Often, the most important research questions in these studies involve establishing characteristics that predict membership in the latent classes, thus describing the composition of the subgroups and suggesting possible points of intervention. More recently, prevention scientists have begun to adopt modern methods for drawing causal inference from observational data because of the bias that can be introduced by confounders. This same issue of confounding exists in any analysis of observational data, including prediction of latent class membership. This study demonstrates a straightforward approach to causal inference in LCA that builds on propensity score methods. We demonstrate this approach by examining the causal effect of early sex on subsequent delinquency latent classes using data from 1,890 adolescents in 11th and 12th grade from wave I of the National Longitudinal Study of Adolescent Health. Prior to the statistical adjustment for potential confounders, early sex was significantly associated with delinquency latent class membership for both genders (p=0.02). However, the propensity score adjusted analysis indicated no evidence for a causal effect of early sex on delinquency class membership (p=0.76) for either gender. Sample R and SAS code is included in an Appendix in the ESM so that prevention scientists may adopt this approach to causal inference in LCA in their own work. PMID:23839479

A framework for estimating causal effects in latent class analysis: is there a causal link between early sex and subsequent profiles of delinquency?

PubMed

Butera, Nicole M; Lanza, Stephanie T; Coffman, Donna L

2014-06-01

Prevention scientists use latent class analysis (LCA) with increasing frequency to characterize complex behavior patterns and profiles of risk. Often, the most important research questions in these studies involve establishing characteristics that predict membership in the latent classes, thus describing the composition of the subgroups and suggesting possible points of intervention. More recently, prevention scientists have begun to adopt modern methods for drawing causal inference from observational data because of the bias that can be introduced by confounders. This same issue of confounding exists in any analysis of observational data, including prediction of latent class membership. This study demonstrates a straightforward approach to causal inference in LCA that builds on propensity score methods. We demonstrate this approach by examining the causal effect of early sex on subsequent delinquency latent classes using data from 1,890 adolescents in 11th and 12th grade from wave I of the National Longitudinal Study of Adolescent Health. Prior to the statistical adjustment for potential confounders, early sex was significantly associated with delinquency latent class membership for both genders (p = 0.02). However, the propensity score adjusted analysis indicated no evidence for a causal effect of early sex on delinquency class membership (p = 0.76) for either gender. Sample R and SAS code is included in an Appendix in the ESM so that prevention scientists may adopt this approach to causal inference in LCA in their own work.

Effects of environmental lead pollution on blood lead and sex hormone levels among occupationally exposed group in an E-waste dismantling area.

PubMed

Yang, Yan; Lu, Xiao Song; Li, Ding Long; Yu, Yun Jiang

2013-06-01

To study the effects of environmental multi-media lead pollution on blood lead and sex hormone levels among lead exposed males engaged in E-waste dismantling, and the correlation between confounding factors and sex hormone levels. An E-waste dismantling area in Taizhou of Zhejiang Province was selected as the research site. One hundred and fifty two samples were collected from the groundwater, soil, rice, corn, chicken, and pork in the dismantling area. The effects of the multi-media lead pollution on the male blood lead and sex hormone levels of FSH, LH, and T, as well as the correlation with confounding factors, were studied. The blood lead concentrations in the males aged under 31, from 31 to 45 and from 46 to 60 were 98.55, 100.23, and 101.45 μg/L, respectively. Of all the environmental media lead exposures, the groundwater, rice and soil were main contributing factors to the lead accumulation in humans. FSH and LH levels increased with the age while the T levels decreased with the age instead. There was a significant correlation between the FSH and LH levels and wearing masks. There was correlation between the FSH, LH, and T levels, and the mean values of lead concentrations in environmental media, and the sex hormone levels were correlated with the confounding factor of wearing masks. Copyright © 2013 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

The Gratton effect remains after controlling for contingencies and stimulus repetitions

PubMed Central

Blais, Chris; Stefanidi, Aikaterini; Brewer, Gene A.

2014-01-01

Highlights: The conflict monitoring hypothesis signals the need for cognitive controlThe Gratton effect is a key result attributed to the conflict monitoring hypothesisSome argue that controlling binding confounds eliminates the Gratton effect A Gratton effect remains in a vocal Stroop task after eliminating confounds The Gratton effect, the observation that the size of the Stroop effect is larger following a congruent trial compared to an incongruent trial, is one pivotal observation in support of the conflict-monitoring hypothesis. Previous reports have demonstrated that non-conflict components, such as feature binding, also contribute to this effect. Critically, Schmidt and De Houwer (2011) report a flanker task and a button-press Stroop task suggesting that there is no conflict adaptation in the Gratton effect; it is entirely caused by feature binding. The current investigation attempts to replicate and extend this important finding across two experiments using a canonical four-choice Stroop task with vocal responses. In contrast to Schmidt and De Houwer, we observe reliable conflict adaptation after controlling for feature binding. We argue that the overall strength of conflict is critical for determining whether a conflict adaptation component will remain in the Gratton effect after explaining binding components. PMID:25386151

Interventional effects for mediation analysis with multiple mediators

PubMed Central

Vansteelandt, Stijn; Daniel, Rhian M.

2016-01-01

The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator–outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that involve repeatedly measured mediators, or multiple correlated mediators. VanderWeele, Vansteelandt, and Robins21 introduced so-called interventional (in)direct effects. These can be identified under much weaker conditions than natural (in)direct effects, but have the drawback of not adding up to the total effect. In this article, we adapt their proposal in order to achieve an exact decomposition of the total effect, and extend it to the multiple mediator setting. Interestingly, the proposed effects capture the path-specific effects of an exposure on an outcome that are mediated by distinct mediators, even when – as often – the structural dependence between the multiple mediators is unknown; for instance, when the direction of the causal effects between the mediators is unknown, or there may be unmeasured common causes of the mediators. PMID:27922534

Interventional Effects for Mediation Analysis with Multiple Mediators.

PubMed

Vansteelandt, Stijn; Daniel, Rhian M

2017-03-01

The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator-outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that involve repeatedly measured mediators, or multiple correlated mediators. VanderWeele, Vansteelandt, and Robins introduced so-called interventional (in)direct effects. These can be identified under much weaker conditions than natural (in)direct effects, but have the drawback of not adding up to the total effect. In this article, we adapt their proposal to achieve an exact decomposition of the total effect, and extend it to the multiple mediator setting. Interestingly, the proposed effects capture the path-specific effects of an exposure on an outcome that are mediated by distinct mediators, even when-as often-the structural dependence between the multiple mediators is unknown, for instance, when the direction of the causal effects between the mediators is unknown, or there may be unmeasured common causes of the mediators.

Interpretational Confounding or Confounded Interpretations of Causal Indicators?

ERIC Educational Resources Information Center

Bainter, Sierra A.; Bollen, Kenneth A.

2014-01-01

In measurement theory, causal indicators are controversial and little understood. Methodological disagreement concerning causal indicators has centered on the question of whether causal indicators are inherently sensitive to interpretational confounding, which occurs when the empirical meaning of a latent construct departs from the meaning…

Air pollution, avoidance behaviour and children's respiratory health: evidence from England.

PubMed

Janke, Katharina

2014-12-01

Despite progress in air pollution control, concerns remain over the health impact of poor air quality. Governments increasingly issue air quality information to enable vulnerable groups to avoid exposure. Avoidance behaviour potentially biases estimates of the health effects of air pollutants. But avoidance behaviour imposes a cost on individuals and therefore may not be taken in all circumstances. This paper exploits panel data at the English local authority level to estimate the relationship between children's daily hospital emergency admissions for respiratory diseases and common air pollutants, while allowing for avoidance behaviour in response to air pollution warnings. A 1% increase in nitrogen dioxide or ozone concentrations increases hospital admissions by 0.1%. For the subset of asthma admissions - where avoidance is less costly - there is evidence of avoidance behaviour. Ignoring avoidance behaviour, however, does not result in statistically significant underestimation of the health effect of air pollution. Copyright © 2014 Elsevier B.V. All rights reserved.

A Contextual Approach to Experiential Avoidance and Social Anxiety: Evidence from an Experimental Interaction and Daily Interactions of People with Social Anxiety Disorder

PubMed Central

Kashdan, Todd B.; Goodman, Fallon R.; Machell, Kyla A.; Kleiman, Evan M.; Monfort, Samuel S.; Ciarrochi, Joseph; Nezlek, John B.

2014-01-01

Experiential avoidance, the tendency to avoid internal, unwanted thoughts and feelings, is hypothesized to be a risk factor for social anxiety. Existing studies of experiential avoidance rely on trait measures with minimal contextual consideration. In two studies, we examined the association between experiential avoidance and anxiety within real-world social interactions. In the first study, we examined the effect of experiential avoidance on social anxiety in everyday life. For two weeks, 37 participants with Social Anxiety Disorder [SAD] and 38 healthy controls provided reports of experiential avoidance and social anxiety symptoms during face-to-face social interactions. Results showed that momentary experiential avoidance was positively related to anxiety symptoms during social interactions and this effect was stronger among people with SAD. People low in EA showed greater sensitivity to the level of situational threat than high EA people. In the second study, we facilitated an initial encounter between strangers. Unlike Study 1, we experimentally created a social situation where there was either an opportunity for intimacy (self-disclosure conversation) or no such opportunity (small-talk conversation). Results showed that greater experiential avoidance during the self-disclosure conversation temporally preceded increases in social anxiety for the remainder of the interaction; no such effect was found in the small-talk conversation. Our findings provide insight into the association between experiential avoidance on social anxiety in laboratory and naturalistic settings, and demonstrate that the effect of EA depends upon level of social threat and opportunity. PMID:24749634