Depression and pain: testing of serial multiple mediators

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Wongpakaran T

2016-07-01

Full Text Available Tinakon Wongpakaran,1 Nahathai Wongpakaran,1 Sitthinant Tanchakvaranont,2 Putipong Bookkamana,3 Manee Pinyopornpanish,1 Kamonporn Wannarit,4 Sirina Satthapisit,5 Daochompu Nakawiro,6 Thanita Hiranyatheb,6 Kulvadee Thongpibul7 1Department of Psychiatry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Kingdom of Thailand; 2Department of Psychiatry, Queen Savang Vadhana Memorial Hospital, Chonburi, Kingdom of Thailand; 3Department of Statistics, Faculty of Science, Chiang Mai University, Chiang Mai, Kingdom of Thailand; 4Department of Psychiatry, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Kingdom of Thailand; 5Department of Psychiatry, Khon Kaen Regional Hospital, Khon Kaen, Kingdom of Thailand; 6Department of Psychiatry, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Kingdom of Thailand; 7Department of Psychology, Faculty of Humanities, Chiang Mai University, Chiang Mai, Kingdom of Thailand Purpose: Despite the fact that pain is related to depression, few studies have been conducted to investigate the variables that mediate between the two conditions. In this study, the authors explored the following mediators: cognitive function, self-sacrificing interpersonal problems, and perception of stress, and the effects they had on pain symptoms among patients with depressive disorders.Participants and methods: An analysis was performed on the data of 346 participants with unipolar depressive disorders. The 17-item Hamilton Depression Rating Scale, Mini-Mental State Examination, the pain subscale of the health-related quality of life (SF-36, the self-sacrificing subscale of the Inventory of Interpersonal Problems, and the Perceived Stress Scale were used. Parallel multiple mediator and serial multiple mediator models were used. An alternative model regarding the effect of self-sacrificing on pain was also proposed.Results: Perceived stress, self-sacrificing interpersonal style, and cognitive

Testing a multiple mediator model of the effect of childhood sexual abuse on adolescent sexual victimization.

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Bramsen, Rikke H; Lasgaard, Mathias; Koss, Mary P; Shevlin, Mark; Elklit, Ask; Banner, Jytte

2013-01-01

The present study modeled the direct relationship between child sexual abuse (CSA) and adolescent peer-to-peer sexual victimization (APSV) and the mediated effect via variables representing the number of sexual partners, sexual risk behavior, and signaling sexual boundaries. A cross-sectional study on the effect of CSA on APSV was conducted, utilizing a multiple mediator model. Mediated and direct effects in the model were estimated employing Mplus using bootstrapped percentile based confidence intervals to test for significance of mediated effects. The study employed 327 Danish female adolescents with a mean age of 14.9 years (SD = 0.5). The estimates from the mediational model indicated full mediation of the effect of CSA on APSV via number of sexual partners and sexual risk behavior. The current study suggests that the link between CSA and APSV was mediated by sexual behaviors specifically pertaining to situations of social peer interaction, rather than directly on prior experiences of sexual victimization. The present study identifies a modifiable target area for intervention to reduce adolescent sexual revictimization. © 2013 American Orthopsychiatric Association.

Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models.

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Preacher, Kristopher J; Hayes, Andrew F

2008-08-01

Hypotheses involving mediation are common in the behavioral sciences. Mediation exists when a predictor affects a dependent variable indirectly through at least one intervening variable, or mediator. Methods to assess mediation involving multiple simultaneous mediators have received little attention in the methodological literature despite a clear need. We provide an overview of simple and multiple mediation and explore three approaches that can be used to investigate indirect processes, as well as methods for contrasting two or more mediators within a single model. We present an illustrative example, assessing and contrasting potential mediators of the relationship between the helpfulness of socialization agents and job satisfaction. We also provide SAS and SPSS macros, as well as Mplus and LISREL syntax, to facilitate the use of these methods in applications.

On the Interpretation and Use of Mediation: Multiple Perspectives on Mediation Analysis

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Agler, Robert; De Boeck, Paul

2017-01-01

Mediation analysis has become a very popular approach in psychology, and it is one that is associated with multiple perspectives that are often at odds, often implicitly. Explicitly discussing these perspectives and their motivations, advantages, and disadvantages can help to provide clarity to conversations and research regarding the use and refinement of mediation models. We discuss five such pairs of perspectives on mediation analysis, their associated advantages and disadvantages, and their implications: with vs. without a mediation hypothesis, specific effects vs. a global model, directness vs. indirectness of causation, effect size vs. null hypothesis testing, and hypothesized vs. alternative explanations. Discussion of the perspectives is facilitated by a small simulation study. Some philosophical and linguistic considerations are briefly discussed, as well as some other perspectives we do not develop here. PMID:29187828

On the Interpretation and Use of Mediation: Multiple Perspectives on Mediation Analysis.

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Agler, Robert; De Boeck, Paul

2017-01-01

Mediation analysis has become a very popular approach in psychology, and it is one that is associated with multiple perspectives that are often at odds, often implicitly. Explicitly discussing these perspectives and their motivations, advantages, and disadvantages can help to provide clarity to conversations and research regarding the use and refinement of mediation models. We discuss five such pairs of perspectives on mediation analysis, their associated advantages and disadvantages, and their implications: with vs. without a mediation hypothesis, specific effects vs. a global model, directness vs. indirectness of causation, effect size vs. null hypothesis testing, and hypothesized vs. alternative explanations. Discussion of the perspectives is facilitated by a small simulation study. Some philosophical and linguistic considerations are briefly discussed, as well as some other perspectives we do not develop here.

Photon-mediated electron multiplication in liquid xenon doped with trimethylamine

International Nuclear Information System (INIS)

Sano, Toshio; Ashikaga, Kinya; Doke, Tadayoshi; Hitachi, Akira; Kikuchi, Jun; Masuda, Kimiaki; Okumura, Yasuaki

1989-01-01

Electron multiplication mediated by photons has been observed in liquid xenon doped with trimethylamine in concentrations of 0, 9.3, 43, 118 and 400 ppm. The effect was observed by irradiating a single wire counter with 1 MeV electrons and gamma rays from 207 Bi sources. The multiplication factor was observed to increase from a value of 23 at a concentration of 9.3 ppm to a value of 45 at a concentration of 118 ppm. Over the same range of concentrations, the threshold anode voltage for photon-mediated electron multiplication (PMEM) decreased from 2.5 to 1.4 kV and the PMEM results in a deterioration of energy resolution. At a concentration of 400 ppm, the resulting electron multiplication was neither stable nor reproducible. (orig.)

Method for evaluating multiple mediators: mediating effects of smoking and COPD on the association between the CHRNA5-A3 variant and lung cancer risk.

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Wang, Jian; Spitz, Margaret R; Amos, Christopher I; Wu, Xifeng; Wetter, David W; Cinciripini, Paul M; Shete, Sanjay

2012-01-01

A mediation model explores the direct and indirect effects between an independent variable and a dependent variable by including other variables (or mediators). Mediation analysis has recently been used to dissect the direct and indirect effects of genetic variants on complex diseases using case-control studies. However, bias could arise in the estimations of the genetic variant-mediator association because the presence or absence of the mediator in the study samples is not sampled following the principles of case-control study design. In this case, the mediation analysis using data from case-control studies might lead to biased estimates of coefficients and indirect effects. In this article, we investigated a multiple-mediation model involving a three-path mediating effect through two mediators using case-control study data. We propose an approach to correct bias in coefficients and provide accurate estimates of the specific indirect effects. Our approach can also be used when the original case-control study is frequency matched on one of the mediators. We employed bootstrapping to assess the significance of indirect effects. We conducted simulation studies to investigate the performance of the proposed approach, and showed that it provides more accurate estimates of the indirect effects as well as the percent mediated than standard regressions. We then applied this approach to study the mediating effects of both smoking and chronic obstructive pulmonary disease (COPD) on the association between the CHRNA5-A3 gene locus and lung cancer risk using data from a lung cancer case-control study. The results showed that the genetic variant influences lung cancer risk indirectly through all three different pathways. The percent of genetic association mediated was 18.3% through smoking alone, 30.2% through COPD alone, and 20.6% through the path including both smoking and COPD, and the total genetic variant-lung cancer association explained by the two mediators was 69.1%.

Method for evaluating multiple mediators: mediating effects of smoking and COPD on the association between the CHRNA5-A3 variant and lung cancer risk.

Directory of Open Access Journals (Sweden)

Jian Wang

Full Text Available A mediation model explores the direct and indirect effects between an independent variable and a dependent variable by including other variables (or mediators. Mediation analysis has recently been used to dissect the direct and indirect effects of genetic variants on complex diseases using case-control studies. However, bias could arise in the estimations of the genetic variant-mediator association because the presence or absence of the mediator in the study samples is not sampled following the principles of case-control study design. In this case, the mediation analysis using data from case-control studies might lead to biased estimates of coefficients and indirect effects. In this article, we investigated a multiple-mediation model involving a three-path mediating effect through two mediators using case-control study data. We propose an approach to correct bias in coefficients and provide accurate estimates of the specific indirect effects. Our approach can also be used when the original case-control study is frequency matched on one of the mediators. We employed bootstrapping to assess the significance of indirect effects. We conducted simulation studies to investigate the performance of the proposed approach, and showed that it provides more accurate estimates of the indirect effects as well as the percent mediated than standard regressions. We then applied this approach to study the mediating effects of both smoking and chronic obstructive pulmonary disease (COPD on the association between the CHRNA5-A3 gene locus and lung cancer risk using data from a lung cancer case-control study. The results showed that the genetic variant influences lung cancer risk indirectly through all three different pathways. The percent of genetic association mediated was 18.3% through smoking alone, 30.2% through COPD alone, and 20.6% through the path including both smoking and COPD, and the total genetic variant-lung cancer association explained by the two

Causal mediation analysis with a binary outcome and multiple continuous or ordinal mediators: Simulations and application to an alcohol intervention

OpenAIRE

Nguyen, Trang Quynh; Webb-Vargas, Yenny; Koning, Ina M.; Stuart, Elizabeth A.

2016-01-01

We investigate a method to estimate the combined effect of multiple continuous/ordinal mediators on a binary outcome: 1) fit a structural equation model with probit link for the outcome and identity/probit link for continuous/ordinal mediators, 2) predict potential outcome probabilities, and 3) compute natural direct and indirect effects. Step 2 involves rescaling the latent continuous variable underlying the outcome to address residual mediator variance/covariance. We evaluate the estimation...

Mindfulness facets, trait emotional intelligence, emotional distress, and multiple health behaviors: A serial two-mediator model.

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Jacobs, Ingo; Wollny, Anna; Sim, Chu-Won; Horsch, Antje

2016-06-01

In the present study, we tested a serial mindfulness facets-trait emotional intelligence (TEI)-emotional distress-multiple health behaviors mediation model in a sample of N = 427 German-speaking occupational therapists. The mindfulness facets-TEI-emotional distress section of the mediation model revealed partial mediation for the mindfulness facets Act with awareness (Act/Aware) and Accept without judgment (Accept); inconsistent mediation was found for the Describe facet. The serial two-mediator model included three mediational pathways that may link each of the four mindfulness facets with multiple health behaviors. Eight out of 12 indirect effects reached significance and fully mediated the links between Act/Aware and Describe to multiple health behaviors; partial mediation was found for Accept. The mindfulness facet Observe was most relevant for multiple health behaviors, but its relation was not amenable to mediation. Implications of the findings will be discussed. © 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Testing Mediation Using Multiple Regression and Structural Equation Modeling Analyses in Secondary Data

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Li, Spencer D.

2011-01-01

Mediation analysis in child and adolescent development research is possible using large secondary data sets. This article provides an overview of two statistical methods commonly used to test mediated effects in secondary analysis: multiple regression and structural equation modeling (SEM). Two empirical studies are presented to illustrate the…

Causal mediation analysis with a binary outcome and multiple continuous or ordinal mediators: Simulations and application to an alcohol intervention.

Science.gov (United States)

Nguyen, Trang Quynh; Webb-Vargas, Yenny; Koning, Ina M; Stuart, Elizabeth A

We investigate a method to estimate the combined effect of multiple continuous/ordinal mediators on a binary outcome: 1) fit a structural equation model with probit link for the outcome and identity/probit link for continuous/ordinal mediators, 2) predict potential outcome probabilities, and 3) compute natural direct and indirect effects. Step 2 involves rescaling the latent continuous variable underlying the outcome to address residual mediator variance/covariance. We evaluate the estimation of risk-difference- and risk-ratio-based effects (RDs, RRs) using the ML, WLSMV and Bayes estimators in Mplus. Across most variations in path-coefficient and mediator-residual-correlation signs and strengths, and confounding situations investigated, the method performs well with all estimators, but favors ML/WLSMV for RDs with continuous mediators, and Bayes for RRs with ordinal mediators. Bayes outperforms WLSMV/ML regardless of mediator type when estimating RRs with small potential outcome probabilities and in two other special cases. An adolescent alcohol prevention study is used for illustration.

Testing a multiple mediation model of Asian American college students' willingness to see a counselor.

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Kim, Paul Youngbin; Park, Irene J K

2009-07-01

Adapting the theory of reasoned action, the present study examined help-seeking beliefs, attitudes, and intent among Asian American college students (N = 110). A multiple mediation model was tested to see if the relation between Asian values and willingness to see a counselor was mediated by attitudes toward seeking professional psychological help and subjective norm. A bootstrapping procedure was used to test the multiple mediation model. Results indicated that subjective norm was the sole significant mediator of the effect of Asian values on willingness to see a counselor. The findings highlight the importance of social influences on help-seeking intent among Asian American college students.

Multiple functions of the S-phase checkpoint mediator.

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Tanaka, Katsunori

2010-01-01

There is mounting evidence that replication defects are the major source of spontaneous genomic instability in cells, and that S-phase checkpoints are the principal defense against such instability. The S-phase checkpoint mediator protein Mrc1/Claspin mediates the checkpoint response to replication stress by facilitating phosphorylation of effector kinase by a sensor kinase. In this review, the multiple functions and the regulation of the S-phase checkpoint mediator are discussed.

Mediatization: a concept, multiple voices

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Pedro Gilberto GOMES

2016-12-01

Full Text Available Mediatization has become increasingly a key concept, fundamental, essential to describe the present and the history of media and communicative change taking place. Thus, it became part of a whole, one can not see them as a separate sphere. In this perspective, the media coverage is used as a concept to describe the process of expansion of the different technical means and consider the interrelationships between the communicative change, means and sociocultural change. However, although many researchers use the concept of mediatization, each gives you the meaning that best suits your needs. Thus, the concept of media coverage is treated with multiple voices. This paper discusses this problem and present a preliminary pre-position on the matter.

The effects of natalizumab on inflammatory mediators in multiple sclerosis: prospects for treatment-sensitive biomarkers

DEFF Research Database (Denmark)

Khademi, M.; Bornsen, L.; Rafatnia, F.

2009-01-01

BACKGROUND: Natalizumab affects systemic cytokine expressions and clinical course in relapsing-remitting multiple sclerosis (RRMS). We analyzed levels of inflammatory cytokines in cerebrospinal fluid (CSF) cells and peripheral blood mononuclear cells (PBMCs), levels of matrix metalloproteinase (MMP...... showed the same deviations of mediators as those in relapse after natalizumab treatment. The open label clinical outcome measures were either stable or improved during therapy. CONCLUSIONS: Natalizumab attenuates pro-inflammatory mediators intrathecally and the reduced pro-inflammatory milieu may allow...... increased production of the anti-inflammatory mediator IL-10. The increased systemic cytokines may impede the improvement of certain clinical measures like fatigue. The affected mediators seem to be sensitive to an immune-modifying treatment which could be used as biomarkers for this therapy Udgivelsesdato...

Efficient nonparametric estimation of causal mediation effects

OpenAIRE

Chan, K. C. G.; Imai, K.; Yam, S. C. P.; Zhang, Z.

2016-01-01

An essential goal of program evaluation and scientific research is the investigation of causal mechanisms. Over the past several decades, causal mediation analysis has been used in medical and social sciences to decompose the treatment effect into the natural direct and indirect effects. However, all of the existing mediation analysis methods rely on parametric modeling assumptions in one way or another, typically requiring researchers to specify multiple regression models involving the treat...

Utilized social support and self-esteem mediate the relationship between perceived social support and suicide ideation. A test of a multiple mediator model.

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Kleiman, Evan M; Riskind, John H

2013-01-01

While perceived social support has received considerable research as a protective factor for suicide ideation, little attention has been given to the mechanisms that mediate its effects. We integrated two theoretical models, Joiner's (2005) interpersonal theory of suicide and Leary's (Leary, Tambor, Terdal, & Downs, 1995) sociometer theory of self-esteem to investigate two hypothesized mechanisms, utilization of social support and self-esteem. Specifically, we hypothesized that individuals must utilize the social support they perceive that would result in increased self-esteem, which in turn buffers them from suicide ideation. Participants were 172 college students who completed measures of social support, self-esteem, and suicide ideation. Tests of simple mediation indicate that utilization of social support and self-esteem may each individually help to mediate the perceived social support/suicide ideation relationship. Additionally, a test of multiple mediators using bootstrapping supported the hypothesized multiple-mediator model. The use of a cross-sectional design limited our ability to find true cause-and-effect relationships. Results suggested that utilized social support and self-esteem both operate as individual moderators in the social support/self-esteem relationship. Results further suggested, in a comprehensive model, that perceived social support buffers suicide ideation through utilization of social support and increases in self-esteem.

Gravity- and non-gravity-mediated couplings in multiple-field inflation

International Nuclear Information System (INIS)

Bernardeau, Francis

2010-01-01

Mechanisms for the generation of primordial non-Gaussian metric fluctuations in the context of multiple-field inflation are reviewed. As long as kinetic terms remain canonical, it appears that nonlinear couplings inducing non-Gaussianities can be split into two types. The extension of the one-field results to multiple degrees of freedom leads to gravity-mediated couplings that are ubiquitous but generally modest. Multiple-field inflation offers however the possibility of generating non-gravity-mediated coupling in isocurvature directions that can eventually induce large non-Gaussianities in the metric fluctuations. The robustness of the predictions of such models is eventually examined in view of a case study derived from a high-energy physics construction.

Analyzing Statistical Mediation with Multiple Informants: A New Approach with an Application in Clinical Psychology.

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Papa, Lesther A; Litson, Kaylee; Lockhart, Ginger; Chassin, Laurie; Geiser, Christian

2015-01-01

Testing mediation models is critical for identifying potential variables that need to be targeted to effectively change one or more outcome variables. In addition, it is now common practice for clinicians to use multiple informant (MI) data in studies of statistical mediation. By coupling the use of MI data with statistical mediation analysis, clinical researchers can combine the benefits of both techniques. Integrating the information from MIs into a statistical mediation model creates various methodological and practical challenges. The authors review prior methodological approaches to MI mediation analysis in clinical research and propose a new latent variable approach that overcomes some limitations of prior approaches. An application of the new approach to mother, father, and child reports of impulsivity, frustration tolerance, and externalizing problems (N = 454) is presented. The results showed that frustration tolerance mediated the relationship between impulsivity and externalizing problems. The new approach allows for a more comprehensive and effective use of MI data when testing mediation models.

Shared Authentic Leadership in Research Teams: Testing a Multiple Mediation Model.

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Guenter, Hannes; Gardner, William L; Davis McCauley, Kelly; Randolph-Seng, Brandon; Prabhu, Veena P

2017-12-01

Research teams face complex leadership and coordination challenges. We propose shared authentic leadership (SAL) as a timely approach to addressing these challenges. Drawing from authentic and functional leadership theories, we posit a multiple mediation model that suggests three mechanisms whereby SAL influences team effectiveness: shared mental models (SMM), team trust, and team coordination. To test our hypotheses, we collected survey data on leadership and teamwork within 142 research teams that recently published an article in a peer-reviewed management journal. The results indicate team coordination represents the primary mediating mechanism accounting for the relationship between SAL and research team effectiveness. While teams with high trust and SMM felt more successful and were more satisfied, they were less successful in publishing in high-impact journals. We also found the four SAL dimensions (i.e., self-awareness, relational transparency, balanced processing, and internalized moral perspective) to associate differently with team effectiveness.

Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo.

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Eyboulet, Fanny; Wydau-Dematteis, Sandra; Eychenne, Thomas; Alibert, Olivier; Neil, Helen; Boschiero, Claire; Nevers, Marie-Claire; Volland, Hervé; Cornu, David; Redeker, Virginie; Werner, Michel; Soutourina, Julie

2015-10-30

Mediator is a large multiprotein complex conserved in all eukaryotes, which has a crucial coregulator function in transcription by RNA polymerase II (Pol II). However, the molecular mechanisms of its action in vivo remain to be understood. Med17 is an essential and central component of the Mediator head module. In this work, we utilised our large collection of conditional temperature-sensitive med17 mutants to investigate Mediator's role in coordinating preinitiation complex (PIC) formation in vivo at the genome level after a transfer to a non-permissive temperature for 45 minutes. The effect of a yeast mutation proposed to be equivalent to the human Med17-L371P responsible for infantile cerebral atrophy was also analyzed. The ChIP-seq results demonstrate that med17 mutations differentially affected the global presence of several PIC components including Mediator, TBP, TFIIH modules and Pol II. Our data show that Mediator stabilizes TFIIK kinase and TFIIH core modules independently, suggesting that the recruitment or the stability of TFIIH modules is regulated independently on yeast genome. We demonstrate that Mediator selectively contributes to TBP recruitment or stabilization to chromatin. This study provides an extensive genome-wide view of Mediator's role in PIC formation, suggesting that Mediator coordinates multiple steps of a PIC assembly pathway. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Identifying the Average Causal Mediation Effects with Multiple Mediators in the Presence of Treatment Non-Compliance

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Park, Soojin

2015-01-01

Identifying the causal mechanisms is becoming more essential in social and medical sciences. In the presence of treatment non-compliance, the Intent-To-Treated effect (hereafter, ITT effect) is identified as long as the treatment is randomized (Angrist et al., 1996). However, the mediated portion of effect is not identified without additional…

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

Science.gov (United States)

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.

Does mediator use contribute to the spacing effect for cued recall? Critical tests of the mediator hypothesis.

Science.gov (United States)

Morehead, Kayla; Dunlosky, John; Rawson, Katherine A; Bishop, Melissa; Pyc, Mary A

2018-04-01

When study is spaced across sessions (versus massed within a single session), final performance is greater after spacing. This spacing effect may have multiple causes, and according to the mediator hypothesis, part of the effect can be explained by the use of mediator-based strategies. This hypothesis proposes that when study is spaced across sessions, rather than massed within a session, more mediators will be generated that are longer lasting and hence more mediators will be available to support criterion recall. In two experiments, participants were randomly assigned to study paired associates using either a spaced or massed schedule. They reported strategy use for each item during study trials and during the final test. Consistent with the mediator hypothesis, participants who had spaced (as compared to massed) practice reported using more mediators on the final test. This use of effective mediators also statistically accounted for some - but not all of - the spacing effect on final performance.

Multiple mediators of the relationships among maternal childhood abuse, intimate partner violence, and offspring psychopathology.

Science.gov (United States)

Miranda, Jenniffer K; de la Osa, Nuria; Granero, Roser; Ezpeleta, Lourdes

2013-09-01

The aim of the study was to examine whether maternal depression, mothers' and fathers' parenting, child physical punishment and negative life events (NLE) mediate the effect of maternal childhood abuse (CA), intimate partner violence (IPV) and cumulative violence (both CA and IPV) on Spanish children's and adolescents' psychopathology. Furthermore, multiple mediator models examine whether IPV mediates the effect of CA on the contextual and family factors mentioned above. Three hundred and eighteen Spanish outpatients aged 7 to 18 and their parents were assessed using a structured interview and other instruments for measuring the study variables. Structural equation models (SEMs) showed multiple pathways explaining psychopathological problems among offspring of mothers who suffered CA, IPV and both of these violent experiences. In particular, mothers' depression mediated the link between maternal CA, IPV, cumulative violence and children's externalizing, and total behavior problems. Child NLE was an important pathway between maternal CA and total behavior problems, as well as between cumulative violence and both externalizing and total problems. IPV contributed to explaining the link between maternal CA and contextual and family factors, such as child physical punishment and NLE, which were in turn, associated with children's behavior problems. Findings show the complex interconnections between different types of violence and their harmful effects on the mental health of women and their offspring, as well as the need to extend our knowledge on this subject.

Analyzing Statistical Mediation with Multiple Informants: A New Approach with an Application in Clinical Psychology

Directory of Open Access Journals (Sweden)

Lesther ePapa

2015-11-01

Full Text Available Testing mediation models is critical for identifying potential variables that need to be targeted to effectively change one or more outcome variables. In addition, it is now common practice for clinicians to use multiple informant (MI data in studies of statistical mediation. By coupling the use of MI data with statistical mediation analysis, clinical researchers can combine the benefits of both techniques. Integrating the information from MIs into a statistical mediation model creates various methodological and practical challenges. The authors review prior methodological approaches to MI mediation analysis in clinical research and propose a new latent variable approach that overcomes some limitations of prior approaches. An application of the new approach to mother, father, and child reports of impulsivity, frustration tolerance, and externalizing problems (N = 454 is presented. The results showed that frustration tolerance mediated the relationship between impulsivity and externalizing problems. Advantages and limitations of the new approach are discussed. The new approach can help clinical researchers overcome limitations of prior techniques. It allows for a more comprehensive and effective use of MI data when testing mediation models.

Daratumumab-mediated lysis of primary multiple myeloma cells is enhanced in combination with the human anti-KIR antibody IPH2102 and lenalidomide

DEFF Research Database (Denmark)

Nijhof, I. S.; Lammerts van Bueren, J. J.; van Kessel, B.

2015-01-01

Despite recent treatment improvements, multiple myeloma remains an incurable disease. Since antibody-dependent cell-mediated cytotoxicity is an important effector mechanism of daratumumab, we explored the possibility of improving daratumumab-mediated cell-mediated cytotoxicity by blocking natural...... killer cell inhibitory receptors with the human monoclonal anti-KIR antibody IPH2102, next to activation of natural killer cells with the immune modulatory drug lenalidomide. In 4-hour antibody-dependent cell-mediated cytotoxicity assays, IPH2102 did not induce lysis of multiple myeloma cell lines...... effective treatment strategies can be designed for multiple myeloma by combining daratumumab with agents that independently modulate natural killer cell function....

Affective mediators of a physical activity intervention for depression in multiple sclerosis.

Science.gov (United States)

Kratz, Anna L; Ehde, Dawn M; Bombardier, Charles H

2014-02-01

Previous analyses showed that a telephone-based intervention to increase physical activity in individuals with multiple sclerosis (MS) and depression resulted in significantly improved depressive symptoms compared to a wait-list control group. The aim of this study was to test positive affect and negative affect as mediators of the effect of the physical activity counseling on depressive symptoms. Ninety-two adults with MS, who met diagnostic criteria for either major depression or dysthymia and who reported low levels of physical activity, were randomized 1:1 to a 12-week telephone-based motivational interviewing (MI) intervention to improve physical activity (n = 44) or to a 12-week wait-list control group (n = 48). Self-reported positive and negative affect, physical activity, and depressive symptoms were gathered at baseline and postintervention. Path-analysis was used to test whether positive affect and negative affect mediated the positive effects of the intervention on depressive symptoms. Both positive and negative affect were significant mediators of the effects of the intervention on depressive symptoms; however, only positive affect mediated the association between changes in physical activity and improved depressive symptoms. Findings support physical activity and positive affect as key mediators of the MI treatment effect on improved mood. Decreases in negative affect were also evident in the treatment group, but were not related to improved physical activity. Findings may suggest the use of exercise-based interventions in conjunction with treatments that specifically target negative affective mechanisms for depression. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Semiotic mediation: from multiplication properties to arithmetical expressions

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Andrea Maffia

2016-04-01

Full Text Available Multiplication is introduced early in primary school, but its properties are usually introduced after the rote memorization of multiplicative facts. In this paper we present a teaching experiment aimed to early introducing arithmetical properties of multiplication. It is realized through an artefact built on the rectangle model for multiplication. Children activity is designed and analyzed using Theory of Semiotic Mediation. The development of the relational meaning of arithmetical expressions is shown through the enchaining of representations from signs related to the activity with the artefact to mathematical ones. In particular, the role of the teacher in the process of semiotic mediation results as crucial. Mediazione semiotica: dalle proprietà della moltiplicazione alle espressioni aritmeticheLa moltiplicazione viene presentata presto nella scuola primaria, ma le sue proprietà sono introdotte solo dopo che le cosiddette tabelline sono state memorizzate. Nell’articolo si presenta un teaching experiment volto a introdurre precocemente le proprietà della moltiplicazione per facilitare la memorizzazione di fatti moltiplicativi. L’esperimento è centrato sull’uso di un artefatto costruito sul modello rettangolare della moltiplicazione. L’attività degli studenti è progettata e analizzata nel quadro della Teoria della Mediazione Semiotica (TMS. Lo sviluppo del significato relazionale delle espressioni aritmetiche viene mostrato attraverso la concatenazione di rappresentazioni che vanno da segni strettamente legati all’attività con l’artefatto fino a segni matematici. In particolare, si evidenzia il ruolo dell’insegnante nello sviluppo del processo di mediazione semiotica.

Stress and multiple sclerosis: A systematic review considering potential moderating and mediating factors and methods of assessing stress

Directory of Open Access Journals (Sweden)

Laia Briones-Buixassa

2015-11-01

Full Text Available Research about the effects of stress on multiple sclerosis has yielded contradictory results. This study aims to systematically review the evidence focusing on two possible causes: the role of stress assessment and potential moderating and mediating factors. The Web of Knowledge (MEDLINE and Web of Science, Scopus, and PsycINFO databases were searched for relevant articles published from 1900 through December 2014 using the terms “stress*” AND “multiple sclerosis.” Twenty-three articles were included. Studies focused on the effect of stress on multiple sclerosis onset ( n  = 9 were mostly retrospective, and semi-structured interviews and scales yielded the most consistent associations. Studies focused on multiple sclerosis progression ( n  = 14 were mostly prospective, and self-reported diaries yielded the most consistent results. The most important modifying factors were stressor duration, severity, and frequency; cardiovascular reactivity and heart rate; and social support and escitalopram intake. Future studies should consider the use of prospective design with self-reported evaluations and the study of moderators and mediators related to amount of stress and autonomic nervous system reactivity to determine the effects of stress on multiple sclerosis.

Stress and multiple sclerosis: A systematic review considering potential moderating and mediating factors and methods of assessing stress.

Science.gov (United States)

Briones-Buixassa, Laia; Milà, Raimon; Mª Aragonès, Josep; Bufill, Enric; Olaya, Beatriz; Arrufat, Francesc Xavier

2015-07-01

Research about the effects of stress on multiple sclerosis has yielded contradictory results. This study aims to systematically review the evidence focusing on two possible causes: the role of stress assessment and potential moderating and mediating factors. The Web of Knowledge (MEDLINE and Web of Science), Scopus, and PsycINFO databases were searched for relevant articles published from 1900 through December 2014 using the terms "stress*" AND "multiple sclerosis." Twenty-three articles were included. Studies focused on the effect of stress on multiple sclerosis onset ( n  = 9) were mostly retrospective, and semi-structured interviews and scales yielded the most consistent associations. Studies focused on multiple sclerosis progression ( n  = 14) were mostly prospective, and self-reported diaries yielded the most consistent results. The most important modifying factors were stressor duration, severity, and frequency; cardiovascular reactivity and heart rate; and social support and escitalopram intake. Future studies should consider the use of prospective design with self-reported evaluations and the study of moderators and mediators related to amount of stress and autonomic nervous system reactivity to determine the effects of stress on multiple sclerosis.

Neuroticism and quality of life: Multiple mediating effects of smartphone addiction and depression.

Science.gov (United States)

Gao, Tingting; Xiang, Yu-Tao; Zhang, Han; Zhang, Zhao; Mei, Songli

2017-12-01

The purposes of this study were to investigate the mediating effect of smartphone addiction and depression on neuroticism and quality of life. Self-reported measures of neuroticism, smart-phone addiction, depression, and quality of life were administered to 722 Chinese university students. Results showed smartphone addiction and depression were both significantly affected neuroticism and quality of life. The direct effect of neuroticism on quality of life was significant, and the chain-mediating effect of smartphone addiction and depression was also significant. In conclusion, neuroticism, smartphone addiction, and depression are important variables that worsen quality of life. Copyright © 2017 Elsevier B.V. All rights reserved.

Individual and family factors associated with self-esteem in young people with epilepsy: A multiple mediation analysis.

Science.gov (United States)

Chew, Judith; Haase, Anne M; Carpenter, John

2017-01-01

As young people experience added demands from living with epilepsy, which may lead to poor psychosocial adjustment, it is essential to examine mechanisms of change to provide practitioners with knowledge to develop effective interventions. The aim of this study was to examine individual and family-level factors - stress and illness perceptions, coping behaviors and family resilience - that promote or maintain young people's self-esteem. From November 2013 to August 2014, young people attending a neurology clinic in KK Women's and Children's Hospital, Singapore, participated in a cross-sectional survey (n=152; 13-16years old). Multiple mediation analyses were conducted to evaluate whether these variables mediated the relationship between illness severity (i.e., low, moderate, high) and self-esteem. Multiple mediation analyses demonstrated that illness severity had a direct effect on young people's self-esteem. Compared to those with moderate illness severity (reference group), young people with low severity had significantly higher self-esteem (c=3.42, pself-esteem through its effects on mediators, such as perceived stress, illness perceptions and family resilience (D 1 : Total ab=3.46, 95% CI 1.13, 5.71; D 2 : Total ab=-2.80, 95% CI -4.35, -1.30). However, young people's coping levels did not predict their self-esteem, when accounting for the effects of other variables. The continued presence of seizure occurrences is likely to place greater demands on young people and their families: in turn, increased stress and negative illness perceptions negatively affected family processes that promote resilience. As the mediating effect of these modifiable factors were above and beyond the contributions of illness characteristics and young people's levels of coping, this has implications for developing individual and family interventions aimed to support young people living with epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Stress Effects on Multiple Memory System Interactions

Science.gov (United States)

Ness, Deborah; Calabrese, Pasquale

2016-01-01

Extensive behavioural, pharmacological, and neurological research reports stress effects on mammalian memory processes. While stress effects on memory quantity have been known for decades, the influence of stress on multiple memory systems and their distinct contributions to the learning process have only recently been described. In this paper, after summarizing the fundamental biological aspects of stress/emotional arousal and recapitulating functionally and anatomically distinct memory systems, we review recent animal and human studies exploring the effects of stress on multiple memory systems. Apart from discussing the interaction between distinct memory systems in stressful situations, we will also outline the fundamental role of the amygdala in mediating such stress effects. Additionally, based on the methods applied in the herein discussed studies, we will discuss how memory translates into behaviour. PMID:27034845

Stress Effects on Multiple Memory System Interactions.

Science.gov (United States)

Ness, Deborah; Calabrese, Pasquale

2016-01-01

Extensive behavioural, pharmacological, and neurological research reports stress effects on mammalian memory processes. While stress effects on memory quantity have been known for decades, the influence of stress on multiple memory systems and their distinct contributions to the learning process have only recently been described. In this paper, after summarizing the fundamental biological aspects of stress/emotional arousal and recapitulating functionally and anatomically distinct memory systems, we review recent animal and human studies exploring the effects of stress on multiple memory systems. Apart from discussing the interaction between distinct memory systems in stressful situations, we will also outline the fundamental role of the amygdala in mediating such stress effects. Additionally, based on the methods applied in the herein discussed studies, we will discuss how memory translates into behaviour.

Stress Effects on Multiple Memory System Interactions

Directory of Open Access Journals (Sweden)

Deborah Ness

2016-01-01

Full Text Available Extensive behavioural, pharmacological, and neurological research reports stress effects on mammalian memory processes. While stress effects on memory quantity have been known for decades, the influence of stress on multiple memory systems and their distinct contributions to the learning process have only recently been described. In this paper, after summarizing the fundamental biological aspects of stress/emotional arousal and recapitulating functionally and anatomically distinct memory systems, we review recent animal and human studies exploring the effects of stress on multiple memory systems. Apart from discussing the interaction between distinct memory systems in stressful situations, we will also outline the fundamental role of the amygdala in mediating such stress effects. Additionally, based on the methods applied in the herein discussed studies, we will discuss how memory translates into behaviour.

Relationship between cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers: Exploring multiple mediation model.

Science.gov (United States)

Cai, Wen-Peng; Pan, Yu; Zhang, Shui-Miao; Wei, Cun; Dong, Wei; Deng, Guang-Hui

2017-10-01

The current study aimed to explore the association of cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers and to understand the multiple mediation effects of social support and resilience on the relationship between cognitive emotion regulation and acute stress responses. A total of 1477 male soldiers completed mental scales, including the cognitive emotion regulation questionnaire-Chinese version, the perceived social support scale, the Chinese version of the Connor-Davidson resilience scale, and the military acute stress scale. As hypothesized, physiological responses, psychological responses, and acute stress were associated with negative-focused cognitive emotion regulation, and negatively associated with positive-focused cognitive emotion regulation, social supports and resilience. Besides, positive-focused cognitive emotion regulation, social support, and resilience were significantly associated with one another, and negative-focused cognitive emotion regulation was negatively associated with social support. Regression analysis and bootstrap analysis showed that social support and resilience had partly mediating effects on negative strategies and acute stress, and fully mediating effects on positive strategies and acute stress. These results thus indicate that military acute stress is significantly associated with cognitive emotion regulation, social support, and resilience, and that social support and resilience have multiple mediation effects on the relationship between cognitive emotion regulation and acute stress responses. Copyright © 2017 Elsevier B.V. All rights reserved.

Insulin-like growth factor 1: common mediator of multiple enterotrophic hormones and growth factors.

Science.gov (United States)

Bortvedt, Sarah F; Lund, P Kay

2012-03-01

To summarize the recent evidence that insulin-like growth factor 1 (IGF1) mediates growth effects of multiple trophic factors and discuss clinical relevance. Recent reviews and original reports indicate benefits of growth hormone (GH) and long-acting glucagon-like peptide 2 (GLP2) analogs in short bowel syndrome and Crohn's disease. This review highlights the evidence that biomarkers of sustained small intestinal growth or mucosal healing and evaluation of intestinal epithelial stem cell biomarkers may improve clinical measures of intestinal growth or response to trophic hormones. Compelling evidence that IGF1 mediates growth effects of GH and GLP2 on intestine or linear growth in preclinical models of resection or Crohn's disease is presented, along with a concept that these hormones or IGF1 may enhance sustained growth if given early after bowel resection. Evidence that suppressor of cytokine signaling protein induction by GH or GLP2 in normal or inflamed intestine may limit IGF1-induced growth, but protect against risk of dysplasia or fibrosis, is reviewed. Whether IGF1 receptor mediates IGF1 action and potential roles of insulin receptors are addressed. IGF1 has a central role in mediating trophic hormone action in small intestine. Better understanding of benefits and risks of IGF1, receptors that mediate IGF1 action, and factors that limit undesirable growth are needed.

Estimation of indirect effect when the mediator is a censored variable.

Science.gov (United States)

Wang, Jian; Shete, Sanjay

2017-01-01

A mediation model explores the direct and indirect effects of an initial variable ( X) on an outcome variable ( Y) by including a mediator ( M). In many realistic scenarios, investigators observe censored data instead of the complete data. Current research in mediation analysis for censored data focuses mainly on censored outcomes, but not censored mediators. In this study, we proposed a strategy based on the accelerated failure time model and a multiple imputation approach. We adapted a measure of the indirect effect for the mediation model with a censored mediator, which can assess the indirect effect at both the group and individual levels. Based on simulation, we established the bias in the estimations of different paths (i.e. the effects of X on M [ a], of M on Y [ b] and of X on Y given mediator M [ c']) and indirect effects when analyzing the data using the existing approaches, including a naïve approach implemented in software such as Mplus, complete-case analysis, and the Tobit mediation model. We conducted simulation studies to investigate the performance of the proposed strategy compared to that of the existing approaches. The proposed strategy accurately estimates the coefficients of different paths, indirect effects and percentages of the total effects mediated. We applied these mediation approaches to the study of SNPs, age at menopause and fasting glucose levels. Our results indicate that there is no indirect effect of association between SNPs and fasting glucose level that is mediated through the age at menopause.

Social anxiety and heavy situational drinking: coping and conformity motives as multiple mediators.

Science.gov (United States)

Terlecki, Meredith A; Buckner, Julia D

2015-01-01

Individuals with clinically elevated social anxiety are at greater risk for alcohol use disorder, and the relation between social anxiety and drinking problems is at least partially accounted for by drinking more in negative emotional (e.g., feeling sad or angry) and personal/intimate (e.g., before sexual intercourse) situations. Identification of cognitive/motivational factors related to drinking in these high-risk situations could inform the development of treatment and prevention interventions for these high-risk drinkers. The current cross-sectional study examined the mediating effect of drinking motives on the relationship between social anxiety and drinking these high-risk situations among undergraduates (N=232). Clinically elevated social anxiety was associated with greater coping and conformity motives. Both coping and conformity motives mediated the relation between social anxiety and heavier alcohol consumption in negative emotional and personal/intimate contexts. Multiple mediation analyses indicated that these motives work additively to mediate the social anxiety-drinking situations relationship, such that heavy situational drinking among undergraduates with clinically elevated social anxiety can be jointly attributed to desire to cope with negative affect and to avoid social scrutiny. Copyright © 2014 Elsevier Ltd. All rights reserved.

Multiple Regression and Mediator Variables can be used to Avoid Double Counting when Economic Values are Derived using Stochastic Herd Simulation

DEFF Research Database (Denmark)

Østergaard, Søren; Ettema, Jehan Frans; Hjortø, Line

Multiple regression and model building with mediator variables was addressed to avoid double counting when economic values are estimated from data simulated with herd simulation modeling (using the SimHerd model). The simulated incidence of metritis was analyzed statistically as the independent v...... in multiparous cows. The merit of using this approach was demonstrated since the economic value of metritis was estimated to be 81% higher when no mediator variables were included in the multiple regression analysis......Multiple regression and model building with mediator variables was addressed to avoid double counting when economic values are estimated from data simulated with herd simulation modeling (using the SimHerd model). The simulated incidence of metritis was analyzed statistically as the independent...... variable, while using the traits representing the direct effects of metritis on yield, fertility and occurrence of other diseases as mediator variables. The economic value of metritis was estimated to be €78 per 100 cow-years for each 1% increase of metritis in the period of 1-100 days in milk...

Assessing Natural Direct and Indirect Effects Through Multiple Pathways

DEFF Research Database (Denmark)

Lange, T; Rasmussen, M; Thygesen, Lau Caspar

2014-01-01

. The approach is an extension of the natural effect models proposed by Lange et al. (Am J Epidemiol. 2012;176(3):190-195). By allowing the analysis of distinct multiple pathways, the suggested approach adds to the capabilities of modern mediation techniques. Furthermore, the approach can be implemented using......Within the fields of epidemiology, interventions research and social sciences researchers are often faced with the challenge of decomposing the effect of an exposure into different causal pathways working through defined mediator variables. The goal of such analyses is often to understand...... the mechanisms of the system or to suggest possible interventions. The case of a single mediator, thus implying only 2 causal pathways (direct and indirect) from exposure to outcome, has been extensively studied. By using the framework of counterfactual variables, researchers have established theoretical...

Impact of emotional competence on supportive care needs, anxiety and depression symptoms of cancer patients: a multiple mediation model.

Science.gov (United States)

Baudry, A-S; Lelorain, S; Mahieuxe, M; Christophe, V

2018-01-01

The aim of this study was to test the effect of intrapersonal and interpersonal emotional competence on cancer patients' supportive care needs, as mediated by anxiety and depression symptoms. Cross-sectional design: 137 cancer patients (42% breast or ovarian cancer, 58% gastrointestinal cancer) in 4 French hospitals completed the Profile of Emotional Competence (PEC), the Hospital Anxiety and Depression Scale (HADS), and the Supportive Care Needs Survey Short Form (SCNS-SF). Bootstrap methods with PROCESS Macro were used to test multiple mediation models. Emotional competence presented a direct or indirect beneficial effect on the satisfaction of supportive care needs, anxiety and depression symptoms. As expected, anxiety and depression symptoms had also strong positive correlations with unmet needs. All multiple mediation models were significant, except for physical needs: intrapersonal and interpersonal emotional competence impacted anxiety and depression symptoms, which in turn impacted psychological, sexual, care/support, and information needs. These innovative results show the important effect of patients' emotional competence on their supportive care need satisfaction, as mediated by anxiety and depression. Consequently, patients with high emotional competence may require less psychosocial input from medical clinicians. Thus, emotional competence may be integrated into health models and psychosocial interventions to improve patient adjustment. Further investigation is, however, needed to know which are the most beneficial specific emotional competences and at what point of the cancer pathway.

Body image mediates the effect of cancer-related stigmatization on depression

DEFF Research Database (Denmark)

Esser, Peter; Mehnert, Anja; Johansen, Christoffer

2018-01-01

OBJECTIVE: Because cancer-related stigmatization is prevalent but difficult to change, research on its impact on psychological burden and respective intervening variables is needed. Therefore, we investigated the effect of stigmatization on depressive symptomatology and whether body image mediates...... this relationship. METHODS: This bicentric study assessed patients of 4 major tumor entities. We measured stigmatization (SIS-D), depressive symptomatology (PHQ-9), and body image (FKB-20). Applying multiple mediator analyses, we calculated the total effect of stigmatization on depressive symptomatology...

Shared Authentic Leadership in Research Teams: Testing a Multiple Mediation Model

NARCIS (Netherlands)

Günter, Hannes; Gardner, William L.; Davis McCauley, Kelly; Randolph-Seng, Brandon; P. Prahbu, Veena

2017-01-01

Research teams face complex leadership and coordination challenges. We propose shared authentic leadership (SAL) as a timely approach to addressing these challenges. Drawing from authentic and functional leadership theories, we posit a multiple mediation model that suggests three mechanisms whereby

Stressors and Caregivers' Depression: Multiple Mediators of Self-Efficacy, Social Support, and Problem-Solving Skill.

Science.gov (United States)

Tang, Fengyan; Jang, Heejung; Lingler, Jennifer; Tamres, Lisa K; Erlen, Judith A

2015-01-01

Caring for an older adult with memory loss is stressful. Caregiver stress could produce negative outcomes such as depression. Previous research is limited in examining multiple intermediate pathways from caregiver stress to depressive symptoms. This study addresses this limitation by examining the role of self-efficacy, social support, and problem solving in mediating the relationships between caregiver stressors and depressive symptoms. Using a sample of 91 family caregivers, we tested simultaneously multiple mediators between caregiver stressors and depression. Results indicate that self-efficacy mediated the pathway from daily hassles to depression. Findings point to the importance of improving self-efficacy in psychosocial interventions for caregivers of older adults with memory loss.

Multiple-state Feshbach resonances mediated by high-order couplings

International Nuclear Information System (INIS)

Hemming, Christopher J.; Krems, Roman V.

2008-01-01

We present a study of multistate Feshbach resonances mediated by high-order couplings. Our analysis focuses on a system with one open scattering state and multiple bound states. The scattering state is coupled to one off-resonant bound state and multiple Feshbach resonances are induced by a sequence of indirect couplings between the closed channels. We derive a general recursive expression that can be used to fit the experimental data on multistate Feshbach resonances involving one continuum state and several bound states and present numerical solutions for several model systems. Our results elucidate general features of multistate Feshbach resonances induced by high-order couplings and suggest mechanisms for controlling collisions of ultracold atoms and molecules with external fields

Stressors and Caregivers’ Depression: Multiple Mediators of Self-Efficacy, Social Support, and Problem-solving Skill

Science.gov (United States)

Tang, Fengyan; Jang, Heejung; Lingler, Jennifer; Tamres, Lisa K.; Erlen, Judith A.

2016-01-01

Caring for an older adult with memory loss is stressful. Caregiver stress could produce negative outcomes such as depression. Previous research is limited in examining multiple intermediate pathways from caregiver stress to depressive symptoms. This study addresses this limitation by examining the role of self-efficacy, social support, and problem-solving in mediating the relationships between caregiver stressors and depressive symptoms. Using a sample of 91 family caregivers, we tested simultaneously multiple mediators between caregiver stressors and depression. Results indicate that self-efficacy mediated the pathway from daily hassles to depression. Findings point to the importance of improving self-efficacy in psychosocial interventions for caregivers of older adults with memory loss. PMID:26317766

Anxiety, affect, self-esteem, and stress: mediation and moderation effects on depression.

Science.gov (United States)

Nima, Ali Al; Rosenberg, Patricia; Archer, Trevor; Garcia, Danilo

2013-01-01

Mediation analysis investigates whether a variable (i.e., mediator) changes in regard to an independent variable, in turn, affecting a dependent variable. Moderation analysis, on the other hand, investigates whether the statistical interaction between independent variables predict a dependent variable. Although this difference between these two types of analysis is explicit in current literature, there is still confusion with regard to the mediating and moderating effects of different variables on depression. The purpose of this study was to assess the mediating and moderating effects of anxiety, stress, positive affect, and negative affect on depression. Two hundred and two university students (males  = 93, females  = 113) completed questionnaires assessing anxiety, stress, self-esteem, positive and negative affect, and depression. Mediation and moderation analyses were conducted using techniques based on standard multiple regression and hierarchical regression analyses. The results indicated that (i) anxiety partially mediated the effects of both stress and self-esteem upon depression, (ii) that stress partially mediated the effects of anxiety and positive affect upon depression, (iii) that stress completely mediated the effects of self-esteem on depression, and (iv) that there was a significant interaction between stress and negative affect, and between positive affect and negative affect upon depression. The study highlights different research questions that can be investigated depending on whether researchers decide to use the same variables as mediators and/or moderators.

Effect of long-term fertilization on humic redox mediators in multiple microbial redox reactions.

Science.gov (United States)

Guo, Peng; Zhang, Chunfang; Wang, Yi; Yu, Xinwei; Zhang, Zhichao; Zhang, Dongdong

2018-03-01

This study investigated the effects of different long-term fertilizations on humic substances (HSs), humic acids (HAs) and humins, functioning as redox mediators for various microbial redox biotransformations, including 2,2',4,4',5,5'- hexachlorobiphenyl (PCB 153 ) dechlorination, dissimilatory iron reduction, and nitrate reduction, and their electron-mediating natures. The redox activity of HSs for various microbial redox metabolisms was substantially enhanced by long-term application of organic fertilizer (pig manure). As a redox mediator, only humin extracted from soils with organic fertilizer amendment (OF-HM) maintained microbial PCB 153 dechlorination activity (1.03 μM PCB 153 removal), and corresponding HA (OF-HA) most effectively enhanced iron reduction and nitrate reduction by Shewanella putrefaciens. Electrochemical analysis confirmed the enhancement of their electron transfer capacity and redox properties. Fourier transform infrared analysis showed that C=C and C=O bonds, and carboxylic or phenolic groups in HSs might be the redox functional groups affected by fertilization. This research enhances our understanding of the influence of anthropogenic fertility on the biogeochemical cycling of elements and in situ remediation ability in agroecosystems through microorganisms' metabolisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Investigating the effect of child maltreatment on early adolescent peer-on-peer sexual aggression: testing a multiple mediator model in a non-incarcerated sample of Danish adolescents.

Science.gov (United States)

Bramsen, Rikke Holm; Lasgaard, Mathias; Koss, Mary P; Elklit, Ask; Banner, Jytte

2014-01-01

The aim of the present study was to investigate the relationship between child maltreatment and severe early adolescent peer-on-peer sexual aggression, using a multiple mediator model. The study comprised 330 male Grade 9 students with a mean age of 14.9 years (SD=0.5). Estimates from the mediation model indicated significant indirect effects of child physical abuse on sexual aggression via peer influence and insecure-hostile masculinity. No significant total effect of child sexual abuse and child neglect on sexual aggression was found. Findings of the present study identify risk factors that are potentially changeable and therefore of value in informing the design of prevention programs aiming at early adolescent peer-on-peer sexual aggression in at-risk youth.

Patient-provider relationship as mediator between adult attachment and self-management in primary care patients with multiple chronic conditions.

Science.gov (United States)

Brenk-Franz, Katja; Strauß, Bernhard; Tiesler, Fabian; Fleischhauer, Christian; Schneider, Nico; Gensichen, Jochen

2017-06-01

The conceptual model of attachment theory has been applied to understand the predispositions of patients in medical care and the patient-provider relationship. In patients with chronic conditions insecure attachment was connected to poorer self-management. The patient-provider relationship is associated with a range of health related outcomes and self-management skills. We determined whether the quality of the patient-provider relationship mediates the link between adult attachment and self-management among primary care patients with multiple chronic diseases. 209 patients with a minimum of three chronic diseases (including type II diabetes, hypertension and at least one other chronic condition) between the ages of 50 and 85 from eight general practices were included in the APRICARE cohort study. Adult attachment was measured via self-report (ECR-RD), self-management skills by the FERUS and the patient-provider relationship by the PRA-D. The health status and chronicity were assessed by the GP. Multiple mediation analyses were used to examine whether aspects of the patient-provider relationship (communication, information, affectivity) are a mediators of associations between adult attachment and self-management. The analysis revealed that the quality of the patient-provider relationship mediated the effect of attachment on self-management in patients with multiple chronic conditions. Particularly the quality of communication and information over the course of treatment has a significant mediating influence. A personalized, attachment-related approach that promotes active patient-provider communication and gives information about the treatment to the patient may improve self-management skills in patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Parent involvement and student academic performance: a multiple mediational analysis.

Science.gov (United States)

Topor, David R; Keane, Susan P; Shelton, Terri L; Calkins, Susan D

2010-01-01

Parent involvement in a child's education is consistently found to be positively associated with a child's academic performance. However, there has been little investigation of the mechanisms that explain this association. The present study examines two potential mechanisms of this association: the child's perception of cognitive competence and the quality of the student-teacher relationship. This study used a sample of 158 seven-year-old participants, their mothers, and their teachers. Results indicated a statistically significant association between parent involvement and a child's academic performance, over and above the impact of the child's intelligence. A multiple mediation model indicated that the child's perception of cognitive competence fully mediated the relation between parent involvement and the child's performance on a standardized achievement test. The quality of the student-teacher relationship fully mediated the relation between parent involvement and teacher ratings of the child's classroom academic performance. Limitations, future research directions, and implications for public policy initiatives are discussed.

Circulating Extracellular Histones Are Clinically Relevant Mediators of Multiple Organ Injury.

Science.gov (United States)

Kawai, Chihiro; Kotani, Hirokazu; Miyao, Masashi; Ishida, Tokiko; Jemail, Leila; Abiru, Hitoshi; Tamaki, Keiji

2016-04-01

Extracellular histones are a damage-associated molecular pattern (DAMP) involved in the pathogenesis of various diseases. The mechanisms of histone-mediated injury in certain organs have been extensively studied, but an understanding of the pathophysiological role of histone-mediated injury in multiple organ injury remains elusive. To elucidate this role, we systemically subjected C57BL/6 mice to various doses of histones and performed a chronological evaluation of the morphological and functional changes in the lungs, liver, and kidneys. Notably, histone administration ultimately led to death after a dose-dependent aggravation of multiple organ injury. In chronological studies, pulmonary and hepatic injuries occurred within 15 minutes, whereas renal injuries presented at a later phase, suggesting that susceptibility to extracellular histones varies among organs. Histones bound to pulmonary and hepatic endothelial cells immediately after administration, leading to endothelial damage, which could be ameliorated by pretreatment with heparin. Furthermore, release of another DAMP, high-mobility group protein box 1, followed the histone-induced tissue damage, and an antibody against the molecule ameliorated hepatic and renal failure in a late phase. These findings indicate that extracellular histones induce multiple organ injury in two progressive stages-direct injury to endothelial cells and the subsequent release of other DAMPs-and that combination therapies against extracellular histones and high-mobility group protein box 1 may be a promising strategy for treating multiple organ injury. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Anxiety, affect, self-esteem, and stress: mediation and moderation effects on depression.

Directory of Open Access Journals (Sweden)

Ali Al Nima

Full Text Available Mediation analysis investigates whether a variable (i.e., mediator changes in regard to an independent variable, in turn, affecting a dependent variable. Moderation analysis, on the other hand, investigates whether the statistical interaction between independent variables predict a dependent variable. Although this difference between these two types of analysis is explicit in current literature, there is still confusion with regard to the mediating and moderating effects of different variables on depression. The purpose of this study was to assess the mediating and moderating effects of anxiety, stress, positive affect, and negative affect on depression.Two hundred and two university students (males  = 93, females  = 113 completed questionnaires assessing anxiety, stress, self-esteem, positive and negative affect, and depression. Mediation and moderation analyses were conducted using techniques based on standard multiple regression and hierarchical regression analyses.The results indicated that (i anxiety partially mediated the effects of both stress and self-esteem upon depression, (ii that stress partially mediated the effects of anxiety and positive affect upon depression, (iii that stress completely mediated the effects of self-esteem on depression, and (iv that there was a significant interaction between stress and negative affect, and between positive affect and negative affect upon depression.The study highlights different research questions that can be investigated depending on whether researchers decide to use the same variables as mediators and/or moderators.

Anxiety, Affect, Self-Esteem, and Stress: Mediation and Moderation Effects on Depression

Science.gov (United States)

Nima, Ali Al; Rosenberg, Patricia; Archer, Trevor; Garcia, Danilo

2013-01-01

Background Mediation analysis investigates whether a variable (i.e., mediator) changes in regard to an independent variable, in turn, affecting a dependent variable. Moderation analysis, on the other hand, investigates whether the statistical interaction between independent variables predict a dependent variable. Although this difference between these two types of analysis is explicit in current literature, there is still confusion with regard to the mediating and moderating effects of different variables on depression. The purpose of this study was to assess the mediating and moderating effects of anxiety, stress, positive affect, and negative affect on depression. Methods Two hundred and two university students (males  = 93, females  = 113) completed questionnaires assessing anxiety, stress, self-esteem, positive and negative affect, and depression. Mediation and moderation analyses were conducted using techniques based on standard multiple regression and hierarchical regression analyses. Main Findings The results indicated that (i) anxiety partially mediated the effects of both stress and self-esteem upon depression, (ii) that stress partially mediated the effects of anxiety and positive affect upon depression, (iii) that stress completely mediated the effects of self-esteem on depression, and (iv) that there was a significant interaction between stress and negative affect, and between positive affect and negative affect upon depression. Conclusion The study highlights different research questions that can be investigated depending on whether researchers decide to use the same variables as mediators and/or moderators. PMID:24039896

Investigating the effect of child maltreatment on early adolescent peer-on-peer sexual aggression: testing a multiple mediator model in a non-incarcerated sample of Danish adolescents

Directory of Open Access Journals (Sweden)

Rikke Holm Bramsen

2014-06-01

Full Text Available Objective: The aim of the present study was to investigate the relationship between child maltreatment and severe early adolescent peer-on-peer sexual aggression, using a multiple mediator model. Methods: The study comprised 330 male Grade 9 students with a mean age of 14.9 years (SD=0.5. Results: Estimates from the mediation model indicated significant indirect effects of child physical abuse on sexual aggression via peer influence and insecure-hostile masculinity. No significant total effect of child sexual abuse and child neglect on sexual aggression was found. Conclusions: Findings of the present study identify risk factors that are potentially changeable and therefore of value in informing the design of prevention programs aiming at early adolescent peer-on-peer sexual aggression in at-risk youth.

Multifunctional Curcumin Mediate Multitherapeutic Effects.

Science.gov (United States)

Shehzad, Adeeb; Qureshi, Munibah; Anwar, Muhammad Nabeel; Lee, Young Sup

2017-09-01

Inflammation can promote the development of arthritis, obesity, cardiovascular, type II diabetes, pancreatitis, metabolic and neurodegenerative diseases, and certain types of cancer. Compounds isolated from plants have been practiced since ancient times for curing various ailments including inflammatory disorders and to support normal physiological functions. Curcumin (diferuloylmethane) is a yellow coloring agent, extracted from turmeric that has been used for the prevention and treatment of various inflammatory diseases. Numerous studies have shown that curcumin modulate multiple molecular targets and can be translated to the clinics for multiple therapeutic processes. There is compelling evidence that curcumin can block cell proliferation, invasion, and angiogenesis as well as reduced the prolonged survival of cancer cells. Curcumin mediates anti-inflammatory effect through downregulation of inflammatory cytokines, transcription factors, protein kinases, and enzymes that promote inflammation and development of chronic diseases. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways by activating caspase cascades. Curcumin is a safe and nontoxic drug that has been reported to be well tolerated. Available clinical trials support the potential role of curcumin for treatment of various inflammatory disorders. However, curcumin's efficacy is hindered by poor absorption and low bioavailability, which limit its translation into clinics. This review outlines the potential pharmacological and clinical role of curcumin, which provide a gateway for the beneficial role of plant isolated compounds in treatment of various inflammatory diseases and cancer. © 2017 Institute of Food Technologists®.

Exercise, Diet, and Stress Management as Mediators between Functional Disability and Health-Related Quality of Life in Multiple Sclerosis

Science.gov (United States)

Sung, Connie; Chiu, Chung-Yi; Lee, Eun-Jeong; Bezyak, Jill; Chan, Fong; Muller, Veronica

2013-01-01

The main objective of this study was to examine the mediational and moderational effect of exercise, diet, and stress management on the relationship between functional disability and health-related quality of life. Quantitative descriptive research design using multiple regression and correlation techniques was used. Participants were 215…

Forest Fragmentation and Selective Logging Have Inconsistent Effects on Multiple Animal-Mediated Ecosystem Processes in a Tropical Forest

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Schleuning, Matthias; Farwig, Nina; Peters, Marcell K.; Bergsdorf, Thomas; Bleher, Bärbel; Brandl, Roland; Dalitz, Helmut; Fischer, Georg; Freund, Wolfram; Gikungu, Mary W.; Hagen, Melanie; Garcia, Francisco Hita; Kagezi, Godfrey H.; Kaib, Manfred; Kraemer, Manfred; Lung, Tobias; Schaab, Gertrud; Templin, Mathias; Uster, Dana; Wägele, J. Wolfgang; Böhning-Gaese, Katrin

2011-01-01

Forest fragmentation and selective logging are two main drivers of global environmental change and modify biodiversity and environmental conditions in many tropical forests. The consequences of these changes for the functioning of tropical forest ecosystems have rarely been explored in a comprehensive approach. In a Kenyan rainforest, we studied six animal-mediated ecosystem processes and recorded species richness and community composition of all animal taxa involved in these processes. We used linear models and a formal meta-analysis to test whether forest fragmentation and selective logging affected ecosystem processes and biodiversity and used structural equation models to disentangle direct from biodiversity-related indirect effects of human disturbance on multiple ecosystem processes. Fragmentation increased decomposition and reduced antbird predation, while selective logging consistently increased pollination, seed dispersal and army-ant raiding. Fragmentation modified species richness or community composition of five taxa, whereas selective logging did not affect any component of biodiversity. Changes in the abundance of functionally important species were related to lower predation by antbirds and higher decomposition rates in small forest fragments. The positive effects of selective logging on bee pollination, bird seed dispersal and army-ant raiding were direct, i.e. not related to changes in biodiversity, and were probably due to behavioural changes of these highly mobile animal taxa. We conclude that animal-mediated ecosystem processes respond in distinct ways to different types of human disturbance in Kakamega Forest. Our findings suggest that forest fragmentation affects ecosystem processes indirectly by changes in biodiversity, whereas selective logging influences processes directly by modifying local environmental conditions and resource distributions. The positive to neutral effects of selective logging on ecosystem processes show that the

Determining the relative importance of the mechanisms of behavior change within Alcoholics Anonymous: a multiple mediator analysis.

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Kelly, John F; Hoeppner, Bettina; Stout, Robert L; Pagano, Maria

2012-02-01

Evidence indicates that Alcoholics Anonymous (AA) participation reduces relapse risk but less is known about the mechanisms through which AA confers this benefit. Initial studies indicate self-efficacy, negative affect, adaptive social networks and spiritual practices are mediators of this effect, but because these have been tested in isolation, their relative importance remains elusive. This study tested multiple mediators simultaneously to help determine the most influential pathways. Prospective, statistically controlled, naturalistic investigation examined the extent to which these previously identified mechanisms mediated AA attendance effects on alcohol outcomes controlling for baseline outcome values, mediators, treatment, and other confounders. Nine clinical sites within the United States. Adults (n = 1726) suffering from alcohol use disorder (AUD) initially enrolled in a randomized study with two arms: aftercare (n = 774); and out-patient (n = 952) comparing three out-patient treatments (Project MATCH). AA attendance during treatment; mediators at 9 months; and outcomes [percentage of days abstinent (PDA) and drinks per drinking day (DDD)] at 15 months. Among out-patients the effect of AA attendance on alcohol outcomes was explained primarily by adaptive social network changes and increases in social abstinence self-efficacy. Among more impaired aftercare patients, in addition to mediation through adaptive network changes and increases in social self-efficacy, AA lead to better outcomes through increasing spirituality/religiosity and by reducing negative affect. The degree to which mediators explained the relationship between AA and outcomes ranged from 43% to 67%. While Alcoholics Anonymous facilitates recovery by mobilizing several processes simultaneously, it is changes in social factors which appear to be of primary importance. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

The role of appraisal and coping style in relation with societal participation in fatigued patients with multiple sclerosis: a cross-sectional multiple mediator analysis.

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van den Akker, Lizanne Eva; Beckerman, Heleen; Collette, Emma Hubertine; Bleijenberg, Gijs; Dekker, Joost; Knoop, Hans; de Groot, Vincent

2016-10-01

To determine the relationship between appraisal and societal participation in fatigued patients with Multiple Sclerosis (MS), and whether this relation is mediated by coping styles. 265 severely-fatigued MS patients. Appraisal, a latent construct, was created from the General Self-Efficacy Scale and the helplessness and acceptance subscales of the Illness Cognition Questionnaire. Coping styles were assessed using the Coping Inventory Stressful Situations (CISS21) and societal participation was assessed using the Impact on Participation and Autonomy. A multiple mediator model was developed and tested by structural equation modeling on cross-sectional data. We corrected for confounding by disease-related factors. Mediation was determined using a product-of-coefficients approach. A significant relationship existed between appraisal and participation (β = 0.21, 95 % CI 0.04-0.39). The pathways via coping styles were not significant. In patients with severe MS-related fatigue, appraisal and societal participation show a positive relationship that is not mediated by coping styles.

Causal relationship between the AHSG gene and BMD through fetuin-A and BMI: multiple mediation analysis.

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Sritara, C; Thakkinstian, A; Ongphiphadhanakul, B; Chailurkit, L; Chanprasertyothin, S; Ratanachaiwong, W; Vathesatogkit, P; Sritara, P

2014-05-01

Using mediation analysis, a causal relationship between the AHSG gene and bone mineral density (BMD) through fetuin-A and body mass index (BMI) mediators was suggested. Fetuin-A, a multifunctional protein of hepatic origin, is associated with bone mineral density. It is unclear if this association is causal. This study aimed at clarification of this issue. A cross-sectional study was conducted among 1,741 healthy workers from the Electricity Generating Authority of Thailand (EGAT) cohort. The alpha-2-Heremans-Schmid glycoprotein (AHSG) rs2248690 gene was genotyped. Three mediation models were constructed using seemingly unrelated regression analysis. First, the ln[fetuin-A] group was regressed on the AHSG gene. Second, the BMI group was regressed on the AHSG gene and the ln[fetuin-A] group. Finally, the BMD model was constructed by fitting BMD on two mediators (ln[fetuin-A] and BMI) and the independent AHSG variable. All three analyses were adjusted for confounders. The prevalence of the minor T allele for the AHSG locus was 15.2%. The AHSG locus was highly related to serum fetuin-A levels (P Multiple mediation analyses showed that AHSG was significantly associated with BMD through the ln[fetuin-A] and BMI pathway, with beta coefficients of 0.0060 (95% CI 0.0038, 0.0083) and 0.0030 (95% CI 0.0020, 0.0045) at the total hip and lumbar spine, respectively. About 27.3 and 26.0% of total genetic effects on hip and spine BMD, respectively, were explained by the mediation effects of fetuin-A and BMI. Our study suggested evidence of a causal relationship between the AHSG gene and BMD through fetuin-A and BMI mediators.

Gratitude and Adolescents' Subjective Well-Being in School: The Multiple Mediating Roles of Basic Psychological Needs Satisfaction at School.

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Tian, Lili; Pi, Luyang; Huebner, E S; Du, Minmin

2016-01-01

Based on the relation between gratitude and general subjective well-being (SWB), and Basic Psychological Needs Theory (Ryan and Deci, 2000), the present study's aim was to use structural equation modeling to test the multiple mediational roles of the satisfaction of three basic psychological needs at school in accounting for the association between gratitude and SWB in school (school satisfaction, school affect) in adolescents. A total of 881 Chinese adolescents (427 males; Mean age = 12.97) completed a multi-measure questionnaire that tapped the targeted variables. Findings revealed that gratitude related significantly, positively to adolescents' SWB in school. Moreover, a multiple-mediators analysis suggested that relatedness and competence needs satisfaction at school mediated the relation between gratitude and SWB in school. Lastly, a multiple-mediators analysis also indicated that autonomy needs satisfaction mediated the relation between relatedness and competence needs and SWB in school. Limitations and practical applications of the study were discussed.

Gratitude and Adolescents’ Subjective Well-Being in School: The Multiple Mediating Roles of Basic Psychological Needs Satisfaction at School

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Tian, Lili; Pi, Luyang; Huebner, E. S.; Du, Minmin

2016-01-01

Based on the relation between gratitude and general subjective well-being (SWB), and Basic Psychological Needs Theory (Ryan and Deci, 2000), the present study’s aim was to use structural equation modeling to test the multiple mediational roles of the satisfaction of three basic psychological needs at school in accounting for the association between gratitude and SWB in school (school satisfaction, school affect) in adolescents. A total of 881 Chinese adolescents (427 males; Mean age = 12.97) completed a multi-measure questionnaire that tapped the targeted variables. Findings revealed that gratitude related significantly, positively to adolescents’ SWB in school. Moreover, a multiple-mediators analysis suggested that relatedness and competence needs satisfaction at school mediated the relation between gratitude and SWB in school. Lastly, a multiple-mediators analysis also indicated that autonomy needs satisfaction mediated the relation between relatedness and competence needs and SWB in school. Limitations and practical applications of the study were discussed. PMID:27708601

Linking and Psychological Functioning in a Chinese Sample: The Multiple Mediation of Response to Positive Affect

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Yang, Hongfei; Li, Juan

2016-01-01

The present study examined the associations between linking, response to positive affect, and psychological functioning in Chinese college students. The results of conducting multiple mediation analyses indicated that emotion- and self-focused positive rumination mediated the relationship between linking and psychological functioning, whereas…

Mediating Effects of Global Negative Effect Expectancies on the Association between Problematic Cannabis Use and Social Anxiety.

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Di Blasi, Maria; Cavani, Paola; Pavia, Laura; Tosto, Crispino; La Grutta, Sabina; Lo Baido, Rosa; Giordano, Cecilia; Schimmenti, Adriano

2017-01-01

The relationship between social anxiety (SA) and cannabis use among adolescents and young adults is a highly debated topic. In this cross-sectional study, we tested whether cannabis use expectancies mediated the association between SA and cannabis use severity in a sample of 343 young adults (74.3% male) who used cannabis. They completed self-report measures for the screening of problematic cannabis use (Cannabis Use Problems Identification Test) and SA symptoms (Social Interaction Anxiety Scale and Social Phobia Scale). A multiple mediation analysis was used to test whether marijuana effect expectancies mediate SA effect on problematic cannabis use. SA was negatively associated with cannabis use severity in this sample, and we found evidence that cannabis use expectancies fully mediated this relationship. Specifically, global negative effect expectancies influence the relationship between SA and problematic cannabis use. These findings may inform current prevention strategies and clinical intervention for young adults who use cannabis.

Mediating Effects of Global Negative Effect Expectancies on the Association between Problematic Cannabis Use and Social Anxiety

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Maria Di Blasi

2017-11-01

Full Text Available The relationship between social anxiety (SA and cannabis use among adolescents and young adults is a highly debated topic. In this cross-sectional study, we tested whether cannabis use expectancies mediated the association between SA and cannabis use severity in a sample of 343 young adults (74.3% male who used cannabis. They completed self-report measures for the screening of problematic cannabis use (Cannabis Use Problems Identification Test and SA symptoms (Social Interaction Anxiety Scale and Social Phobia Scale. A multiple mediation analysis was used to test whether marijuana effect expectancies mediate SA effect on problematic cannabis use. SA was negatively associated with cannabis use severity in this sample, and we found evidence that cannabis use expectancies fully mediated this relationship. Specifically, global negative effect expectancies influence the relationship between SA and problematic cannabis use. These findings may inform current prevention strategies and clinical intervention for young adults who use cannabis.

C/EBPβ Mediates Growth Hormone-Regulated Expression of Multiple Target Genes

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Cui, Tracy X.; Lin, Grace; LaPensee, Christopher R.; Calinescu, Anda-Alexandra; Rathore, Maanjot; Streeter, Cale; Piwien-Pilipuk, Graciela; Lanning, Nathan; Jin, Hui; Carter-Su, Christin; Qin, Zhaohui S.

2011-01-01

Regulation of c-Fos transcription by GH is mediated by CCAAT/enhancer binding protein β (C/EBPβ). This study examines the role of C/EBPβ in mediating GH activation of other early response genes, including Cyr61, Btg2, Socs3, Zfp36, and Socs1. C/EBPβ depletion using short hairpin RNA impaired responsiveness of these genes to GH, as seen for c-Fos. Rescue with wild-type C/EBPβ led to GH-dependent recruitment of the coactivator p300 to the c-Fos promoter. In contrast, rescue with C/EBPβ mutated at the ERK phosphorylation site at T188 failed to induce GH-dependent recruitment of p300, indicating that ERK-mediated phosphorylation of C/EBPβ at T188 is required for GH-induced recruitment of p300 to c-Fos. GH also induced the occupancy of phosphorylated C/EBPβ and p300 on Cyr61, Btg2, and Socs3 at predicted C/EBP-cAMP response element-binding protein motifs in their promoters. Consistent with a role for ERKs in GH-induced expression of these genes, treatment with U0126 to block ERK phosphorylation inhibited their GH-induced expression. In contrast, GH-dependent expression of Zfp36 and Socs1 was not inhibited by U0126. Thus, induction of multiple early response genes by GH in 3T3-F442A cells is mediated by C/EBPβ. A subset of these genes is regulated similarly to c-Fos, through a mechanism involving GH-stimulated ERK 1/2 activation, phosphorylation of C/EBPβ, and recruitment of p300. Overall, these studies suggest that C/EBPβ, like the signal transducer and activator of transcription proteins, regulates multiple genes in response to GH. PMID:21292824

Generalized causal mediation and path analysis: Extensions and practical considerations.

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Albert, Jeffrey M; Cho, Jang Ik; Liu, Yiying; Nelson, Suchitra

2018-01-01

Causal mediation analysis seeks to decompose the effect of a treatment or exposure among multiple possible paths and provide casually interpretable path-specific effect estimates. Recent advances have extended causal mediation analysis to situations with a sequence of mediators or multiple contemporaneous mediators. However, available methods still have limitations, and computational and other challenges remain. The present paper provides an extended causal mediation and path analysis methodology. The new method, implemented in the new R package, gmediation (described in a companion paper), accommodates both a sequence (two stages) of mediators and multiple mediators at each stage, and allows for multiple types of outcomes following generalized linear models. The methodology can also handle unsaturated models and clustered data. Addressing other practical issues, we provide new guidelines for the choice of a decomposition, and for the choice of a reference group multiplier for the reduction of Monte Carlo error in mediation formula computations. The new method is applied to data from a cohort study to illuminate the contribution of alternative biological and behavioral paths in the effect of socioeconomic status on dental caries in adolescence.

Direct and indirect influences of fate control belief, gambling expectancy bias, and self-efficacy on problem gambling and negative mood among Chinese college students: a multiple mediation analysis.

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Tang, Catherine So-Kum; Wu, Anise M S

2010-12-01

A multiple mediation model was proposed to integrate core concepts of the social axioms framework and the social cognitive theory in order to understand gambling behavior. It was hypothesized that the influence of general fate control belief on problem gambling and negative mood would be mediated by gambling-specific beliefs. Data from 773 Chinese college recreational gamblers were collected. The bootstrapping procedure was used to test the multiple mediation hypotheses. Significant indirect effects of fate control belief on problem gambling and negative mood through two gambling-specific mediators were found. Gambling expectancy bias was a more salient mediator than gambling self-efficacy. Fate control belief was also found to have a significant direct effect on negative mood. In general, a high level of general fate control belief was related to greater gambling expectancy bias and lower self-efficacy in resisting gambling, which were in turn related to problem gambling and negative mood. Limitations and implications of the study were discussed.

THE EFFECT OF BANK IMAGE AND TRUST ON LOYALITY MEDIATED BY CUSTOMER SATISFACTION

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Sumadi Sumadi

2015-09-01

Full Text Available The purpose of this study is to analyze the effect of the bank’s image and trust on customer satisfaction, as well as the effect of the image of the bank, trust, and satisfaction on customer loyalty. The study used sample of 100 people who were taken by purposive sampling technique. This research utilized multiple linear regression analysis and path analysis. Based on the hypothesis test, the results show that the image of the bank was significantly has positive effect on customer satisfaction, but trust has no significant effect on customer satisfaction. In addition, the bank’s image has no significant effect on customer loyalty. Moreover, trust and customer satisfaction significantly have positive effect on customer loyalty. Mediation test shows that customer satisfaction mediates the effect of the bank’s image on customer loyalty and customer satisfaction does not mediate trust on customer loyalty. Info

Effects of peer-mediated implementation of visual scripts in middle school.

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Ganz, Jennifer B; Heath, Amy K; Lund, Emily M; Camargo, Siglia P H; Rispoli, Mandy J; Boles, Margot; Plaisance, Lauren

2012-05-01

Although research has investigated the impact of peer-mediated interventions and visual scripts on social and communication skills in children with autism spectrum disorders, no studies to date have investigated peer-mediated implementation of scripts. This study investigated the effects of peer-implemented scripts on a middle school student with autism, intellectual impairments, and speech-language impairment via a multiple baseline single-case research design across behaviors. The target student demonstrated improvements in three communicative behaviors when implemented by a trained peer; however, behaviors did not generalize to use with an untrained typically developing peer.

Mediation designs for tobacco prevention research

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MacKinnon, David P.; Taborga, Marcia P.; Morgan-Lopez, Antonio A.

2010-01-01

This paper describes research designs and statistical analyses to investigate how tobacco prevention programs achieve their effects on tobacco use. A theoretical approach to program development and evaluation useful for any prevention program guides the analysis. The theoretical approach focuses on action theory for how the program affects mediating variables and on conceptual theory for how mediating variables are related to tobacco use. Information on the mediating mechanisms by which tobacco prevention programs achieve effects is useful for the development of efficient programs and provides a test of the theoretical basis of prevention efforts. Examples of these potential mediating mechanisms are described including mediated effects through attitudes, social norms, beliefs about positive consequences, and accessibility to tobacco. Prior research provides evidence that changes in social norms are a critical mediating mechanism for successful tobacco prevention. Analysis of mediating variables in single group designs with multiple mediators are described as well as multiple group randomized designs which are the most likely to accurately uncover important mediating mechanisms. More complicated dismantling and constructive designs are described and illustrated based on current findings from tobacco research. Mediation analysis for categorical outcomes and more complicated statistical methods are outlined. PMID:12324176

Mediating Effects of Social Support on Quality of Life for Parents of Adults with Autism

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Marsack, Christina N.; Samuel, Preethy S.

2017-01-01

The aim of this study was to examine the mediating effect of formal and informal social support on the relationship of caregiver burden and quality of life (QOL), using a sample of 320 parents (aged 50 or older) of adult children with autism spectrum disorder (ASD). Multiple linear regression and mediation analyses indicated that caregiver burden…

Effects of the Educational Leadership of Nursing Unit Managers on Team Effectiveness: Mediating Effects of Organizational Communication.

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Choi, Eun Ha; Kim, Eun-Kyung; Kim, Pil Bong

2018-03-31

EDUCATIONAL LEADERSHIP OF NURSING UNIT MANAGERS ON TEAM EFFECTIVENESS: Mediating Effects of Organizational Communication Satisfaction. This study identifies the effects of the educational leadership of nursing unit managers on team effectiveness and the mediating effects of organizational communication satisfaction; it highlights the importance of educational leadership and organizational communication and provides the data needed to enhance the education capacity of managers. The participants were 216 nursing unit managers of staff nurses at a tertiary hospital located in C Region, South Korea, and nurses who had worked for more than six months at the same hospital. This study was conducted using questionnaires on educational leadership, team effectiveness, and organizational communication satisfaction. Data analysis was performed with a t-test, ANOVA, Scheffé, Pearson's correlation coefficient, and simple and multiple regression analyses using SPSS version 23.0. Mediation analysis was tested using Baron and Kenny's regression analysis and a Sobel test. The mean score for the educational leadership of nursing unit managers was 3.74(±0.68); for organizational communication satisfaction, 3.14(±0.51); and for team effectiveness, 3.52(±0.49). Educational leadership was significantly positively correlated with team effectiveness and organizational communication satisfaction. Organizational communication satisfaction demonstrated a complete mediating effect on the relationship between educational leadership and team effectiveness (β=.61, pcommunication satisfaction among nurses; this supports the idea that educational leadership can contribute to team effectiveness. This suggests that the educational leadership and communication capacity of nursing unit managers must be improved to enhance the performance of nursing organizations. Copyright © 2018. Published by Elsevier B.V.

mediation: R Package for Causal Mediation Analysis

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Dustin Tingley

2014-09-01

Full Text Available In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting such an analysis. The package is organized into two distinct approaches. Using the model-based approach, researchers can estimate causal mediation effects and conduct sensitivity analysis under the standard research design. Furthermore, the design-based approach provides several analysis tools that are applicable under different experimental designs. This approach requires weaker assumptions than the model-based approach. We also implement a statistical method for dealing with multiple (causally dependent mediators, which are often encountered in practice. Finally, the package also offers a methodology for assessing causal mediation in the presence of treatment noncompliance, a common problem in randomized trials.

Reasons for Testing Mediation in the Absence of an Intervention Effect: A Research Imperative in Prevention and Intervention Research.

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O'Rourke, Holly P; MacKinnon, David P

2018-03-01

Mediation models are used in prevention and intervention research to assess the mechanisms by which interventions influence outcomes. However, researchers may not investigate mediators in the absence of intervention effects on the primary outcome variable. There is emerging evidence that in some situations, tests of mediated effects can be statistically significant when the total intervention effect is not statistically significant. In addition, there are important conceptual and practical reasons for investigating mediation when the intervention effect is nonsignificant. This article discusses the conditions under which mediation may be present when an intervention effect does not have a statistically significant effect and why mediation should always be considered important. Mediation may be present in the following conditions: when the total and mediated effects are equal in value, when the mediated and direct effects have opposing signs, when mediated effects are equal across single and multiple-mediator models, and when specific mediated effects have opposing signs. Mediation should be conducted in every study because it provides the opportunity to test known and replicable mediators, to use mediators as an intervention manipulation check, and to address action and conceptual theory in intervention models. Mediators are central to intervention programs, and mediators should be investigated for the valuable information they provide about the success or failure of interventions.

Women and Retirement: The Effect of Multiple Careers on Retirement Adjustment.

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Connidis, Ingrid

1982-01-01

The concept of career set is employed as the basis for a framework designed to analyze the impact of women's involvement in multiple careers on their adjustment to retirement. The author concludes that the familial careers engaged in by married, working women have a mediative effect on their transition to retirement. (Author/CT)

Inflammatory Mediator Profiling of n-butanol Exposed Upper Airways in Individuals with Multiple Chemical Sensitivity

DEFF Research Database (Denmark)

Dantoft, Thomas Meinertz; Skovbjerg, Sine; Andersson, Linus

2015-01-01

Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by reports of recurrent symptoms in response to low level exposure to various chemical substances. Recent findings suggests that dysregulation of the immune system may play a role in MCS pathophysiology. The aim of this study...... inflammatory mediator profiles (P>0.05) at baseline. Likewise, direct comparison of mediator levels in the MCS group and controls after n-butanol exposure revealed no significant group differences. We demonstrate no abnormal upper airway inflammatory mediator levels in MCS subjects before or after a symptom...

Practical Guidance for Conducting Mediation Analysis With Multiple Mediators Using Inverse Odds Ratio Weighting

OpenAIRE

Nguyen, Quynh C.; Osypuk, Theresa L.; Schmidt, Nicole M.; Glymour, M. Maria; Tchetgen Tchetgen, Eric J.

2015-01-01

Despite the recent flourishing of mediation analysis techniques, many modern approaches are difficult to implement or applicable to only a restricted range of regression models. This report provides practical guidance for implementing a new technique utilizing inverse odds ratio weighting (IORW) to estimate natural direct and indirect effects for mediation analyses. IORW takes advantage of the odds ratio's invariance property and condenses information on the odds ratio for the relationship be...

Why are Tailored Messages More Effective? A Multiple Mediation Analysis of a Breast Cancer Screening Intervention.

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Jensen, Jakob D; King, Andy J; Carcioppolo, Nicholas; Davis, LaShara

2012-10-01

Past research has found that tailoring increases the persuasive effectiveness of a message. However, the observed effect has been small and the explanatory mechanism remains unknown. To address these shortcomings, a tailoring software program was created that personalized breast cancer screening pamphlets according to risk, health belief model constructs, and visual preference. Women aged 40 and older ( N = 119) participated in a 2 (tailored vs. stock message) × 2 (charts/graphs vs. illustrated visuals) × 3 (nested replications of the visuals) experiment. Participants provided with tailored illustrated pamphlets expressed greater breast cancer screening intentions than those provided with other pamphlets. In a test of 10 different mediators, perceived message relevance was found to fully mediate the tailoring × visual interaction.

Multiple mediation analysis of the relationship between rapid naming and reading

DEFF Research Database (Denmark)

Poulsen, Mads; Juul, Holger; Elbro, Carsten

2015-01-01

It is well established that rapid automatised naming (RAN) correlates with reading ability. Despite several attempts, no single component process (mediator) has been identified that fully accounts for the correlation. The present paper estimated the explanatory value of several mediators....... The influence of the mediators on the RAN-reading correlation was estimated as indirect effects in mediation analyses. Phonological awareness and letter knowledge significantly mediated the RAN-reading relationship, each accounted for a moderate part of the correlation between RAN and reading fluency. Thus...

Perceiving a calling, living a calling, and job satisfaction: testing a moderated, multiple mediator model.

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Duffy, Ryan D; Bott, Elizabeth M; Allan, Blake A; Torrey, Carrie L; Dik, Bryan J

2012-01-01

The current study examined the relation between perceiving a calling, living a calling, and job satisfaction among a diverse group of employed adults who completed an online survey (N = 201). Perceiving a calling and living a calling were positively correlated with career commitment, work meaning, and job satisfaction. Living a calling moderated the relations of perceiving a calling with career commitment and work meaning, such that these relations were more robust for those with a stronger sense they were living their calling. Additionally, a moderated, multiple mediator model was run to examine the mediating role of career commitment and work meaning in the relation of perceiving a calling and job satisfaction, while accounting for the moderating role of living a calling. Results indicated that work meaning and career commitment fully mediated the relation between perceiving a calling and job satisfaction. However, the indirect effects of work meaning and career commitment were only significant for individuals with high levels of living a calling, indicating the importance of living a calling in the link between perceiving a calling and job satisfaction. Implications for research and practice are discussed. (c) 2012 APA, all rights reserved.

Improving quality-of-life outcomes for patients with cancer through mediating effects of depressive symptoms and functional status: a three-path mediation model.

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Hsu, Mei-Chi; Tu, Chun-Hsien

2014-09-01

To test a hypothetical three-path mediation model evaluating the effects of functional status and depressive symptoms on the relationship between fatigue and quality of life in patients with cancer on the basis of the Theory of Unpleasant Symptoms. Patients with cancer often experience two or more concurrent, interrelated, mutually influential symptoms. Multiple unpleasant symptoms that have been proposed as mediating variables affecting quality of life in a model proposed in recent cancer studies are scanty. This study was a cross-sectional, descriptive, correlational design. Three hundred and twenty-six patients with cancer from oncology clinics were recruited in Taiwan between 2010-2011. Mediation models were tested and confirmed by applying structural modelling using Analysis of Moment Structures and the joint significance test. Fatigue affects patient quality of life directly or indirectly through functional status and depressive symptoms. These two mediating variables exhibited direct effects on quality of life. A path analysis approach revealed that 47·28 and 67·70% of the total effects of functional status and depressive symptoms, respectively, on the quality-of-life mediation models are attributable to 29·6 and 44·7% of the total effects between fatigue and quality of life, which mediated through two mediators, respectively. Quality of life may be enhanced by simultaneously improving physiological and psychological factors. An understanding of mediating effects is valuable in nursing care of patients with cancer, particularly in the early phase of treatment or in newly diagnosed stages I-III or recently treated patients with cancer in different disease stages. © 2013 John Wiley & Sons Ltd.

Specific emotions as mediators of the effect of intergroup contact on prejudice: findings across multiple participant and target groups.

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Seger, Charles R; Banerji, Ishani; Park, Sang Hee; Smith, Eliot R; Mackie, Diane M

2017-08-01

Emotions are increasingly being recognised as important aspects of prejudice and intergroup behaviour. Specifically, emotional mediators play a key role in the process by which intergroup contact reduces prejudice towards outgroups. However, which particular emotions are most important for prejudice reduction, as well as the consistency and generality of emotion-prejudice relations across different in-group-out-group relations, remain uncertain. To address these issues, in Study 1 we examined six distinct positive and negative emotions as mediators of the contact-prejudice relations using representative samples of U.S. White, Black, and Asian American respondents (N = 639). Admiration and anger (but not other emotions) were significant mediators of the effects of previous contact on prejudice, consistently across different perceiver and target ethnic groups. Study 2 examined the same relations with student participants and gay men as the out-group. Admiration and disgust mediated the effect of past contact on attitude. The findings confirm that not only negative emotions (anger or disgust, based on the specific types of threat perceived to be posed by an out-group), but also positive, status- and esteem-related emotions (admiration) mediate effects of contact on prejudice, robustly across several different respondent and target groups.

[Lentivirus-mediated shRNA silencing of LAMP2A inhibits the proliferation of multiple myeloma cells].

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Li, Lixuan; Li, Jia

2015-05-01

To study the effects of lentivirus-mediated short hairpin RNA (shRNA) silencing of lysosome-associated membrane protein type 2A (LAMP2A) expression on the proliferation of multiple myeloma cells. The constructed shRNA lentiviral vector was applied to infect human multiple myeloma cell line MM.1S, and stable expression cell line was obtained by puromycin screening. Western blotting was used to verify the inhibitory effect on LAMP2A protein expression. MTT assay was conducted to detect the effect of knocked-down LAMP2A on MM.1S cell proliferation, and the anti-tumor potency of suberoylanilide hydroxamic acid (SAHA) against the obtained MM.1S LAMP2A(shRNA) stable cell line. Lactate assay was performed to observe the impact of low LAMP2A expression on cell glycolysis. The stable cell line with low LAMP2A expression were obtained with the constructed human LAMP2A-shRNA lentiviral vector. Down-regulation of LAMP2A expression significantly inhibited MM.1S cell proliferation and enhanced the anti-tumor activity of SAHA. Interestingly, decreased LAMP2A expression also inhibited MM.1S cell lactic acid secretion. Down-regulation of LAMP2A expression could inhibit cell proliferation in multiple myeloma cells.

The mediator effect of personality traits on the relationship between childhood abuse and depressive symptoms in schizophrenia.

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Okubo, Ryo; Inoue, Takeshi; Hashimoto, Naoki; Suzukawa, Akio; Tanabe, Hajime; Oka, Matsuhiko; Narita, Hisashi; Ito, Koki; Kako, Yuki; Kusumi, Ichiro

2017-11-01

Previous studies indicated that personality traits have a mediator effect on the relationship between childhood abuse and depressive symptoms in major depressive disorder and nonclinical general adult subjects. In the present study, we aimed to test the hypothesis that personality traits mediate the relationship between childhood abuse and depressive symptoms in schizophrenia. We used the following questionnaires to evaluate 255 outpatients with schizophrenia: the Child Abuse and Trauma Scale, temperament and character inventory, and Patients Health Questionnire-9. Univariate analysis, multiple regression analysis, and structured equation modeling (SEM) were used to analyze the data. The relationship between neglect and sexual abuse and the severity of depressive symptoms was mostly mediated by the personality traits of high harm avoidance, low self-directedness, and low cooperativeness. This finding was supported by the results of stepwise multiple regression analysis and the acceptable fit indices of SEM. Thus, our results suggest that personality traits mediate the relationship between childhood abuse and depressive symptoms in schizophrenia. The present study and our previous studies also suggest that this mediator effect could occur independent of the presence or type of mental disorder. Clinicians should routinely assess childhood abuse history, personality traits, and their effects in schizophrenia. Copyright © 2017. Published by Elsevier B.V.

Brain mediators of the effects of noxious heat on pain.

Science.gov (United States)

Atlas, Lauren Y; Lindquist, Martin A; Bolger, Niall; Wager, Tor D

2014-08-01

Recent human neuroimaging studies have investigated the neural correlates of either noxious stimulus intensity or reported pain. Although useful, analyzing brain relationships with stimulus intensity and behavior separately does not address how sensation and pain are linked in the central nervous system. In this study, we used multi-level mediation analysis to identify brain mediators of pain--regions in which trial-by-trial responses to heat explained variability in the relationship between noxious stimulus intensity (across 4 levels) and pain. This approach has the potential to identify multiple circuits with complementary roles in pain genesis. Brain mediators of noxious heat effects on pain included targets of ascending nociceptive pathways (anterior cingulate, insula, SII, and medial thalamus) and also prefrontal and subcortical regions not associated with nociceptive pathways per se. Cluster analysis revealed that mediators were grouped into several distinct functional networks, including the following: somatosensory, paralimbic, and striatal-cerebellar networks that increased with stimulus intensity; and 2 networks co-localized with "default mode" regions in which stimulus intensity-related decreases mediated increased pain. We also identified "thermosensory" regions that responded to increasing noxious heat but did not predict pain reports. Finally, several regions did not respond to noxious input, but their activity predicted pain; these included ventromedial prefrontal cortex, dorsolateral prefrontal cortex, cerebellar regions, and supplementary motor cortices. These regions likely underlie both nociceptive and non-nociceptive processes that contribute to pain, such as attention and decision-making processes. Overall, these results elucidate how multiple distinct brain systems jointly contribute to the central generation of pain. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Stressors and anxiety in dementia caregiving: multiple mediation analysis of rumination, experiential avoidance, and leisure.

Science.gov (United States)

Romero-Moreno, R; Losada, A; Márquez-González, M; Mausbach, B T

2016-11-01

Despite the robust associations between stressors and anxiety in dementia caregiving, there is a lack of research examining which factors contribute to explain this relationship. This study was designed to test a multiple mediation model of behavioral and psychological symptoms of dementia (BPSD) and anxiety that proposes higher levels of rumination and experiential avoidance and lower levels of leisure satisfaction as potential mediating variables. The sample consisted of 256 family caregivers. In order to test a simultaneously parallel multiple mediation model of the BPSD to anxiety pathway, a PROCESS method was used and bias-corrected and accelerated bootstrapping method was used to test confidence intervals. Higher levels of stressors significantly predicted anxiety. Greater stressors significantly predicted higher levels of rumination and experiential avoidance, and lower levels of leisure satisfaction. These three coping variables significantly predicted anxiety. Finally, rumination, experiential avoidance, and leisure satisfaction significantly mediated the link between stressors and anxiety. The explained variance for the final model was 47.09%. Significant contrasts were found between rumination and leisure satisfaction, with rumination being a significantly higher mediator. The results suggest that caregivers' experiential avoidance, rumination, and leisure satisfaction may function as mechanisms through which BPSD influence on caregivers' anxiety. Training caregivers in reducing their levels of experiential avoidance and rumination by techniques that foster their ability of acceptance of their negative internal experiences, and increase their level of leisure satisfaction, may be helpful to reduce their anxiety symptoms developed by stressors.

Association between social support and post-traumatic stress disorder symptoms among Chinese patients with ovarian cancer: A multiple mediation model.

Directory of Open Access Journals (Sweden)

Chunli Liu

Full Text Available Post-traumatic stress disorder (PTSD symptoms can develop after person experiences one or more traumatic events. Little research, however, has been done on PTSD symptoms of patients with ovarian cancer. The present study aimed to estimate the prevalence of PTSD symptoms in patients with ovarian cancer in China; the effects of demographic and clinical variables on PTSD symptoms; multiple mediation roles in the association between social support and PTSD symptoms in patients with ovarian cancer in China. We collected demographic and clinical information of patients with ovarian cancer in the first and second hospitals of China Medical University between January 1, 2014 and December 31, 2015. Qualified patients were asked to complete the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C, Duke-UNC Functional Social Support Questionnaire, Herth Hope Index (HHI, and Resilience Scale-14 (RS-14. 201 patients provided responses. We performed hierarchical linear regression to assess the correlation between social support and PTSD symptoms and bootstrapping to test the mediating role of hope and resilience as potential mediators. After controlling demographic and clinical characteristics, social support negatively correlated with PTSD symptoms (β = -0.406, P < 0.01. Social support explained 14.7% of the variance in PTSD symptoms. Hope and resilience explained 17.0% of the variance in PTSD symptoms. The proportion of the hope mediating effect was 43.37% for social support and the proportion of the resilience mediating effect was 10.64% for social support. Hope and resilience partly mediated the correlation between social support and PTSD symptoms despite accounting for different proportions of the mediating effect. Future intervention plans should pay more attention to social support as well as hope and resilience to prevent, relieve and treat PTSD symptoms.

Association between social support and post-traumatic stress disorder symptoms among Chinese patients with ovarian cancer: A multiple mediation model

Science.gov (United States)

Liu, Chunli; Zhang, Yi; Jiang, Hong; Wu, Hui

2017-01-01

Post-traumatic stress disorder (PTSD) symptoms can develop after person experiences one or more traumatic events. Little research, however, has been done on PTSD symptoms of patients with ovarian cancer. The present study aimed to estimate the prevalence of PTSD symptoms in patients with ovarian cancer in China; the effects of demographic and clinical variables on PTSD symptoms; multiple mediation roles in the association between social support and PTSD symptoms in patients with ovarian cancer in China. We collected demographic and clinical information of patients with ovarian cancer in the first and second hospitals of China Medical University between January 1, 2014 and December 31, 2015. Qualified patients were asked to complete the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C), Duke-UNC Functional Social Support Questionnaire, Herth Hope Index (HHI), and Resilience Scale-14 (RS-14). 201 patients provided responses. We performed hierarchical linear regression to assess the correlation between social support and PTSD symptoms and bootstrapping to test the mediating role of hope and resilience as potential mediators. After controlling demographic and clinical characteristics, social support negatively correlated with PTSD symptoms (β = -0.406, P Social support explained 14.7% of the variance in PTSD symptoms. Hope and resilience explained 17.0% of the variance in PTSD symptoms. The proportion of the hope mediating effect was 43.37% for social support and the proportion of the resilience mediating effect was 10.64% for social support. Hope and resilience partly mediated the correlation between social support and PTSD symptoms despite accounting for different proportions of the mediating effect. Future intervention plans should pay more attention to social support as well as hope and resilience to prevent, relieve and treat PTSD symptoms. PMID:28475593

Multiple signaling pathways mediated by dopamine and calcium ionophore A23187 in human platelets

International Nuclear Information System (INIS)

Saeed, S.A.; Waqar, M.A.

2009-01-01

This study was undertaken to investigate the mechanism(s) of platelet aggregation induced by the synergistic action of dopamine (DA) and a Ca/sup +2/-ionophore, A23187. DA showed non significant effect on platelet aggregation over a wide range of concentrations (up to 500 micro M), but did potentiate the aggregation response of A23187. Aggregation induced by A23187 was inhibited by calcium channel blockers (diltiazem and verpamil), receptor blockers (chlorpromazine and haloperidol) and a cyclo-oxygenase inhibitor (indomethacin). However, the inhibitory effect of these blockers was more pronounced (with a selectivity ratio of 1.5-28) in the aggregation induced by synergistic effect of A23187 and DA. A phosphatidylinositol 3-kinase (P1 3-Kinase) inhibitor, wortmanin (1C/sub 50/. 25-30 nM), inhibited aggregation induced by either A23187 or DA and act synergistically. This synergistic effect on platelet aggregation is mediated through multiple signaling pathways. (author)

Changes in illness perceptions mediated the effect of cognitive behavioural therapy in severe functional somatic syndromes

DEFF Research Database (Denmark)

Christensen, Sara Sletten; Frostholm, Lisbeth; Ørnbøl, Eva

2014-01-01

Objective Although there is substantial evidence that cognitive behavioural therapy alleviates symptoms in functional somatic syndromes, the mechanisms of change are less investigated. This study examined whether changes in illness perceptions mediated the effect of cognitive behavioural therapy....... Methods We analysed additional data from a randomised controlled trial comparing completers of cognitive behavioural group therapy (46 patients) to an enhanced usual care group (66 patients). Proposed mediators (illness perceptions) and primary (physical health) and secondary (somatic symptoms and illness...... worry) outcomes were assessed by means of questionnaires at referral, baseline, end of treatment, and 10 and 16 months after randomisation. Multiple mediation analysis determined whether (1) changes in specific illness perceptions during treatment mediated the effect of cognitive behavioural therapy...

Evidence for Multiple Mediator Complexes in Yeast Independently Recruited by Activated Heat Shock Factor.

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Anandhakumar, Jayamani; Moustafa, Yara W; Chowdhary, Surabhi; Kainth, Amoldeep S; Gross, David S

2016-07-15

Mediator is an evolutionarily conserved coactivator complex essential for RNA polymerase II transcription. Although it has been generally assumed that in Saccharomyces cerevisiae, Mediator is a stable trimodular complex, its structural state in vivo remains unclear. Using the "anchor away" (AA) technique to conditionally deplete select subunits within Mediator and its reversibly associated Cdk8 kinase module (CKM), we provide evidence that Mediator's tail module is highly dynamic and that a subcomplex consisting of Med2, Med3, and Med15 can be independently recruited to the regulatory regions of heat shock factor 1 (Hsf1)-activated genes. Fluorescence microscopy of a scaffold subunit (Med14)-anchored strain confirmed parallel cytoplasmic sequestration of core subunits located outside the tail triad. In addition, and contrary to current models, we provide evidence that Hsf1 can recruit the CKM independently of core Mediator and that core Mediator has a role in regulating postinitiation events. Collectively, our results suggest that yeast Mediator is not monolithic but potentially has a dynamic complexity heretofore unappreciated. Multiple species, including CKM-Mediator, the 21-subunit core complex, the Med2-Med3-Med15 tail triad, and the four-subunit CKM, can be independently recruited by activated Hsf1 to its target genes in AA strains. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Does Alcoholics Anonymous work differently for men and women? A moderated multiple-mediation analysis in a large clinical sample.

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Kelly, John F; Hoeppner, Bettina B

2013-06-01

Alcoholics Anonymous (AA) began as a male organization, but about one third is now female. Studies have found that women participate at least as much as men and benefit equally from AA, but it is unclear whether women benefit from AA in the same or different ways as men. This study tested whether gender moderated the mechanisms through which AA aids recovery. A cohort study of alcohol dependent adults (N=1726; 24% female; Project MATCH) was assessed on AA attendance during treatment; with mediators at 9 months; outcomes (Percent Days Abstinent [PDA] and Drinks per Drinking Day [DDD]) at 15 months. Multiple mediator models tested whether purported mechanisms (i.e., self-efficacy, depression, social networks, spirituality/religiosity) explained AA's effects differently for men and women controlling for baseline values, mediators, treatment, and other confounders. For PDA, the proportion of AA's effect accounted for by the mediators was similar for men (53%) and women (49%). Both men and women were found to benefit from changes in social factors but these mechanisms were more important among men. For DDD, the mediators accounted for 70% of the effect of AA for men and 41% for women. Again, men benefitted mostly from social changes. Independent of AA's effects, negative affect self-efficacy was shown to have a strong relationship to outcome for women but not men. The recovery benefits derived from AA differ in nature and magnitude between men and women and may reflect differing needs based on recovery challenges related to gender-based social roles and drinking contexts. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Entrepreneurs Experience and Firm Innovativeness: Multiple Mediation of Attitudinal and Behavioral Competencies

OpenAIRE

Bernard Nassiuma; Jamin Masasabi; Denyse Snelder; Anne Nangulu

2018-01-01

This study was anchored on a postpositivism paradigm and the Theory of perceived attributes and individual innovativeness, regarding the multiple serial mediations of attitudinal and behavioral competencies in the relationship between the entrepreneurs’ experience and firm innovativeness. To test the hypothesized relationship a cross-sectional design and qualitative approach were employed. The study drew on a sample of 698 Micro and Small-scale entrepreneurs in Western Kenya. Questionnaires ...

Curcumin mediates anticancer effects by modulating multiple cell signaling pathways.

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Kunnumakkara, Ajaikumar B; Bordoloi, Devivasha; Harsha, Choudhary; Banik, Kishore; Gupta, Subash C; Aggarwal, Bharat B

2017-08-01

Curcumin, a component of a spice native to India, was first isolated in 1815 by Vogel and Pelletier from the rhizomes of Curcuma longa (turmeric) and, subsequently, the chemical structure of curcumin as diferuloylmethane was reported by Milobedzka et al. [(1910) 43., 2163-2170]. Since then, this polyphenol has been shown to exhibit antioxidant, anti-inflammatory, anticancer, antiviral, antibacterial, and antifungal activities. The current review primarily focuses on the anticancer potential of curcumin through the modulation of multiple cell signaling pathways. Curcumin modulates diverse transcription factors, inflammatory cytokines, enzymes, kinases, growth factors, receptors, and various other proteins with an affinity ranging from the pM to the mM range. Furthermore, curcumin effectively regulates tumor cell growth via modulation of numerous cell signaling pathways and potentiates the effect of chemotherapeutic agents and radiation against cancer. Curcumin can interact with most of the targets that are modulated by FDA-approved drugs for cancer therapy. The focus of this review is to discuss the molecular basis for the anticancer activities of curcumin based on preclinical and clinical findings. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

[Effects decomposition in mediation analysis: a numerical example].

Science.gov (United States)

Zugna, Daniela; Richiardi, Lorenzo

2018-01-01

Mediation analysis aims to decompose the total effect of the exposure on the outcome into a direct effect (unmediated) and an indirect effect (mediated by a mediator). When the interest also lies on understanding whether the exposure effect differs in different sub-groups of study population or under different scenarios, the mediation analysis needs to be integrated with interaction analysis. In this setting it is necessary to decompose the total effect not only into two components, the direct and indirect effects, but other two components linked to interaction. The interaction between the exposure and the mediator in their effect on the outcome could indeed act through the effect of the exposure on the mediator or through the mediator when the mediator is not totally explained by the exposure. We describe options for decomposition, proposed in literature, of the total effect and we illustrate them through a hypothetical example of the effect of age at diagnosis of cancer on survival, mediated and unmediated by the therapeutical approach, and a numerical example.

ANGUSTIFOLIA mediates one of the multiple SCRAMBLED signaling pathways regulating cell growth pattern in Arabidopsis thaliana.

Science.gov (United States)

Kwak, Su-Hwan; Song, Sang-Kee; Lee, Myeong Min; Schiefelbein, John

2015-09-25

In Arabidopsis thaliana, an atypical leucine-rich repeat receptor-like kinase, SCRAMBLED (SCM), is required for multiple developmental processes including root epidermal cell fate determination, silique dehiscence, inflorescence growth, ovule morphogenesis, and tissue morphology. Previous work suggested that SCM regulates these multiple pathways using distinct mechanisms via interactions with specific downstream factors. ANGUSTIFOLIA (AN) is known to regulate cell and tissue morphogenesis by influencing cortical microtubule arrangement, and recently, the AN protein was reported to interact with the SCM protein. Therefore, we examined whether AN might be responsible for mediating some of the SCM-dependent phenotypes. We discovered that both scm and an mutant lines cause an abnormal spiral or twisting growth of roots, but only the scm mutant affected root epidermal patterning. The siliques of the an and scm mutants also exhibited spiral growth, as previously reported, but only the scm mutant altered silique dehiscence. Interestingly, we discovered that the spiral growth of roots and siliques of the scm mutant is rescued by a truncated SCM protein that lacks its kinase domain, and that a juxtamembrane domain of SCM was sufficient for AN binding in the yeast two-hybrid analysis. These results suggest that the AN protein is one of the critical downstream factors of SCM pathways specifically responsible for mediating its effects on cell/tissue morphogenesis through cortical microtubule arrangement. Copyright © 2015 Elsevier Inc. All rights reserved.

Perceived medication adherence barriers mediating effects between gastrointestinal symptoms and health-related quality of life in pediatric inflammatory bowel disease.

Science.gov (United States)

Varni, James W; Shulman, Robert J; Self, Mariella M; Saeed, Shehzad A; Zacur, George M; Patel, Ashish S; Nurko, Samuel; Neigut, Deborah A; Franciosi, James P; Saps, Miguel; Denham, Jolanda M; Dark, Chelsea Vaughan; Bendo, Cristiane B; Pohl, John F

2018-01-01

The primary objective was to investigate the mediating effects of patient-perceived medication adherence barriers in the relationship between gastrointestinal symptoms and generic health-related quality of life (HRQOL) in adolescents with inflammatory bowel disease (IBD). The secondary objective explored patient health communication and gastrointestinal worry as additional mediators with medication adherence barriers in a serial multiple mediator model. The Pediatric Quality of Life Inventory™ Gastrointestinal Symptoms, Medicines, Communication, Gastrointestinal Worry, and Generic Core Scales were completed in a 9-site study by 172 adolescents with IBD. Gastrointestinal Symptoms Scales measuring stomach pain, constipation, or diarrhea and perceived medication adherence barriers were tested for bivariate and multivariate linear associations with HRQOL. Mediational analyses were conducted to test the hypothesized mediating effects of perceived medication adherence barriers as an intervening variable between gastrointestinal symptoms and HRQOL. The predictive effects of gastrointestinal symptoms on HRQOL were mediated in part by perceived medication adherence barriers. Patient health communication was a significant additional mediator. In predictive analytics models utilizing multiple regression analyses, demographic variables, gastrointestinal symptoms (stomach pain, constipation, or diarrhea), and perceived medication adherence barriers significantly accounted for 45, 38, and 29 percent of the variance in HRQOL (all Ps barriers explain in part the effects of gastrointestinal symptoms on HRQOL in adolescents with IBD. Patient health communication to healthcare providers and significant others further explain the mechanism in the relationship between gastrointestinal symptoms, perceived medication adherence barriers, and HRQOL.

The Role of Mediators in the Indirect Effects of Religiosity on Therapeutic Compliance in African Migrant HIV-Positive Patients.

Science.gov (United States)

Mambet Doue, Constance; Roussiau, Nicolas

2016-12-01

This research investigates the indirect effects of religiosity (practice and belief) on therapeutic compliance in 81 HIV-positive patients who are migrants from sub-Saharan Africa (23 men and 58 women). Using analyses of mediation and standard multiple regression, including a resampling procedure by bootstrapping, the role of these mediators (magical-religious beliefs and nonuse of toxic substances) was tested. The results show that, through magical-religious beliefs, religiosity has a negative indirect effect, while with the nonuse of toxic substances, religious practice has a positive indirect effect. Beyond religiosity, the role of mediators is highlighted in the interaction with therapeutic compliance.

Application of the 2012 revised diagnostic definitions for paediatric multiple sclerosis and immune-mediated central nervous system demyelination disorders

NARCIS (Netherlands)

van Pelt, E. Danielle; Neuteboom, Rinze F.; Ketelslegers, Immy A.; Boon, Maartje; Catsman-Berrevoets, Coriene E.; Hintzen, Rogier Q.

Background Recently, the International Paediatric Multiple Sclerosis Study Group (IPMSSG) definitions for the diagnosis of immune-mediated acquired demyelinating syndromes (ADS) of the central nervous system, including paediatric multiple sclerosis (MS), have been revised. Objective To evaluate the

The Effect of Fearful Expressions on Multiple Face Tracking

Directory of Open Access Journals (Sweden)

Hongjun Jin

2015-07-01

Full Text Available How does the visual system realize dynamic tracking? This topic has become popular within cognitive science in recent years. The classical theory argues that multiple object tracking is accomplished via pre-attention visual indexes as part of a cognitively impenetrable low-level visual system. The present research aimed to investigate whether and how tracking processes are influenced by facial expressions that convey abundant social information about one’s mental state and situated environment. The results showed that participants tracked fearful faces more effectively than neutral faces. However, this advantage was only present under the low-attentional load condition, and distractor face emotion did not impact tracking performance. These findings imply that visual tracking is not driven entirely by low-level vision and encapsulated by high-level representations; rather, that facial expressions, a kind of social information, are able to influence dynamic tracking. Furthermore, the effect of fearful expressions on multiple face tracking is mediated by the availability of attentional resources.

Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma

DEFF Research Database (Denmark)

Overdijk, M. B.; Verploegen, S.; Bogels, M.

2015-01-01

Daratumumab (DARA) is a human CD38-specific IgG1 antibody that is in clinical development for the treatment of multiple myeloma (MM). The potential for IgG1 antibodies to induce macrophage-mediated phagocytosis, in combination with the known presence of macrophages in the tumor microenvironment...... in MM and other hematological tumors, led us to investigate the contribution of antibody-dependent, macrophage-mediated phagocytosis to DARA's mechanism of action. Live cell imaging revealed that DARA efficiently induced macrophage-mediated phagocytosis, in which individual macrophages rapidly...... and sequentially engulfed multiple tumor cells. DARA-dependent phagocytosis by mouse and human macrophages was also observed in an in vitro flow cytometry assay, using a range of MM and Burkitt's lymphoma cell lines. Phagocytosis contributed to DARA's anti-tumor activity in vivo, in both a subcutaneous...

The effects of normal aging on multiple aspects of financial decision-making.

Directory of Open Access Journals (Sweden)

Dorien F Bangma

Full Text Available Financial decision-making (FDM is crucial for independent living. Due to cognitive decline that accompanies normal aging, older adults might have difficulties in some aspects of FDM. However, an improved knowledge, personal experience and affective decision-making, which are also related to normal aging, may lead to a stable or even improved age-related performance in some other aspects of FDM. Therefore, the present explorative study examines the effects of normal aging on multiple aspects of FDM.One-hundred and eighty participants (range 18-87 years were assessed with eight FDM tests and several standard neuropsychological tests. Age effects were evaluated using hierarchical multiple regression analyses. The validity of the prediction models was examined by internal validation (i.e. bootstrap resampling procedure as well as external validation on another, independent, sample of participants (n = 124. Multiple regression and correlation analyses were applied to investigate the mediation effect of standard measures of cognition on the observed effects of age on FDM.On a relatively basic level of FDM (e.g., paying bills or using FDM styles no significant effects of aging were found. However more complex FDM, such as making decisions in accordance with specific rules, becomes more difficult with advancing age. Furthermore, an older age was found to be related to a decreased sensitivity for impulsive buying. These results were confirmed by the internal and external validation analyses. Mediation effects of numeracy and planning were found to explain parts of the association between one aspect of FDM (i.e. Competence in decision rules and age; however, these cognitive domains were not able to completely explain the relation between age and FDM.Normal aging has a negative influence on a complex aspect of FDM, however, other aspects appear to be unaffected by normal aging or improve.

The role of appraisal and coping style in relation with societal participation in fatigued patients with multiple sclerosis: a cross-sectional multiple mediator analysis

NARCIS (Netherlands)

Akker, L.E. van den; Beckerman, H.; Collette, E.H.; Bleijenberg, G.; Dekker, J.; Knoop, H.; Groot, V. de; Jong, B.A. de; et al.,

2016-01-01

To determine the relationship between appraisal and societal participation in fatigued patients with Multiple Sclerosis (MS), and whether this relation is mediated by coping styles. 265 severely-fatigued MS patients. Appraisal, a latent construct, was created from the General Self-Efficacy Scale and

The role of appraisal and coping style in relation with societal participation in fatigued patients with multiple sclerosis : a cross-sectional multiple mediator analysis

NARCIS (Netherlands)

van den Akker, Lizanne Eva; Beckerman, Heleen; Collette, Emma Hubertine; Bleijenberg, Gijs; Dekker, Joost; Knoop, Hans; de Groot, Vincent; TREFAMS-ACE study group, study group; de Groot, V.; Beckerman, H.; Malekzadeh, A.; van den Akker, L. E.; Looijmans, M.; Sanches, S. A.; Dekker, J.; Collette, E. H.; van Oosten, B. W.; Teunissen, C. E.; Blankenstein, M. A.; Eijssen, I. C J M; Rietberg, M.; Heine, M.; Verschuren, O.; Kwakkel, G.; Visser-Meily, J. M A; van de Port, I. G L; Lindeman, E.; Blikman, L. J M; van Meeteren, J.; Bussmann, J. B J; Stam, H. J.; Hintzen, R. Q.; Hacking, H. G A; Hoogervorst, E. L.; Frequin, S. T F M; Knoop, H.; de Jong, B. A.; de Laat, F. A J; Verhulsdonck, M. C.; van Munster, E. T H; Oosterwijk, C. J.; Aarts, G. J.

2016-01-01

To determine the relationship between appraisal and societal participation in fatigued patients with Multiple Sclerosis (MS), and whether this relation is mediated by coping styles. 265 severely-fatigued MS patients. Appraisal, a latent construct, was created from the General Self-Efficacy Scale and

Gender difference in sickness absence from work: a multiple mediation analysis of psychosocial factors.

Science.gov (United States)

Casini, Annalisa; Godin, Isabelle; Clays, Els; Kittel, France

2013-08-01

Previous research has shown that job characteristics, private life and psychosocial factors partially account for gender difference in work absences because of sickness. Most studies have analysed these factors separately. The aim of the present study was to evaluate whether these explanatory factors act as mediators when they are considered simultaneously. The evaluated data set comprises the merger of two Belgian longitudinal studies, BELSTRESS III and SOMSTRESS. It includes 3821 workers (1541 men) aged 21-66 years, employed in eight organizations. A multiple mediation analysis was performed to explain the higher prevalence among women. Estimated factors were occupational grade, total number of paid working hours per week, job strain, overcommitment, home-work interference and social support at and outside work. Prospective data concerning duration and frequency of medically justified sickness absence (registered by the organizations) were used as outcomes. Overall, the mediating factors partially account for gender difference in sickness absence. The strongest mediator for both outcomes is job strain. In addition, difference in absence duration is mediated by social support at work, whereas difference in frequency is mediated by professional grade and home-work interference. Our results call attention to the necessity to elaborate actual preventive actions aiming at favouring a better positioning of women on the labour market in term of hierarchical level as well as in terms of quality of work for reducing sickness absence in this group.

Phosphoinositide protein kinase PDPK1 is a crucial cell signaling mediator in multiple myeloma.

Science.gov (United States)

Chinen, Yoshiaki; Kuroda, Junya; Shimura, Yuji; Nagoshi, Hisao; Kiyota, Miki; Yamamoto-Sugitani, Mio; Mizutani, Shinsuke; Sakamoto, Natsumi; Ri, Masaki; Kawata, Eri; Kobayashi, Tsutomu; Matsumoto, Yosuke; Horiike, Shigeo; Iida, Shinsuke; Taniwaki, Masafumi

2014-12-15

Multiple myeloma is a cytogenetically/molecularly heterogeneous hematologic malignancy that remains mostly incurable, and the identification of a universal and relevant therapeutic target molecule is essential for the further development of therapeutic strategy. Herein, we identified that 3-phosphoinositide-dependent protein kinase 1 (PDPK1), a serine threonine kinase, is expressed and active in all eleven multiple myeloma-derived cell lines examined regardless of the type of cytogenetic abnormality, the mutation state of RAS and FGFR3 genes, or the activation state of ERK and AKT. Our results revealed that PDPK1 is a pivotal regulator of molecules that are essential for myelomagenesis, such as RSK2, AKT, c-MYC, IRF4, or cyclin Ds, and that PDPK1 inhibition caused the growth inhibition and the induction of apoptosis with the activation of BIM and BAD, and augmented the in vitro cytotoxic effects of antimyeloma agents in myeloma cells. In the clinical setting, PDPK1 was active in myeloma cells of approximately 90% of symptomatic patients at diagnosis, and the smaller population of patients with multiple myeloma exhibiting myeloma cells without active PDPK1 showed a significantly less frequent proportion of the disease stage III by the International Staging System and a significantly more favorable prognosis, including the longer overall survival period and the longer progression-free survival period by bortezomib treatment, than patients with active PDPK1, suggesting that PDPK1 activation accelerates the disease progression and the resistance to treatment in multiple myeloma. Our study demonstrates that PDPK1 is a potent and a universally targetable signaling mediator in multiple myeloma regardless of the types of cytogenetic/molecular profiles. ©2014 American Association for Cancer Research.

Relationships among symptom severity, coping styles, and quality of life in community-dwelling women with urinary incontinence: a multiple mediator model.

Science.gov (United States)

Xu, Dongjuan; Liu, Nana; Qu, Haili; Chen, Liqin; Wang, Kefang

2016-01-01

To investigate the relationships among symptom severity, coping styles, and quality of life (QOL) in community-dwelling women with urinary incontinence (UI). A total of 592 women with UI participated in this cross-sectional study. Bivariate Pearson's correlation was used to examine the correlations between symptom severity, coping styles, and QOL. Multivariate regression models and Sobel tests were used to test the mediating effect of coping styles. Additionally, a multiple mediator model was used to examine the mediating role of coping styles collectively. All regression models were adjusted for age, education, marital status, income, duration of UI, and type of UI. Participants tended to use avoidant and palliative coping styles and not use instrumental coping style. Avoidant and palliative coping styles were associated with poor QOL, and partially mediated the association between symptom severity and QOL. Nearly 73% of the adverse effect of symptom severity on QOL was mediated by avoidant and palliative coping styles. The use of avoidant and palliative coping styles was higher with more severe urine leakage, and QOL tended to be poorer. Coping styles should be addressed in UI management. It may be of particular value to look closely at negative coping styles and implement education and training of patients in improving their coping skills related to managing UI, which will in turn improve their QOL.

Mediation and moderation of treatment effects in randomised controlled trials of complex interventions.

Science.gov (United States)

Emsley, Richard; Dunn, Graham; White, Ian R

2010-06-01

Complex intervention trials should be able to answer both pragmatic and explanatory questions in order to test the theories motivating the intervention and help understand the underlying nature of the clinical problem being tested. Key to this is the estimation of direct effects of treatment and indirect effects acting through intermediate variables which are measured post-randomisation. Using psychological treatment trials as an example of complex interventions, we review statistical methods which crucially evaluate both direct and indirect effects in the presence of hidden confounding between mediator and outcome. We review the historical literature on mediation and moderation of treatment effects. We introduce two methods from within the existing causal inference literature, principal stratification and structural mean models, and demonstrate how these can be applied in a mediation context before discussing approaches and assumptions necessary for attaining identifiability of key parameters of the basic causal model. Assuming that there is modification by baseline covariates of the effect of treatment (i.e. randomisation) on the mediator (i.e. covariate by treatment interactions), but no direct effect on the outcome of these treatment by covariate interactions leads to the use of instrumental variable methods. We describe how moderation can occur through post-randomisation variables, and extend the principal stratification approach to multiple group methods with explanatory models nested within the principal strata. We illustrate the new methodology with motivating examples of randomised trials from the mental health literature.

Association between social support and post-traumatic stress disorder symptoms among Chinese patients with ovarian cancer: A multiple mediation model.

Science.gov (United States)

Liu, Chunli; Zhang, Yi; Jiang, Hong; Wu, Hui

2017-01-01

Post-traumatic stress disorder (PTSD) symptoms can develop after person experiences one or more traumatic events. Little research, however, has been done on PTSD symptoms of patients with ovarian cancer. The present study aimed to estimate the prevalence of PTSD symptoms in patients with ovarian cancer in China; the effects of demographic and clinical variables on PTSD symptoms; multiple mediation roles in the association between social support and PTSD symptoms in patients with ovarian cancer in China. We collected demographic and clinical information of patients with ovarian cancer in the first and second hospitals of China Medical University between January 1, 2014 and December 31, 2015. Qualified patients were asked to complete the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C), Duke-UNC Functional Social Support Questionnaire, Herth Hope Index (HHI), and Resilience Scale-14 (RS-14). 201 patients provided responses. We performed hierarchical linear regression to assess the correlation between social support and PTSD symptoms and bootstrapping to test the mediating role of hope and resilience as potential mediators. After controlling demographic and clinical characteristics, social support negatively correlated with PTSD symptoms (β = -0.406, P accounting for different proportions of the mediating effect. Future intervention plans should pay more attention to social support as well as hope and resilience to prevent, relieve and treat PTSD symptoms.

Mediational Model of Multiple Sclerosis Impairments, Family Needs, and Caregiver Mental Health in Guadalajara, Mexico

Directory of Open Access Journals (Sweden)

Melody N. Mickens

2018-01-01

Full Text Available Individuals with multiple sclerosis (MS, especially those living in Latin America, often require assistance from family caregivers throughout the duration of the disease. Previous research suggests that family caregivers may experience positive and negative outcomes from providing care to individuals with MS, but few studies have examined the unmet needs of individuals providing care to family members with MS and how these unmet needs may mediate the relationship between MS symptoms and caregiver mental health. The current study examined the relationships among MS impairments (functional, neurological, cognitive, behavioral, and emotional, unmet family needs (household, informational, financial, social support, and health, and caregiver mental health (satisfaction with life, anxiety, burden, and depression in a sample of 81 MS caregivers from Guadalajara, Mexico. A structural equation model demonstrated the mediational effect of unmet family needs on the relationship between MS impairments and caregiver mental health. These findings suggest that intervention research on MS caregivers in Latin America may consider focusing on caregiver mental health problems by addressing unmet family needs and teaching caregivers ways to manage the impairments of the individual with MS.

A multiple mediator analysis approach to quantify the effects of the ADH1B and ALDH2 genes on hepatocellular carcinoma risk.

Science.gov (United States)

Shih, Stephannie; Huang, Yen-Tsung; Yang, Hwai-I

2018-06-01

Previous work suggested a genetic component affecting the risk of hepatocellular carcinoma (HCC) and mediation analyses have elucidated potential indirect pathways of these genetic effects. Specifically, the effects of alcohol dehydrogenase (ADH1B) and aldehyde dehydrogenase (ALDH2) genes on HCC risk vary based on alcohol consumption habits. However, alcohol consumption may not be the only mediator in the identified pathway: factors related to alcohol consumption may contribute to the same indirect pathway. Thus, we developed a multimediator model to quantify the genetic effects on HCC risk through sequential dichotomous mediators under the counterfactual framework. Our method provided a closed form formula for the mediation effects through different indirect paths, which requires no assumption for the rarity of outcome. In simulation studies of a finite sample, we presented the utility of the method with the variance of the effects estimated using the delta method and bootstrapping. We applied our method to data from participants in Taiwan (580 cases and 3,207 controls) and quantified the mediation effects of single nucleotide polymorphisms (SNPs) in the ADH1B and ALDH2 genes on HCC through alcohol consumption (yes/no) and high alanine transaminase (ALT) levels (greater than or equal to 45 U/L or below 45 U/L). Assuming a dominant risk model, we identified that the SNPs' effects through alcohol consumption is more significant than through ALT levels on HCC risk. This new method provides insight to the magnitude of various casual mechanisms as a closed form solution and can be readily applied in other genomic studies. © 2018 WILEY PERIODICALS, INC.

Perceived Academic Control: Mediating the Effects of Optimism and Social Support on College Students' Psychological Health

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Ruthig, Joelle C.; Haynes, Tara L.; Stupnisky, Robert H.; Perry, Raymond P.

2009-01-01

The first year of college presents numerous challenges experienced as overwhelming by some freshmen who may become overly stressed and depressed. This longitudinal study examined perceived academic control (PAC) as a mediator of optimism and social support's buffering effects on freshman students' psychological health. Multiple regressions…

Estimating and Testing Mediation Effects with Censored Data

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Wang, Lijuan; Zhang, Zhiyong

2011-01-01

This study investigated influences of censored data on mediation analysis. Mediation effect estimates can be biased and inefficient with censoring on any one of the input, mediation, and output variables. A Bayesian Tobit approach was introduced to estimate and test mediation effects with censored data. Simulation results showed that the Bayesian…

A default Bayesian hypothesis test for mediation

NARCIS (Netherlands)

Nuijten, M.B.; Wetzels, R.; Matzke, D.; Dolan, C.V.; Wagenmakers, E.J.

2015-01-01

In order to quantify the relationship between multiple variables, researchers often carry out a mediation analysis. In such an analysis, a mediator (e.g., knowledge of a healthy diet) transmits the effect from an independent variable (e.g., classroom instruction on a healthy diet) to a dependent

Mediation Analysis: A Practitioner's Guide.

Science.gov (United States)

VanderWeele, Tyler J

2016-01-01

This article provides an overview of recent developments in mediation analysis, that is, analyses used to assess the relative magnitude of different pathways and mechanisms by which an exposure may affect an outcome. Traditional approaches to mediation in the biomedical and social sciences are described. Attention is given to the confounding assumptions required for a causal interpretation of direct and indirect effect estimates. Methods from the causal inference literature to conduct mediation in the presence of exposure-mediator interactions, binary outcomes, binary mediators, and case-control study designs are presented. Sensitivity analysis techniques for unmeasured confounding and measurement error are introduced. Discussion is given to extensions to time-to-event outcomes and multiple mediators. Further flexible modeling strategies arising from the precise counterfactual definitions of direct and indirect effects are also described. The focus throughout is on methodology that is easily implementable in practice across a broad range of potential applications.

A classical regression framework for mediation analysis: fitting one model to estimate mediation effects.

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Saunders, Christina T; Blume, Jeffrey D

2017-10-26

Mediation analysis explores the degree to which an exposure's effect on an outcome is diverted through a mediating variable. We describe a classical regression framework for conducting mediation analyses in which estimates of causal mediation effects and their variance are obtained from the fit of a single regression model. The vector of changes in exposure pathway coefficients, which we named the essential mediation components (EMCs), is used to estimate standard causal mediation effects. Because these effects are often simple functions of the EMCs, an analytical expression for their model-based variance follows directly. Given this formula, it is instructive to revisit the performance of routinely used variance approximations (e.g., delta method and resampling methods). Requiring the fit of only one model reduces the computation time required for complex mediation analyses and permits the use of a rich suite of regression tools that are not easily implemented on a system of three equations, as would be required in the Baron-Kenny framework. Using data from the BRAIN-ICU study, we provide examples to illustrate the advantages of this framework and compare it with the existing approaches. © The Author 2017. Published by Oxford University Press.

Statistical properties of four effect-size measures for mediation models.

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Miočević, Milica; O'Rourke, Holly P; MacKinnon, David P; Brown, Hendricks C

2018-02-01

This project examined the performance of classical and Bayesian estimators of four effect size measures for the indirect effect in a single-mediator model and a two-mediator model. Compared to the proportion and ratio mediation effect sizes, standardized mediation effect-size measures were relatively unbiased and efficient in the single-mediator model and the two-mediator model. Percentile and bias-corrected bootstrap interval estimates of ab/s Y , and ab(s X )/s Y in the single-mediator model outperformed interval estimates of the proportion and ratio effect sizes in terms of power, Type I error rate, coverage, imbalance, and interval width. For the two-mediator model, standardized effect-size measures were superior to the proportion and ratio effect-size measures. Furthermore, it was found that Bayesian point and interval summaries of posterior distributions of standardized effect-size measures reduced excessive relative bias for certain parameter combinations. The standardized effect-size measures are the best effect-size measures for quantifying mediated effects.

Distinct brain systems mediate the effects of nociceptive input and self-regulation on pain.

Directory of Open Access Journals (Sweden)

Choong-Wan Woo

2015-01-01

Full Text Available Cognitive self-regulation can strongly modulate pain and emotion. However, it is unclear whether self-regulation primarily influences primary nociceptive and affective processes or evaluative ones. In this study, participants engaged in self-regulation to increase or decrease pain while experiencing multiple levels of painful heat during functional magnetic resonance imaging (fMRI imaging. Both heat intensity and self-regulation strongly influenced reported pain, but they did so via two distinct brain pathways. The effects of stimulus intensity were mediated by the neurologic pain signature (NPS, an a priori distributed brain network shown to predict physical pain with over 90% sensitivity and specificity across four studies. Self-regulation did not influence NPS responses; instead, its effects were mediated through functional connections between the nucleus accumbens and ventromedial prefrontal cortex. This pathway was unresponsive to noxious input, and has been broadly implicated in valuation, emotional appraisal, and functional outcomes in pain and other types of affective processes. These findings provide evidence that pain reports are associated with two dissociable functional systems: nociceptive/affective aspects mediated by the NPS, and evaluative/functional aspects mediated by a fronto-striatal system.

Ethnic and Racial Socialization and Self-Esteem of Asian Adoptees: The Mediating Role of Multiple Identities

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Mohanty, Jayashree

2013-01-01

Positive identity development during adolescence in general is a complex process and may pose additional challenges for adolescents adopted from a different culture. Using a web-based survey design with a sample of 100 internationally adopted Asian adolescent and young adults, the present study examined the mediating role of multiple identities…

War-related trauma exposure and multiple risk behaviors among school-going adolescents in Northern Uganda: the mediating role of depression symptoms.

Science.gov (United States)

Okello, James; Nakimuli-Mpungu, Etheldreda; Musisi, Seggane; Broekaert, Eric; Derluyn, Ilse

2013-11-01

The relationship between war-related trauma exposure, depressive symptoms and multiple risk behaviors among adolescents is less clear in sub-Saharan Africa. We analyzed data collected from a sample of school-going adolescents four years postwar. Participants completed interviews assessing various risk behaviors defined by the Youth Self Report (YSR) and a sexual risk behavior survey, and were screened for post-traumatic stress, anxiety and depression symptoms based on the Impact of Events Scale Revised (IESR) and Hopkins Symptom Checklist for Adolescents (HSCL-37A) respectively. Multivariate logistic regression was used to assess factors independently associated with multiple risk behaviors. The logistic regression model of Baron and Kenny (1986) was used to evaluate the mediating role of depression in the relationship between stressful war events and multiple risk behaviors. Of 551 participants, 139 (25%) reported multiple (three or more) risk behaviors in the past year. In the multivariate analyses, depression symptoms remained uniquely associated with multiple risk behavior after adjusting for potential confounders including socio-demographic characteristics, war-related trauma exposure variables, anxiety and post-traumatic stress symptoms. In mediation analysis, depression symptoms mediated the associations between stressful war events and multiple risk behaviors. The psychometric properties of the questionnaires used in this study are not well established in war affected African samples thus ethno cultural variation may decrease the validity of our measures. Adolescents with depression may be at a greater risk of increased engagement in multiple risk behaviors. Culturally sensitive and integrated interventions to treat and prevent depression among adolescents in post-conflict settings are urgently needed. © 2013 Elsevier B.V. All rights reserved.

Humanizing Outgroups Through Multiple Categorization

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Prati, Francesca; Crisp, Richard J.; Meleady, Rose; Rubini, Monica

2016-01-01

In three studies, we examined the impact of multiple categorization on intergroup dehumanization. Study 1 showed that perceiving members of a rival university along multiple versus simple categorical dimensions enhanced the tendency to attribute human traits to this group. Study 2 showed that multiple versus simple categorization of immigrants increased the attribution of uniquely human emotions to them. This effect was explained by the sequential mediation of increased individuation of the outgroup and reduced outgroup threat. Study 3 replicated this sequential mediation model and introduced a novel way of measuring humanization in which participants generated attributes corresponding to the outgroup in a free response format. Participants generated more uniquely human traits in the multiple versus simple categorization conditions. We discuss the theoretical implications of these findings and consider their role in informing and improving efforts to ameliorate contemporary forms of intergroup discrimination. PMID:26984016

The mediation of mothers' self-fulfilling effects on their children's alcohol use: self-verification, informational conformity, and modeling processes.

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Madon, Stephanie; Guyll, Max; Buller, Ashley A; Scherr, Kyle C; Willard, Jennifer; Spoth, Richard

2008-08-01

This research examined whether self-fulfilling prophecy effects are mediated by self-verification, informational conformity, and modeling processes. The authors examined these mediational processes across multiple time frames with longitudinal data obtained from two samples of mother-child dyads (N-sub-1 = 486; N-sub-2 = 287), with children's alcohol use as the outcome variable. The results provided consistent support for the mediational process of self-verification. In both samples and across several years of adolescence, there was a significant indirect effect of mothers' beliefs on children's alcohol use through children's self-assessed likelihood of drinking alcohol in the future. Comparatively less support was found for informational conformity and modeling processes as mediators of mothers' self-fulfilling effects. The potential for self-fulfilling prophecies to produce long-lasting changes in targets' behavior via self-verification processes are discussed. (c) 2008 APA, all rights reserved

The Mediation of Mothers’ Self-Fulfilling Effects on Their Children’s Alcohol Use: Self-Verification, Informational Conformity and Modeling Processes

Science.gov (United States)

Madon, Stephanie; Guyll, Max; Buller, Ashley A.; Scherr, Kyle C.; Willard, Jennifer; Spoth, Richard

2010-01-01

This research examined whether self-fulfilling prophecy effects are mediated by self-verification, informational conformity, and modeling processes. The authors examined these mediational processes across multiple time frames with longitudinal data obtained from two samples of mother – child dyads (N1 = 487; N2 = 287). Children’s alcohol use was the outcome variable. The results provided consistent support for the mediational process of self-verification. In both samples and across several years of adolescence, there was a significant indirect effect of mothers’ beliefs on children’s alcohol use through children’s self-assessed likelihood of drinking alcohol in the future. Comparatively less support was found for informational conformity and modeling processes as mediators of mothers’ self-fulfilling effects. The potential for self-fulfilling prophecies to produce long lasting changes in targets’ behavior via self-verification processes are discussed. PMID:18665708

Ethnic and racial socialization and self-esteem of Asian adoptees: the mediating role of multiple identities.

Science.gov (United States)

Mohanty, Jayashree

2013-02-01

Positive identity development during adolescence in general is a complex process and may pose additional challenges for adolescents adopted from a different culture. Using a web-based survey design with a sample of 100 internationally adopted Asian adolescent and young adults, the present study examined the mediating role of multiple identities (i.e., ethnic, adoptive and interpersonal ego identities) in explaining the relationship between ethnic and racial socializations, ethnic neighborhood, and self-esteem. The results showed that (a) adoptive identity mediated the influence of racial socialization on psychological well-being, and (b) ethnic affirmation mediated the influence of ethnic socialization on adoptees' well-being. This study illustrates the importance of providing supportive counseling services for adoptees who are exploring their adoptive identity. Copyright © 2012 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Effects and mediators of psychosocial work characteristics on somatic symptoms six years later: Prospective findings from the Mannheim Industrial Cohort Studies (MICS).

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Herr, Raphael M; Li, Jian; Loerbroks, Adrian; Angerer, Peter; Siegrist, Johannes; Fischer, Joachim E

2017-07-01

Ample evidence documented the adverse health effects of work stressors, and recent research has increasingly focused on somatic symptoms which are very common and costly. Prospective evidence is however sparse and yielded mixed findings. Furthermore, there is reason to assume that depression and anxiety might mediate the effects of adverse psychosocial work conditions on somatic symptoms. This study aimed to investigate longitudinal effects of work stressors on somatic symptoms and the potential mediation by anxiety and/or depression. Six year follow-up data from 352 individuals - free of potentially stress-related chronic disease - were utilized. Somatic symptoms were assessed by 19 items of an established list of complaints at baseline and follow-up. The effort-reward-imbalance (ERI) model measured adverse psychosocial work conditions and over-commitment (OC). Linear regressions adjusted for socio-demographics, social status, lifestyle, and baseline symptoms estimated the effects of the ERI ratio, effort, reward, OC, and the ERI ratio×OC interaction on somatic symptoms six years later. Furthermore, single and multiple mediation by anxiety and/or depression was investigated. There was a strong longitudinal effect of the ERI ratio, as well as of its subcomponents, and OC on somatic symptoms (all Bs≥|0.49|; p-values ≤0.004). Moreover, the ERI ratio×OC interaction was significant (p-value=0.047). Multiple mediation analyses revealed especially anxiety to mediate the effect of work stressors on somatic symptoms (Sobel test=0.007). Adverse psychosocial work conditions seem to longitudinally affect somatic symptoms, potentially moderated by OC, and mediated by anxiety. Copyright © 2017 Elsevier Inc. All rights reserved.

Monte Carlo based statistical power analysis for mediation models: methods and software.

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Zhang, Zhiyong

2014-12-01

The existing literature on statistical power analysis for mediation models often assumes data normality and is based on a less powerful Sobel test instead of the more powerful bootstrap test. This study proposes to estimate statistical power to detect mediation effects on the basis of the bootstrap method through Monte Carlo simulation. Nonnormal data with excessive skewness and kurtosis are allowed in the proposed method. A free R package called bmem is developed to conduct the power analysis discussed in this study. Four examples, including a simple mediation model, a multiple-mediator model with a latent mediator, a multiple-group mediation model, and a longitudinal mediation model, are provided to illustrate the proposed method.

Inhibition of Ubc13-mediated Ubiquitination by GPS2 Regulates Multiple Stages of B Cell Development.

Science.gov (United States)

Lentucci, Claudia; Belkina, Anna C; Cederquist, Carly T; Chan, Michelle; Johnson, Holly E; Prasad, Sherry; Lopacinski, Amanda; Nikolajczyk, Barbara S; Monti, Stefano; Snyder-Cappione, Jennifer; Tanasa, Bogdan; Cardamone, M Dafne; Perissi, Valentina

2017-02-17

Non-proteolytic ubiquitin signaling mediated by Lys 63 ubiquitin chains plays a critical role in multiple pathways that are key to the development and activation of immune cells. Our previous work indicates that GPS2 (G-protein Pathway Suppressor 2) is a multifunctional protein regulating TNFα signaling and lipid metabolism in the adipose tissue through modulation of Lys 63 ubiquitination events. However, the full extent of GPS2-mediated regulation of ubiquitination and the underlying molecular mechanisms are unknown. Here, we report that GPS2 is required for restricting the activation of TLR and BCR signaling pathways and the AKT/FOXO1 pathway in immune cells based on direct inhibition of Ubc13 enzymatic activity. Relevance of this regulatory strategy is confirmed in vivo by B cell-targeted deletion of GPS2, resulting in developmental defects at multiple stages of B cell differentiation. Together, these findings reveal that GPS2 genomic and non-genomic functions are critical for the development and cellular homeostasis of B cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The effect of chronic seaweed subsidies on herbivory: plant-mediated fertilization pathway overshadows lizard-mediated predator pathways.

Science.gov (United States)

Piovia-Scott, Jonah; Spiller, David A; Takimoto, Gaku; Yang, Louie H; Wright, Amber N; Schoener, Thomas W

2013-08-01

Flows of energy and materials link ecosystems worldwide and have important consequences for the structure of ecological communities. While these resource subsidies typically enter recipient food webs through multiple channels, most previous studies focussed on a single pathway of resource input. We used path analysis to evaluate multiple pathways connecting chronic marine resource inputs (in the form of seaweed deposits) and herbivory in a shoreline terrestrial ecosystem. We found statistical support for a fertilization effect (seaweed increased foliar nitrogen content, leading to greater herbivory) and a lizard numerical response effect (seaweed increased lizard densities, leading to reduced herbivory), but not for a lizard diet-shift effect (seaweed increased the proportion of marine-derived prey in lizard diets, but lizard diet was not strongly associated with herbivory). Greater seaweed abundance was associated with greater herbivory, and the fertilization effect was larger than the combined lizard effects. Thus, the bottom-up, plant-mediated effect of fertilization on herbivory overshadowed the top-down effects of lizard predators. These results, from unmanipulated shoreline plots with persistent differences in chronic seaweed deposition, differ from those of a previous experimental study of the short-term effects of a pulse of seaweed deposition: while the increase in herbivory in response to chronic seaweed deposition was due to the fertilization effect, the short-term increase in herbivory in response to a pulse of seaweed deposition was due to the lizard diet-shift effect. This contrast highlights the importance of the temporal pattern of resource inputs in determining the mechanism of community response to resource subsidies.

Protein expression profiling of inflammatory mediators in human temporal lobe epilepsy reveals co-activation of multiple chemokines and cytokines

Directory of Open Access Journals (Sweden)

Kan Anne A

2012-08-01

Full Text Available Abstract Mesial temporal lobe epilepsy (mTLE is a chronic and often treatment-refractory brain disorder characterized by recurrent seizures originating from the hippocampus. The pathogenic mechanisms underlying mTLE remain largely unknown. Recent clinical and experimental evidence supports a role of various inflammatory mediators in mTLE. Here, we performed protein expression profiling of 40 inflammatory mediators in surgical resection material from mTLE patients with and without hippocampal sclerosis, and autopsy controls using a multiplex bead-based immunoassay. In mTLE patients we identified 21 upregulated inflammatory mediators, including 10 cytokines and 7 chemokines. Many of these upregulated mediators have not previously been implicated in mTLE (for example, CCL22, IL-7 and IL-25. Comparing the three patient groups, two main hippocampal expression patterns could be distinguished, pattern I (for example, IL-10 and IL-25 showing increased expression in mTLE + HS patients compared to mTLE-HS and controls, and pattern II (for example, CCL4 and IL-7 showing increased expression in both mTLE groups compared to controls. Upregulation of a subset of inflammatory mediators (for example, IL-25 and IL-7 could not only be detected in the hippocampus of mTLE patients, but also in the neocortex. Principle component analysis was used to cluster the inflammatory mediators into several components. Follow-up analyses of the identified components revealed that the three patient groups could be discriminated based on their unique expression profiles. Immunocytochemistry showed that IL-25 IR (pattern I and CCL4 IR (pattern II were localized in astrocytes and microglia, whereas IL-25 IR was also detected in neurons. Our data shows co-activation of multiple inflammatory mediators in hippocampus and neocortex of mTLE patients, indicating activation of multiple pro- and anti-epileptogenic immune pathways in this disease.

Serotonin: A mediator of the gut-brain axis in multiple sclerosis.

Science.gov (United States)

Malinova, Tsveta S; Dijkstra, Christine D; de Vries, Helga E

2017-11-01

The significance of the gut microbiome for the pathogenesis of multiple sclerosis (MS) has been established, although the underlying signaling mechanisms of this interaction have not been sufficiently explored. We address this point and use serotonin (5-hydroxytryptamine (5-HT))-a microbial-modulated neurotransmitter (NT) as a showcase to demonstrate that NTs regulated by the gut microbiome are potent candidates for mediators of the gut-brain axis in demyelinating disorders. Methods, Results, and Conclusion: Our comprehensive overview of literature provides evidence that 5-HT levels in the gut are controlled by the microbiome, both via secretion and through regulation of metabolites. In addition, we demonstrate that the gut microbiome can influence the formation of the serotonergic system (SS) in the brain. We also show that SS alterations have been related to MS directly-altered expression of 5-HT transporters in central nervous system (CNS) and indirectly-beneficial effects of 5-HT modulating drugs on the course of the disease and higher prevalence of depression in patients with MS. Finally, we discuss briefly the role of other microbiome-modulated NTs such as γ-aminobutyric acid and dopamine in MS to highlight a new direction for future research aiming to relate microbiome-regulated NTs to demyelinating disorders.

Light indirectly mediates bivalve habitat modification and impacts on seagrass

DEFF Research Database (Denmark)

Castorani, Max C. N.; Glud, Ronnie; Hasler-Sheetal, Harald

2015-01-01

Environmental context may influence the sign, strength, andmechanisms of species interactions but few studies have experimentally tested the potential for abiotic conditions to mediate interactions through multiple cooccurring stress pathways. Abiotic conditionsmay mediate species interactions...... by directly or indirectly influencing the effects of habitat-modifying organisms that are capable of simultaneously ameliorating and exacerbating multiple stressors. Itwas hypothesized that light availability changes seagrassmetabolismand thereby indirectly regulates bivalve habitat modification...

The Relationship Between Resilience and Internet Addiction: A Multiple Mediation Model Through Peer Relationship and Depression.

Science.gov (United States)

Zhou, Pingyan; Zhang, Cai; Liu, Jian; Wang, Zhe

2017-10-01

Heavy use of the Internet may lead to profound academic problems in elementary students, such as poor grades, academic probation, and even expulsion from school. It is of great concern that Internet addiction problems in elementary school students have increased sharply in recent years. In this study, 58,756 elementary school students from the Henan province of China completed four questionnaires to explore the mechanisms of Internet addiction. The results showed that resilience was negatively correlated with Internet addiction. There were three mediational paths in the model: (a) the mediational path through peer relationship with an effect size of 50.0 percent, (b) the mediational path through depression with an effect size of 15.6 percent, (c) the mediational path through peer relationship and depression with an effect size of 13.7 percent. The total mediational effect size was 79.27 percent. The effect size through peer relationship was the strongest among the three mediation paths. The current findings suggest that resilience is a predictor of Internet addiction. Improving children's resilience (such as toughness, emotional control, and problem solving) can be an effective way to reduce Internet addiction behavior. The current findings provide useful information for early detection and intervention for Internet addiction.

Fashion, Mediations & Method Assemblages

DEFF Research Database (Denmark)

Sommerlund, Julie; Jespersen, Astrid Pernille

of handling multiple, fluid realities with multiple, fluid methods. Empirically, the paper works with mediation in fashion - that is efforts the active shaping of relations between producer and consumer through communication, marketing and PR. Fashion mediation is by no means simple, but organise complex...

Stressors and Caregivers’ Depression: Multiple Mediators of Self-Efficacy, Social Support, and Problem-solving Skill

OpenAIRE

Tang, Fengyan; Jang, Heejung; Lingler, Jennifer; Tamres, Lisa K.; Erlen, Judith A.

2015-01-01

Caring for an older adult with memory loss is stressful. Caregiver stress could produce negative outcomes such as depression. Previous research is limited in examining multiple intermediate pathways from caregiver stress to depressive symptoms. This study addresses this limitation by examining the role of self-efficacy, social support, and problem-solving in mediating the relationships between caregiver stressors and depressive symptoms. Using a sample of 91 family caregivers, we tested simul...

Charge-signal multiplication mediated by urea wires inside Y-shaped carbon nanotubes

International Nuclear Information System (INIS)

Lv, Mei; Liu, Zengrong; He, Bing; Xiu, Peng; Tu, Yusong

2014-01-01

In previous studies, we reported molecular dynamics (MD) simulations showing that single-file water wires confined inside Y-shaped single-walled carbon nanotubes (Y-SWNTs) held strong and robust capability to convert and multiply charge signals [Y. S. Tu, P. Xiu, R. Z. Wan, J. Hu, R. H. Zhou, and H. P. Fang, Proc. Natl. Acad. Sci. U.S.A. 106, 18120 (2009); Y. Tu, H. Lu, Y. Zhang, T. Huynh, and R. Zhou, J. Chem. Phys. 138, 015104 (2013)]. It is fascinating to see whether the signal multiplication can be realized by other kinds of polar molecules with larger dipole moments (which make the experimental realization easier). In this article, we use MD simulations to study the urea-mediated signal conversion and multiplication with Y-SWNTs. We observe that when a Y-SWNT with an external charge of magnitude 1.0 e (the model of a signal at the single-electron level) is solvated in 1 M urea solutions, urea can induce drying of the Y-SWNT and fill its interiors in single-file, forming Y-shaped urea wires. The external charge can effectively control the dipole orientation of the urea wire inside the main channel (i.e., the signal can be readily converted), and this signal can further be multiplied into 2 (or more) output signals by modulating dipole orientations of urea wires in bifurcated branch channels of the Y-SWNT. This remarkable signal transduction capability arises from the strong dipole-induced ordering of urea wires under extreme confinement. We also discuss the advantage of urea as compared with water in the signal multiplication, as well as the robustness and biological implications of our findings. This study provides the possibility for multiplying signals by using urea molecules (or other polar organic molecules) with Y-shaped nanochannels and might also help understand the mechanism behind signal conduction in both physical and biological systems

Mediators of Physical Activity on Neurocognitive Function: A Review at Multiple Levels of Analysis.

Science.gov (United States)

Stillman, Chelsea M; Cohen, Jamie; Lehman, Morgan E; Erickson, Kirk I

2016-01-01

Physical activity (PA) is known to maintain and improve neurocognitive health. However, there is still a poor understanding of the mechanisms by which PA exerts its effects on the brain and cognition in humans. Many of the most widely discussed mechanisms of PA are molecular and cellular and arise from animal models. While information about basic cellular and molecular mechanisms is an important foundation from which to build our understanding of how PA promotes cognitive health in humans, there are other pathways that could play a role in this relationship. For example, PA-induced changes to cellular and molecular pathways likely initiate changes to macroscopic properties of the brain and/or to behavior that in turn influence cognition. The present review uses a more macroscopic lens to identify potential brain and behavioral/socioemotional mediators of the association between PA and cognitive function. We first summarize what is known regarding cellular and molecular mechanisms, and then devote the remainder of the review to discussing evidence for brain systems and behavioral/socioemotional pathways by which PA influences cognition. It is our hope that discussing mechanisms at multiple levels of analysis will stimulate the field to examine both brain and behavioral mediators. Doing so is important, as it could lead to a more complete characterization of the processes by which PA influences neurocognitive function, as well as a greater variety of targets for modifying neurocognitive function in clinical contexts.

Mediators of Physical Activity on Neurocognitive Function: A Review at Multiple Levels of Analysis

Directory of Open Access Journals (Sweden)

Chelsea M. Stillman

2016-12-01

Full Text Available Physical activity (PA is known to maintain and improve neurocognitive health. However, there is still a poor understanding of the mechanisms by which PA exerts its effects on the brain and cognition in humans. Many of the most widely discussed mechanisms of PA are molecular and cellular and arise from animal models. While information about basic cellular and molecular mechanisms is an important foundation from which to build our understanding of how PA promotes cognitive health in humans, there are other pathways that could play a role in this relationship. For example, PA-induced changes to cellular and molecular pathways likely initiate changes to macroscopic properties of the brain and/or to behavior that in turn influence cognition. The present review uses a more macroscopic lens to identify potential brain and behavioral/socioemotional mediators of the association between PA and cognitive function. We first summarize what is known regarding cellular and molecular mechanisms, and then devote the remainder of the review to discussing evidence for brain systems and behavioral/socioemotional pathways by which PA influences cognition. It is our hope that discussing mechanisms at multiple levels of analysis will stimulate the field to examine both brain and behavioral mediators. Doing so is important, as it could lead to a more complete characterization of the processes by which PA influences neurocognitive function, as well as a greater variety of targets for modifying neurocognitive function in clinical contexts.

The mediating effect of calling on the relationship between medical school students' academic burnout and empathy.

Science.gov (United States)

Chae, Su Jin; Jeong, So Mi; Chung, Yoon-Sok

2017-09-01

This study is aimed at identifying the relationships between medical school students' academic burnout, empathy, and calling, and determining whether their calling has a mediating effect on the relationship between academic burnout and empathy. A mixed method study was conducted. One hundred twenty-seven medical students completed a survey. Scales measuring academic burnout, medical students' empathy, and calling were utilized. For statistical analysis, correlation analysis, descriptive statistics analysis, and hierarchical multiple regression analyses were conducted. For qualitative approach, eight medical students participated in a focus group interview. The study found that empathy has a statistically significant, negative correlation with academic burnout, while having a significant, positive correlation with calling. Sense of calling proved to be an effective mediator of the relationship between academic burnout and empathy. This result demonstrates that calling is a key variable that mediates the relationship between medical students' academic burnout and empathy. As such, this study provides baseline data for an education that could improve medical students' empathy skills.

Biological Activity of Lenalidomide and Its Underlying Therapeutic Effects in Multiple Myeloma

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Roberta Martiniani

2012-01-01

Full Text Available Lenalidomide is a synthetic compound derived by modifying the chemical structure of thalidomide. It belongs to the second generation of immunomodulatory drugs (IMiDs and possesses pleiotropic properties. Even if lenalidomide has been shown to be active in the treatment of several hematologic malignancies, this review article is mostly focalized on its mode of action in multiple myeloma. The present paper is about the direct and indirect antitumor effects of lenalidomide on malignant plasmacells, bone marrow microenvironment, bone resorption and host’s immune response. The molecular mechanisms and targets of lenalidomide remain largely unknown, but recent evidence shows cereblon (CRBN as a possible mediator of its therapeutical effects.

Reception analysis seen from the multiple mediation model: some issues for the debat

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Guilermo Orozco

2008-12-01

Full Text Available This paper is an application of the "Multiple Mediation" Model, as it has been developing by the author during the last 10 years. The model is used as a way to substantiate a reconceptualization of different aspects of the television reception process. As understood by Orozco, it is continually under construction, and emerges from analysis made by different thinkers. Its formulation has been and will continue to be the outcome of much reflexivity between existing theoretical and epistemological assumptions (within the Cultural Studies and Critical Audience Research traditions and empirical, mostly qualitative, data.

Standardized Effect Size Measures for Mediation Analysis in Cluster-Randomized Trials

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Stapleton, Laura M.; Pituch, Keenan A.; Dion, Eric

2015-01-01

This article presents 3 standardized effect size measures to use when sharing results of an analysis of mediation of treatment effects for cluster-randomized trials. The authors discuss 3 examples of mediation analysis (upper-level mediation, cross-level mediation, and cross-level mediation with a contextual effect) with demonstration of the…

Teacher’s Autonomy Support and Engagement in Math: Multiple Mediating Roles of Self-efficacy, Intrinsic Value, and Boredom

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Wang, Jia; Liu, Ru-De; Ding, Yi; Xu, Le; Liu, Ying; Zhen, Rui

2017-01-01

Previous studies have highlighted the impacts of environmental factors (teacher’s autonomy support) and individual factors (self-efficacy, intrinsic value, and boredom) on academic engagement. This study aimed to investigate these variables and examine the relations among them. Three structural equation models tested the multiple mediational roles of self-efficacy, intrinsic value, and boredom in the relation between teacher’s autonomy support and behavioral, emotional, and cognitive engagement, respectively, in math. A total of 637 Chinese middle school students (313 males, 324 females; mean age = 14.82) voluntarily participated in this study. Results revealed that self-efficacy, intrinsic value, and boredom played important and mediating roles between perceived teacher’s autonomy support and student engagement. Specifically, these three individual variables partly mediated the relations between perceived teacher’s autonomy support and behavioral and cognitive engagement, while fully mediating the relation between perceived teacher’s autonomy support and emotional engagement. These findings complement and extend the understanding of factors affecting students’ engagement in math. PMID:28690560

Multiple Mediation of Self-Esteem and Perceived Social Support in the Relationship between Loneliness and Life Satisfaction

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Yildiz, Mehmet Ali

2017-01-01

The purpose of this study is to test serial-multiple mediation role of self-esteem and perceived social support on the relationship between university students' loneliness and life satisfaction. The participants of this study consisted of 398 undergraduate students, with 289 females and 109 males aged between 17 and 41 with a mean age of 21.79 (SD…

Explaining the effects of a 1-year intervention promoting a low fat diet in adolescent girls: a mediation analysis

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Maes Lea

2007-11-01

Full Text Available Abstract Background Although it is important to investigate how interventions work, no formal mediation analyses have been conducted to explain behavioral outcomes in school-based fat intake interventions in adolescents. The aim of the present study was to examine mediation effects of changes in psychosocial determinants of dietary fat intake (attitude, social support, self-efficacy, perceived benefits and barriers on changes in fat intake in adolescent girls. Methods Data from a 1-year prospective intervention study were used. A random sample of 804 adolescent girls was included in the study. Girls in the intervention group (n = 415 were exposed to a multi-component school-based intervention program, combining environmental changes with a computer tailored fat intake intervention and parental support. Fat intake and psychosocial determinants of fat intake were measured with validated self-administered questionnaires. To assess mediating effects, a product-of-coefficient test, appropriate for cluster randomized controlled trials, was used. Results None of the examined psychosocial factors showed a reliable mediating effect on changes in fat intake. The single-mediator model revealed a statistically significant suppression effect of perceived barriers on changes in fat intake (p = 0.011. In the multiple-mediator model, this effect was no longer significant, which was most likely due to changes in perceived barriers being moderately related to changes in self-efficacy (-0.30 and attitude (-0.25. The overall mediated-suppressed effect of the examined psychosocial factors was virtually zero (total mediated effect = 0.001; SE = 7.22; p = 0.992. Conclusion Given the lack of intervention effects on attitudes, social support, self-efficacy and perceived benefits and barriers, it is suggested that future interventions should focus on the identification of effective strategies for changing these theoretical mediators in the desired direction

Interpersonal sensitivity mediates the effects of child abuse and affective temperaments on depressive symptoms in the general adult population

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Otsuka A

2017-10-01

Full Text Available Ayano Otsuka,1 Yoshikazu Takaesu,1 Mitsuhiko Sato,1 Jiro Masuya,1 Masahiko Ichiki,1 Ichiro Kusumi,2 Takeshi Inoue1 1Department of Psychiatry, Tokyo Medical University, Tokyo, 2Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan Background: Recent studies have suggested that multiple factors interact with the onset and prognosis of major depressive disorders. In this study, we investigated how child abuse, affective temperaments, and interpersonal sensitivity are interrelated, and how they affect depressive symptoms in the general adult population. Subjects and methods: A total of 415 volunteers from the general adult population completed the Patient Health Questionnaire-9, the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire version, the Child Abuse and Trauma Scale, and the Interpersonal Sensitivity Measure, which are all self-administered questionnaires. Data were subjected to structural equation modeling (Mplus, and single and multiple regression analyses. Results: The effect of child abuse on depressive symptoms was mediated by interpersonal sensitivity and 4 affective temperaments, including depressive, cyclothymic, anxious, and irritable temperaments. In addition, the effect of these temperaments on depressive symptoms was mediated by interpersonal sensitivity, indicating the indirect enhancement of depressive symptoms. In contrast to these 4 temperaments, the hyperthymic temperament did not mediate the effect of child abuse on depressive symptoms; its effect was not mediated by interpersonal sensitivity. However, a greater hyperthymic temperament predicted decreased depressive symptoms and interpersonal sensitivity, independent of any mediation effect. Limitations: Because this is a cross-sectional study, long-term prospective studies are necessary to confirm its findings. Therefore, recall bias should be considered when interpreting the results. As the subjects were

Social Adversity and Antisocial Behavior: Mediating Effects of Autonomic Nervous System Activity.

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Fagan, Shawn E; Zhang, Wei; Gao, Yu

2017-11-01

The display of antisocial behaviors in children and adolescents has been of interest to criminologists and developmental psychologists for years. Exposure to social adversity is a well-documented predictor of antisocial behavior. Additionally, measures of autonomic nervous system (ANS) activity, including heart rate variability (HRV), pre-ejection period (PEP), and heart rate, have been associated with antisocial behaviors including rule-breaking and aggression. Social neuroscience research has begun to investigate how neurobiological underpinnings affect the relationship between social adversity and antisocial/psychopathic behavior in children and adolescents. This study investigated the potential mediating effects of ANS activity on the relationship between social adversity and antisocial behavior in a group of 7- to 10-year-old children from the community (N = 339; 48.2% male). Moderated multiple mediation analyses revealed that low resting heart rate, but not PEP or HRV, mediated the relationship between social adversity and antisocial behavior in males only. Social adversity but not ANS measures were associated with antisocial behavior in females. Findings have implications for understanding the neural influences that underlie antisocial behavior, illustrate the importance of the social environment regarding the expression of these behaviors, and highlight essential gender differences.

Variation in copper effects on kairomone-mediated responses in Daphnia pulicaria.

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DeMille, C M; Arnott, S E; Pyle, G G

2016-04-01

Chemical signals play an integral role in many predator-prey relationships but their effectiveness can be altered by environmental conditions. Prey species can detect predator kairomones, which induce anti-predator defenses. An example of this predator-prey relationship exists between Daphnia spp. and Chaoborus spp.; however, when living in water contaminated with low concentrations of copper (Cu) Daphnia can fail to respond to Chaoborus kairomone and, in turn, become more susceptible to predation. This has implications for Daphnia living in regions with Cu contamination, such as areas where mining activity has resulted in increased levels of metals in the surrounding lakes. We examined kairomone-mediated responses of multiple Daphnia pulicaria clones obtained from 8 lakes in Ontario, Canada, in the absence and presence of environmentally-relevant Cu concentrations. Life history traits and morphological anti-predator defenses were assessed using neonates collected from mothers that were exposed to kairomone and Cu treatments. We found that kairomone-mediated responses and Cu-tolerance varied among D. pulicaria clones. Clones exposed to kairomone, in the absence of Cu additions, had diverse responses, including larger neonates, delayed reproduction, or altered brood size relative to no-kairomone controls. These kairomone-induced responses act as antipredator defense strategies against Chaoborus by preventing predation or stabilizing population growth. When exposed to Cu, two clones were able to respond to kairomone, while four clones no longer induced a response to kairomone. This variation in non-lethal effects of Cu on aquatic organisms suggests that toxicity tests should incorporate multiple genotypes and include predator-prey interactions. Copyright © 2016 Elsevier Inc. All rights reserved.

How do text-messaging smoking cessation interventions confer benefit? A multiple mediation analysis of Text2Quit.

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Hoeppner, Bettina B; Hoeppner, Susanne S; Abroms, Lorien C

2017-04-01

To determine the degree to which the observed benefit of Text2Quit was accounted for by psychosocial mechanisms derived from its quit smoking messaging versus from the use of extra-programmatic smoking cessation treatments and services. Prospective, multiple mediation model of a randomized controlled trial (RCT). United States nation-wide. A total of 409 adult daily smokers participated. Participants were, on average, 35 years of age, predominantly female (68%), white (79%), lacked a college degree (70%), had medium nicotine dependence (average Fagerström Nicotine Dependence Score score of 5.2) and more than half (62%) had made a previous quit attempt. Adult daily smokers browsing the web for smoking cessation support (n = 409; recruited 19 May2011-10 July 2012) were randomized to receive smoking cessation support via Text2Quit versus a smoking cessation material. Mediators (i.e. changes in psychosocial constructs of health behavior change, use of extra-programmatic treatment) were assessed at 1 month using single-item measures and outcome (i.e. self-reported 7-day point prevalence abstinence) at 6-month follow-up. Mediators accounted for 35% of the effect of Text2Quit on smoking cessation. Only psychosocial mechanisms had complete mediational paths, with increases in self-efficacy [b = 0.10 (0.06-0.15)], quitting know-how [b = 0.07 (0.03-0.11)] and the sense that someone cared [b = 0.06 (0.01-0.11)], partially explaining the conferred benefit of Text2Quit. Use of outside resources, including treatments promoted explicitly by Text2Quit, i.e. medication [b = 0.001 (-0.01 to 0.01), quitline [b = -0.002 (-0.01 to 0.04)], treatments and resources not promoted by Text2Quit, i.e. online forums [b = 0.01 (-0.01 to 0.04)] and self-help materials [b = -0.01 (-0.04 to 0.02)], did not have complete mediational paths. An interaction effect existed for medication use that suggested that for participants not using medication, Text2Quit conferred substantial

Statistical grand rounds: understanding the mechanism: mediation analysis in randomized and nonrandomized studies.

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Mascha, Edward J; Dalton, Jarrod E; Kurz, Andrea; Saager, Leif

2013-10-01

In comparative clinical studies, a common goal is to assess whether an exposure, or intervention, affects the outcome of interest. However, just as important is to understand the mechanism(s) for how the intervention affects outcome. For example, if preoperative anemia was shown to increase the risk of postoperative complications by 15%, it would be important to quantify how much of that effect was due to patients receiving intraoperative transfusions. Mediation analysis attempts to quantify how much, if any, of the effect of an intervention on outcome goes though prespecified mediator, or "mechanism" variable(s), that is, variables sitting on the causal pathway between exposure and outcome. Effects of an exposure on outcome can thus be divided into direct and indirect, or mediated, effects. Mediation is claimed when 2 conditions are true: the exposure affects the mediator and the mediator (adjusting for the exposure) affects the outcome. Understanding how an intervention affects outcome can validate or invalidate one's original hypothesis and also facilitate further research to modify the responsible factors, and thus improve patient outcome. We discuss the proper design and analysis of studies investigating mediation, including the importance of distinguishing mediator variables from confounding variables, the challenge of identifying potential mediators when the exposure is chronic versus acute, and the requirements for claiming mediation. Simple designs are considered, as well as those containing multiple mediators, multiple outcomes, and mixed data types. Methods are illustrated with data collected by the National Surgical Quality Improvement Project (NSQIP) and utilized in a companion paper which assessed the effects of preoperative anemic status on postoperative outcomes.

Knowledge acquisition in ecological poduct design: the effects of computer-mediated communication and elicitation method

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Sauer, J.; Schramme, S.; Rüttinger, B.

2000-01-01

This article presents a study that examines multiple effects of using different means of computer-mediated communication and knowledge elicitation methods during a product design process. The experimental task involved a typical scenario in product design, in which a knowledge engineer consults two experts to generate knowledge about a design issue. Employing a 3x2 between-subjects design, three conference types (face-to-face, computer, multivedia) and two knowledge elicitation methods (struc...

[Influence of Nurse Managers' Authentic Leadership on Nurses' Organizational Commitment and Job Satisfaction: Focused on the Mediating Effects of Empowerment].

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Choi, Han Gyo; Ahn, Sung Hee

2016-02-01

The aim of this study was to examine the mediating effect of empowerment in the relationship of nurse managers' authentic leadership, with nurses' organizational commitment and job satisfaction. The participants in this study were 273 registered nurses working in five University hospitals located in Seoul and Gyeonggi Province. The measurements included the Authentic Leadership Questionnaire, Condition of Work Effectiveness Questionnaire-II, Organizational Commitment Questionnaire and Korea-Minnesota Satisfaction Questionnaire. Data were analyzed using t-test, ANOVA, Scheffé test, Pearson correlation coefficients, simple and multiple regression techniques with the SPSS 18.0 program. Mediation analysis was performed according to the Baron and Kenny method and Sobel test. There were significant correlations among authentic leadership, empowerment, organizational commitment and job satisfaction. Empowerment showed perfect mediating effects in the relationship between authentic leadership and organizational commitment. It had partial mediating effects in the relationship between authentic leadership and job satisfaction. In this study, nurse managers' authentic leadership had significant influences on nurses organizational commitment and job satisfaction via empowerment. Therefore, to enhance nurses' organizational commitment and job satisfaction, it is necessary to build effective strategies to enhance nurse manager's authentic leadership and to develop empowering education programs for nurses.

Organ-Protective Effects of Red Wine Extract, Resveratrol, in Oxidative Stress-Mediated Reperfusion Injury

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Fu-Chao Liu

2015-01-01

Full Text Available Resveratrol, a polyphenol extracted from red wine, possesses potential antioxidative and anti-inflammatory effects, including the reduction of free radicals and proinflammatory mediators overproduction, the alteration of the expression of adhesion molecules, and the inhibition of neutrophil function. A growing body of evidence indicates that resveratrol plays an important role in reducing organ damage following ischemia- and hemorrhage-induced reperfusion injury. Such protective phenomenon is reported to be implicated in decreasing the formation and reaction of reactive oxygen species and pro-nflammatory cytokines, as well as the mediation of a variety of intracellular signaling pathways, including the nitric oxide synthase, nicotinamide adenine dinucleotide phosphate oxidase, deacetylase sirtuin 1, mitogen-activated protein kinase, peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, hemeoxygenase-1, and estrogen receptor-related pathways. Reperfusion injury is a complex pathophysiological process that involves multiple factors and pathways. The resveratrol is an effective reactive oxygen species scavenger that exhibits an antioxidative property. In this review, the organ-protective effects of resveratrol in oxidative stress-related reperfusion injury will be discussed.

Understanding large multiprotein complexes: applying a multiple allosteric networks model to explain the function of the Mediator transcription complex.

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Lewis, Brian A

2010-01-15

The regulation of transcription and of many other cellular processes involves large multi-subunit protein complexes. In the context of transcription, it is known that these complexes serve as regulatory platforms that connect activator DNA-binding proteins to a target promoter. However, there is still a lack of understanding regarding the function of these complexes. Why do multi-subunit complexes exist? What is the molecular basis of the function of their constituent subunits, and how are these subunits organized within a complex? What is the reason for physical connections between certain subunits and not others? In this article, I address these issues through a model of network allostery and its application to the eukaryotic RNA polymerase II Mediator transcription complex. The multiple allosteric networks model (MANM) suggests that protein complexes such as Mediator exist not only as physical but also as functional networks of interconnected proteins through which information is transferred from subunit to subunit by the propagation of an allosteric state known as conformational spread. Additionally, there are multiple distinct sub-networks within the Mediator complex that can be defined by their connections to different subunits; these sub-networks have discrete functions that are activated when specific subunits interact with other activator proteins.

Effect Size Measures for Mediation Models: Quantitative Strategies for Communicating Indirect Effects

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Preacher, Kristopher J.; Kelley, Ken

2011-01-01

The statistical analysis of mediation effects has become an indispensable tool for helping scientists investigate processes thought to be causal. Yet, in spite of many recent advances in the estimation and testing of mediation effects, little attention has been given to methods for communicating effect size and the practical importance of those…

The mediating effect of calling on the relationship between medical school students’ academic burnout and empathy

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Su Jin Chae

2017-09-01

Full Text Available Purpose This study is aimed at identifying the relationships between medical school students’ academic burnout, empathy, and calling, and determining whether their calling has a mediating effect on the relationship between academic burnout and empathy. Methods A mixed method study was conducted. One hundred twenty-seven medical students completed a survey. Scales measuring academic burnout, medical students’ empathy, and calling were utilized. For statistical analysis, correlation analysis, descriptive statistics analysis, and hierarchical multiple regression analyses were conducted. For qualitative approach, eight medical students participated in a focus group interview. Results The study found that empathy has a statistically significant, negative correlation with academic burnout, while having a significant, positive correlation with calling. Sense of calling proved to be an effective mediator of the relationship between academic burnout and empathy. Conclusion This result demonstrates that calling is a key variable that mediates the relationship between medical students’ academic burnout and empathy. As such, this study provides baseline data for an education that could improve medical students’ empathy skills.

Childhood trauma and eating psychopathology: a mediating role for dissociation and emotion dysregulation?

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Moulton, Stuart J; Newman, Emily; Power, Kevin; Swanson, Vivien; Day, Kenny

2015-01-01

The present study examined the relationship between different forms of childhood trauma and eating psychopathology using a multiple mediation model that included emotion dysregulation and dissociation as hypothesised mediators. 142 female undergraduate psychology students studying at two British Universities participated in this cross-sectional study. Participants completed measures of childhood trauma (emotional abuse, physical abuse, sexual abuse, emotional neglect and physical neglect), eating psychopathology, dissociation and emotion dysregulation. Multiple mediation analysis was conducted to investigate the study's proposed model. Results revealed that the multiple mediation model significantly predicted eating psychopathology. Additionally, both emotion dysregulation and dissociation were found to be significant mediators between childhood trauma and eating psychopathology. A specific indirect effect was observed between childhood emotional abuse and eating psychopathology through emotion dysregulation. Findings support previous research linking childhood trauma to eating psychopathology. They indicate that multiple forms of childhood trauma should be assessed for individuals with eating disorders. The possible maintaining role of emotion regulation processes should also be considered in the treatment of eating disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

R2 effect-size measures for mediation analysis.

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Fairchild, Amanda J; Mackinnon, David P; Taborga, Marcia P; Taylor, Aaron B

2009-05-01

R(2) effect-size measures are presented to assess variance accounted for in mediation models. The measures offer a means to evaluate both component paths and the overall mediated effect in mediation models. Statistical simulation results indicate acceptable bias across varying parameter and sample-size combinations. The measures are applied to a real-world example using data from a team-based health promotion program to improve the nutrition and exercise habits of firefighters. SAS and SPSS computer code are also provided for researchers to compute the measures in their own data.

R2 effect-size measures for mediation analysis

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Fairchild, Amanda J.; MacKinnon, David P.; Taborga, Marcia P.; Taylor, Aaron B.

2010-01-01

R2 effect-size measures are presented to assess variance accounted for in mediation models. The measures offer a means to evaluate both component paths and the overall mediated effect in mediation models. Statistical simulation results indicate acceptable bias across varying parameter and sample-size combinations. The measures are applied to a real-world example using data from a team-based health promotion program to improve the nutrition and exercise habits of firefighters. SAS and SPSS computer code are also provided for researchers to compute the measures in their own data. PMID:19363189

How Multiple Social Identities Are Related to Creativity.

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Steffens, Niklas K; Gocłowska, Małgorzata A; Cruwys, Tegan; Galinsky, Adam D

2016-02-01

The present research examined whether possessing multiple social identities (i.e., groups relevant to one's sense of self) is associated with creativity. In Study 1, the more identities individuals reported having, the more names they generated for a new commercial product (i.e., greater idea fluency). In Study 2, multiple identities were associated with greater fluency and originality (mediated by cognitive flexibility, but not by persistence). Study 3 validated these findings using a highly powered sample. We again found that multiple identities increase fluency and originality, and that flexibility (but not persistence) mediated the effect on originality. Study 3 also ruled out several alternative explanations (self-affirmation, novelty seeking, and generalized persistence). Across all studies, the findings were robust to controlling for personality, and there was no evidence of a curvilinear relationship between multiple identities and creativity. These results suggest that possessing multiple social identities is associated with enhanced creativity via cognitive flexibility. © 2015 by the Society for Personality and Social Psychology, Inc.

Early alveolar and systemic mediator release in patients at different risks for ARDS after multiple trauma.

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Raymondos, Konstantinos; Martin, Michael U; Schmudlach, Tanja; Baus, Stefan; Weilbach, Christian; Welte, Tobias; Krettek, Christian; Frink, Michael; Hildebrand, Frank

2012-02-01

Alveolar IL-8 has been reported to early identify patients at-risk to develop ARDS. However, it remains unknown how alveolar IL-8 is related to pulmonary and systemic inflammation in patients predisposed for ARDS. We studied 24 patients 2-6h after multiple trauma. Patients with IL-8 >200 pg/ml in bronchoalveolar lavage (BAL) were assigned to the group at high risk for ARDS (H, n = 8) and patients with BAL IL-8 mediators. The enhanced alveolar and systemic inflammation associated with alveolar IL-8 release should be considered to identify high-risk patients for pulmonary complications after multiple trauma to adjust surgical and other treatment strategies to the individual risk profile. Copyright © 2011 Elsevier Ltd. All rights reserved.

The Effect of Education Level on Psychological Empowerment and Burnout-The Mediating Role of Workplace Learning Behaviors

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Sarit Rashkovits; Yael Livne

2013-01-01

The study investigates the relationship between education level, workplace learning behaviors, psychological empowerment and burnout in a sample of 191 teachers. We hypothesized that education level will positively affect psychological state of increased empowerment and decreased burnout, and we purposed that these effects will be mediated by workplace learning behaviors. We used multiple regression analyses to test the model that included also the 6 following control var...

Pathways from fear of falling to quality of life: the mediating effect of the self-concept of health and physical independence.

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Hsu, Yawen; Alfermann, Dorothee; Lu, Frank J H; Lin, Linda L

2013-01-01

Fear of falling leads to many adverse consequences and may compromise the quality of life of older adults. Psychological factors are potential mediators between the fear of falling and quality of life, but have yet to be explored in detail. This study presents results from examining the mediating effect of the self-concept of health and physical independence. Data from Western and Eastern countries were compared. Concerns about falling, the level of participation in physical activities, the self-concept of health and physical independence, and health-related quality of life were measured using samples from Taiwan (n = 193) and Germany (n = 182). Multiple regression models were used to test the mediating effects. The relationship between fear of falling and quality of life was partially mediated through participation in physical activities and the self-concept of health and physical independence in both the Taiwanese and German samples. In particular, the self-concept of health and physical independence of the Taiwanese sample resulted in the strongest mediating effect. Potential mediating mechanisms through both participation in physical activities and the self-concept of health and physical independence provide useful information for understanding related theories and for explicating interventions. Cultural factors should also be accounted for when conducting research and programs related to the fear of falling.

[Mediating effects on depression regarding the relationship between negative life events and suicide ideation among college students].

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Wu, Jiao; Wu, Yun-tao; Feng, Shu-xiu; Meng, Heng; Chen, Hui

2012-11-01

To understand the relationship between negative life events and suicide ideation, and how it was influenced by the mediating effect of depression. 1145 college students from one university were selected using cluster sampling. Both Symptom Check List (SCL-90) and Questionnaire were administered to measure depression and suicide ideation in the past week and on the prevalence of negative life events and related information. Recent negative life events would include physical illness, academic problem, financial problem and interpersonal conflict etc. Multiple logistic regressions were used to identify the mediating effect of depression. Physical illness (OR = 2.5, P = 0.028), interpersonal conflict (OR = 7.2, P = 0.002) and financial problem (OR = 1.6, P = 0.026) were significantly associated with suicide ideation, but academically-related problems did not seem to be significantly associated with suicide ideation (OR = 1.8, P = 0.090). After adjusted for depression, both physical illness and interpersonal conflicts were not but financial problem remained significantly associated with suicide ideation (OR = 1.7, P = 0.014). Our data showed that depression fully mediated the relationship between physical illness, interpersonal conflict and suicide ideation, but did not mediate the relationship between financial problem and suicide ideation. Depression played different mediating roles between different negative life events and suicide ideation. The findings from this study might be able to provide some clues for the prevention interventions on college students.

Trust in Supervisor and Job Engagement: Mediating Effects of Psychological Safety and Felt Obligation.

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Basit, Ameer A

2017-11-17

In the social context of job engagement, the role of trust in supervisor in predicting engagement of employees has received attention in research. Very limited research, however, has investigated the mechanisms mediating this dynamic relationship. To address this important gap in knowledge, the aim of this study was to examine psychological safety and felt obligation as two psychological mechanisms mediating the effect of trust in supervisor on job engagement. Drawing from job engagement and social exchange theories, the mediating roles of psychological safety and felt obligation in the trust-engagement relationship were empirically investigated in the Malaysian context. Using self-report questionnaires, data were collected from 337 nurses employed in a public hospital located near Kuala Lumpur, Malaysia. Results fully supported the proposed serial multiple mediator model. Trust in supervisor was indirectly related to job engagement via psychological safety followed by felt obligation. This study provides empirical evidence that trust in supervisor makes employees feel psychologically safe to employ and express their selves in their job roles. This satisfaction of the psychological safety need is interpreted by employees as an important socioemotional benefit that, in turn, makes them feel obligated to pay back to their organization through their enhanced level of job engagement. Implications for theory and practice were discussed.

The relationship between office type and job satisfaction: Testing a multiple mediation model through ease of interaction and well-being.

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Otterbring, Tobias; Pareigis, Jörg; Wästlund, Erik; Makrygiannis, Alexander; Lindström, Anton

2018-05-01

Objectives This cross-sectional study investigated the associations between office type (cellular, shared-room, small open-plan, and medium-sized open-plan) and employees' ease of interaction with coworkers, subjective well-being, and job satisfaction. Methods A brief survey including measures of office type, ease of interaction with coworkers, subjective well-being, and job satisfaction was sent electronically to 1500 Swedish real-estate agents, 271 of whom returned usable surveys. The data were analyzed using a regression-based serial multiple mediation model (PROCESS Model 6), which tested whether the relationship between office type and job satisfaction would be mediated by ease of interaction and, in turn, subjective well-being. Results A negative relationship was found between the number of coworkers sharing an office and employees' job satisfaction. This association was serially mediated by ease of interaction with coworkers and subjective well-being, with employees working in small and medium-sized open-plan offices reporting lower levels of both these aspects than employees who work in either cellular or shared-room offices. Conclusions Open-plan offices may have short-term financial benefits, but these benefits may be lower than the costs associated with decreased job satisfaction and well-being. Therefore, decision-makers should consider the impact of office type on employees rather than focusing solely on cost-effective office layout, flexibility, and productivity.

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

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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.

Immunomodulatory Effects Mediated by Dopamine

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Alvarez-Herrera, Samantha; Pérez-Sánchez, Gilberto; Becerril-Villanueva, Enrique; Cruz-Fuentes, Carlos; Flores-Gutierrez, Enrique Octavio; Quintero-Fabián, Saray

2016-01-01

Dopamine (DA), a neurotransmitter in the central nervous system (CNS), has modulatory functions at the systemic level. The peripheral and central nervous systems have independent dopaminergic system (DAS) that share mechanisms and molecular machinery. In the past century, experimental evidence has accumulated on the proteins knowledge that is involved in the synthesis, reuptake, and transportation of DA in leukocytes and the differential expression of the D1-like (D1R and D5R) and D2-like receptors (D2R, D3R, and D4R). The expression of these components depends on the state of cellular activation and the concentration and time of exposure to DA. Receptors that are expressed in leukocytes are linked to signaling pathways that are mediated by changes in cAMP concentration, which in turn triggers changes in phenotype and cellular function. According to the leukocyte lineage, the effects of DA are associated with such processes as respiratory burst, cytokine and antibody secretion, chemotaxis, apoptosis, and cytotoxicity. In clinical conditions such as schizophrenia, Parkinson disease, Tourette syndrome, and multiple sclerosis (MS), there are evident alterations during immune responses in leukocytes, in which changes in DA receptor density have been observed. Several groups have proposed that these findings are useful in establishing clinical status and clinical markers. PMID:27795960

Immunomodulatory Effects Mediated by Dopamine

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Rodrigo Arreola

2016-01-01

Full Text Available Dopamine (DA, a neurotransmitter in the central nervous system (CNS, has modulatory functions at the systemic level. The peripheral and central nervous systems have independent dopaminergic system (DAS that share mechanisms and molecular machinery. In the past century, experimental evidence has accumulated on the proteins knowledge that is involved in the synthesis, reuptake, and transportation of DA in leukocytes and the differential expression of the D1-like (D1R and D5R and D2-like receptors (D2R, D3R, and D4R. The expression of these components depends on the state of cellular activation and the concentration and time of exposure to DA. Receptors that are expressed in leukocytes are linked to signaling pathways that are mediated by changes in cAMP concentration, which in turn triggers changes in phenotype and cellular function. According to the leukocyte lineage, the effects of DA are associated with such processes as respiratory burst, cytokine and antibody secretion, chemotaxis, apoptosis, and cytotoxicity. In clinical conditions such as schizophrenia, Parkinson disease, Tourette syndrome, and multiple sclerosis (MS, there are evident alterations during immune responses in leukocytes, in which changes in DA receptor density have been observed. Several groups have proposed that these findings are useful in establishing clinical status and clinical markers.

Applying causal mediation analysis to personality disorder research.

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Walters, Glenn D

2018-01-01

This article is designed to address fundamental issues in the application of causal mediation analysis to research on personality disorders. Causal mediation analysis is used to identify mechanisms of effect by testing variables as putative links between the independent and dependent variables. As such, it would appear to have relevance to personality disorder research. It is argued that proper implementation of causal mediation analysis requires that investigators take several factors into account. These factors are discussed under 5 headings: variable selection, model specification, significance evaluation, effect size estimation, and sensitivity testing. First, care must be taken when selecting the independent, dependent, mediator, and control variables for a mediation analysis. Some variables make better mediators than others and all variables should be based on reasonably reliable indicators. Second, the mediation model needs to be properly specified. This requires that the data for the analysis be prospectively or historically ordered and possess proper causal direction. Third, it is imperative that the significance of the identified pathways be established, preferably with a nonparametric bootstrap resampling approach. Fourth, effect size estimates should be computed or competing pathways compared. Finally, investigators employing the mediation method are advised to perform a sensitivity analysis. Additional topics covered in this article include parallel and serial multiple mediation designs, moderation, and the relationship between mediation and moderation. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Effects of biotic interactions and dispersal on the presence-absence of multiple species

International Nuclear Information System (INIS)

Mohd, Mohd Hafiz; Murray, Rua; Plank, Michael J.; Godsoe, William

2017-01-01

One of the important issues in ecology is to predict which species will be present (or absent) across a geographical region. Dispersal is thought to have an important influence on the range limits of species, and understanding this problem in a multi-species community with priority effects (i.e. initial abundances determine species presence-absence) is a challenging task because dispersal also interacts with biotic and abiotic factors. Here, we propose a simple multi-species model to investigate the joint effects of biotic interactions and dispersal on species presence-absence. Our results show that dispersal can substantially expand species ranges when biotic and abiotic forces are present; consequently, coexistence of multiple species is possible. The model also exhibits ecologically interesting priority effects, mediated by intense biotic interactions. In the absence of dispersal, competitive exclusion of all but one species occurs. We find that dispersal reduces competitive exclusion effects that occur in no-dispersal case and promotes coexistence of multiple species. These results also show that priority effects are still prevalent in multi-species communities in the presence of dispersal process. We also illustrate the existence of threshold values of competitive strength (i.e. transcritical bifurcations), which results in different species presence-absence in multi-species communities with and without dispersal.

Self-efficacy mediates the effects of topiramate and GRIK1 genotype on drinking.

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Kranzler, Henry R; Armeli, Stephen; Wetherill, Reagan; Feinn, Richard; Tennen, Howard; Gelernter, Joel; Covault, Jonathan; Pond, Timothy

2016-03-01

Previous studies indicate that topiramate reduces alcohol use among problem drinkers, with one study showing that the effect was moderated by a polymorphism (rs2832407) in GRIK1, the gene encoding the GluK1 kainate subunit. We examined whether the interactive effect of medication and genotype (1) altered the association between daily self-efficacy and later-day drinking; and (2) had an indirect effect on drinking via self-efficacy. In a 12-week, placebo-controlled trial of topiramate, we used daily interactive voice response technology to measure self-efficacy (i.e. confidence in avoiding heavy drinking later in the day) and drinking behavior in 122 European-American heavy drinkers. Topiramate's effects on both self-efficacy and drinking level were moderated by rs2832407. C-allele homozygotes treated with topiramate showed higher levels of self-efficacy and lower levels of nighttime drinking across the 12-week trial. Further, the interactive effect of topiramate and genotype on mean nighttime drinking levels was mediated by mean levels of self-efficacy. By modeling topiramate's effects on nighttime drinking across multiple levels of analysis, we found that self-efficacy, a key psychologic construct, mediated the effect of topiramate, which was moderated by rs2832407 genotype. Thus, it may be possible to use an individualized assessment (i.e. genotype) to select treatment to optimize the reduction in heavy drinking and thereby provide a personalized treatment approach. © 2014 Society for the Study of Addiction.

Self-Efficacy Mediates the Effects of Topiramate and GRIK1 Genotype on Drinking

Science.gov (United States)

Kranzler, Henry R.; Armeli, Stephen; Wetherill, Reagan; Feinn, Richard; Tennen, Howard; Gelernter, Joel; Covault, Jonathan; Pond, Timothy

2014-01-01

Previous studies indicate that topiramate reduces alcohol use among problem drinkers, with one study showing that the effect was moderated by a polymorphism (rs2832407) in GRIK1, the gene encoding the GluK1 kainate subunit. We examined whether the interactive effect of medication and genotype (a) altered the association between daily self-efficacy and later day drinking and (b) had an indirect effect on drinking via self-efficacy. Methods In a 12-week, placebo-controlled trial of topiramate, we used daily interactive voice response technology to measure self-efficacy (i.e., confidence in avoiding heavy drinking later in the day) and drinking behavior in 122 European-American heavy drinkers. Results Topiramate’s effects on both self-efficacy and drinking level were moderated by rs2832407. C-allele homozygotes treated with topiramate showed higher levels of self-efficacy and lower levels of nighttime drinking across the 12-week trial. Further, the interactive effect of topiramate and genotype on mean nighttime drinking levels was mediated by mean levels of self-efficacy. Conclusion By modeling topiramate’s effects on nighttime drinking across multiple levels of analysis, we found that self-efficacy, a key psychological construct, mediated the effect of topiramate, which was moderated by rs2832407 genotype. Thus, it may be possible to use an individualized assessment (i.e., genotype) to select treatment (i.e., topiramate or psychotherapy aimed at enhancing self-efficacy) to optimize the reduction in heavy drinking to provide a personalized treatment approach. PMID:25496338

Temporal expression profiling identifies pathways mediating effect of causal variant on phenotype.

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Saumya Gupta

2015-06-01

Full Text Available Even with identification of multiple causal genetic variants for common human diseases, understanding the molecular processes mediating the causal variants' effect on the disease remains a challenge. This understanding is crucial for the development of therapeutic strategies to prevent and treat disease. While static profiling of gene expression is primarily used to get insights into the biological bases of diseases, it makes differentiating the causative from the correlative effects difficult, as the dynamics of the underlying biological processes are not monitored. Using yeast as a model, we studied genome-wide gene expression dynamics in the presence of a causal variant as the sole genetic determinant, and performed allele-specific functional validation to delineate the causal effects of the genetic variant on the phenotype. Here, we characterized the precise genetic effects of a functional MKT1 allelic variant in sporulation efficiency variation. A mathematical model describing meiotic landmark events and conditional activation of MKT1 expression during sporulation specified an early meiotic role of this variant. By analyzing the early meiotic genome-wide transcriptional response, we demonstrate an MKT1-dependent role of novel modulators, namely, RTG1/3, regulators of mitochondrial retrograde signaling, and DAL82, regulator of nitrogen starvation, in additively effecting sporulation efficiency. In the presence of functional MKT1 allele, better respiration during early sporulation was observed, which was dependent on the mitochondrial retrograde regulator, RTG3. Furthermore, our approach showed that MKT1 contributes to sporulation independent of Puf3, an RNA-binding protein that steady-state transcription profiling studies have suggested to mediate MKT1-pleiotropic effects during mitotic growth. These results uncover interesting regulatory links between meiosis and mitochondrial retrograde signaling. In this study, we highlight the advantage

Leader-team congruence in power distance values and team effectiveness: the mediating role of procedural justice climate.

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Cole, Michael S; Carter, Min Z; Zhang, Zhen

2013-11-01

We examine the effect of (in)congruence between leaders' and teams' power distance values on team effectiveness. We hypothesize that the (in)congruence between these values would differentially predict team effectiveness, with procedural justice climate serving as a mediator. Using multisource data and polynomial regression, we found that similarities (and differences) between leaders' and their teams' power distance values can have consequential effects on teams' justice climate and, ultimately, their effectiveness (viz., team performance and team organizational citizenship behavior). We conclude that to fully understand the implications of power distance, one should consider the multiple perspectives of both leaders and team members. (c) 2013 APA, all rights reserved.

Multiple group membership and well-being

DEFF Research Database (Denmark)

Sønderlund, Anders L.; Morton, Thomas A.; Ryan, Michelle K.

2017-01-01

multiple group membership and well-being, but only for individuals high in SIC. This effect was mediated by perceived identity expression and access to social support. Study 2 (N = 104) also found that multiple group memberships indirectly contributed to well-being via perceived identity expression......A growing body of research points to the value of multiple group memberships for individual well-being. However, much of this work considers group memberships very broadly and in terms of number alone. We conducted two correlational studies exploring how the relationship between multiple group...... and social support, as well as identity compatibility and perceived social inclusion. But, in this study the relationship between multiple group memberships and well-being outcomes was moderated by the perceived value and visibility of group memberships to others. Specifically, possessing multiple, devalued...

A randomized, multicentre study of directed daylight exposure times of 11/2 vs. 21/2 h in daylight-mediated photodynamic therapy with methyl aminolaevulinate in patients with multiple thin actinic keratoses of the face and scalp

DEFF Research Database (Denmark)

Wiegell, S.R.; Fabricius, S.; Philipsen, P.A.

2011-01-01

, time of day or time of year during which the treatment was performed. Treatment was well tolerated, with a mean ± SD maximal pain score of 1·3 ± 1·5. Conclusions: Daylight-mediated MAL-PDT is an effective, convenient and nearly pain-free treatment for patients with multiple thin AKs. Daylight-mediated......, the inconvenience of clinic attendance and discomfort during therapy are significant drawbacks. Daylight-mediated PDT could potentially reduce these and may serve as an alternative to conventional PDT. Objectives: To compare the efficacy of methyl aminolaevulinate (MAL)-PDT with 11/2 vs. 21/2 h of daylight exposure...

Peer substance use as a mediator between early pubertal timing and adolescent substance use: longitudinal associations and moderating effect of maltreatment.

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Negriff, Sonya; Trickett, Penelope K

2012-11-01

Early pubertal timing has received considerable empirical support as a risk for adolescent substance use. However, few studies have examined the mediators linking these variables. Therefore, the aims of this study were (1) to examine peer substance use as a mediator between pubertal timing and adolescent substance use longitudinally and (2) to test gender and maltreatment experience as moderators of the mediational model. Data were obtained from time 1, 2, and 3 of a longitudinal study of maltreatment and development. At time 1 the sample was comprised of 303 maltreated and 151 comparison children aged 9-13 years (213 females and 241 males). Longitudinal mediation was tested using structural equation modeling and moderating effects were tested using multiple group analysis. Peer substance use mediated the relationship between early pubertal timing and later adolescent substance use for the total sample. Moderation analyses indicated this significant indirect effect did not differ for males and females. However, it did differ for maltreated versus comparison adolescents with the mediational effect only remaining significant for the comparison group. This is one of the first studies to examine peer substance use as a mediator of pubertal timing and adolescent substance use using a longitudinal design. Early maturing males are at equal risk to early maturing females for interacting with peers that may draw them into substance use. Additionally, the findings indicate that while peers are mediators for comparison adolescents a different mechanism may link early puberty to substance use for maltreated adolescents. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Direct and Indirect Effects of Five Factor Personality and Gender on Depressive Symptoms Mediated by Perceived Stress

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Kim, Song E.; Cho, Juhee; Kwon, Min-Jung; Chang, Yoosoo; Ryu, Seungho; Shin, Hocheol

2016-01-01

This study was designed to investigate associations among five factor personality traits, perceived stress, and depressive symptoms and to examine the roles of personality and perceived stress in the relationship between gender and depressive symptoms. The participants (N = 3,950) were part of a cohort study for health screening and examination at the Kangbuk Samsung Hospital. Personality was measured with the Revised NEO Personality Inventory (NEO-PI-R). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Perceived stress level was evaluated with a self-reported stress questionnaire developed for the Korea National Health and Nutrition Examination Survey. A higher degree of neuroticism and lower degrees of extraversion, agreeableness, and conscientiousness were significantly associated with greater perceived stress and depressive symptoms. Neuroticism and extraversion had significant direct and indirect effects (via stress as a mediator) on depressive symptoms in both genders. Agreeableness and conscientiousness had indirect effects on depression symptoms in both genders. Multiple mediation models were used to examine the mediational roles of each personality factor and perceived stress in the link between gender and depressive symptoms. Four of the personality factors (except openness) were significant mediators, along with stress, on the relationship between gender and depressive symptoms. Our findings suggest that the links between personality factors and depressive symptoms are mediated by perceived stress. As such, personality is an important factor to consider when examining the link between gender and depression. PMID:27120051

Direct and Indirect Effects of Five Factor Personality and Gender on Depressive Symptoms Mediated by Perceived Stress.

Science.gov (United States)

Kim, Song E; Kim, Han-Na; Cho, Juhee; Kwon, Min-Jung; Chang, Yoosoo; Ryu, Seungho; Shin, Hocheol; Kim, Hyung-Lae

2016-01-01

This study was designed to investigate associations among five factor personality traits, perceived stress, and depressive symptoms and to examine the roles of personality and perceived stress in the relationship between gender and depressive symptoms. The participants (N = 3,950) were part of a cohort study for health screening and examination at the Kangbuk Samsung Hospital. Personality was measured with the Revised NEO Personality Inventory (NEO-PI-R). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Perceived stress level was evaluated with a self-reported stress questionnaire developed for the Korea National Health and Nutrition Examination Survey. A higher degree of neuroticism and lower degrees of extraversion, agreeableness, and conscientiousness were significantly associated with greater perceived stress and depressive symptoms. Neuroticism and extraversion had significant direct and indirect effects (via stress as a mediator) on depressive symptoms in both genders. Agreeableness and conscientiousness had indirect effects on depression symptoms in both genders. Multiple mediation models were used to examine the mediational roles of each personality factor and perceived stress in the link between gender and depressive symptoms. Four of the personality factors (except openness) were significant mediators, along with stress, on the relationship between gender and depressive symptoms. Our findings suggest that the links between personality factors and depressive symptoms are mediated by perceived stress. As such, personality is an important factor to consider when examining the link between gender and depression.

Do Multiple Forms of Social Capital Mediate the Relationship Between Parental Violence and Children's Maladaptive Behaviors?

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Kim, Sangwon; Lee, Yanghee

2018-03-01

Many things can harm children's well-being. Among them, exposure to parental violence makes children vulnerable and often leads to aggression and/or depression. However, not all children who have suffered parental violence show aggressive behavior or depressive mood. Social capital, defined as resources accruing from interpersonal relationships, was proposed to significantly mediate the relationships among adverse experiences and their negative impacts. In previous studies, social capital accrued from parents played a positive role for children in violent situations, but children exposed to parental violence need alternative sources of social capital. This study targeted fourth-grade Korean children and aimed to identify and test the role of various forms of social capital to help children overcome negative consequences from parental violence. Siblings, friends, teachers, neighbors, and online acquaintances were sources of social capital, and the results showed that social capital from siblings, teachers, neighbors, or online acquaintances mediated in the relationships between parental violence and aggressive behavior. In addition, social capital from siblings and online acquaintances mediated in the relationships between parental violence and depressive mood. The findings have implications in terms of intervention. It is suggested that multiple forms of social capital from children's immediate environments are helpful in their adaptation from exposure to parental violence, and thus, relationship-based interventions are recommended.

Mediators of the effects on fatigue of pragmatic rehabilitation for chronic fatigue syndrome.

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Wearden, Alison J; Emsley, Richard

2013-10-01

To examine potential mediators of the effect of pragmatic rehabilitation on improvements in fatigue following a randomized controlled trial for patients with chronic fatigue syndrome (CFS/ME) in primary care (IRCTN 74156610). Patients fulfilled the Oxford criteria for CFS. Ninety-five patients were randomized to pragmatic rehabilitation and 100 to general practitioner (GP) treatment as usual. The outcome was the Chalder fatigue scale score (0123 scoring) at end of treatment (20 weeks) and 1-year follow up (70 weeks). First, the effect of treatment on potential mediators was assessed. Then fatigue was regressed on significant mediators, treatment allocation, and baseline measures of fatigue and significant mediators. Reduction in limiting activities at 20 weeks mediated the positive effect of pragmatic rehabilitation on fatigue at 70 weeks (mediated effect size = -2.64, SE = 0.81, p = .001, proportion of effect mediated = 82.0%). Reduction in catastrophizing at 20 weeks mediated the positive effect of pragmatic rehabilitation on fatigue at 70 weeks (mediated effect size = -1.39, SE = 0.61, p = .023, proportion of effect mediated = 43.2%). Reductions in 70-week measures of fear avoidance, embarrassment avoidance, limiting activities, and all-or-nothing behavior all mediated improvement in fatigue at 70 weeks, although the causal direction of these cross-sectional effects cannot be determined. There were no between-group differences on measures of exercise capacity (a timed step test). Improvements in fatigue following pragmatic rehabilitation are related to changes in behavioral responses to and beliefs about fatigue.

Membrane Transporters as Mediators of Cisplatin Effects and Side Effects

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Giuliano Ciarimboli

2012-01-01

Full Text Available Transporters are important mediators of specific cellular uptake and thus, not only for effects, but also for side effects, metabolism, and excretion of many drugs such as cisplatin. Cisplatin is a potent cytostatic drug, whose use is limited by its severe acute and chronic nephro-, oto-, and peripheral neurotoxicity. For this reason, other platinum derivatives, such as carboplatin and oxaliplatin, with less toxicity but still with antitumoral action have been developed. Several transporters, which are expressed on the cell membranes, have been associated with cisplatin transport across the plasma membrane and across the cell: the copper transporter 1 (Ctr1, the copper transporter 2 (Ctr2, the P-type copper-transporting ATPases ATP7A and ATP7B, the organic cation transporter 2 (OCT2, and the multidrug extrusion transporter 1 (MATE1. Some of these transporters are also able to accept other platinum derivatives as substrate. Since membrane transporters display a specific tissue distribution, they can be important molecules that mediate the entry of platinum derivatives in target and also nontarget cells possibly mediating specific effects and side effects of the chemotherapeutic drug. This paper summarizes the literature on toxicities of cisplatin compared to that of carboplatin and oxaliplatin and the interaction of these platinum derivatives with membrane transporters.

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

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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.

Negative affect and smoking motives sequentially mediate the effect of panic attacks on tobacco-relevant processes.

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Farris, Samantha G; Zvolensky, Michael J; Blalock, Janice A; Schmidt, Norman B

2014-05-01

Empirical work has documented a robust and consistent relation between panic attacks and smoking behavior. Theoretical models posit smokers with panic attacks may rely on smoking to help them manage chronically elevated negative affect due to uncomfortable bodily states, which may explain higher levels of nicotine dependence and quit problems. The current study examined the effects of panic attack history on nicotine dependence, perceived barriers for quitting, smoking inflexibility when emotionally distressed, and expired carbon monoxide among 461 treatment-seeking smokers. A multiple mediator path model was evaluated to examine the indirect effects of negative affect and negative affect reduction motives as mediators of the panic attack-smoking relations. Panic attack history was indirectly related to greater levels of nicotine dependence (b = 0.039, CI95% = 0.008, 0.097), perceived barriers to smoking cessation (b = 0.195, CI95% = 0.043, 0.479), smoking inflexibility/avoidance when emotionally distressed (b = 0.188, CI95% = 0.041, 0.445), and higher levels of expired carbon monoxide (b = 0.071, CI95% = 0.010, 0.230) through the sequential effects of negative affect and negative affect smoking motives. The present results provide empirical support for the sequential mediating role of negative affect and smoking motives for negative affect reduction in the relation between panic attacks and a variety of smoking variables in treatment-seeking smokers. These mediating variables are likely important processes to address in smoking cessation treatment, especially in panic-vulnerable smokers.

The Relationship Between Poor Quality of Life and Desire to Hasten Death: A Multiple Mediation Model Examining the Contributions of Depression, Demoralization, Loss of Control, and Low Self-worth.

Science.gov (United States)

Robinson, Sophie; Kissane, David W; Brooker, Joanne; Hempton, Courtney; Burney, Susan

2017-02-01

The risk of suicide is elevated in palliative care patients compared with the general population. Various psychological factors, including depression, demoralization, loss of control, and low self-worth, have been associated with a desire to hasten death. The aim of this study was to investigate whether depression, demoralization, loss of control, and low self-worth mediated the relationship between global quality of life and desire to hasten death. A sample of 162 palliative care patients completed measures of global quality of life, depression, demoralization, perceived control, self-worth, and desire to hasten death. A multiple mediation model with bootstrapping sampling tested the total (combined) indirect effect and individual indirect effects of depression, the two subscales of demoralization (Meaning and Purpose, and Distress and Coping Ability), perceived control, and self-worth. Depressive symptoms, loss of meaning and purpose, loss of control, and low self-worth mediated the direct effect of global quality of life on desire to hasten death. The Distress and Coping Ability component of demoralization was not a significant mediator. Depression, loss of meaning and purpose, loss of control, and low self-worth are strong clinical markers for desire to hasten death. Targeting these symptoms through existentially oriented therapies, such as meaning-centered therapy, may ameliorate suicidal thinking. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

MEDIATOR18 and MEDIATOR20 confer susceptibility to Fusarium oxysporum in Arabidopsis thaliana

OpenAIRE

Fallath, Thorya; Kidd, Brendan N.; Stiller, Jiri; Davoine, Celine; Bj?rklund, Stefan; Manners, John M.; Kazan, Kemal; Schenk, Peer M.

2017-01-01

The conserved protein complex known as Mediator conveys transcriptional signals by acting as an intermediary between transcription factors and RNA polymerase II. As a result, Mediator subunits play multiple roles in regulating developmental as well as abiotic and biotic stress pathways. In this report we identify the head domain subunits MEDIATOR18 and MEDIATOR20 as important susceptibility factors for Fusarium oxysporum infection in Arabidopsis thaliana. Mutants of MED18 and MED20 display do...

Causal mediation analysis for longitudinal data with exogenous exposure.

Science.gov (United States)

Bind, M-A C; Vanderweele, T J; Coull, B A; Schwartz, J D

2016-01-01

Mediation analysis is a valuable approach to examine pathways in epidemiological research. Prospective cohort studies are often conducted to study biological mechanisms and often collect longitudinal measurements on each participant. Mediation formulae for longitudinal data have been developed. Here, we formalize the natural direct and indirect effects using a causal framework with potential outcomes that allows for an interaction between the exposure and the mediator. To allow different types of longitudinal measures of the mediator and outcome, we assume two generalized mixed-effects models for both the mediator and the outcome. The model for the mediator has subject-specific random intercepts and random exposure slopes for each cluster, and the outcome model has random intercepts and random slopes for the exposure, the mediator, and their interaction. We also expand our approach to settings with multiple mediators and derive the mediated effects, jointly through all mediators. Our method requires the absence of time-varying confounding with respect to the exposure and the mediator. This assumption is achieved in settings with exogenous exposure and mediator, especially when exposure and mediator are not affected by variables measured at earlier time points. We apply the methodology to data from the Normative Aging Study and estimate the direct and indirect effects, via DNA methylation, of air pollution, and temperature on intercellular adhesion molecule 1 (ICAM-1) protein levels. Our results suggest that air pollution and temperature have a direct effect on ICAM-1 protein levels (i.e. not through a change in ICAM-1 DNA methylation) and that temperature has an indirect effect via a change in ICAM-1 DNA methylation. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Self-management and quality of life in chronic obstructive pulmonary disease (COPD): The mediating effects of positive affect.

Science.gov (United States)

Benzo, Roberto P; Abascal-Bolado, Beatriz; Dulohery, Megan M

2016-04-01

This study aimed to increase our understanding of general self-management (SM) abilities in COPD by determining if SM can predict disease specific quality of life (QoL), by investigating whether specific SM domains are significant in COPD and by exploring the mediating effect of the positive/negative affect in the association between SM and QoL. Cross-sectional study based on 292 patients with COPD. Measures included demographics, lung function, gait speed, health care utilization, positive/negative affect, SM abilities, breathlessness and disease specific QoL. We performed, correlation, multiple regression models and mediation analysis (positive/negative affect being mediator between SM and QoL association). After controlling for breathlessness, living alone, marital status, hospitalization history, age and lung function, SM related to QoL (pnegative affect ratio completely mediates the relationship of SM with QoL. SM is independently associated with disease specific QoL in COPD after adjustment significant covariates but positive/negative affect ratio completely mediates the relationship of SM with QoL. Measuring positive/negative affect and addressing investment behavior and self-efficacy are important in implementing COPD-SM programs. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

SPSS and SAS procedures for estimating indirect effects in simple mediation models.

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Preacher, Kristopher J; Hayes, Andrew F

2004-11-01

Researchers often conduct mediation analysis in order to indirectly assess the effect of a proposed cause on some outcome through a proposed mediator. The utility of mediation analysis stems from its ability to go beyond the merely descriptive to a more functional understanding of the relationships among variables. A necessary component of mediation is a statistically and practically significant indirect effect. Although mediation hypotheses are frequently explored in psychological research, formal significance tests of indirect effects are rarely conducted. After a brief overview of mediation, we argue the importance of directly testing the significance of indirect effects and provide SPSS and SAS macros that facilitate estimation of the indirect effect with a normal theory approach and a bootstrap approach to obtaining confidence intervals, as well as the traditional approach advocated by Baron and Kenny (1986). We hope that this discussion and the macros will enhance the frequency of formal mediation tests in the psychology literature. Electronic copies of these macros may be downloaded from the Psychonomic Society's Web archive at www.psychonomic.org/archive/.

Comments: Causal Interpretations of Mediation Effects

Science.gov (United States)

Jo, Booil; Stuart, Elizabeth A.

2012-01-01

The authors thank Dr. Lindsay Page for providing a nice illustration of the use of the principal stratification framework to define causal effects, and a Bayesian model for effect estimation. They hope that her well-written article will help expose education researchers to these concepts and methods, and move the field of mediation analysis in…

Gender-Related Differential Effects of Obesity on Health-Related Quality of Life via Obesity-Related Comorbidities: A Mediation Analysis of a French Nationwide Survey.

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Audureau, Etienne; Pouchot, Jacques; Coste, Joël

2016-05-01

Negative effects of obesity on health-related quality of life (HRQoL) have been reported, especially in women, but the relative contribution of cardiometabolic and other obesity-related comorbidities to such effects remains unclear. Our objective was to model the association by sex between body mass index and HRQoL and to precisely quantify the indirect effects mediated by obesity-related comorbidities. Data were drawn from the latest French Decennial Health Survey, a nationwide cross-sectional study conducted in 2003 (21 239 adults aged 25-64 years analyzed). HRQoL was measured by the 36-item short-form health survey questionnaire. A mediation analysis based on the counterfactual framework was performed to quantify the proportion of obesity effects on HRQoL mediated by related comorbidities, including cardiometabolic risk factors (diabetes mellitus, hypertension, dyslipidemia) and diseases (ischemic heart disease, cerebrovascular, and peripheral vascular disease), musculoskeletal disorders, and asthma. After multiple linear regression, inverse associations were found between increasing body mass index category and physically oriented and most mentally oriented 36-item short-form health survey dimensions, with evidence of greater effects in women. Mediation analysis revealed that obesity effects were significantly mediated by several comorbidities, more apparently in men (eg, proportion of obesity class II total effect mediated via cardiometabolic factors: general health 27.0% [men] versus 13.6% [women]; proportion of obesity class II total effect mediated via total count of comorbidities: physical functioning 17.8% [men] versus 7.7% [women] and general health 37.1% [men] versus 20.3% [women]). Women have a greater overall impact of obesity on HRQoL, but with proportionally lower effects mediated by cardiometabolic and other obesity-related conditions, suggesting the possible role of other specific psychosocial processes. © 2016 American Heart Association, Inc.

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

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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. To explore the combined effect of measurement error and omitted confounders in the same model, the effect 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.

Rumination mediates the relationship between overgeneral autobiographical memory and depression in patients with major depressive disorder.

Science.gov (United States)

Liu, Yansong; Yu, Xinnian; Yang, Bixiu; Zhang, Fuquan; Zou, Wenhua; Na, Aiguo; Zhao, Xudong; Yin, Guangzhong

2017-03-21

Overgeneral autobiographical memory has been identified as a risk factor for the onset and maintenance of depression. However, little is known about the underlying mechanisms that might explain overgeneral autobiographical memory phenomenon in depression. The purpose of this study was to test the mediation effects of rumination on the relationship between overgeneral autobiographical memory and depressive symptoms. Specifically, the mediation effects of brooding and reflection subtypes of rumination were examined in patients with major depressive disorder. Eighty-seven patients with major depressive disorder completed the 17-item Hamilton Depression Rating Scale, Ruminative Response Scale, and Autobiographical Memory Test. Bootstrap mediation analysis for simple and multiple mediation models through the PROCESS macro was applied. Simple mediation analysis showed that rumination significantly mediated the relationship between overgeneral autobiographical memory and depression symptoms. Multiple mediation analyses showed that brooding, but not reflection, significantly mediated the relationship between overgeneral autobiographical memory and depression symptoms. Our results indicate that global rumination partly mediates the relationship between overgeneral autobiographical memory and depressive symptoms in patients with major depressive disorder. Furthermore, the present results suggest that the mediating role of rumination in the relationship between overgeneral autobiographical memory and depression is mainly due to the maladaptive brooding subtype of rumination.

Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor.

Science.gov (United States)

Zhao, Yangbing; Moon, Edmund; Carpenito, Carmine; Paulos, Chrystal M; Liu, Xiaojun; Brennan, Andrea L; Chew, Anne; Carroll, Richard G; Scholler, John; Levine, Bruce L; Albelda, Steven M; June, Carl H

2010-11-15

Redirecting T lymphocyte antigen specificity by gene transfer can provide large numbers of tumor-reactive T lymphocytes for adoptive immunotherapy. However, safety concerns associated with viral vector production have limited clinical application of T cells expressing chimeric antigen receptors (CAR). T lymphocytes can be gene modified by RNA electroporation without integration-associated safety concerns. To establish a safe platform for adoptive immunotherapy, we first optimized the vector backbone for RNA in vitro transcription to achieve high-level transgene expression. CAR expression and function of RNA-electroporated T cells could be detected up to a week after electroporation. Multiple injections of RNA CAR-electroporated T cells mediated regression of large vascularized flank mesothelioma tumors in NOD/scid/γc(-/-) mice. Dramatic tumor reduction also occurred when the preexisting intraperitoneal human-derived tumors, which had been growing in vivo for >50 days, were treated by multiple injections of autologous human T cells electroporated with anti-mesothelin CAR mRNA. This is the first report using matched patient tumor and lymphocytes showing that autologous T cells from cancer patients can be engineered to provide an effective therapy for a disseminated tumor in a robust preclinical model. Multiple injections of RNA-engineered T cells are a novel approach for adoptive cell transfer, providing flexible platform for the treatment of cancer that may complement the use of retroviral and lentiviral engineered T cells. This approach may increase the therapeutic index of T cells engineered to express powerful activation domains without the associated safety concerns of integrating viral vectors. Copyright © 2010 AACR.

Identity as a Moderator and Mediator of Communication Effects: Evidence and Implications for Message Design.

Science.gov (United States)

Comello, Maria Leonora G; Farman, Lisa

2016-10-02

Advertisements, movies, and other forms of media content have potential to change behaviors and antecedent psychological states by appealing to identity. However, the mechanisms that are responsible for persuasive effects of such content have not been adequately specified. A recently proposed model of communication effects (the prism model) advances the study of mechanisms and argues that identity can serve as both a moderator and mediator of communication effects on behavior-relevant outcomes. These intervening roles are made possible by the complex nature of identity (including multiple self-concepts and sensitivity to cues) and messages that cue the importance of and activate particular self-concepts. This article builds on development of the model by presenting empirical support based on re-analysis of an experiment in which participants viewed either a more-stigmatizing or less-stigmatizing portrayal of a recovering drug addict. In line with the model's propositions, exposure to the less-stigmatizing condition led to increases in perspective taking which then led to more acceptance (mediation by identity), while level of perspective taking also changed the effect of condition on acceptance (moderation by identity). These results provide support for the model's proposition of simultaneous intervening roles. The authors discuss implications for strategic communication research and practice.

Mediation analysis with time varying exposures and mediators.

Science.gov (United States)

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.

A General Model for Testing Mediation and Moderation Effects

Science.gov (United States)

MacKinnon, David P.

2010-01-01

This paper describes methods for testing mediation and moderation effects in a dataset, both together and separately. Investigations of this kind are especially valuable in prevention research to obtain information on the process by which a program achieves its effects and whether the program is effective for subgroups of individuals. A general model that simultaneously estimates mediation and moderation effects is presented, and the utility of combining the effects into a single model is described. Possible effects of interest in the model are explained, as are statistical methods to assess these effects. The methods are further illustrated in a hypothetical prevention program example. PMID:19003535

Effects of daratumumab on natural killer cells and impact on clinical outcomes in relapsed or refractory multiple myeloma

DEFF Research Database (Denmark)

Casneuf, Tineke; Xu, Xu Steven; Adams, Homer C

2017-01-01

Daratumumab, a human CD38 imunoglobulin G 1κ monoclonal antibody, has demonstrated clinical activity and a manageable safety profile in monotherapy and combination therapy clinical trials in relapsed and/or refractory multiple myeloma. CD38 is expressed at high levels on myeloma cells and......, to a lesser extent, on immune effector cells, including natural killer (NK) cells, which are important for daratumumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Here, the pharmacodynamic effects of daratumumab monotherapy on NK cells, and the effect of NK cell dynamics on daratumumab efficacy...

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

Science.gov (United States)

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

Managing the side effects of multiple sclerosis therapy: pharmacotherapy options for patients.

Science.gov (United States)

Rommer, Paulus S; Zettl, Uwe K

2018-04-01

Multiple sclerosis (MS) is an immune-mediated and neurodegenerative disease with an unpredictable outcome. Immune-modulatory treatment aims at decreasing long-term disability. With the increasing number of treatment options, it is essential to fully digest the possible side effects of the available therapeutics and to monitor patients is essential. Areas covered: All approved disease-modifying drugs (DMD) for MS are discussed in this review. Mode of action, adverse effects, reported risks for infections and malignancies, and pregnancy related issues are discussed in the review. The authors also provide suggestions for monitoring therapy. For all approved DMDs the pivotal studies have been included for possible side effects, as well as reports by health authorities. For this manuscript, PubMed was checked for reports on side effects for various drugs. Expert opinion: Treatment options in MS are manifold, each carrying different risks. The safety-risk profile for approved agents is favorable. Knowing and monitoring these possible side effects is essential to minimize risks associated with treatment. Presently, the long-term experience for some of these therapies is missing and this must be addressed.

Evidence of Multiple Mediating Pathways in Associations Between Constructs of Stigma and Self-Reported Suicide Attempts in a Cross-Sectional Study of Gay and Bisexual Men.

Science.gov (United States)

Salway, Travis; Gesink, Dionne; Ibrahim, Selahadin; Ferlatte, Olivier; Rhodes, Anne E; Brennan, David J; Marchand, Rick; Trussler, Terry

2018-05-01

Gay and bisexual men (GBM) are more likely to attempt suicide than heterosexual men. This disparity is commonly interpreted using minority stress theory; however, specific pathways from antigay stigma to suicidal behavior are poorly understood. We aimed to estimate associations between multiple constructs of stigma and suicide attempts among adult GBM, and to measure the proportion of these associations mediated by distinct suicide risk factors, thus identifying proximal points of intervention. Data were drawn from a Canadian community-based survey of adult GBM. Structural equation modeling was used to compare associations between three latent constructs-enacted stigma (e.g., discrimination, harassment), anticipated prejudice (worry about encountering antigay/bisexual prejudice), and sexuality concealment-and self-reported suicide attempts (last 12 months). Coefficients were estimated for direct, indirect, and total pathways and evaluated based on magnitude and statistical significance. The proportion of associations mediated by depression, drug/alcohol use, and social isolation was calculated using indirect paths. Among 7872 respondents, 3.4% reported a suicide attempt in the past 12 months. The largest total association was observed for enacted stigma, and this association was partially mediated by depression and drug/alcohol use. The total association of anticipated prejudice was relatively smaller and mediated by depression and social isolation. Concealment had an inverse association with suicide attempts as mediated by depression but was also positively associated with suicide attempts when mediated through social isolation. Multiple constructs of antigay stigma were associated with suicide attempts; however, mediating pathways differed by construct, suggesting that a combination of strategies is required to prevent suicide in adult GBM.

When the test of mediation is more powerful than the test of the total effect.

Science.gov (United States)

O'Rourke, Holly P; MacKinnon, David P

2015-06-01

Although previous research has studied power in mediation models, the extent to which the inclusion of a mediator will increase power has not been investigated. To address this deficit, in a first study we compared the analytical power values of the mediated effect and the total effect in a single-mediator model, to identify the situations in which the inclusion of one mediator increased statistical power. The results from this first study indicated that including a mediator increased statistical power in small samples with large coefficients and in large samples with small coefficients, and when coefficients were nonzero and equal across models. Next, we identified conditions under which power was greater for the test of the total mediated effect than for the test of the total effect in the parallel two-mediator model. These results indicated that including two mediators increased power in small samples with large coefficients and in large samples with small coefficients, the same pattern of results that had been found in the first study. Finally, we assessed the analytical power for a sequential (three-path) two-mediator model and compared the power to detect the three-path mediated effect to the power to detect both the test of the total effect and the test of the mediated effect for the single-mediator model. The results indicated that the three-path mediated effect had more power than the mediated effect from the single-mediator model and the test of the total effect. Practical implications of these results for researchers are then discussed.

The effects of cultural values on mental health among the Taiwanese people: mediating of attitudes toward emotional expression.

Science.gov (United States)

Chu, Li-Chuan

2015-03-01

Empirical evidence has demonstrated that an individual's cultural values can influence his or her mental health. This study extends previous research by proposing and testing a model that examines mediating processes underlying the relationship between individuals' cultural values and their mental health. This 2-stage study used data collected from 208 (at time 1) and 159 (at time 2) full-time staff employed by private enterprises in Taiwan. The author tested hypotheses through the use of hierarchical multiple regression. The results showed that under horizontal individualism and vertical collectivism, the predictors of negative mental health (ie, somatic symptoms, anxiety and insomnia, social dysfunction and/or severe depression) were partially and almost completely achieved through the mediating effect of the negative attitudes toward emotional expression. © 2012 APJPH.

PKA/AMPK signaling in relation to adiponectin's antiproliferative effect on multiple myeloma cells.

Science.gov (United States)

Medina, E A; Oberheu, K; Polusani, S R; Ortega, V; Velagaleti, G V N; Oyajobi, B O

2014-10-01

Obesity increases the risk of developing multiple myeloma (MM). Adiponectin is a cytokine produced by adipocytes, but paradoxically decreased in obesity, that has been implicated in MM progression. Herein, we evaluated how prolonged exposure to adiponectin affected the survival of MM cells as well as putative signaling mechanisms. Adiponectin activates protein kinase A (PKA), which leads to decreased AKT activity and increased AMP-activated protein kinase (AMPK) activation. AMPK, in turn, induces cell cycle arrest and apoptosis. Adiponectin-induced apoptosis may be mediated, at least in part, by the PKA/AMPK-dependent decline in the expression of the enzyme acetyl-CoA-carboxylase (ACC), which is essential to lipogenesis. Supplementation with palmitic acid, the preliminary end product of fatty acid synthesis, rescues MM cells from adiponectin-induced apoptosis. Furthermore, 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), an ACC inhibitor, exhibited potent antiproliferative effects on MM cells that could also be inhibited by fatty acid supplementation. Thus, adiponectin's ability to reduce survival of MM cells appears to be mediated through its ability to suppress lipogenesis. Our findings suggest that PKA/AMPK pathway activators, or inhibitors of ACC, may be useful adjuvants to treat MM. Moreover, the antimyeloma effect of adiponectin supports the concept that hypoadiponectinemia, as occurs in obesity, promotes MM tumor progression.

The essential role of t cells in multiple sclerosis: A reappraisal

Directory of Open Access Journals (Sweden)

Cris S Constantinescu

2014-04-01

Full Text Available Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system in which destruction of myelin and nerve axons has been shown to be mediated by immune mechanisms. Although the focus of research has been traditionally on T cells as key mediators of the immunopathology, more recent efforts at understanding this complex disorder have been directed increasingly at other cellular and humoral elements of the immune response. This review is a reappraisal of the crucial role of T cells, in particular the CD4+ helper T-cell subset, in multiple sclerosis. Recent evidence is discussed underlining the predominant contribution of T-cell-associated genes to the genome-wide association study results of multiple sclerosis susceptibility, the loss of T-cell quiescence in the conversion from clinically isolated syndrome to clinically definite multiple sclerosis, and the fact that T cells represent the main target of effective immunomodulatory and immunosuppressive treatments in multiple sclerosis.

School Processes Mediate School Compositional Effects: Model Specification and Estimation

Science.gov (United States)

Liu, Hongqiang; Van Damme, Jan; Gielen, Sarah; Van Den Noortgate, Wim

2015-01-01

School composition effects have been consistently verified, but few studies ever attempted to study how school composition affects school achievement. Based on prior research findings, we employed multilevel mediation modeling to examine whether school processes mediate the effect of school composition upon school outcomes based on the data of 28…

Activator Gcn4 employs multiple segments of Med15/Gal11, including the KIX domain, to recruit mediator to target genes in vivo.

Science.gov (United States)

Jedidi, Iness; Zhang, Fan; Qiu, Hongfang; Stahl, Stephen J; Palmer, Ira; Kaufman, Joshua D; Nadaud, Philippe S; Mukherjee, Sujoy; Wingfield, Paul T; Jaroniec, Christopher P; Hinnebusch, Alan G

2010-01-22

Mediator is a multisubunit coactivator required for initiation by RNA polymerase II. The Mediator tail subdomain, containing Med15/Gal11, is a target of the activator Gcn4 in vivo, critical for recruitment of native Mediator or the Mediator tail subdomain present in sin4Delta cells. Although several Gal11 segments were previously shown to bind Gcn4 in vitro, the importance of these interactions for recruitment of Mediator and transcriptional activation by Gcn4 in cells was unknown. We show that interaction of Gcn4 with the Mediator tail in vitro and recruitment of this subcomplex and intact Mediator to the ARG1 promoter in vivo involve additive contributions from three different segments in the N terminus of Gal11. These include the KIX domain, which is a critical target of other activators, and a region that shares a conserved motif (B-box) with mammalian coactivator SRC-1, and we establish that B-box is a critical determinant of Mediator recruitment by Gcn4. We further demonstrate that Gcn4 binds to the Gal11 KIX domain directly and, by NMR chemical shift analysis combined with mutational studies, we identify the likely binding site for Gcn4 on the KIX surface. Gcn4 is distinctive in relying on comparable contributions from multiple segments of Gal11 for efficient recruitment of Mediator in vivo.

A default Bayesian hypothesis test for mediation.

Science.gov (United States)

Nuijten, Michèle B; Wetzels, Ruud; Matzke, Dora; Dolan, Conor V; Wagenmakers, Eric-Jan

2015-03-01

In order to quantify the relationship between multiple variables, researchers often carry out a mediation analysis. In such an analysis, a mediator (e.g., knowledge of a healthy diet) transmits the effect from an independent variable (e.g., classroom instruction on a healthy diet) to a dependent variable (e.g., consumption of fruits and vegetables). Almost all mediation analyses in psychology use frequentist estimation and hypothesis-testing techniques. A recent exception is Yuan and MacKinnon (Psychological Methods, 14, 301-322, 2009), who outlined a Bayesian parameter estimation procedure for mediation analysis. Here we complete the Bayesian alternative to frequentist mediation analysis by specifying a default Bayesian hypothesis test based on the Jeffreys-Zellner-Siow approach. We further extend this default Bayesian test by allowing a comparison to directional or one-sided alternatives, using Markov chain Monte Carlo techniques implemented in JAGS. All Bayesian tests are implemented in the R package BayesMed (Nuijten, Wetzels, Matzke, Dolan, & Wagenmakers, 2014).

The effect of approach/avoidance training on alcohol consumption is mediated by change in alcohol action tendency.

Directory of Open Access Journals (Sweden)

Jason M Sharbanee

Full Text Available Training people to respond to alcohol images by making avoidance joystick movements can affect subsequent alcohol consumption, and has shown initial efficacy as a treatment adjunct. However, the mechanisms that underlie the training's efficacy are unknown. The present study aimed to determine 1 whether the training's effect is mediated by a change in action tendency or a change in selective attention, and 2 whether the training's effect is moderated by individual differences in working memory capacity (WMC. Three groups of social drinkers (total N = 74 completed either approach-alcohol training, avoid-alcohol training or a sham-training on the Approach-Avoidance Task (AAT. Participants' WMC was assessed prior to training, while their alcohol-related action tendency and selective attention were assessed before and after the training on the recently developed Selective-Attention/Action Tendency Task (SA/ATT, before finally completing an alcohol taste-test. There was no significant main effect of approach/avoidance training on alcohol consumption during the taste-test. However, there was a significant indirect effect of training on alcohol consumption mediated by a change in action tendency, but no indirect effect mediated by a change in selective attention. There was inconsistent evidence of WMC moderating training efficacy, with moderation found only for the effect of approach-alcohol training on the AAT but not on the SA/ATT. Thus approach/avoidance training affects alcohol consumption specifically by changing the underlying action tendency. Multiple training sessions may be required in order to observe more substantive changes in drinking behaviour.

An improved null model for assessing the net effects of multiple stressors on communities.

Science.gov (United States)

Thompson, Patrick L; MacLennan, Megan M; Vinebrooke, Rolf D

2018-01-01

Ecological stressors (i.e., environmental factors outside their normal range of variation) can mediate each other through their interactions, leading to unexpected combined effects on communities. Determining whether the net effect of stressors is ecologically surprising requires comparing their cumulative impact to a null model that represents the linear combination of their individual effects (i.e., an additive expectation). However, we show that standard additive and multiplicative null models that base their predictions on the effects of single stressors on community properties (e.g., species richness or biomass) do not provide this linear expectation, leading to incorrect interpretations of antagonistic and synergistic responses by communities. We present an alternative, the compositional null model, which instead bases its predictions on the effects of stressors on individual species, and then aggregates them to the community level. Simulations demonstrate the improved ability of the compositional null model to accurately provide a linear expectation of the net effect of stressors. We simulate the response of communities to paired stressors that affect species in a purely additive fashion and compare the relative abilities of the compositional null model and two standard community property null models (additive and multiplicative) to predict these linear changes in species richness and community biomass across different combinations (both positive, negative, or opposite) and intensities of stressors. The compositional model predicts the linear effects of multiple stressors under almost all scenarios, allowing for proper classification of net effects, whereas the standard null models do not. Our findings suggest that current estimates of the prevalence of ecological surprises on communities based on community property null models are unreliable, and should be improved by integrating the responses of individual species to the community level as does our

Active video games: the mediating effect of aerobic fitness on body composition.

Science.gov (United States)

Maddison, Ralph; Mhurchu, Cliona Ni; Jull, Andrew; Prapavessis, Harry; Foley, Louise S; Jiang, Yannan

2012-05-03

Increased understanding of why and how physical activity impacts on health outcomes is needed to increase the effectiveness of physical activity interventions. A recent randomized controlled trial of an active video game (PlayStation EyeToy™) intervention showed a statistically significant treatment effect on the primary outcome, change from baseline in body mass index (BMI), which favored the intervention group at 24 weeks. In this short paper we evaluate the mediating effects of the secondary outcomes. To identify mediators of the effect of an active video games intervention on body composition. Data from a two-arm parallel randomized controlled trial of an active video game intervention (n = 322) were analyzed. The primary outcome was change from baseline in BMI. A priori secondary outcomes were considered as potential mediators of the intervention on BMI, including aerobic fitness (VO2Max), time spent in moderate-to-vigorous physical activity (MVPA), and food snacking at 24 weeks. Only aerobic fitness at 24 weeks met the conditions for mediation, and was a significant mediator of BMI. Playing active video games can have a positive effect on body composition in overweight or obese children and this effect is most likely mediated through improved aerobic fitness. Future trials should examine other potential mediators related to this type of intervention. Australian New Zealand Clinical Trials Registry Website: http://www.anzctr.org.au. Study ID number: ACTRN12607000632493.

Interleukin-12 induces sustained activation of multiple host inflammatory mediator systems in chimpanzees

NARCIS (Netherlands)

Lauw, F. N.; Dekkers, P. E.; te Velde, A. A.; Speelman, P.; Levi, M. [=Marcel M.; Kurimoto, M.; Hack, C. E.; van Deventer, S. J.; van der Poll, T.

1999-01-01

To determine in vivo effects of interleukin (IL)-12 on host inflammatory mediator systems, 4 healthy chimpanzees received recombinant human IL-12 (1 microg/kg) by intravenous injection. IL-12 induced increases in plasma concentrations of IL-15, IL-18, and interferon-gamma (IFN-gamma), plus a marked

Rationally engineered nanoparticles target multiple myeloma cells, overcome cell-adhesion-mediated drug resistance, and show enhanced efficacy in vivo

International Nuclear Information System (INIS)

Kiziltepe, T; Ashley, J D; Stefanick, J F; Qi, Y M; Alves, N J; Handlogten, M W; Suckow, M A; Navari, R M; Bilgicer, B

2012-01-01

In the continuing search for effective cancer treatments, we report the rational engineering of a multifunctional nanoparticle that combines traditional chemotherapy with cell targeting and anti-adhesion functionalities. Very late antigen-4 (VLA-4) mediated adhesion of multiple myeloma (MM) cells to bone marrow stroma confers MM cells with cell-adhesion-mediated drug resistance (CAM-DR). In our design, we used micellar nanoparticles as dynamic self-assembling scaffolds to present VLA-4-antagonist peptides and doxorubicin (Dox) conjugates, simultaneously, to selectively target MM cells and to overcome CAM-DR. Dox was conjugated to the nanoparticles through an acid-sensitive hydrazone bond. VLA-4-antagonist peptides were conjugated via a multifaceted synthetic procedure for generating precisely controlled number of targeting functionalities. The nanoparticles were efficiently internalized by MM cells and induced cytotoxicity. Mechanistic studies revealed that nanoparticles induced DNA double-strand breaks and apoptosis in MM cells. Importantly, multifunctional nanoparticles overcame CAM-DR, and were more efficacious than Dox when MM cells were cultured on fibronectin-coated plates. Finally, in a MM xenograft model, nanoparticles preferentially homed to MM tumors with ∼10 fold more drug accumulation and demonstrated dramatic tumor growth inhibition with a reduced overall systemic toxicity. Altogether, we demonstrate the disease driven engineering of a nanoparticle-based drug delivery system, enabling the model of an integrative approach in the treatment of MM

The Multiple Roles of the Task Design Mediator in Telecollaboration

Science.gov (United States)

Fuchs, Carolin; Snyder, Bill; Tung, Bruce; Jung Han, Yu

2017-01-01

This case study explores how a Chinese-American novice teacher acted as mediator in a telecollaboration with student teacher (ST) peers in the USA who designed tasks for his English as a foreign language (EFL) learners in China. The novice teacher was instrumental in mediating the student teachers' task design process by providing feedback…

Mediatization

DEFF Research Database (Denmark)

Hjarvard, Stig

2017-01-01

Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... to these general questions by distinguishing between two concepts: mediation and mediatization. The media effects tradition generally considers the effects of the media to be a result of individuals being exposed to media content, i.e. effects are seen as an outcome of mediated communication. Mediatization...... research is concerned with long-term structural changes involving media, culture, and society, i.e. the influences of the media are understood in relation to how media are implicated in social and cultural changes and how these processes come to create new conditions for human communication and interaction...

Estimating scaled treatment effects with multiple outcomes.

Science.gov (United States)

Kennedy, Edward H; Kangovi, Shreya; Mitra, Nandita

2017-01-01

In classical study designs, the aim is often to learn about the effects of a treatment or intervention on a single outcome; in many modern studies, however, data on multiple outcomes are collected and it is of interest to explore effects on multiple outcomes simultaneously. Such designs can be particularly useful in patient-centered research, where different outcomes might be more or less important to different patients. In this paper, we propose scaled effect measures (via potential outcomes) that translate effects on multiple outcomes to a common scale, using mean-variance and median-interquartile range based standardizations. We present efficient, nonparametric, doubly robust methods for estimating these scaled effects (and weighted average summary measures), and for testing the null hypothesis that treatment affects all outcomes equally. We also discuss methods for exploring how treatment effects depend on covariates (i.e., effect modification). In addition to describing efficiency theory for our estimands and the asymptotic behavior of our estimators, we illustrate the methods in a simulation study and a data analysis. Importantly, and in contrast to much of the literature concerning effects on multiple outcomes, our methods are nonparametric and can be used not only in randomized trials to yield increased efficiency, but also in observational studies with high-dimensional covariates to reduce confounding bias.

Active video games: the mediating effect of aerobic fitness on body composition

Directory of Open Access Journals (Sweden)

Maddison Ralph

2012-05-01

Full Text Available Abstract Background Increased understanding of why and how physical activity impacts on health outcomes is needed to increase the effectiveness of physical activity interventions. A recent randomized controlled trial of an active video game (PlayStation EyeToy™ intervention showed a statistically significant treatment effect on the primary outcome, change from baseline in body mass index (BMI, which favored the intervention group at 24 weeks. In this short paper we evaluate the mediating effects of the secondary outcomes. Objective To identify mediators of the effect of an active video games intervention on body composition. Methods Data from a two-arm parallel randomized controlled trial of an active video game intervention (n = 322 were analyzed. The primary outcome was change from baseline in BMI. A priori secondary outcomes were considered as potential mediators of the intervention on BMI, including aerobic fitness (VO2Max, time spent in moderate-to-vigorous physical activity (MVPA, and food snacking at 24 weeks. Results Only aerobic fitness at 24 weeks met the conditions for mediation, and was a significant mediator of BMI. Conclusion Playing active video games can have a positive effect on body composition in overweight or obese children and this effect is most likely mediated through improved aerobic fitness. Future trials should examine other potential mediators related to this type of intervention. Trial registration Australian New Zealand Clinical Trials Registry Website: http://www.anzctr.org.au Study ID number: ACTRN12607000632493

Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo

OpenAIRE

Eyboulet, Fanny; Wydau-Dematteis, Sandra; Eychenne, Thomas; Alibert, Olivier; Neil, Helen; Boschiero, Claire; Nevers, Marie-Claire; Volland, Herv?; Cornu, David; Redeker, Virginie; Werner, Michel; Soutourina, Julie

2015-01-01

Mediator is a large multiprotein complex conserved in all eukaryotes, which has a crucial coregulator function in transcription by RNA polymerase II (Pol II). However, the molecular mechanisms of its action in vivo remain to be understood. Med17 is an essential and central component of the Mediator head module. In this work, we utilised our large collection of conditional temperature-sensitive med17 mutants to investigate Mediator's role in coordinating preinitiation complex (PIC) formation i...

Causal Mediation Analysis with Multiple Mediators

OpenAIRE

Daniel, R M; De Stavola, B L; Cousens, S N; Vansteelandt, S

2014-01-01

: In diverse fields of empirical research-including many in the biological sciences-attempts are made to decompose the effect of an exposure on an outcome into its effects via a number of different pathways. For example, we may wish to separate the effect of heavy alcohol consumption on systolic blood pressure (SBP) into effects via body mass index (BMI), via gamma-glutamyl transpeptidase (GGT), and via other pathways. Much progress has been made, mainly due to contributions from the field of...

Associations of social support and stress with postpartum maternal mental health symptoms: Main effects, moderation, and mediation.

Science.gov (United States)

Schwab-Reese, Laura M; Schafer, Ellen J; Ashida, Sato

2017-07-01

Poor maternal mental health during the postpartum period can have significant effects on the health of mothers, infants, and families. The findings from cross-sectional studies suggest that stress and social support are related to maternal mental health. This study contributes to the literature through the use of longitudinal data, and examines moderation and mediation among these factors. In 2012-2013, mothers completed surveys assessing stress, social support, and depressive and anxiety symptoms following birth (n = 125), and 3 months (n = 110) and 6 months (n = 99) after birth. The authors examined temporal associations, moderation, and mediation of social support on the relationship between stress and postpartum depressive and anxiety symptoms using modified Poisson regression models and the counterfactual approach to mediation. Current levels of stress and social support were associated with depressive and anxiety symptoms, both independently and when considered together at multiple time points. Social support did not strongly moderate or mediate the relationships between stress and maternal mental health. Interventions to reduce current perceptions of stress and increase social support for mothers during the postpartum period may help improve maternal mental health symptoms. Efforts are needed to assess the current needs of mothers continuously.

Improving Collaborative Play between Children with Autism Spectrum Disorders and Their Siblings: The Effectiveness of a Robot-Mediated Intervention Based on Lego® Therapy

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Huskens, Bibi; Palmen, Annemiek; Van der Werff, Marije; Lourens, Tino; Barakova, Emilia

2015-01-01

The aim of the study was to investigate the effectiveness of a brief robot-mediated intervention based on Lego® therapy on improving collaborative behaviors (i.e., interaction initiations, responses, and play together) between children with ASD and their siblings during play sessions, in a therapeutic setting. A concurrent multiple baseline design…

Mediating mechanisms of a military Web-based alcohol intervention.

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Williams, Jason; Herman-Stahl, Mindy; Calvin, Sara L; Pemberton, Michael; Bradshaw, Michael

2009-03-01

This study explored the mediating mechanisms of two Web-based alcohol interventions in a sample of active duty United States military personnel. Personnel were recruited from eight bases and received the Drinker's Check-Up (N=1483), Alcohol Savvy (N=688), or served as controls (N=919). The interventions drew on motivational interviewing and social learning theory and targeted multiple mediators including social norms, perceived risks and benefits, readiness to change, and coping strategies. Baseline data were collected prior to the intervention and follow-up data on alcohol consumption were gathered 1 month and 6 months after program completion. Two mediation models were examined: (1) a longitudinal two-wave model with outcomes and mediators assessed concurrently at the 1-month follow-up; and (2) a three-wave model in which the causal chain was fully lagged. Results indicated strong support for the role of perceived descriptive norms in transmitting the effects of the Drinker's Check-Up, with consistent mediation across the majority of alcohol outcome measures for both the concurrent and fully lagged mediation models. These results suggest that web-based interventions that are effective in lowering perceived norms about the frequency and quantity of drinking may be a viable strategy for reducing alcohol consumption in military populations. The results did not support program mediation by the other targeted variables, indicating the need for future research on the effective components of alcohol interventions. The mediation models also suggest reasons why program effects were not found for some outcomes or were different across programs.

Mediation of psychosocial determinants in the relation between socio-economic status and adolescents' diet quality.

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Michels, Nathalie; Vynckier, Lisa; Moreno, Luis A; Beghin, Laurent; de la O, Alex; Forsner, Maria; Gonzalez-Gross, Marcela; Huybrechts, Inge; Iguacel, Isabel; Kafatos, Antonio; Kersting, Mathilde; Leclercq, Catherine; Manios, Yannis; Marcos, Ascension; Molnar, Denes; Sjöström, Michael; Widhalm, Kurt; De Henauw, Stefaan

2018-04-01

To examine the underlying reasons for the positive relation between socio-economic status (SES) and the diet quality of adolescents. In 2081 adolescents (12.5-17.5 years) of the European HELENA study, a continuous variable on diet quality via 2-day 24-h recalls was available. SES was reflected by parental education, parental occupation and family affluence. Mediation by several psychosocial determinants was tested: self-efficacy, availability at school and home, social support, barriers, benefits, awareness and some self-reported influencers (parents, school, taste, health, friends, food readily available, easy preparation, hunger, price and habits). Multiple mediation analyses were adjusted for age, sex and country. The availability of soft drinks and fruit at home, social support, parental influence, barriers, price influence, taste influence, health influence and food being readily available were significant mediators. The multiple mediation indirect effect accounted for 23-64% of the total effect. Both occupation and education and both maternal and paternal factors could be explained by the mediation. The unavailability of soft drinks was the strongest mediator (17-44% of the total effect). Up to 64% of the positive relation between SES and the diet quality in adolescence could be explained by several healthy eating determinants. Focusing on these factors in low-SES populations can minimize social inequalities in diet and health by improving the diet of these specific adolescents.

Mediating role of activity level in the depressive realism effect.

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Blanco, Fernando; Matute, Helena; A Vadillo, Miguel

2012-01-01

Several classic studies have concluded that the accuracy of identifying uncontrollable situations depends heavily on depressive mood. Nondepressed participants tend to exhibit an optimistic illusion of control, whereas depressed participants tend to better detect a lack of control. Recently, we suggested that the different activity levels (measured as the probability of responding during a contingency learning task) exhibited by depressed and nondepressed individuals is partly responsible for this effect. The two studies presented in this paper provide further support for this mediational hypothesis, in which mood is the distal cause of the illusion of control operating through activity level, the proximal cause. In Study 1, the probability of responding, P(R), was found to be a mediator variable between the depressive symptoms and the judgments of control. In Study 2, we intervened directly on the mediator variable: The P(R) for both depressed and nondepressed participants was manipulated through instructions. Our results confirm that P(R) manipulation produced differences in the participants' perceptions of uncontrollability. Importantly, the intervention on the mediator variable cancelled the effect of the distal cause; the participants' judgments of control were no longer mood dependent when the P(R) was manipulated. This result supports the hypothesis that the so-called depressive realism effect is actually mediated by the probability of responding.

Investigation of Mediational Processes Using Parallel Process Latent Growth Curve Modeling

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Cheong, JeeWon; MacKinnon, David P.; Khoo, Siek Toon

2010-01-01

This study investigated a method to evaluate mediational processes using latent growth curve modeling. The mediator and the outcome measured across multiple time points were viewed as 2 separate parallel processes. The mediational process was defined as the independent variable influencing the growth of the mediator, which, in turn, affected the growth of the outcome. To illustrate modeling procedures, empirical data from a longitudinal drug prevention program, Adolescents Training and Learning to Avoid Steroids, were used. The program effects on the growth of the mediator and the growth of the outcome were examined first in a 2-group structural equation model. The mediational process was then modeled and tested in a parallel process latent growth curve model by relating the prevention program condition, the growth rate factor of the mediator, and the growth rate factor of the outcome. PMID:20157639

Resilience Mediates the Longitudinal Relationships Between Social Support and Mental Health Outcomes in Multiple Sclerosis.

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Koelmel, Emily; Hughes, Abbey J; Alschuler, Kevin N; Ehde, Dawn M

2017-06-01

To investigate the longitudinal relationships between social support and subsequent mental health outcomes in individuals with multiple sclerosis (MS), and to examine resilience as a mediator between social support and subsequent mental health outcomes in this population. Observational, longitudinal cohort study. Participants were assessed at 4 time points over 12 months in the context of a previously reported randomized controlled trial. Telephone-based measures administered to community-based participants. Individuals (N=163) with MS and 1 or more of the following symptoms: depression, fatigue, and pain. Not applicable. Mental health outcomes included (1) depressive symptomatology, assessed using the Patient Health Questionnaire-9; (2) anxious symptomatology, assessed using the short form of the Emotional Distress-Anxiety Scale from the Patient-Reported Outcomes Measurement Information System; and (3) general mental health status, assessed using the Mental Component Summary score from the Short Form-8 Health Survey. Resilience was assessed using the Connor-Davidson Resilience Scale. At any given time, social support from significant others, family members, and friends was significantly associated with subsequent mental health outcomes for all 3 measures assessed (all P values social support significantly mediated the relationships between social support and subsequent mental health outcomes. After controlling for resilience, most of the direct relationships between social support and mental health outcomes were no longer significant. There are significant longitudinal relationships between social support, resilience, and mental health outcomes for people with MS. Given the mediating role of resilience in supporting better mental health outcomes, future clinical research and practice may benefit from an emphasis on resilience-focused psychological interventions. Copyright © 2016 American Congress of Rehabilitation Medicine. All rights reserved.

Mediating and/or moderating roles of psychological empowerment.

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Meng, Lina; Jin, Yi; Guo, Jiajia

2016-05-01

The purpose of this study was to explore the mediating and/or moderating effects of psychological empowerment in the relationship between structural empowerment and burnout among nurses in China. Burnout is prevalent among nurses. Previous studies have found that empowering organizational structures contribute to reduce nurses' burnout. However, little is known about the mediating or moderating role of psychological empowerment in the relationship between structural empowerment and burnout among nurses in China. A cross-sectional design was conducted. A total of 244 nurses participated in this study. The data were collected in March 2013. Multiple regressions were used to test the hypothesized models. Psychological empowerment was found to be a significant mediator of the relationship between structural empowerment and burnout (standardized β=-0.553, Sobel test: z=7.79, pmoderating effect of psychological empowerment in that relationship was not verified. Both structural and psychological empowerment negatively correlated with burnout. The psychological empowerment had a mediating effect on burnout. It is important for nurse managers to develop strategies to ensure that empowering structures are in place and to facilitate nurses' perception of psychological empowerment. Copyright © 2015 Elsevier Inc. All rights reserved.

Characterization of CD4+ T cell-mediated cytotoxicity in patients with multiple myeloma.

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Zhang, Xiaole; Gao, Lei; Meng, Kai; Han, Chunting; Li, Qiang; Feng, Zhenjun; Chen, Lei

2018-05-01

Multiple myeloma (MM) is an incurable cancer characterized by the development of malignant plasma cells. The CD8 T cell-mediated cytotoxicity is considered a major player in antitumor immunity, but in MM patients, the CD8 T cells displayed senescence markers and were functionally impaired. To investigate whether cytotoxic CD4 T cells could act as a treatment alternative in MM, we examined the frequency and function of naturally occurring cytotoxic CD4 T cells in MM patients. The cytotoxic CD4 T cells were identified as granzyme-A, granzyme B-, and perforin-expressing CD4 T cells, and their frequencies were significantly upregulated in MM patients when compared with healthy controls. The frequencies of cytotoxic CD4 T cells in MM patients were not associated with the frequencies of cytotoxic CD8 T cells, but were negatively associated with disease severity. Interestingly, the expression levels of inhibitory molecules, including PD-1 and CTLA-4, were significantly lower in cytotoxic CD4 T cells than in cytotoxic CD8 T cells. When co-incubated with autologous CD38 + CD138 + plasma cells, CD4 T cells were capable of eliminating plasma cells with varying degrees of efficacy. In MM patients, the frequency of circulating plasma cells was negatively correlated with the frequency of cytotoxic CD4 T cells. Therefore, CD4 T cell-mediated cytotoxicity existed naturally in MM patients and could potentially act as an option in antitumor therapies. Copyright © 2018 Elsevier Inc. All rights reserved.

Relapse May Serve as a Mediator Variable in Longitudinal Outcomes in Multiple Sclerosis.

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Stone, Lael Anne; Cutter, Gary Raymond; Fisher, Elizabeth; Richert, Nancy; McCartin, Jennifer; Ohayon, Joan; Bash, Craig; McFarland, Henry

2016-05-01

Contrast-enhancing lesions (CEL) on magnetic resonance imaging (MRI) are believed to represent inflammatory disease activity in multiple sclerosis (MS), but their relationship to subsequent long-term disability and progression is unclear, particularly at longer time periods such as 8-10 years. Between 1989 and 1994, 111 MS patients were seen at the National Institutes of Health for clinical evaluations and 3 monthly contrast-enhanced MRI scans. Of these, 94 patients were re-evaluated a mean of 8 years later (range 6.1-10.5 years) with a single MRI scan and clinical evaluation. CEL number and volume were determined at baseline and follow-up. The number of relapses was ascertained over the follow-up period and annualized relapse rates were calculated. Other MRI parameters, such as T2 hyperintensity volume, T1 volume, and brain parenchymal fraction, were also calculated. While there was no direct correlation between CEL number or volume at baseline and disability status at follow-up, CEL measures at baseline did correlate with number of relapses observed in the subsequent years, and the number of relapses in turn correlated with subsequent disability as well as transition to progressive MS. While number and volume of CEL at baseline do not directly correlate with disability in the longer term in MS, our data suggest that 1 route to disability involves relapses as a mediator variable in the causal sequence of MS progression from CEL to disability. Further studies using relapse as a mediator variable in a larger data set may be warranted. Copyright © 2015 by the American Society of Neuroimaging.

The relationship between academic self-concept, intrinsic motivation, test anxiety, and academic achievement among nursing students: mediating and moderating effects.

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Khalaila, Rabia

2015-03-01

The impact of cognitive factors on academic achievement is well documented. However, little is known about the mediating and moderating effects of non-cognitive, motivational and situational factors on academic achievement among nursing students. The aim of this study is to explore the direct and/or indirect effects of academic self-concept on academic achievement, and examine whether intrinsic motivation moderates the negative effect of test anxiety on academic achievement. This descriptive-correlational study was carried out on a convenience sample of 170 undergraduate nursing students, in an academic college in northern Israel. Academic motivation, academic self-concept and test anxiety scales were used as measuring instruments. Bootstrapping with resampling strategies was used for testing multiple mediators' model and examining the moderator effect. A higher self-concept was found to be directly related to greater academic achievement. Test anxiety and intrinsic motivation were found to be significant mediators in the relationship between self-concept and academic achievement. In addition, intrinsic motivation significantly moderated the negative effect of test anxiety on academic achievement. The results suggested that institutions should pay more attention to the enhancement of motivational factors (e.g., self-concept and motivation) and alleviate the negative impact of situational factors (e.g., test anxiety) when offering psycho-educational interventions designed to improve nursing students' academic achievements. Copyright © 2014 Elsevier Ltd. All rights reserved.

Artists and Multiple Job Holding—Breadwinning Work as Mediating Between Bohemian and Entrepreneurial Identities and Behavior

Directory of Open Access Journals (Sweden)

Sofia Lindström

2016-10-01

Full Text Available Artists are known to manage low income and work insecurity by holding multiple jobs. Through an analysis of interview data, this study explores the narratives of 20 visual artists in Sweden regarding breadwinning work. Positive and negative experiences of such work are analyzed in relation to the artists’ work behavior and identity as either ‘bohemian’ or ‘entrepreneurial.’ Breadwinning work may be seen by artists as either enabling autonomy from the market or hindering the construction of a professional identity, depending on these behaviors/identities. However, conditions such as low wage, temporary contracts, and low control over work hours ultimately decides artist’s experiences of breadwinning work. This article adds to the existing knowledge on artistic labour markets by highlighting the role of multiple job holding in mediating between an understanding of the bohemian art for art’s sake artist role and the entrepreneurial role of the artist. NB: The endnotes 7 and 8 have switched places, where endnote 7 should belong to the text of endnote 8 and vice versa

Redox-Mediated and Ionizing-Radiation-Induced Inflammatory Mediators in Prostate Cancer Development and Treatment

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Miao, Lu; Holley, Aaron K.; Zhao, Yanming; St. Clair, William H.

2014-01-01

Abstract Significance: Radiation therapy is widely used for treatment of prostate cancer. Radiation can directly damage biologically important molecules; however, most effects of radiation-mediated cell killing are derived from the generated free radicals that alter cellular redox status. Multiple proinflammatory mediators can also influence redox status in irradiated cells and the surrounding microenvironment, thereby affecting prostate cancer progression and radiotherapy efficiency. Recent Advances: Ionizing radiation (IR)–generated oxidative stress can regulate and be regulated by the production of proinflammatory mediators. Depending on the type and stage of the prostate cancer cells, these proinflammatory mediators may lead to different biological consequences ranging from cell death to development of radioresistance. Critical Issues: Tumors are heterogeneous and dynamic communication occurs between stromal and prostate cancer cells, and complicated redox-regulated mechanisms exist in the tumor microenvironment. Thus, antioxidant and anti-inflammatory strategies should be carefully evaluated for each patient at different stages of the disease to maximize therapeutic benefits while minimizing unintended side effects. Future Directions: Compared with normal cells, tumor cells are usually under higher oxidative stress and secrete more proinflammatory mediators. Thus, redox status is often less adaptive in tumor cells than in their normal counterparts. This difference can be exploited in a search for new cancer therapeutics and treatment regimes that selectively activate cell death pathways in tumor cells with minimal unintended consequences in terms of chemo- and radio-resistance in tumor cells and toxicity in normal tissues. Antioxid. Redox Signal. 20, 1481–1500. PMID:24093432

Parenting and Family Stress as Mediators of the Long-Term Effects of Child Abuse.

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Wind, Tiffany Weissmann; Silvern, Louise

1994-01-01

Data on child physical/sexual abuse, family stress histories, perceived parental warmth, and current psychological functioning were gathered from 259 working women. Multiple regression analyses showed that parental warmth strongly influenced or mediated the relationship of intrafamilial child abuse to depression and self-esteem levels. However,…

The effect of individual factors on health behaviors among college students: the mediating effects of eHealth literacy.

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Hsu, WanChen; Chiang, ChiaHsun; Yang, ShuChing

2014-12-12

College students' health behavior is a topic that deserves attention. Individual factors and eHealth literacy may affect an individual's health behaviors. The integrative model of eHealth use (IMeHU) provides a parsimonious account of the connections among the digital divide, health care disparities, and the unequal distribution and use of communication technologies. However, few studies have explored the associations among individual factors, eHealth literacy, and health behaviors, and IMeHU has not been empirically investigated. This study examines the associations among individual factors, eHealth literacy, and health behaviors using IMeHU. The Health Behavior Scale is a 12-item instrument developed to measure college students' eating, exercise, and sleep behaviors. The eHealth Literacy Scale is a 12-item instrument designed to measure college students' functional, interactive, and critical eHealth literacy. A nationally representative sample of 525 valid college students in Taiwan was surveyed. A questionnaire was administered to collect background information about participants' health status, degree of health concern, major, and the frequency with which they engaged in health-related discussions. This study used Amos 6.0 to conduct a confirmatory factor analysis to identify the best measurement models for the eHealth Literacy Scale and the Health Behavior Scale. We then conducted a multiple regression analysis to examine the associations among individual factors, eHealth literacy, and health behaviors. Additionally, causal steps approach was used to explore indirect (mediating) effects and Sobel tests were used to test the significance of the mediating effects. The study found that perceptions of better health status (t520=2.14-6.12, PeHealth literacy and adoption of healthy eating, exercise, and sleep behaviors. Moreover, eHealth literacy played an intermediary role in the association between individual factors and health behaviors (Sobel test=2.09-2.72, Pe

Two-condition within-participant statistical mediation analysis: A path-analytic framework.

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Montoya, Amanda K; Hayes, Andrew F

2017-03-01

Researchers interested in testing mediation often use designs where participants are measured on a dependent variable Y and a mediator M in both of 2 different circumstances. The dominant approach to assessing mediation in such a design, proposed by Judd, Kenny, and McClelland (2001), relies on a series of hypothesis tests about components of the mediation model and is not based on an estimate of or formal inference about the indirect effect. In this article we recast Judd et al.'s approach in the path-analytic framework that is now commonly used in between-participant mediation analysis. By so doing, it is apparent how to estimate the indirect effect of a within-participant manipulation on some outcome through a mediator as the product of paths of influence. This path-analytic approach eliminates the need for discrete hypothesis tests about components of the model to support a claim of mediation, as Judd et al.'s method requires, because it relies only on an inference about the product of paths-the indirect effect. We generalize methods of inference for the indirect effect widely used in between-participant designs to this within-participant version of mediation analysis, including bootstrap confidence intervals and Monte Carlo confidence intervals. Using this path-analytic approach, we extend the method to models with multiple mediators operating in parallel and serially and discuss the comparison of indirect effects in these more complex models. We offer macros and code for SPSS, SAS, and Mplus that conduct these analyses. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Multiple trauma in children: critical care overview.

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Wetzel, Randall C; Burns, R Cartland

2002-11-01

Multiple trauma is more than the sum of the injuries. Management not only of the physiologic injury but also of the pathophysiologic responses, along with integration of the child's emotional and developmental needs and the child's family, forms the basis of trauma care. Multiple trauma in children also elicits profound psychological responses from the healthcare providers involved with these children. This overview will address the pathophysiology of multiple trauma in children and the general principles of trauma management by an integrated trauma team. Trauma is a systemic disease. Multiple trauma stimulates the release of multiple inflammatory mediators. A lethal triad of hypothermia, acidosis, and coagulopathy is the direct result of trauma and secondary injury from the systemic response to trauma. Controlling and responding to the secondary pathophysiologic sequelae of trauma is the cornerstone of trauma management in the multiply injured, critically ill child. Damage control surgery is a new, rational approach to the child with multiple trauma. The selection of children for damage control surgery depends on the severity of injury. Major abdominal vascular injuries and multiple visceral injuries are best considered for this approach. The effective management of childhood multiple trauma requires a combined team approach, consideration of the child and family, an organized trauma system, and an effective quality assurance and improvement mechanism.

Do attentional capacities and processing speed mediate the effect of age on executive functioning?

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Gilsoul, Jessica; Simon, Jessica; Hogge, Michaël; Collette, Fabienne

2018-02-06

The executive processes are well known to decline with age, and similar data also exists for attentional capacities and processing speed. Therefore, we investigated whether these two last nonexecutive variables would mediate the effect of age on executive functions (inhibition, shifting, updating, and dual-task coordination). We administered a large battery of executive, attentional and processing speed tasks to 104 young and 71 older people, and we performed mediation analyses with variables showing a significant age effect. All executive and processing speed measures showed age-related effects while only the visual scanning task performance (selective attention) was explained by age when controlled for gender and educational level. Regarding mediation analyses, visual scanning partially mediated the age effect on updating while processing speed partially mediated the age effect on shifting, updating and dual-task coordination. In a more exploratory way, inhibition was also found to partially mediate the effect of age on the three other executive functions. Attention did not greatly influence executive functioning in aging while, in agreement with the literature, processing speed seems to be a major mediator of the age effect on these processes. Interestingly, the global pattern of results seems also to indicate an influence of inhibition but further studies are needed to confirm the role of that variable as a mediator and its relative importance by comparison with processing speed.

Mediating role of activity level in the depressive realism effect.

Directory of Open Access Journals (Sweden)

Fernando Blanco

Full Text Available Several classic studies have concluded that the accuracy of identifying uncontrollable situations depends heavily on depressive mood. Nondepressed participants tend to exhibit an optimistic illusion of control, whereas depressed participants tend to better detect a lack of control. Recently, we suggested that the different activity levels (measured as the probability of responding during a contingency learning task exhibited by depressed and nondepressed individuals is partly responsible for this effect. The two studies presented in this paper provide further support for this mediational hypothesis, in which mood is the distal cause of the illusion of control operating through activity level, the proximal cause. In Study 1, the probability of responding, P(R, was found to be a mediator variable between the depressive symptoms and the judgments of control. In Study 2, we intervened directly on the mediator variable: The P(R for both depressed and nondepressed participants was manipulated through instructions. Our results confirm that P(R manipulation produced differences in the participants' perceptions of uncontrollability. Importantly, the intervention on the mediator variable cancelled the effect of the distal cause; the participants' judgments of control were no longer mood dependent when the P(R was manipulated. This result supports the hypothesis that the so-called depressive realism effect is actually mediated by the probability of responding.

Mediating Role of Activity Level in the Depressive Realism Effect

Science.gov (United States)

Blanco, Fernando; Matute, Helena; A. Vadillo, Miguel

2012-01-01

Several classic studies have concluded that the accuracy of identifying uncontrollable situations depends heavily on depressive mood. Nondepressed participants tend to exhibit an optimistic illusion of control, whereas depressed participants tend to better detect a lack of control. Recently, we suggested that the different activity levels (measured as the probability of responding during a contingency learning task) exhibited by depressed and nondepressed individuals is partly responsible for this effect. The two studies presented in this paper provide further support for this mediational hypothesis, in which mood is the distal cause of the illusion of control operating through activity level, the proximal cause. In Study 1, the probability of responding, P(R), was found to be a mediator variable between the depressive symptoms and the judgments of control. In Study 2, we intervened directly on the mediator variable: The P(R) for both depressed and nondepressed participants was manipulated through instructions. Our results confirm that P(R) manipulation produced differences in the participants’ perceptions of uncontrollability. Importantly, the intervention on the mediator variable cancelled the effect of the distal cause; the participants’ judgments of control were no longer mood dependent when the P(R) was manipulated. This result supports the hypothesis that the so-called depressive realism effect is actually mediated by the probability of responding. PMID:23029435

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

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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

College drinking behaviors: mediational links between parenting styles, parental bonds, depression, and alcohol problems.

Science.gov (United States)

Patock-Peckham, Julie A; Morgan-Lopez, Antonio A

2007-09-01

Mediational links between parenting styles (authoritative, authoritarian, permissive), parental bond (positive, negative), depression, alcohol use and abuse were tested. A 2-group, multiple-indicator, multiple-cause structural equation model with 441 (216 female, 225 male) college students was examined. In general, a poor parental bond with one's father was highly predictive of depression, a well-known predictor of alcohol abuse and related problems for both genders. In contrast, a positive parental bond with one's father significantly mediated the positive effects of authoritative fathering on depression, which then decreased alcohol use problems for both genders. For women, a negative parental bond with one's father significantly mediated the effect of having an authoritarian father on depression, which increased alcohol use problems. These findings suggest that parental influences on pathways to alcohol abuse through depression (primarily through fathers for both genders) are distinct from pathways stemming from poor impulse control (with influences primarily from the same-sex parents for both genders).

Transparent mediation-based access to multiple yeast data sources using an ontology driven interface.

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Briache, Abdelaali; Marrakchi, Kamar; Kerzazi, Amine; Navas-Delgado, Ismael; Rossi Hassani, Badr D; Lairini, Khalid; Aldana-Montes, José F

2012-01-25

Saccharomyces cerevisiae is recognized as a model system representing a simple eukaryote whose genome can be easily manipulated. Information solicited by scientists on its biological entities (Proteins, Genes, RNAs...) is scattered within several data sources like SGD, Yeastract, CYGD-MIPS, BioGrid, PhosphoGrid, etc. Because of the heterogeneity of these sources, querying them separately and then manually combining the returned results is a complex and time-consuming task for biologists most of whom are not bioinformatics expert. It also reduces and limits the use that can be made on the available data. To provide transparent and simultaneous access to yeast sources, we have developed YeastMed: an XML and mediator-based system. In this paper, we present our approach in developing this system which takes advantage of SB-KOM to perform the query transformation needed and a set of Data Services to reach the integrated data sources. The system is composed of a set of modules that depend heavily on XML and Semantic Web technologies. User queries are expressed in terms of a domain ontology through a simple form-based web interface. YeastMed is the first mediation-based system specific for integrating yeast data sources. It was conceived mainly to help biologists to find simultaneously relevant data from multiple data sources. It has a biologist-friendly interface easy to use. The system is available at http://www.khaos.uma.es/yeastmed/.

Methods for Mediation Analysis with Missing Data

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Zhang, Zhiyong; Wang, Lijuan

2013-01-01

Despite wide applications of both mediation models and missing data techniques, formal discussion of mediation analysis with missing data is still rare. We introduce and compare four approaches to dealing with missing data in mediation analysis including list wise deletion, pairwise deletion, multiple imputation (MI), and a two-stage maximum…

Leadership and change commitment in the life insurance service context in Taiwan: the mediating-moderating role of job satisfaction.

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Yang, Yi-Feng

2011-06-01

The effects of transformational leadership and satisfaction were studied along with their interconnected effects (mediation and moderation) on commitment to change in the life insurance industry in two samples, sales managers and salespersons. A multiple mediated-moderated regression approach showed mediation and moderation to have statistically significant main effects on change commitment. Transformational leadership and satisfaction made a more important contribution to change commitment while job satisfaction had a mediating and moderating role that could enhance the relationships between leadership and change commitment. This information is of importance in building successful change commitment associations with customers.

The effect of age on fluid intelligence is fully mediated by physical health.

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Bergman, Ingvar; Almkvist, Ove

2013-01-01

The present study investigated the extent to which the effect of age on cognitive ability is predicted by individual differences in physical health. The sample consisted of 118 volunteer subjects who were healthy and ranging in age from 26 to 91. The examinations included a clinical investigation, magnetic resonance imaging (MRI) brain neuroimaging, and a comprehensive neuropsychological assessment. The effect of age on fluid IQ with and without visual spatial praxis and on crystallized IQ was tested whether being fully-, partially- or non-mediated by physical health. Structural equation analyses showed that the best and most parsimonious fit to the data was provided by models that were fully mediated for fluid IQ without praxis, non-mediated for crystallized IQ and partially mediated for fluid IQ with praxis. The diseases of the circulatory and nervous systems were the major mediators. It was concluded from the pattern of findings that the effect of age on fluid intelligence is fully mediated by physical health, while crystallized intelligence is non-mediated and visual spatial praxis is partially mediated, influenced mainly by direct effects of age. Our findings imply that improving health by acting against the common age-related circulatory- and nervous system diseases and risk factors will oppose the decline in fluid intelligence with age. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Inflammatory Mediator Profiling of n-butanol Exposed Upper Airways in Individuals with Multiple Chemical Sensitivity.

Directory of Open Access Journals (Sweden)

Thomas Meinertz Dantoft

Full Text Available Multiple Chemical Sensitivity (MCS is a chronic condition characterized by reports of recurrent symptoms in response to low level exposure to various chemical substances. Recent findings suggests that dysregulation of the immune system may play a role in MCS pathophysiology.The aim of this study was to examine baseline and low dose n-butanol-induced upper airway inflammatory response profiles in MCS subjects versus healthy controls.Eighteen participants with MCS and 18 age- and sex-matched healthy controls were enrolled in the study. Epithelial lining fluid was collected from the nasal cavity at three time points: baseline, within 15 minutes after being exposed to 3.7 ppm n-butanol in an exposure chamber and four hours after exposure termination. A total of 19 cytokines and chemokines were quantified. Furthermore, at baseline and during the exposure session, participants rated the perceived intensity, valence and levels of symptoms and autonomic recordings were obtained.The physiological and psychophysical measurements during the n-butanol exposure session verified a specific response in MCS individuals only. However, MCS subjects and healthy controls displayed similar upper airway inflammatory mediator profiles (P>0.05 at baseline. Likewise, direct comparison of mediator levels in the MCS group and controls after n-butanol exposure revealed no significant group differences.We demonstrate no abnormal upper airway inflammatory mediator levels in MCS subjects before or after a symptom-eliciting exposure to low dose n-butanol, implying that upper airways of MCS subjects are functionally intact at the level of cytokine and chemokine production and secretory capacity. This suggests that previous findings of increased cytokine plasma levels in MCS are unlikely to be caused by systemic priming via excessive upper airway inflammatory processes.

Inflammatory Mediator Profiling of n-butanol Exposed Upper Airways in Individuals with Multiple Chemical Sensitivity.

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Dantoft, Thomas Meinertz; Skovbjerg, Sine; Andersson, Linus; Claeson, Anna-Sara; Lind, Nina; Nordin, Steven; Brix, Susanne

2015-01-01

Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by reports of recurrent symptoms in response to low level exposure to various chemical substances. Recent findings suggests that dysregulation of the immune system may play a role in MCS pathophysiology. The aim of this study was to examine baseline and low dose n-butanol-induced upper airway inflammatory response profiles in MCS subjects versus healthy controls. Eighteen participants with MCS and 18 age- and sex-matched healthy controls were enrolled in the study. Epithelial lining fluid was collected from the nasal cavity at three time points: baseline, within 15 minutes after being exposed to 3.7 ppm n-butanol in an exposure chamber and four hours after exposure termination. A total of 19 cytokines and chemokines were quantified. Furthermore, at baseline and during the exposure session, participants rated the perceived intensity, valence and levels of symptoms and autonomic recordings were obtained. The physiological and psychophysical measurements during the n-butanol exposure session verified a specific response in MCS individuals only. However, MCS subjects and healthy controls displayed similar upper airway inflammatory mediator profiles (P>0.05) at baseline. Likewise, direct comparison of mediator levels in the MCS group and controls after n-butanol exposure revealed no significant group differences. We demonstrate no abnormal upper airway inflammatory mediator levels in MCS subjects before or after a symptom-eliciting exposure to low dose n-butanol, implying that upper airways of MCS subjects are functionally intact at the level of cytokine and chemokine production and secretory capacity. This suggests that previous findings of increased cytokine plasma levels in MCS are unlikely to be caused by systemic priming via excessive upper airway inflammatory processes.

How Does Trust Affect the Performance of Ongoing Teams? The Mediating Role of Reflexivity, Monitoring and Effort

NARCIS (Netherlands)

de Jong, B.A.; Elfring, T.

2010-01-01

In this study, we investigate how trust affects the performance of ongoing teams. We propose a multiple mediator model in which different team processes act as mediating mechanisms that transmit the positive effects of trust to team performance. Drawing on a data set of ongoing tax consulting teams,

Determination of multiple scattering effects

International Nuclear Information System (INIS)

Langevin, M.

1981-01-01

The integration of Sigmund and Winterbon numerical values is extended to the reduced thickness tau=2000. The diagram obtained allows a simple determination of the multiple scattering effect for different targets and projectiles [fr

Psychotic Symptoms and Attitudes toward Medication Mediate the Effect of Insight on Personal-Social Functions in Patients with Schizophrenia: One-Year Randomized Controlled Trial and Follow-Up.

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Zheng, Yingjun; Ning, Yuping; She, Shenglin; Deng, Yongjie; Chen, Yuwei; Yi, Wenying; Lu, Xiaodan; Chen, Xinrui; Li, Juanhua; Li, Ruikeng; Zhang, Jie; Xiao, Di; Wu, Haibo; Wu, Chao

2018-02-14

This study aimed to investigate the mediating pathway of 3 factors (psychotic symptoms, attitude toward medication, and cognitive processing speed) on the effect of insight on personal-social functioning in patients with schizophrenia. Chinese inpatients with schizophrenia (n = 168; mean age 18 ± 50 years) diagnosed according to the DSM-IV were randomly assigned to treatment with antipsychotic medication alone or combined treatment. Positive and Negative Syndrome Scale (PANSS), Drug Attitude Inventory (DAI), Assessment of Insight (SAI), and Social-Personal Performance Scale (PSPS) scores were evaluated at baseline and at 3, 6, and 12 months. Cognitive function was assessed at baseline. Multiple mediation analyses were conducted with baseline data, end point data, and changes-in-scale scores between baseline and the end point, respectively. At baseline and at 12 months, only psychotic symptoms mediated the effect of insight on personal-social functioning. For changes-in-scale scores over the 12-month follow-up, in patients receiving treatment with medication alone, the effect of improved insight on improved personal-social function was mediated by psychotic symptoms only; in patients receiving a combined treatment, the effect of improved insight on improved personal-social functioning was mediated by both psychotic symptoms and attitudes toward medication, independently. The link between insight and personal-social functions is mainly mediated by psychotic symptoms. Psychosocial intervention improves the predicting effect of insight on personal-social function by improving both the attitude toward medication and psychotic symptoms independently. © 2018 S. Karger AG, Basel.

Multiple Mediation Analysis of the Relationship between Rapid Naming and Reading

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Poulsen, Mads; Juul, Holger; Elbro, Carsten

2015-01-01

It is well established that rapid automatised naming (RAN) correlates with reading ability. Despite several attempts, no single component process (mediator) has been identified that fully accounts for the correlation. The present paper estimated the explanatory value of several mediators for the RAN--reading correlation. One hundred and sixty-nine…

Depression, anxiety and loss of resilience after multiple traumas: an illustration of a mediated moderation model of sensitization in a group of children who survived the Nazi Holocaust.

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Fossion, Pierre; Leys, Christophe; Kempenaers, Chantal; Braun, Stephanie; Verbanck, Paul; Linkowski, Paul

2013-12-01

Depressive and anxiety disorders (DAD) have become a major public health problem. Multiple trauma is known to increase the risk of DAD through a sensitization mechanism. We investigate the hypothesis that resilience is a mediator of this mechanism. Former Hidden Children (FHC), the Jewish youths who spent World War II in various hideaway shelters across Nazi-occupied Europe, were compared with a control group. In each group, we measured the presence of multiple traumas, the resilience with the Resilience Scale for Adults, which has a six factors solution, and the DAD with the Hopkins Symptoms Checklist. We test a mediated moderation model with childhood trauma as the predictor; Later trauma as the moderator; Resilience as the mediator; and DAD as the outcome variable. Results are consistent with a sensitization model of DAD mediated by resilience: confrontation with a primary trauma during childhood followed by secondary trauma(s) after childhood damages resilience, which, in turn, results in higher level of DAD. We are unable to differentiate if the sensitization process is a consequence of the nature of the trauma endured by FHC (long-standing exposure to extreme external events) or a consequence of the fact that this first trauma occurred during childhood. Resilience construct is multi-factorial and a limited damaging of some of the factors is sufficient to lead to DAD even if other factors remain unaltered. Resilience can be altered by multiple traumas and, therefore, needs to be bolstered in therapy sessions. Copyright © 2013. Published by Elsevier B.V.

Perceived Social Support and Early Adolescents' Achievement : The Mediational Roles of Motivational Beliefs and Emotions

NARCIS (Netherlands)

Ahmed, Wondimu; Minnaert, Alexander; van der Werf, Greetje; Kuyper, Hans

Although a bulk of literature shows that perceived social support (PSS) influences academic achievement, the mechanisms through which this effect operates received little empirical attention. The present study examined the multiple mediational effects of motivational beliefs (competence beliefs and

Morphological Awareness in Vocabulary Acquisition among Chinese-Speaking Children: Testing Partial Mediation via Lexical Inference Ability

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Zhang, Haomin

2015-01-01

The goal of this study was to investigate the effect of Chinese-specific morphological awareness on vocabulary acquisition among young Chinese-speaking students. The participants were 288 Chinese-speaking second graders from three different cities in China. Multiple regression analysis and mediation analysis were used to uncover the mediated and…

Quantum theory of multiple-input-multiple-output Markovian feedback with diffusive measurements

International Nuclear Information System (INIS)

Chia, A.; Wiseman, H. M.

2011-01-01

Feedback control engineers have been interested in multiple-input-multiple-output (MIMO) extensions of single-input-single-output (SISO) results of various kinds due to its rich mathematical structure and practical applications. An outstanding problem in quantum feedback control is the extension of the SISO theory of Markovian feedback by Wiseman and Milburn [Phys. Rev. Lett. 70, 548 (1993)] to multiple inputs and multiple outputs. Here we generalize the SISO homodyne-mediated feedback theory to allow for multiple inputs, multiple outputs, and arbitrary diffusive quantum measurements. We thus obtain a MIMO framework which resembles the SISO theory and whose additional mathematical structure is highlighted by the extensive use of vector-operator algebra.

Effects of peer-mediated instruction to teach use of speech-generating devices to students with autism in social game routines.

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Trottier, Nadine; Kamp, Lorraine; Mirenda, Pat

2011-03-01

Supporting social interactions between students with autism spectrum disorders (ASDs) and their typically developing peers presents many challenges. The purpose of this study was to investigate the effects of a peer-mediated intervention designed to teach two students with ASD to use speech-generating devices (SGDs) to engage in interactions with peers in a social context at school. Six peer confederates (three from each student with ASD's general education classroom) were taught to support SGD use during game activities. A multiple baseline design was used to examine the relationship between peer-mediated instruction and an increase in total communicative acts (CAs) by the two students with ASD. Results provide evidence that the confederates acquired the skills needed to support SGD use by students with ASD. The results also suggest that the intervention was effective at increasing total appropriate CAs by students with ASD. In addition, social validity ratings by all of the confederates were positive. Results are discussed regarding educational implications, limitations, and future research.

Endogenous TasiRNAs mediate non-cell autonomous effects on gene regulation in Arabidopsis thaliana.

Directory of Open Access Journals (Sweden)

Rebecca Schwab

Full Text Available BACKGROUND: Different classes of small RNAs (sRNAs refine the expression of numerous genes in higher eukaryotes by directing protein partners to complementary nucleic acids, where they mediate gene silencing. Plants encode a unique class of sRNAs, called trans-acting small interfering RNAs (tasiRNAs, which post-transcriptionally regulate protein-coding transcripts, as do microRNAs (miRNAs, and both sRNA classes control development through their targets. TasiRNA biogenesis requires multiple components of the siRNA pathway and also miRNAs. But while 21mer siRNAs originating from transgenes can mediate silencing across several cell layers, miRNA action seems spatially restricted to the producing or closely surrounding cells. PRINCIPAL FINDINGS: We have previously described the isolation of a genetrap reporter line for TAS3a, the major locus producing AUXIN RESPONS FACTOR (ARF-regulating tasiRNAs in the Arabidopsis shoot. Its activity is limited to the adaxial (upper side of leaf primordia, thus spatially isolated from ARF-activities, which are located in the abaxial (lower side. We show here by in situ hybridization and reporter fusions that the silencing activities of ARF-regulating tasiRNAs are indeed manifested non-cell autonomously to spatially control ARF activities. CONCLUSIONS/SIGNIFICANCE: Endogenous tasiRNAs are thus mediators of a mobile developmental signal and might provide effective gene silencing at a distance beyond the reach of most miRNAs.

Converging, Synergistic Actions of Multiple Stress Hormones Mediate Enduring Memory Impairments after Acute Simultaneous Stresses.

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Chen, Yuncai; Molet, Jenny; Lauterborn, Julie C; Trieu, Brian H; Bolton, Jessica L; Patterson, Katelin P; Gall, Christine M; Lynch, Gary; Baram, Tallie Z

2016-11-02

Stress influences memory, an adaptive process crucial for survival. During stress, hippocampal synapses are bathed in a mixture of stress-released molecules, yet it is unknown whether or how these interact to mediate the effects of stress on memory. Here, we demonstrate novel synergistic actions of corticosterone and corticotropin-releasing hormone (CRH) on synaptic physiology and dendritic spine structure that mediate the profound effects of acute concurrent stresses on memory. Spatial memory in mice was impaired enduringly after acute concurrent stresses resulting from loss of synaptic potentiation associated with disrupted structure of synapse-bearing dendritic spines. Combined application of the stress hormones corticosterone and CRH recapitulated the physiological and structural defects provoked by acute stresses. Mechanistically, corticosterone and CRH, via their cognate receptors, acted synergistically on the spine-actin regulator RhoA, promoting its deactivation and degradation, respectively, and destabilizing spines. Accordingly, blocking the receptors of both hormones, but not each alone, rescued memory. Therefore, the synergistic actions of corticosterone and CRH at hippocampal synapses underlie memory impairments after concurrent and perhaps also single, severe acute stresses, with potential implications to spatial memory dysfunction in, for example, posttraumatic stress disorder. Stress influences memory, an adaptive process crucial for survival. During stress, adrenal corticosterone and hippocampal corticotropin-releasing hormone (CRH) permeate memory-forming hippocampal synapses, yet it is unknown whether (and how) these hormones interact to mediate effects of stress. Here, we demonstrate novel synergistic actions of corticosterone and CRH on hippocampal synaptic plasticity and spine structure that mediate the memory-disrupting effects of stress. Combined application of both hormones provoked synaptic function collapse and spine disruption

News framing and public opinion: A mediation analysis of framing effects on political attitudes

NARCIS (Netherlands)

Lecheler, S.K.; de Vreese, C.H.

2012-01-01

There is no satisfactory account of the psychological processes that mediate a news framing effect. Based on an experimental study (N = 1,537), this article presents a mediation analysis of a news framing effect on opinion, testing for two important mediation processes: belief importance and belief

Intergenerational Solidarity and Satisfaction With Life: Mediation Effects With Emerging Adults

Directory of Open Access Journals (Sweden)

Susana Coimbra

2013-05-01

Full Text Available The increasing dependency of emerging adults (EA on their family of origin and their lower future expectations challenge intergenerational family support exchanges and may affect their impact on satisfaction with life. This study aims to examine the mediation effect of familism, filial maturity, and relationship satisfaction between different directions of support (received, given and anticipated between both and satisfaction with life. Data was collected through the administration of self-report questionnaires to a convenience sample of 243 EA (18-30 years old of both genders, students and workers, of different socioeconomic statuses. Results corroborate the mediation effect of the study variables and suggest that the magnitude of this impact depends on the direction of the support: partial mediations are observed for the received support, whereas total mediations are observed for the given support.

MEDIATOR18 and MEDIATOR20 confer susceptibility to Fusarium oxysporum in Arabidopsis thaliana

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Stiller, Jiri; Davoine, Celine; Björklund, Stefan; Manners, John M.; Kazan, Kemal; Schenk, Peer M.

2017-01-01

The conserved protein complex known as Mediator conveys transcriptional signals by acting as an intermediary between transcription factors and RNA polymerase II. As a result, Mediator subunits play multiple roles in regulating developmental as well as abiotic and biotic stress pathways. In this report we identify the head domain subunits MEDIATOR18 and MEDIATOR20 as important susceptibility factors for Fusarium oxysporum infection in Arabidopsis thaliana. Mutants of MED18 and MED20 display down-regulation of genes associated with jasmonate signaling and biosynthesis while up-regulation of salicylic acid associated pathogenesis related genes and reactive oxygen producing and scavenging genes. We propose that MED18 and MED20 form a sub-domain within Mediator that controls the balance of salicylic acid and jasmonate associated defense pathways. PMID:28441405

The applied model of imagery use: Examination of moderation and mediation effects.

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Koehn, S; Stavrou, N A M; Young, J A; Morris, T

2016-08-01

The applied model of mental imagery use proposed an interaction effect between imagery type and imagery ability. This study had two aims: (a) the examination of imagery ability as a moderating variable between imagery type and dispositional flow, and (b) the testing of alternative mediation models. The sample consisted of 367 athletes from Scotland and Australia, who completed the Sport Imagery Questionnaire, Sport Imagery Ability Questionnaire, and Dispositional Flow Scale-2. Hierarchical regression analysis showed direct effects of imagery use and imagery ability on flow, but no significant interaction. Mediation analysis revealed a significant indirect path, indicating a partially mediated relationship (P = 0.002) between imagery use, imagery ability, and flow. Partial mediation was confirmed when the effect of cognitive imagery use and cognitive imagery ability was tested, and a full mediation model was found between motivational imagery use, motivational imagery ability, and flow. The results are discussed in conjunction with potential future research directions on advancing theory and applications. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Suppressive effects of lysozyme on polyphosphate-mediated vascular inflammatory responses

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Chung, Jiwoo [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566 (Korea, Republic of); Ku, Sae-Kwang [Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610 (Korea, Republic of); Lee, Suyeon [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566 (Korea, Republic of); Bae, Jong-Sup, E-mail: baejs@knu.ac.kr [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566 (Korea, Republic of)

2016-06-10

Lysozyme, found in relatively high concentration in blood, saliva, tears, and milk, protects us from the ever-present danger of bacterial infection. Previous studies have reported proinflammatory responses of endothelial cells to the release of polyphosphate(PolyP). In this study, we examined the anti-inflammatory responses and mechanisms of lysozyme and its effects on PolyP-induced septic activities in human umbilical vein endothelial cells (HUVECs) and mice. The survival rates, septic biomarker levels, behavior of human neutrophils, and vascular permeability were determined in PolyP-activated HUVECs and mice. Lysozyme suppressed the PolyP-mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion/migration of leukocytes, and activation and/or production of nuclear factor-κB, tumor necrosis factor-α, and interleukin-6. Furthermore, lysozyme demonstrated protective effects on PolyP-mediated lethal death and the levels of the related septic biomarkers. Therefore, these results indicated the therapeutic potential of lysozyme on various systemic inflammatory diseases, such as sepsis or septic shock. -- Highlights: •PolyP is shown to be an important mediator of vascular inflammation. •Lysozyme inhibited PolyP-mediated hyperpermeability. •Lysozyme inhibited PolyP-mediated septic response. •Lysozyme reduced PolyP-induced septic mortality.

Suppressive effects of lysozyme on polyphosphate-mediated vascular inflammatory responses

International Nuclear Information System (INIS)

Chung, Jiwoo; Ku, Sae-Kwang; Lee, Suyeon; Bae, Jong-Sup

2016-01-01

Lysozyme, found in relatively high concentration in blood, saliva, tears, and milk, protects us from the ever-present danger of bacterial infection. Previous studies have reported proinflammatory responses of endothelial cells to the release of polyphosphate(PolyP). In this study, we examined the anti-inflammatory responses and mechanisms of lysozyme and its effects on PolyP-induced septic activities in human umbilical vein endothelial cells (HUVECs) and mice. The survival rates, septic biomarker levels, behavior of human neutrophils, and vascular permeability were determined in PolyP-activated HUVECs and mice. Lysozyme suppressed the PolyP-mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion/migration of leukocytes, and activation and/or production of nuclear factor-κB, tumor necrosis factor-α, and interleukin-6. Furthermore, lysozyme demonstrated protective effects on PolyP-mediated lethal death and the levels of the related septic biomarkers. Therefore, these results indicated the therapeutic potential of lysozyme on various systemic inflammatory diseases, such as sepsis or septic shock. -- Highlights: •PolyP is shown to be an important mediator of vascular inflammation. •Lysozyme inhibited PolyP-mediated hyperpermeability. •Lysozyme inhibited PolyP-mediated septic response. •Lysozyme reduced PolyP-induced septic mortality.

Social relationships, depressive symptoms and suicidality in Korea: Examining mediating and moderating effects in men and women.

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Lee, Min-Ah

2016-02-01

It has been widely recognized that social relationships and depressive symptoms predict suicidality. However, there are few empirical studies examining relationships among these three factors using an integrative approach. This study aimed to examine the effects of perceived quality of social relationships and depressive symptoms on suicidality and to analyze whether the effect of perceived quality of social relationships on suicidality is mediated by depressive symptoms or whether the perceived quality of social relationships has a moderating effect on the relationship between depressive symptoms and suicidality in men and women. The data were drawn from the 2012 Korean General Social Survey, a nationally representative survey. Multiple regression models and subsample analyses were conducted according to gender. A higher perceived quality of social relationships decreased suicidality while depressive symptoms increased suicidality. The effect of perceived quality of social relationships was partially mediated by depressive symptoms. Perceived quality of social relationships also significantly interacted with depressive symptoms, suggesting that the harmful effect of depressive symptoms was ameliorated as perceived quality of social relationships increased. A subsample analysis according to gender, however, indicated a significant gender difference in that the perceived quality of social relationships moderated the effect of depressive symptoms only in women. The findings suggest that enhanced quality of social relationships can protect people from suicidal risk and are more effective for women with depressive symptoms than for men with the same symptoms. © The Author(s) 2015.

BIM is the primary mediator of MYC-induced apoptosis in multiple solid tissues.

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Muthalagu, Nathiya; Junttila, Melissa R; Wiese, Katrin E; Wolf, Elmar; Morton, Jennifer; Bauer, Barbara; Evan, Gerard I; Eilers, Martin; Murphy, Daniel J

2014-09-11

MYC is one of the most frequently overexpressed oncogenes in human cancer, and even modestly deregulated MYC can initiate ectopic proliferation in many postmitotic cell types in vivo. Sensitization of cells to apoptosis limits MYC's oncogenic potential. However, the mechanism through which MYC induces apoptosis is controversial. Some studies implicate p19ARF-mediated stabilization of p53, followed by induction of proapoptotic BH3 proteins NOXA and PUMA, whereas others argue for direct regulation of BH3 proteins, especially BIM. Here, we use a single experimental system to systematically evaluate the roles of p19ARF and BIM during MYC-induced apoptosis, in vitro, in vivo, and in combination with a widely used chemotherapeutic, doxorubicin. We find a common specific requirement for BIM during MYC-induced apoptosis in multiple settings, which does not extend to the p53-responsive BH3 family member PUMA, and find no evidence of a role for p19ARF during MYC-induced apoptosis in the tissues examined. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Multiple effects of the special AT-rich binding protein 1 (SATB1) in colon carcinoma.

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Frömberg, Anja; Rabe, Michael; Aigner, Achim

2014-12-01

SATB1 (special AT-rich binding protein 1) is a global chromatin organizer regulating the expression of a large number of genes. Overexpression has been found in various solid tumors and positively correlated with prognostic and clinicopathological properties. In colorectal cancer (CRC), SATB1 overexpression and its correlation with poor differentiation, invasive depth, TNM (tumor, nodes, metastases) stage and prognosis have been demonstrated. However, more detailed studies on the SATB1 functions in CRC are warranted. In this article, we comprehensively analyze the cellular and molecular role of SATB1 in CRC cell lines with different SATB1 expression levels by using RNAi-mediated knockdown. Using siRNAs with different knockdown efficacies, we demonstrate antiproliferative, cell cycle-inhibitory and proapoptotic effects of SATB1 knockdown in a SATB1 gene dose-dependent manner. Tumor growth inhibition is confirmed in vivo in a subcutaneous tumor xenograft mouse model using stable knockdown cells. The in-depth analysis of cellular effects reveals increased activities of caspases-3, -7, -8, -9 and other mediators of apoptotic pathways. Similarly, the analysis of E- and N-cadherin, slug, twist, β-catenin and MMP7 indicates SATB1 effects on epithelial-mesenchymal transition (EMT) and matrix breakdown. Our results also establish SATB1 effects on receptor tyrosine kinases and (proto-)oncogenes such as HER receptors and Pim-1. Taken together, this suggests a more complex molecular interplay between tumor-promoting and possible inhibitory effects in CRC by affecting multiple pathways and molecules involved in proliferation, cell cycle, EMT, invasion and cell survival. © 2014 UICC.

Under What Assumptions Do Site-by-Treatment Instruments Identify Average Causal Effects?

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Reardon, Sean F.; Raudenbush, Stephen W.

2013-01-01

The increasing availability of data from multi-site randomized trials provides a potential opportunity to use instrumental variables methods to study the effects of multiple hypothesized mediators of the effect of a treatment. We derive nine assumptions needed to identify the effects of multiple mediators when using site-by-treatment interactions…

Effective capacity of multiple antenna channels: Correlation and keyhole

KAUST Repository

Zhong, Caijun

2012-01-01

In this study, the authors derive the effective capacity limits for multiple antenna channels which quantify the maximum achievable rate with consideration of link-layer delay-bound violation probability. Both correlated multiple-input single-output and multiple-input multiple-output keyhole channels are studied. Based on the closed-form exact expressions for the effective capacity of both channels, the authors look into the asymptotic high and low signal-to-noise ratio regimes, and derive simple expressions to gain more insights. The impact of spatial correlation on effective capacity is also characterised with the aid of a majorisation theory result. It is revealed that antenna correlation reduces the effective capacity of the channels and a stringent quality-of-service requirement causes a severe reduction in the effective capacity but can be alleviated by increasing the number of antennas. © 2012 The Institution of Engineering and Technology.

Attentional control mediates the effect of social anxiety on positive affect☆

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Morrison, Amanda S.; Heimberg, Richard G.

2015-01-01

The goal of the present studies was to examine whether attentional control, a self-regulatory attentional mechanism, mediates the effect of social anxiety on positive affect. We tested this mediation in two studies using undergraduate students selected to represent a broad range of severity of social anxiety. Self-report assessments of social anxiety, attentional control, and positive affect were collected in a cross-sectional design (Study 1) and in a longitudinal design with three assessment points (Study 2). Results of both studies supported the hypothesized mediational model. Specifically, social anxiety was inversely related to attentional control, which itself positively predicted positive affect. This mediation remained significant even when statistically controlling for the effects of depression. Additionally, the hypothesized model provided superior model fit to theoretically-grounded equivalent models in both studies. Implications of these findings for understanding diminished positive affect in social anxiety are discussed. PMID:23254261

Inverse odds ratio-weighted estimation for causal mediation analysis.

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Tchetgen Tchetgen, Eric J

2013-11-20

An important scientific goal of studies in the health and social sciences is increasingly to determine to what extent the total effect of a point exposure is mediated by an intermediate variable on the causal pathway between the exposure and the outcome. A causal framework has recently been proposed for mediation analysis, which gives rise to new definitions, formal identification results and novel estimators of direct and indirect effects. In the present paper, the author describes a new inverse odds ratio-weighted approach to estimate so-called natural direct and indirect effects. The approach, which uses as a weight the inverse of an estimate of the odds ratio function relating the exposure and the mediator, is universal in that it can be used to decompose total effects in a number of regression models commonly used in practice. Specifically, the approach may be used for effect decomposition in generalized linear models with a nonlinear link function, and in a number of other commonly used models such as the Cox proportional hazards regression for a survival outcome. The approach is simple and can be implemented in standard software provided a weight can be specified for each observation. An additional advantage of the method is that it easily incorporates multiple mediators of a categorical, discrete or continuous nature. Copyright © 2013 John Wiley & Sons, Ltd.

Music, radio and mediatization

DEFF Research Database (Denmark)

Michelsen, Morten; Krogh, Mads

2016-01-01

of mediatization where media as such seem to be ascribed agency. Instead, we consider historical accounts of music–radio in order to address the complex nonlinearity of concrete processes of mediatization as they take place in the multiple meetings between a decentred notion of radio and musical life.......Mediatization has become a key concept for understanding the relations between media and other cultural and social fields. Contributing to the discussions related to the concept of mediatization, this article discusses how practices of radio and music(al life) influence each other. We follow Deacon......’s and Stanyer’s advice to supplement the concept of mediatization with ‘a series of additional concepts at lower levels of abstraction’ and suggest, in this respect, the notion of heterogeneous milieus of music–radio. Hereby, we turn away from the all-encompassing perspectives related to the concept...

Training Effects on Computer-Mediated Peer Review

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Liou, Hsien-Chin; Peng, Zhong-Yan

2009-01-01

The interactive functions of weblogs facilitate computer-mediated peer reviews for collaborative writing. As limited research has been conducted on examining the training effects of peer reviews on students' peer comments, their revision quality, and their perceptions when composing in weblogs, the present case study aims to fill the gap. Thirteen…

Identification as a Mediator of Celebrity Effects.

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Basil, Michael D.

1996-01-01

This study examined personal concern, perceived risk, and sexual behavior of 147 college students a year after Magic Johnson announced he tested positive for HIV (Human Immunodeficiency Virus). It found that identification mediates message effects, suggesting that a spokesperson with whom an audience can identify insures the greatest likelihood of…

Carrier-mediated transport of peptides by the kidney

International Nuclear Information System (INIS)

Skopicki, H.A.

1988-01-01

Small peptide transport was characterized to determine if: (1) Multiple carriers are present in the luminal membrane of renal proximal tubular cells; (2) Carrier-mediated peptide transport is limited by size; and (3) Gentamicin inhibits carrier-mediated reabsorption of peptides. Uptake of glycyl-[ 3 H]proline (Gly-Pro) into renal brush border membrane vesicles demonstrated a dual affinity carrier system. Whether multiple carriers are present was further investigated by characterizing the uptake of [ 3 H]pyroglutamyl-histidine. To determine if carrier-mediated transport of peptides is limited by size of the molecule, uptake of the hydrolytically resistant tripeptide, [ 3 H]pryroglutamyl-histidyl-tryptophan (pGlu-His-Trp), and tetrapeptide, [ 3 H]pyroglutamyl-histidyl-tryptophyl-serine (pGlu-His-Trp-Ser) were assessed. These data indicate: multiple carriers exist on the luminal membrane of renal proximal tubular cells for the transport of dipeptides, and tripeptide pGlu-His-Trp and the tetrapeptide pGlu-His-Trp-Ser are not taken up by a carrier-mediated mechanism, suggesting that the carrier may be limited by the size of the substrate

Narrative perspective shift at retrieval: The psychological-distance-mediated-effect on emotional intensity of positive and negative autobiographical memory.

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Gu, Xuan; Tse, Chi-Shing

2016-10-01

The present study manipulated participants' narrative perspectives (1st-personal pronoun "I" and 3rd-personal pronoun "He/She") to vary their field and observer visual perspectives that they took to retrieve autobiographical events and examine how the shifts in narrative perspective could influence the self-rated emotional intensity of autobiographical memory. Results showed that when narrative perspectives effectively shifted participants' visual perspectives from field to observer, they felt attenuated emotional intensities of positive and negative autobiographical memories. However, this did not occur when narrative perspectives effectively shifted the visual perspectives from observer to field. Multiple mediator models further showed that the changes in psychological distance and imagery vividness (a distance-related construct) of autobiographical memory mediated the relationship between the narrative perspective shift from the 1st- to 3rd-person and the reduction in the intensities of negative and positive emotion. This provides support for the role of psychological distancing in reducing the emotional intensity of autobiographical memory. Copyright © 2016 Elsevier Inc. All rights reserved.

Associations between trait emotional intelligence and loneliness in Chinese undergraduate students: mediating effects of self-esteem and social support.

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Zou, Jilin

2014-06-01

Prior studies indicate that trait emotional intelligence (EI) is associated negatively with loneliness. However, the mechanisms underlying the relationship are not clear. This study assessed whether both self-esteem and social support mediated the associations between trait EI and loneliness. 469 Chinese undergraduate participants whose age ranged from 18 to 23 years (208 women) were asked to complete four self-report questionnaires, including the Wong Law Emotional Intelligence Scale, the Social and Emotional Loneliness Scale, the Rosenberg Self-esteem Scale, and the Multi-Dimensional Scale of Perceived Social Support. Analyses indicated that self-esteem and social support fully mediated the associations between trait EI and loneliness. Effect contrasts indicated that the specific indirect effect through social support was significantly greater than that through self-esteem. Moreover, a multiple-group analysis indicated that no path differed significantly by sex. These results suggest that social support is more important than self-esteem in the association between trait EI and loneliness. Furthermore, both sexes appear to share the same mechanism underlying this association.

Lysosomes as mediators of drug resistance in cancer.

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Zhitomirsky, Benny; Assaraf, Yehuda G

2016-01-01

Drug resistance remains a leading cause of chemotherapeutic treatment failure and cancer-related mortality. While some mechanisms of anticancer drug resistance have been well characterized, multiple mechanisms remain elusive. In this respect, passive ion trapping-based lysosomal sequestration of multiple hydrophobic weak-base chemotherapeutic agents was found to reduce the accessibility of these drugs to their target sites, resulting in a markedly reduced cytotoxic effect and drug resistance. Recently we have demonstrated that lysosomal sequestration of hydrophobic weak base drugs triggers TFEB-mediated lysosomal biogenesis resulting in an enlarged lysosomal compartment, capable of enhanced drug sequestration. This study further showed that cancer cells with an increased number of drug-accumulating lysosomes are more resistant to lysosome-sequestered drugs, suggesting a model of drug-induced lysosome-mediated chemoresistance. In addition to passive drug sequestration of hydrophobic weak base chemotherapeutics, other mechanisms of lysosome-mediated drug resistance have also been reported; these include active lysosomal drug sequestration mediated by ATP-driven transporters from the ABC superfamily, and a role for lysosomal copper transporters in cancer resistance to platinum-based chemotherapeutics. Furthermore, lysosomal exocytosis was suggested as a mechanism to facilitate the clearance of chemotherapeutics which highly accumulated in lysosomes, thus providing an additional line of resistance, supplementing the organelle entrapment of chemotherapeutics away from their target sites. Along with these mechanisms of lysosome-mediated drug resistance, several approaches were recently developed for the overcoming of drug resistance or exploiting lysosomal drug sequestration, including lysosomal photodestruction and drug-induced lysosomal membrane permeabilization. In this review we explore the current literature addressing the role of lysosomes in mediating cancer drug

Does food vendor density mediate the association between neighborhood deprivation and BMI?: a G-computation mediation analysis.

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Zhang, Y Tara; Laraia, Barbara A; Mujahid, Mahasin S; Tamayo, Aracely; Blanchard, Samuel D; Warton, E Margaret; Kelly, N Maggi; Moffet, Howard H; Schillinger, Dean; Adler, Nancy; Karter, Andrew J

2015-05-01

In previous research, neighborhood deprivation was positively associated with body mass index (BMI) among adults with diabetes. We assessed whether the association between neighborhood deprivation and BMI is attributable, in part, to geographic variation in the availability of healthful and unhealthful food vendors. Subjects were 16,634 participants of the Diabetes Study of Northern California, a multiethnic cohort of adults living with diabetes. Neighborhood deprivation and healthful (supermarket and produce) and unhealthful (fast food outlets and convenience stores) food vendor kernel density were calculated at each participant's residential block centroid. We estimated the total effect, controlled direct effect, natural direct effect, and natural indirect effect of neighborhood deprivation on BMI. Mediation effects were estimated using G-computation, a maximum likelihood substitution estimator of the G-formula that allows for complex data relations such as multiple mediators and sequential causal pathways. We estimated that if neighborhood deprivation was reduced from the most deprived to the least deprived quartile, average BMI would change by -0.73 units (95% confidence interval: -1.05, -0.32); however, we did not detect evidence of mediation by food vendor density. In contrast to previous findings, a simulated reduction in neighborhood deprivation from the most deprived to the least deprived quartile was associated with dramatic declines in both healthful and unhealthful food vendor density. Availability of food vendors, both healthful and unhealthful, did not appear to explain the association between neighborhood deprivation and BMI in this population of adults with diabetes.

Elaborating on Internet addiction and cyberchondria – relationships, direct and mediated effects

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Eliza Ivanova

2014-09-01

Full Text Available The present paper focuses on the effects of personality traits on the levels of Internet addiction and cyberchondria and their consequent effects on well-being. For the purposes of the research, mediation analyses were carried out, clarifying the influence of personality traits on well-being mediated by Internet addiction, cyberchondria and anxiety aroused by online health information seeking. It was established that Neuroticism leads to decreased well-being through the mediating influence of health anxiety, escalation and persistence of health concerns. Health anxiety is a mediator in the relationship between Openness to Experience and well-being. It was established that low levels of Agreeableness and Conscientiousness, and high levels of Openness, and Neuroticism, influence Internet addiction, which in turn leads to decreased well-being. Furthermore, we established the mediated influence of Internet addiction on the tendency for cyberchondria and health anxiety through using the Internet for health information and judgment biases.

Does mindfulness enhance critical thinking? Evidence for the mediating effects of executive functioning in the relationship between mindfulness and critical thinking

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Chris eNoone

2016-01-01

Full Text Available Mindfulness originated in the Buddhist tradition as a way of cultivating clarity of thought. Despite the fact that this behaviour is best captured using critical thinking assessments, no studies have examined the effects of mindfulness on critical thinking or the mechanisms underlying any such possible relationship. Even so, mindfulness has been suggested as being beneficial for critical thinking in higher education. Critical thinking is recognised as an important higher-order cognitive process which involves the ability to analyse and evaluate evidence and arguments. Such non-automatic, reflective responses generally require the engagement of executive functioning which includes updating, inhibition and shifting of representations in working memory. Based on research showing that mindfulness enhances aspects of executive functioning and certain higher-order cognitive processes, we hypothesised that individuals higher in facets of dispositional mindfulness would demonstrate greater critical thinking performance, and that this relationship would be mediated by executive functioning. Cross-sectional assessment of these constructs in a sample of 178 university students was achieved using the observing and non-reactivity sub-scales of the Five Factor Mindfulness Questionnaire, a battery of executive functioning tasks and the Halpern Critical Thinking Assessment. Our hypotheses were tested by constructing a multiple meditation model which was analysed using Structural Equation Modelling. Evidence was found for inhibition mediating the relationships between both observing and non-reactivity and critical thinking in different ways. Indirect-only (or full mediation was demonstrated for the relationship between observing, inhibition and critical thinking. Competitive mediation was demonstrated for the relationship between non-reactivity, inhibition and critical thinking. This suggests additional mediators of the relationship between non-reactivity and

Mediators of the association of major depressive syndrome and anxiety syndrome with postpartum smoking relapse.

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Correa-Fernández, Virmarie; Ji, Lingyun; Castro, Yessenia; Heppner, Whitney L; Vidrine, Jennifer Irvin; Costello, Tracy J; Mullen, Patricia Dolan; Cofta-Woerpel, Ludmila; Velasquez, Mary M; Greisinger, Anthony; Cinciripini, Paul M; Wetter, David W

2012-08-01

Based on conceptual models of addiction and affect regulation, this study examined the mechanisms linking current major depressive syndrome (MDS) and anxiety syndrome (AS) to postpartum smoking relapse. Data were collected in a randomized clinical trial from 251 women who quit smoking during pregnancy. Simple and multiple mediation models of the relations of MDS and AS with postpartum relapse were examined using linear regression, continuation ratio logit models, and a bootstrapping procedure to test the indirect effects. Both MDS and AS significantly predicted postpartum smoking relapse. After adjusting for MDS, AS significantly predicted relapse. However, after adjusting for AS, MDS no longer predicted relapse. Situationally based self-efficacy, expectancies of controlling negative affect by means other than smoking, and various dimensions of primary and secondary tobacco dependence individually mediated the effect of both MDS and AS on relapse. In multiple mediation models, self-efficacy in negative/affective situations significantly mediated the effect of MDS and AS on relapse. The findings underscore the negative impact of depression and anxiety on postpartum smoking relapse and suggest that the effects of MDS on postpartum relapse may be largely explained by comorbid AS. The current investigation provided mixed support for affect regulation models of addiction. Cognitive and tobacco dependence-related aspects of negative and positive reinforcement significantly mediated the relationship of depression and anxiety with relapse, whereas affect and stress did not. The findings emphasize the unique role of low agency with respect to abstaining from smoking in negative affective situations as a key predictor of postpartum smoking relapse. © 2012 American Psychological Association

Mediating effects of bullying involvement on the relationship of body mass index with social phobia, depression, suicidality, and self-esteem and sex differences in adolescents in Taiwan.

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Yen, Cheng-Fang; Liu, Tai-Ling; Ko, Chih-Hung; Wu, Yu-Yu; Cheng, Chung-Ping

2014-03-01

The aims of this study were to examine the mediating effect of bullying involvement on the relationships between body mass index (BMI) and mental health problems, including social phobia, depression, suicidality, and low self-esteem among adolescents in Taiwan. The moderation effect of sex on the mediating role of bullying involvement was also examined. Five thousand two hundred and fifty-two students of high schools completed the questionnaires. Victimization and perpetration of passive and active bullying were assessed using the Chinese version of the School Bullying Experience Questionnaire. BMI was calculated from self-reported weight and height measurements. The Social Phobia Inventory, the Mandarin Chinese version of the Center for Epidemiological Studies-Depression Scale, the suicidality-related questionnaire from the epidemiological version of the Kiddie-Schedule for Affective Disorders and Schizophrenia, and the Rosenberg Self-Esteem Scale were applied to assess social phobia, depression, suicidality, and low self-esteem, respectively. The mediating effect of bullying involvement on the associations between increased BMI and mental health problems was examined by the Sobel test. The moderation effect of sex on the mediating role of bullying involvement was tested by the multiple-group structural equation model. Victimization of passive and active bullying and perpetration of passive bullying, but not perpetration of active bullying, had a mediating effect on the relationships between increased BMI and all four mental health problems. Sex did not have a significant moderation effect on the mediating role of bullying involvement. Bullying involvement should be a target of prevention and intervention in developing a strategy to improve mental health among adolescents with increased BMI. Copyright © 2013 Elsevier Ltd. All rights reserved.

Testing Moderator and Mediator Effects in Counseling Psychology Research

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Frazier, Patricia A.; Tix, Andrew P.; Barron, Kenneth E.

2004-01-01

The goals of this article are to (a) describe differences between moderator and mediator effects; (b) provide nontechnical descriptions of how to examine each type of effect, including study design, analysis, and interpretation of results; (c) demonstrate how to analyze each type of effect; and (d) provide suggestions for further reading. The…

Degenerate Power in Multilevel Mediation: The Non-Monotonic Relationship between Power & Effect Size

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Kelcey, Ben

2015-01-01

Like studies focused on the detection of a main or total effect, a principal consideration in the design of studies examining mediation is the power with which mediation effects can be detected if they exist (e.g., Raudenbush, 1997). However, unlike studies concerning the detection of main effects, literature has not established power formulas for…

Feedback enhances the positive effects and reduces the negative effects of multiple-choice testing.

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Butler, Andrew C; Roediger, Henry L

2008-04-01

Multiple-choice tests are used frequently in higher education without much consideration of the impact this form of assessment has on learning. Multiple-choice testing enhances retention of the material tested (the testing effect); however, unlike other tests, multiple-choice can also be detrimental because it exposes students to misinformation in the form of lures. The selection of lures can lead students to acquire false knowledge (Roediger & Marsh, 2005). The present research investigated whether feedback could be used to boost the positive effects and reduce the negative effects of multiple-choice testing. Subjects studied passages and then received a multiple-choice test with immediate feedback, delayed feedback, or no feedback. In comparison with the no-feedback condition, both immediate and delayed feedback increased the proportion of correct responses and reduced the proportion of intrusions (i.e., lure responses from the initial multiple-choice test) on a delayed cued recall test. Educators should provide feedback when using multiple-choice tests.

Assessing Mediational Models: Testing and Interval Estimation for Indirect Effects.

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Biesanz, Jeremy C; Falk, Carl F; Savalei, Victoria

2010-08-06

Theoretical models specifying indirect or mediated effects are common in the social sciences. An indirect effect exists when an independent variable's influence on the dependent variable is mediated through an intervening variable. Classic approaches to assessing such mediational hypotheses ( Baron & Kenny, 1986 ; Sobel, 1982 ) have in recent years been supplemented by computationally intensive methods such as bootstrapping, the distribution of the product methods, and hierarchical Bayesian Markov chain Monte Carlo (MCMC) methods. These different approaches for assessing mediation are illustrated using data from Dunn, Biesanz, Human, and Finn (2007). However, little is known about how these methods perform relative to each other, particularly in more challenging situations, such as with data that are incomplete and/or nonnormal. This article presents an extensive Monte Carlo simulation evaluating a host of approaches for assessing mediation. We examine Type I error rates, power, and coverage. We study normal and nonnormal data as well as complete and incomplete data. In addition, we adapt a method, recently proposed in statistical literature, that does not rely on confidence intervals (CIs) to test the null hypothesis of no indirect effect. The results suggest that the new inferential method-the partial posterior p value-slightly outperforms existing ones in terms of maintaining Type I error rates while maximizing power, especially with incomplete data. Among confidence interval approaches, the bias-corrected accelerated (BC a ) bootstrapping approach often has inflated Type I error rates and inconsistent coverage and is not recommended; In contrast, the bootstrapped percentile confidence interval and the hierarchical Bayesian MCMC method perform best overall, maintaining Type I error rates, exhibiting reasonable power, and producing stable and accurate coverage rates.

Limits on the expression of enzyme-mediated solvent isotope effects

International Nuclear Information System (INIS)

Northrop, D.B.

1981-01-01

Steady-state analysis of primary solvent isotope effects on enzyme-catalyzed reactions, mediated by solvent-shielded di- or triprotic groups on the enzyme, yields equations describing the upper limit of intramolecular isotopic discrimation. For diprotic groups [P/sub H]/[P/sub D/] = 3k/sub H//k/sub D/ + 3), and for triprotic groups [P/sub H/]/[P/sub D/] = [7(k/sub H//k/sub D/ 2 = 10k/sub H/k/sub D/ + 1]/[(k/sub H//k/sub D/) 2 + 10k/sub H//k/sub D/ + 7]. Given a normal intrinsic isotope effect of k/sub H//k/sub D/ = 7, maximal isotopic discrimation in 50:50 H 2 O:D 2 O is therefore 2.2 and 3.3, respectively, versus 1.0 for a monoprotic group. Intermediate values of isotope discrimination may be interpreted with respect to distinguishing enzyme-mediated catalytic mechanisms from those of direct transfer between solvent and substrate, and to identifying mediating groups, by comparisons of isotopic discrimination at high and low concentrations of substrates and by reference to intrinsic and intermolecular isotope effects

Effect of Different Mediated Agents on Morphology and Crystallinity of Synthesized Silver Nanowires Prepared by Polyol Process

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Mohammad Taghi Satoungar

2016-01-01

Full Text Available Synthesis and characterization of multiple crystalline silver nanowires (NWs with uniform diameters were carried out by using 1,2-propandiol and ethylene glycol (EG as comediated solvents and FeCl3 as mediated agent in the presence of poly(vinyl pyrrolidone (PVP. Experimental data and structural characterizations revealed that AgNWs have evolved from the multiple crystalline seeds initially generated by reduction of AgNO3 with EG and 1,2-propandiol followed by reducing Fe(III to Fe(II which in turn reacts with and removes adsorbed atomic oxygen from the surfaces of silver seeds. In addition, uniform silver nanowires were obtained by using FeCl2 and AlCl3 as mediated agents in EG solution. Field emission scanning electron microscopy (FESEM and transmission electron microscopy (TEM showed uniform nanowires in both diameter and length. UV-Vis spectra showed adsorption peaks confirming the formation of nanowires. X-ray diffraction (XRD patterns displayed the final product with high crystallinity and purity. In this study, a growth mechanism for forming AgNWs was proposed and a comparison between different mediated agents was carried out.

Moderated mediation analysis: An illustration using the association of gender with delinquency and mental health.

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Miles, Jeremy N V; Kulesza, Magdalena; Ewing, Brett; Shih, Regina A; Tucker, Joan S; D'Amico, Elizabeth J

When researchers find an association between two variables, it is useful to evaluate the role of other constructs in this association. While assessing these mediation effects, it is important to determine if results are equal for different groups. It is possible that the strength of a mediation effect may differ for males and females, for example - such an effect is known as moderated mediation. Participants were 2532 adolescents from diverse ethnic/racial backgrounds and equally distributed across gender. The goal of this study was to investigate parental respect as a potential mediator of the relationship between gender and delinquency and mental health, and to determine whether observed mediation is moderated by gender. Parental respect mediated the association between gender and both delinquency and mental health. Specifically, parental respect was a protective factor against delinquency and mental health problems for both females and males. Demonstrated the process of estimating models in Lavaan, using two approaches (i.e. single group regression and multiple group regression model), and including covariates in both models.

From Animal House to Old School: a multiple mediation analysis of the association between college drinking movie exposure and freshman drinking and its consequences.

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Osberg, Timothy M; Billingsley, Katherine; Eggert, Meredith; Insana, Maribeth

2012-08-01

Does exposure to college drinking movies impact upon subsequent college student drinking? If so, what mechanisms mediate such an effect? In the first study to address these questions, we assessed college drinking movie exposure in a sample of 479 college freshmen early in their first semester and examined its relation to subsequent drinking and drinking consequences one month later. Hypothesized mediators of this effect included college alcohol beliefs (beliefs that drinking is central to college life), positive and negative alcohol expectancies, and descriptive and injunctive norms. Using bootstrapping procedures, results indicated that movie exposure exerted direct effects on both drinking and drinking consequences. Movie exposure also had significant indirect effects on drinking through all of the hypothesized mediators, with the exception of negative alcohol expectancies. All mediated movie exposure's effects on drinking consequences, with the exception of injunctive norms. Contrast analyses revealed that college alcohol beliefs had the strongest mediational effects in the relationship between movie exposure and both drinking and consequences. The implications of these findings for precollege alcohol education programs are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Relationships among race, education, criminal thinking, and recidivism: moderator and mediator effects.

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Walters, Glenn D

2014-02-01

Moderator and mediator relationships linking variables from three different theoretical traditions-race (subcultural theory), education (life-course theory), and criminal thinking (social learning theory)-and recidivism were examined in 1,101 released male federal prison inmates. Preliminary regression analyses indicated that racial status (White, Black, Hispanic) moderated the relationship between criminal thinking, as measured by the General Criminal Thinking (GCT) score of the Psychological Inventory of Criminal Thinking Styles (PICTS), and recidivism. Further analysis, however, revealed that it was not racial status, per se, that moderated the relationship between the PICTS and recidivism, but educational attainment. Whereas the PICTS was largely effective in predicting recidivism in inmates with 12 or more years of education, it was largely ineffective in predicting recidivism in inmates with fewer than 12 years of education. When education and the GCT score were compared as possible mediators of the race-recidivism relationship only the GCT successfully mediated this relationship. Sensitivity testing showed that the GCT mediating effect was moderately robust to violations of the sequential ignorability assumption on which causal mediation analysis rests. Moderator and mediator analyses are potentially important avenues through which theoretical constructs can be integrated and assessment strategies devised.

Lactoferricin mediates anabolic and anti-catabolic effects in the intervertebral disc.

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Kim, Jae-Sung; Ellman, Michael B; An, Howard S; Yan, Dongyao; van Wijnen, Andre J; Murphy, Gillian; Hoskin, David W; Im, Hee-Jeong

2012-04-01

Lactoferricin (LfcinB) antagonizes biological effects mediated by angiogenic and catabolic growth factors, in addition to pro-inflammatory cytokines and chemokines in human endothelial cells and tumor cells. However, the effect of LfcinB on intervertebral disc (IVD) cell metabolism has not yet been investigated. Using bovine nucleus pulposus (NP) cells, we analyzed the effect of LfcinB on proteoglycan (PG) accumulation, PG synthesis, and anabolic gene expression. We assessed expression of genes for matrix-degrading enzymes such as matrix metalloproteases (MMPs) and a disintegrin-like and metalloprotease with thrombospondin motifs (ADAMTS family), as well as their endogenous inhibitors, tissue inhibitor of metalloproteases (TIMPs). In order to understand the specific molecular mechanisms by which LfcinB exerts its biological effects, we investigated intracellular signaling pathways in NP cells. LfcinB increased PG accumulation mainly via PG synthesis in a dose-dependent manner. Simultaneously, LfcinB dose-dependently downregulated catabolic enzymes. LfcinB's anti-catabolic effects were further demonstrated by a dose-dependent increase in multiple TIMP family members. Our results demonstrate that ERK and/or p38 mitogen-activated protein kinase pathways are the key signaling cascades that exert the biological effects of LfcinB in NP cells, regulating transcription of aggrecan, SOX-9, TIMP-1, TIMP-2, TIMP-3, and iNOS. Our results suggest that LfcinB has anabolic and potent anti-catabolic biological effects on bovine IVD cells that may have considerable promise in the treatment of disc degeneration in the future. Copyright © 2011 Wiley Periodicals, Inc.

ON THE ANATOMY OF MEDIATIZED NEWS BROADCASTING: METAMORPHOSES AND MULTIPLE NARRATIVES

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Demétrio de Azeredo Soster

2013-06-01

Full Text Available This article discusses mediatization in news journalism, which is characterized by the institution, in current times, of a new “place” for the media. From this standpoint, they are no longer regarded as mere media, but as structuring elements of a new communicational bios. In the course of society’s transition from the media towards a mediatized society, news production practices become complex and process practices, as well as narrative and content distribution forms emerge, that are distinct from those seen until then. Television news broadcast emerges, therefore, in a new format, made up of the cluster of diverse media that refer to such programs, demanding new identification and recognition protocols. These changes will be examined as they relate to the news telecasts TV Folha, of TV Cultura, based on four movements resulting from the mediatization process in journalism: self-referentiality, co-referentiality, decentralization and dialogy.

On the anatomy of mediatized news broadcasting: metamorphoses and multiple narratives

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Fabiana Piccinin

2013-12-01

Full Text Available This article discusses mediatization in news journalism, which is characterized by the institution, in current times, of a new “place” for the media. From this standpoint, they are no longer regarded as mere media, but as structuring elements of a new communicational bios. In the course of society’s transition from the media towards a mediatized society, news production practices become complex and process practices, as well as narrative and content distribution forms emerge, that are distinct from those seen until then. Television news broadcast emerges, therefore, in a new format, made up of the cluster of diverse media that refer to such programs, demanding new identification and recognition protocols. These changes will be examined as they relate to the news telecasts TV Folha, of TV Cultura, based on four movements resulting from the mediatization process in journalism: self-referentiality, co-referentiality, decentralization and dialogy.

A dominant mutation in mediator of paramutation2, one of three second-largest subunits of a plant-specific RNA polymerase, disrupts multiple siRNA silencing processes.

Science.gov (United States)

Sidorenko, Lyudmila; Dorweiler, Jane E; Cigan, A Mark; Arteaga-Vazquez, Mario; Vyas, Meenal; Kermicle, Jerry; Jurcin, Diane; Brzeski, Jan; Cai, Yu; Chandler, Vicki L

2009-11-01

Paramutation involves homologous sequence communication that leads to meiotically heritable transcriptional silencing. We demonstrate that mop2 (mediator of paramutation2), which alters paramutation at multiple loci, encodes a gene similar to Arabidopsis NRPD2/E2, the second-largest subunit of plant-specific RNA polymerases IV and V. In Arabidopsis, Pol-IV and Pol-V play major roles in RNA-mediated silencing and a single second-largest subunit is shared between Pol-IV and Pol-V. Maize encodes three second-largest subunit genes: all three genes potentially encode full length proteins with highly conserved polymerase domains, and each are expressed in multiple overlapping tissues. The isolation of a recessive paramutation mutation in mop2 from a forward genetic screen suggests limited or no functional redundancy of these three genes. Potential alternative Pol-IV/Pol-V-like complexes could provide maize with a greater diversification of RNA-mediated transcriptional silencing machinery relative to Arabidopsis. Mop2-1 disrupts paramutation at multiple loci when heterozygous, whereas previously silenced alleles are only up-regulated when Mop2-1 is homozygous. The dramatic reduction in b1 tandem repeat siRNAs, but no disruption of silencing in Mop2-1 heterozygotes, suggests the major role for tandem repeat siRNAs is not to maintain silencing. Instead, we hypothesize the tandem repeat siRNAs mediate the establishment of the heritable silent state-a process fully disrupted in Mop2-1 heterozygotes. The dominant Mop2-1 mutation, which has a single nucleotide change in a domain highly conserved among all polymerases (E. coli to eukaryotes), disrupts both siRNA biogenesis (Pol-IV-like) and potentially processes downstream (Pol-V-like). These results suggest either the wild-type protein is a subunit in both complexes or the dominant mutant protein disrupts both complexes. Dominant mutations in the same domain in E. coli RNA polymerase suggest a model for Mop2-1 dominance

Callous-Unemotional Traits and Effortful Control Mediate the Effect of Parenting Intervention on Preschool Conduct Problems.

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Elizur, Yoel; Somech, Lior Y

2018-02-24

Parenting intervention (PI) is an effective treatment for children's conduct problems (CP) that has been shown to be mediated by improved parenting practices and parenting self-efficacy. Recently, Hitkashrut's randomized controlled trial demonstrated that ineffective parenting (IP) mediated effects on callous-unemotional (CU) traits and effortful control (EC), while controlling for more general treatment effects on CP. These temperament and personality-based features predict the formation of early-onset antisocial trajectories with poor long-term prognosis. The objective of this study was to use Hitkashrut's 3-wave dataset to test posttreatment EC and CU mediation of treatment effect on 1-year follow-up CP, and to determine whether mediation by each child-level potential mediator remains significant when tested concurrently with the parenting mediator. Parents of 209 3-5 year-old preschoolers (163 boys; 46 girls), with subclinical-clinical range CP were assigned to 14-session co-parent training groups (n = 140 couples), or to minimal intervention control groups (n = 69 couples). Assessments were based on both parents' questionnaires. An intent-to-treat analysis showed that EC and CU traits simultaneously mediated treatment effects on CP in one EC/CU mediational model. The concurrent testing of child- and parent-level mediators showed mediation by IP and CU traits in the CU/IP model, and IP mediation in the EC/IP model. Similar results were obtained in mediational analyses that controlled for the shared variance between the mediators and CP at T2. Overall, the findings support an intervention model of coaching parents of high-CP children to promote moral self-regulatory competencies while concurrently applying behavioral methods that directly target CP.

Extending the Similarity-Attraction Effect : The effects of When-Similarity in mediated communication

NARCIS (Netherlands)

Kaptein, M.C.; Castaneda, D.; Fernandez, N.; Nass, C.

2014-01-01

The feeling of connectedness experienced in computer-mediated relationships can be explained by the similarity-attraction effect (SAE). Though SAE is well established in psychology, the effects of some types of similarity have not yet been explored. In 2 studies, we demonstrate similarity-attraction

Discrimination and alcohol-related problems among college students: a prospective examination of mediating effects.

Science.gov (United States)

Hatzenbuehler, Mark L; Corbin, William R; Fromme, Kim

2011-06-01

Discrimination is a risk factor for health-risk behaviors, including alcohol abuse. Far less is known about the mechanisms through which discrimination leads to alcohol-related problems, particularly during high-risk developmental periods such as young adulthood. The present study tested a mediation model using prospective data from a large, diverse sample of 1539 college students. This model hypothesized that discrimination would be associated with established cognitive (positive alcohol expectancies) and affective (negative affect and coping motives) risk factors for alcohol-related problems, which would account for the prospective association between discrimination and alcohol problems. Structural equation modeling indicated that discrimination was associated cross-sectionally with negative affect and more coping motives for drinking, but not with greater alcohol expectancies. Coping motives mediated the prospective relationship between discrimination and alcohol-related problems. Additionally, results indicated significant indirect effects from discrimination to alcohol-related problems through negative affect and coping motives. These associations were evident for multiple groups confronting status-based discrimination, including women, racial/ethnic minorities, and lesbian/gay/bisexual individuals. This study identified potential affective mechanisms linking discrimination to alcohol-related problems. Results suggest several avenues for prevention and intervention efforts with individuals from socially disadvantaged groups. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Dealing with feelings: positive and negative discrete emotions as mediators of news framing effects

NARCIS (Netherlands)

Lecheler, S.; Schuck, A.R.T.; de Vreese, C.H.

2013-01-01

The underlying psychological processes that enable framing effects are often described as cognitive. Yet, recent studies suggest that framing effects may also be mediated by emotional response. The role of specific emotions in mediating the framing effect process, however, has yet to be fully

DARPP-32 interaction with adducin may mediate rapid environmental effects on striatal neurons.

Science.gov (United States)

Engmann, Olivia; Giralt, Albert; Gervasi, Nicolas; Marion-Poll, Lucile; Gasmi, Laila; Filhol, Odile; Picciotto, Marina R; Gilligan, Diana; Greengard, Paul; Nairn, Angus C; Hervé, Denis; Girault, Jean-Antoine

2015-12-07

Environmental enrichment has multiple effects on behaviour, including modification of responses to psychostimulant drugs mediated by striatal neurons. However, the underlying molecular and cellular mechanisms are not known. Here we show that DARPP-32, a hub signalling protein in striatal neurons, interacts with adducins, which are cytoskeletal proteins that cap actin filaments' fast-growing ends and regulate synaptic stability. DARPP-32 binds to adducin MARCKS domain and this interaction is modulated by DARPP-32 Ser97 phosphorylation. Phospho-Thr75-DARPP-32 facilitates β-adducin Ser713 phosphorylation through inhibition of a cAMP-dependent protein kinase/phosphatase-2A cascade. Caffeine or 24-h exposure to a novel enriched environment increases adducin phosphorylation in WT, but not T75A mutant mice. This cascade is implicated in the effects of brief exposure to novel enriched environment on dendritic spines in nucleus accumbens and cocaine locomotor response. Our results suggest a molecular pathway by which environmental changes may rapidly alter responsiveness of striatal neurons involved in the reward system.

Multiple sclerosis severity and concern about falling: Physical, cognitive and psychological mediating factors.

Science.gov (United States)

van Vliet, Rob; Hoang, Phu; Lord, Stephen; Gandevia, Simon; Delbaere, Kim

2015-01-01

Concern about falling can have devastating physical and psychological consequences in people with multiple sclerosis (MS). However, little is known about physical and cognitive determinants for increased concern about falling inthis group. To investigate direct and indirect relationships between MS severity and concern about falling using structural equation modelling (SEM). Two hundred and ten community-dwelling people (21-73 years) with MS Disease Steps 0-5 completed several physical, cognitive and psychological assessments. Concern about falling was assessed using the Falls Efficacy Scale-International. Concern about falling was significantly associated with MS Disease Step and also balance, muscle strength, disability, previous falls, and executive functioning. SEM revealed a strong direct path between MS Disease Step and concern about falling (r = 0.31, p concern about falling in people with MS and had an excellent goodness-of-fit. The relationship between MS severity and increased concern about falling was primarily mediated by reduced physical ability (especially if this resulted in disability and falls) and less so by executive functioning. This suggests people with MS have a realistic appraisal of their concern about falling.

Anxiety Sensitivity and Pre-Cessation Smoking Processes: Testing the Independent and Combined Mediating Effects of Negative Affect–Reduction Expectancies and Motives

Science.gov (United States)

Farris, Samantha G.; Leventhal, Adam M.; Schmidt, Norman B.; Zvolensky, Michael J.

2015-01-01

Objective: Anxiety sensitivity appears to be relevant in understanding the nature of emotional symptoms and disorders associated with smoking. Negative-reinforcement smoking expectancies and motives are implicated as core regulatory processes that may explain, in part, the anxiety sensitivity–smoking interrelations; however, these pathways have received little empirical attention. Method: Participants (N = 471) were adult treatment-seeking daily smokers assessed for a smoking-cessation trial who provided baseline data; 157 participants provided within-treatment (pre-cessation) data. Anxiety sensitivity was examined as a cross-sectional predictor of several baseline smoking processes (nicotine dependence, perceived barriers to cessation, severity of prior withdrawal-related quit problems) and pre-cessation processes including nicotine withdrawal and smoking urges (assessed during 3 weeks before the quit day). Baseline negative-reinforcement smoking expectancies and motives were tested as simultaneous mediators via parallel multiple mediator models. Results: Higher levels of anxiety sensitivity were related to higher levels of nicotine dependence, greater perceived barriers to smoking cessation, more severe withdrawal-related problems during prior quit attempts, and greater average withdrawal before the quit day; effects were indirectly explained by the combination of both mediators. Higher levels of anxiety sensitivity were not directly related to pre-cessation smoking urges but were indirectly related through the independent and combined effects of the mediators. Conclusions: These empirical findings bolster theoretical models of anxiety sensitivity and smoking and identify targets for nicotine dependence etiology research and cessation interventions. PMID:25785807

Therapeutic effects of D-aspartate in a mouse model of multiple sclerosis

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Sanaz Afraei

2017-07-01

Full Text Available Experimental autoimmune encephalomyelitis (EAE is an animal model of multiple sclerosis. EAE is mainly mediated by adaptive and innate immune responses that leads to an inflammatory demyelization and axonal damage. The aim of the present research was to examine the therapeutic efficacy of D-aspartic acid (D-Asp on a mouse EAE model. EAE induction was performed in female C57BL/6 mice by myelin 40 oligodendrocyte glycoprotein (35-55 in a complete Freund's adjuvant emulsion, and D-Asp was used to test its efficiency in the reduction of EAE. During the course of study, clinical evaluation was assessed, and on Day 21, post-immunization blood samples were taken from the heart of mice for the evaluation of interleukin 6 and other chemical molecules. The mice were sacrificed, and their brain and cerebellum were removed for histological analysis. Our findings indicated that D-Asp had beneficial effects on EAE by attenuation in the severity and delay in the onset of the disease. Histological analysis showed that treatment with D-Asp can reduce inflammation. Moreover, in D-Asp-treated mice, the serum level of interleukin 6 was significantly lower than that in control animals, whereas the total antioxidant capacity was significantly higher. The data indicates that D-Asp possess neuroprotective property to prevent the onset of the multiple sclerosis.

Mediators of Psychological Well-being in Adolescent Boys.

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Lubans, David R; Smith, Jordan J; Morgan, Philip J; Beauchamp, Mark R; Miller, Andrew; Lonsdale, Chris; Parker, Philip; Dally, Kerry

2016-02-01

The aim of this study was to explore the effect of the Active Teen Leaders Avoiding Screen-time (ATLAS) intervention on psychological well-being in adolescent boys and to examine the potential mediating mechanisms that might explain this effect. ATLAS was evaluated using a cluster randomized controlled trial in 14 secondary schools located in low-income communities (N = 361 adolescent boys, mean age = 12.7 ± .5 years). The 20-week intervention was guided by self-determination theory and involved: professional development for teachers, provision of fitness equipment to schools, enhanced school sport sessions, researcher-led seminars, a smartphone application, and parental strategies for reducing screen time. Assessments were conducted at baseline and immediately post intervention (8 months). Psychological well-being was measured using the Flourishing Scale. Motivational regulations (intrinsic, identified, introjected, controlled, and amotivation) and basic psychological needs (autonomy, competence, and relatedness) in school sport, muscular fitness, resistance training skill competency, and recreational screen time were examined as potential mediating mechanisms of the intervention effect. The intervention effect on well-being was small but statistically significant. Within a multiple mediator model, changes in autonomy needs satisfaction, recreational screen time, and muscular fitness significantly mediated the effect of the intervention on psychological well-being. In addition to the physical health benefits, targeted physical activity programs for adolescent boys may have utility for mental health promotion through the mechanisms of increasing autonomy support and muscular fitness and reducing screen time. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Low-Intensity Ultrasound-Induced Anti-inflammatory Effects Are Mediated by Several New Mechanisms Including Gene Induction, Immunosuppressor Cell Promotion, and Enhancement of Exosome Biogenesis and Docking

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Qian Yang

2017-10-01

Full Text Available Background: Low-intensity ultrasound (LIUS was shown to be beneficial in mitigating inflammation and facilitating tissue repair in various pathologies. Determination of the molecular mechanisms underlying the anti-inflammatory effects of LIUS allows to optimize this technique as a therapy for the treatment of malignancies and aseptic inflammatory disorders.Methods: We conducted cutting-edge database mining approaches to determine the anti-inflammatory mechanisms exerted by LIUS.Results: Our data revealed following interesting findings: (1 LIUS anti-inflammatory effects are mediated by upregulating anti-inflammatory gene expression; (2 LIUS induces the upregulation of the markers and master regulators of immunosuppressor cells including MDSCs (myeloid-derived suppressor cells, MSCs (mesenchymal stem cells, B1-B cells and Treg (regulatory T cells; (3 LIUS not only can be used as a therapeutic approach to deliver drugs packed in various structures such as nanobeads, nanospheres, polymer microspheres, and lipidosomes, but also can make use of natural membrane vesicles as small as exosomes derived from immunosuppressor cells as a novel mechanism to fulfill its anti-inflammatory effects; (4 LIUS upregulates the expression of extracellular vesicle/exosome biogenesis mediators and docking mediators; (5 Exosome-carried anti-inflammatory cytokines and anti-inflammatory microRNAs inhibit inflammation of target cells via multiple shared and specific pathways, suggesting exosome-mediated anti-inflammatory effect of LIUS feasible; and (6 LIUS-mediated physical effects on tissues may activate specific cellular sensors that activate downstream transcription factors and signaling pathways.Conclusions: Our results have provided novel insights into the mechanisms underlying anti-inflammatory effects of LIUS, and have provided guidance for the development of future novel therapeutic LIUS for cancers, inflammatory disorders, tissue regeneration and tissue repair.

Effects of L-arabinose efflux on λ Red recombination-mediated gene knockout in multiple-antimicrobial-resistant Salmonella enterica serovar Choleraesuis.

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Liao, Shi-Wei; Lee, Jen-Jie; Ptak, Christopher P; Wu, Ying-Chen; Hsuan, Shih-Ling; Kuo, Chih-Jung; Chen, Ter-Hsin

2018-03-01

In this study, six swine-derived multiple-antimicrobial-resistant (MAR) strains of Salmonella Choleraesuis (S. Choleraesuis) were demonstrated to possess higher efflux pump activity than the wild-type (WT). L-Arabinose, a common inducer for gene expression, modulated S. Choleraesuis efflux pump activity in a dose-dependent manner. At low L-arabinose concentrations, increasing L-arabinose led to a corresponding increase in fluorophore efflux, while at higher L-arabinose concentrations, increasing L-arabinose decreased fluorophore efflux activity. The WT S. Choleraesuis that lacks TolC (ΔtolC), an efflux protein associated with bacterial antibiotic resistance and virulence, was demonstrated to possess a significantly reduced ability to extrude L-arabinose. Further, due to the rapid export of L-arabinose, an efficient method for recombination-mediated gene knockout, the L-arabinose-inducible bacteriophage λ Red recombinase system, has a reduced recombination frequency (~ 12.5%) in clinically isolated MAR Salmonella strains. An increased recombination frequency (up to 60%) can be achieved using a higher concentration of L-arabinose (fivefold) for genetic manipulation and functional analysis for MAR Salmonella using the λ Red system. The study suggests that L-arabinose serves not only as an inducer of the TolC-dependent efflux system but also acts as a competitive substrate of the efflux system. In addition, understanding the TolC-dependent efflux of L-arabinose should facilitate the optimization of L-arabinose induction in strains with high efflux activity.

A Bifactor Approach to Model Multifaceted Constructs in Statistical Mediation Analysis

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Gonzalez, Oscar; MacKinnon, David P.

2018-01-01

Statistical mediation analysis allows researchers to identify the most important mediating constructs in the causal process studied. Identifying specific mediators is especially relevant when the hypothesized mediating construct consists of multiple related facets. The general definition of the construct and its facets might relate differently to…

Anxiety, Affect, Self-Esteem, and Stress: Mediation and Moderation Effects on Depression

OpenAIRE

Nima, Ali Al; Rosenberg, Patricia; Archer, Trevor; Garcia, Danilo

2013-01-01

Background Mediation analysis investigates whether a variable (i.e., mediator) changes in regard to an independent variable, in turn, affecting a dependent variable. Moderation analysis, on the other hand, investigates whether the statistical interaction between independent variables predict a dependent variable. Although this difference between these two types of analysis is explicit in current literature, there is still confusion with regard to the mediating and moderating effects of differ...

Covariate measurement error correction methods in mediation analysis with failure time data.

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Zhao, Shanshan; Prentice, Ross L

2014-12-01

Mediation analysis is important for understanding the mechanisms whereby one variable causes changes in another. Measurement error could obscure the ability of the potential mediator to explain such changes. This article focuses on developing correction methods for measurement error in the mediator with failure time outcomes. We consider a broad definition of measurement error, including technical error, and error associated with temporal variation. The underlying model with the "true" mediator is assumed to be of the Cox proportional hazards model form. The induced hazard ratio for the observed mediator no longer has a simple form independent of the baseline hazard function, due to the conditioning event. We propose a mean-variance regression calibration approach and a follow-up time regression calibration approach, to approximate the partial likelihood for the induced hazard function. Both methods demonstrate value in assessing mediation effects in simulation studies. These methods are generalized to multiple biomarkers and to both case-cohort and nested case-control sampling designs. We apply these correction methods to the Women's Health Initiative hormone therapy trials to understand the mediation effect of several serum sex hormone measures on the relationship between postmenopausal hormone therapy and breast cancer risk. © 2014, The International Biometric Society.

Validation and genotyping of multiple human polymorphic inversions mediated by inverted repeats reveals a high degree of recurrence.

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Cristina Aguado

2014-03-01

Full Text Available In recent years different types of structural variants (SVs have been discovered in the human genome and their functional impact has become increasingly clear. Inversions, however, are poorly characterized and more difficult to study, especially those mediated by inverted repeats or segmental duplications. Here, we describe the results of a simple and fast inverse PCR (iPCR protocol for high-throughput genotyping of a wide variety of inversions using a small amount of DNA. In particular, we analyzed 22 inversions predicted in humans ranging from 5.1 kb to 226 kb and mediated by inverted repeat sequences of 1.6-24 kb. First, we validated 17 of the 22 inversions in a panel of nine HapMap individuals from different populations, and we genotyped them in 68 additional individuals of European origin, with correct genetic transmission in ∼ 12 mother-father-child trios. Global inversion minor allele frequency varied between 1% and 49% and inversion genotypes were consistent with Hardy-Weinberg equilibrium. By analyzing the nucleotide variation and the haplotypes in these regions, we found that only four inversions have linked tag-SNPs and that in many cases there are multiple shared SNPs between standard and inverted chromosomes, suggesting an unexpected high degree of inversion recurrence during human evolution. iPCR was also used to check 16 of these inversions in four chimpanzees and two gorillas, and 10 showed both orientations either within or between species, providing additional support for their multiple origin. Finally, we have identified several inversions that include genes in the inverted or breakpoint regions, and at least one disrupts a potential coding gene. Thus, these results represent a significant advance in our understanding of inversion polymorphism in human populations and challenge the common view of a single origin of inversions, with important implications for inversion analysis in SNP-based studies.

Estimation of Indirect Effects in the Presence of Unmeasured Confounding for the Mediator-Outcome Relationship in a Multilevel 2-1-1 Mediation Model

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Talloen, Wouter; Moerkerke, Beatrijs; Loeys, Tom; De Naeghel, Jessie; Van Keer, Hilde; Vansteelandt, Stijn

2016-01-01

To assess the direct and indirect effect of an intervention, multilevel 2-1-1 studies with intervention randomized at the upper (class) level and mediator and outcome measured at the lower (student) level are frequently used in educational research. In such studies, the mediation process may flow through the student-level mediator (the within…

Mediator Effect of TPM between TQM and Business Performance in Malaysia Automotive Industry

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Ahmad, M. F.; Zakuan, N.; Rasi, Raja Zuraidah R. M.; Hisyamudin, M. N. N.

2015-05-01

Total Quality Management (TQM) is vital management tool in ensuring a company can success in the continuously growing competition in the global market. In order to survive in the global market with intense competition amongst regions and enterprises, the adoption of tools and techniques are essential in improving business performance. However, only few previous studies have examined the mediators and moderators between TQM and business performance. This present research proposed a TQM performance model with mediator effect of TPM with structural equation modelling, which is a more comprehensive model for developing countries, specifically for Malaysia. A questionnaire was prepared and sent to 1500 companies from automotive industry and the related vendors in Malaysia, giving a 21.3 per cent rate. The result concludes that TPM is partial mediation between and TQM and Business Performance with indirect effect (IE) is 0.25 which can be categorised as high mediator effect.

Insight into Genotype-Phenotype Associations through eQTL Mapping in Multiple Cell Types in Health and Immune-Mediated Disease.

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James E Peters

2016-03-01

Full Text Available Genome-wide association studies (GWAS have transformed our understanding of the genetics of complex traits such as autoimmune diseases, but how risk variants contribute to pathogenesis remains largely unknown. Identifying genetic variants that affect gene expression (expression quantitative trait loci, or eQTLs is crucial to addressing this. eQTLs vary between tissues and following in vitro cellular activation, but have not been examined in the context of human inflammatory diseases. We performed eQTL mapping in five primary immune cell types from patients with active inflammatory bowel disease (n = 91, anti-neutrophil cytoplasmic antibody-associated vasculitis (n = 46 and healthy controls (n = 43, revealing eQTLs present only in the context of active inflammatory disease. Moreover, we show that following treatment a proportion of these eQTLs disappear. Through joint analysis of expression data from multiple cell types, we reveal that previous estimates of eQTL immune cell-type specificity are likely to have been exaggerated. Finally, by analysing gene expression data from multiple cell types, we find eQTLs not previously identified by database mining at 34 inflammatory bowel disease-associated loci. In summary, this parallel eQTL analysis in multiple leucocyte subsets from patients with active disease provides new insights into the genetic basis of immune-mediated diseases.

Acoustically mediated long-range interaction among multiple spherical particles exposed to a plane standing wave

International Nuclear Information System (INIS)

Zhang, Shenwei; Qiu, Chunyin; Wang, Mudi; Ke, Manzhu; Liu, Zhengyou

2016-01-01

In this work, we study the acoustically mediated interaction forces among multiple well-separated spherical particles trapped in the same node or antinode plane of a standing wave. An analytical expression of the acoustic interaction force is derived, which is accurate even for the particles beyond the Rayleigh limit. Interestingly, the multi-particle system can be decomposed into a series of independent two-particle systems described by pairwise interactions. Each pairwise interaction is a long-range interaction, as characterized by a soft oscillatory attenuation (at the power exponent of n  = −1 or −2). The vector additivity of the acoustic interaction force, which is not well expected considering the nonlinear nature of the acoustic radiation force, is greatly useful for exploring a system consisting of a large number of particles. The capability of self-organizing a big particle cluster can be anticipated through such acoustically controllable long-range interaction. (paper)

The mediating effect of psychosocial factors on suicidal probability among adolescents.

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Hur, Ji-Won; Kim, Won-Joong; Kim, Yong-Ku

2011-01-01

Suicidal probability is an actual tendency including negative self-evaluation, hopelessness, suicidal ideation, and hostility. The purpose of this study was to examine the role of psychosocial variances in the suicidal probability of adolescents, especially the role of mediating variance. This study investigated the mediating effects of psychosocial factors such as depression, anxiety, self-esteem, stress, and social support on the suicidal probability among 1,586 adolescents attending middle and high schools in the Kyunggi Province area of South Korea. The relationship between depression and anxiety/suicidal probability was mediated by both social resources and self-esteem. Furthermore, the influence of social resources was mediated by interpersonal and achievement stress as well as self-esteem. This study suggests that suicidal probability in adolescents has various relationships, including mediating relations, with several psychosocial factors. The interventions on suicidal probability in adolescents should focus on social factors as well as clinical symptoms.

Ratio-of-Mediator-Probability Weighting for Causal Mediation Analysis in the Presence of Treatment-by-Mediator Interaction

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Hong, Guanglei; Deutsch, Jonah; Hill, Heather D.

2015-01-01

Conventional methods for mediation analysis generate biased results when the mediator--outcome relationship depends on the treatment condition. This article shows how the ratio-of-mediator-probability weighting (RMPW) method can be used to decompose total effects into natural direct and indirect effects in the presence of treatment-by-mediator…

mediation: R package for causal mediation analysis

OpenAIRE

Tingley, Dustin; Yamamoto, Teppei; Hirose, Kentaro; Keele, Luke; Imai, Kosuke

2012-01-01

In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting su...

Longitudinal mediators of achievement in mathematics and reading in typical and atypical development.

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Barnes, Marcia A; Raghubar, Kimberly P; English, Lianne; Williams, Jeffrey M; Taylor, Heather; Landry, Susan

2014-03-01

Longitudinal studies of neurodevelopmental disorders that are diagnosed at or before birth and are associated with specific learning difficulties at school-age provide one method for investigating developmental precursors of later-emerging academic disabilities. Spina bifida myelomeningocele (SBM) is a neurodevelopmental disorder associated with particular problems in mathematics, in contrast to well-developed word reading. Children with SBM (n=30) and typically developing children (n=35) were used to determine whether cognitive abilities measured at 36 and 60 months of age mediated the effect of group on mathematical and reading achievement outcomes at 8.5 and 9.5 years of age. A series of multiple mediator models showed that: visual-spatial working memory at 36 months and phonological awareness at 60 months partially mediated the effect of group on math calculations, phonological awareness partially mediated the effect of group on small addition and subtraction problems on a test of math fluency, and visual-spatial working memory mediated the effect of group on a test of math problem solving. Groups did not differ on word reading, and phonological awareness was the only mediator for reading fluency and reading comprehension. The findings are discussed with reference to theories of mathematical development and disability and with respect to both common and differing cognitive correlates of math and reading. Copyright © 2013 Elsevier Inc. All rights reserved.

Rumination mediates the prospective effect of low self-esteem on depression: a five-wave longitudinal study.

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Kuster, Farah; Orth, Ulrich; Meier, Laurenz L

2012-06-01

Previous research supports the vulnerability model of low self-esteem and depression, which states that low self-esteem operates as a prospective risk factor for depression. However, it is unclear which processes mediate the effect of low self-esteem. To test for the mediating effect of rumination, the authors used longitudinal mediation models, which included exclusively prospective effects and controlled for autoregressive effects of the constructs. Data came from 663 individuals (aged 16 to 62 years), who were assessed 5 times over an 8-month period. The results indicated that low self-esteem predicted subsequent rumination, which in turn predicted subsequent depression, and that rumination partially mediated the prospective effect of low self-esteem on depression. These findings held for both men and women, and for both affective-cognitive and somatic symptoms of depression. Future studies should test for the mediating effects of additional intrapersonal and interpersonal processes.

Dispositional optimism and sleep quality: a test of mediating pathways.

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Uchino, Bert N; Cribbet, Matthew; de Grey, Robert G Kent; Cronan, Sierra; Trettevik, Ryan; Smith, Timothy W

2017-04-01

Dispositional optimism has been related to beneficial influences on physical health outcomes. However, its links to global sleep quality and the psychological mediators responsible for such associations are less studied. This study thus examined if trait optimism predicted global sleep quality, and if measures of subjective well-being were statistical mediators of such links. A community sample of 175 participants (93 men, 82 women) completed measures of trait optimism, depression, and life satisfaction. Global sleep quality was assessed using the Pittsburgh Sleep Quality Index. Results indicated that trait optimism was a strong predictor of better PSQI global sleep quality. Moreover, this association was mediated by depression and life satisfaction in both single and multiple mediator models. These results highlight the importance of optimism for the restorative process of sleep, as well as the utility of multiple mediator models in testing distinct psychological pathways.

Tariff-Mediated Network Effects Versus Strategic Disounting

DEFF Research Database (Denmark)

Zucchini, Leon; Claussen, Jörg; Trüg, Moritz

2013-01-01

. Alternatively, research on strategic discounting suggests that small operators use on-net discounts to advertise with low on-net prices. We test the relative strength of these effects using data on tariff setting in German mobile telecommunications between 2001 and 2009. We find that large operators are more......Mobile telecommunication operators routinely charge subscribers lower prices for calls on their own network than for calls to other networks (on-net discounts). Studies on tariff-mediated network effects suggest this is due to large operators using on-net discounts to damage smaller rivals...

Cognitive behavioural therapy for MS-related fatigue explained: A longitudinal mediation analysis.

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van den Akker, L E; Beckerman, H; Collette, E H; Knoop, H; Bleijenberg, G; Twisk, J W; Dekker, J; de Groot, V

2018-03-01

Cognitive behavioural therapy (CBT) effectively reduces fatigue directly following treatment in patients with Multiple Sclerosis (MS), but little is known about the process of change during and after CBT. Additional analysis of a randomized clinical trial. To investigate which psychological factors mediate change in fatigue during and after CBT. TREFAMS-CBT studied the effectiveness of a 16-week CBT treatment for MS-related fatigue. Ninety-one patients were randomized (44 to CBT, 47 to the MS-nurse consultations). Mediation during CBT treatment was studied using assessments at baseline, 8 and 16weeks. Mediation of the change in fatigue from post-treatment to follow-up was studied separately using assessments at 16, 26 and 52weeks. Proposed mediators were: changes in illness cognitions, general self-efficacy, coping styles, daytime sleepiness, concentration and physical activity, fear of disease progression, fatigue perceptions, depression and physical functioning. Mediators were separately analysed according to the product-of-coefficients approach. Confidence intervals were calculated with a bootstrap procedure. During treatment the decrease in fatigue brought on by CBT was mediated by improved fatigue perceptions, increased physical activity, less sleepiness, less helplessness, and improved physical functioning. Post-treatment increases in fatigue levels were mediated by reduced physical activity, reduced concentration, and increased sleepiness. These results suggests that focusing on improving fatigue perceptions, perceived physical activity, daytime sleepiness, helplessness, and physical functioning may further improve the effectiveness of CBT for fatigue in patients with MS. Maintenance of treatment effects may be obtained by focusing on improving physical activity, concentration and sleepiness. Copyright © 2018 Elsevier Inc. All rights reserved.

Different Mechanisms of Inflammation Induced in Virus and Autoimmune-Mediated Models of Multiple Sclerosis in C57BL6 Mice

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Abhinoy Kishore

2013-01-01

Full Text Available Multiple sclerosis (MS is an inflammatory demyelinating disease of the human central nervous system (CNS. Neurotropic demyelinating strain of MHV (MHV-A59 or its isogenic recombinant strain RSA59 induces MS-like disease in mice mediated by microglia, along with a small population of T cells. The mechanism of demyelination is at least in part due to microglia-mediated myelin stripping, with some direct axonal injury. Immunization with myelin oligodendrocyte glycoprotein (MOG induces experimental autoimmune encephalomyelitis (EAE, a mainly CD4+ T-cell-mediated disease, although CD8+ T cells may play a significant role in demyelination. It is possible that both autoimmune and nonimmune mechanisms such as direct viral toxicity may induce MS. Our study directly compares CNS pathology in autoimmune and viral-induced MS models. Mice with viral-induced and EAE demyelinating diseases demonstrated similar patterns and distributions of demyelination that accumulated over the course of the disease. However, significant differences in acute inflammation were noted. Inflammation was restricted mainly to white matter at all times in EAE, whereas inflammation initially largely involved gray matter in acute MHV-induced disease and then is subsequently localized only in white matter in the chronic disease phase. The presence of dual mechanisms of demyelination may be responsible for the failure of immunosuppression to promote long-term remission in many MS patients.

Does Food Insecurity Affect Parental Characteristics and Child Behavior? Testing Mediation Effects

OpenAIRE

Huang, Jin; Oshima, Karen M. Matta; Kim, Youngmi

2010-01-01

Using two waves of data from the Child Development Supplement in the Panel Study of Income Dynamics, this study investigates whether parental characteristics (parenting stress, parental warmth, psychological distress, and parent’s self-esteem) mediate household food insecurity’s relations with child behavior problems. Fixed-effects analyses examine data from a low-income sample of 416 children from 249 households. This study finds that parenting stress mediates the effects of food insecurity ...

Inhibition of STAT3 signaling and induction of SHP1 mediate antiangiogenic and antitumor activities of ergosterol peroxide in U266 multiple myeloma cells

International Nuclear Information System (INIS)

Rhee, Yun-Hee; Jeong, Soo-Jin; Lee, Hyo-Jeong; Lee, Hyo-Jung; Koh, Wonil; Jung, Ji Hoon; Kim, Sun-Hee; Sung-Hoon, Kim

2012-01-01

Ergosterol peroxide (EP) derived from edible mushroom has been shown to exert anti-tumor activity in several cancer cells. In the present study, anti-angiogenic activity of EP was investigated with the underlying molecular mechanisms in human multiple myeloma U266 cells. Despite weak cytotoxicity against U266 cells, EP suppressed phosphorylation, DNA binding activity and nuclear translocalization of signal transducer and activator of transcription 3 (STAT3) in U266 cells at nontoxic concentrations. Also, EP inhibited phosphorylation of the upstream kinases Janus kinase 2 (JAK2) and Src in a time-dependent manner. Furthermore, EP increased the expression of protein tyrosine phosphatase SHP-1 at protein and mRNA levels, and conversely silencing of the SHP-1 gene clearly blocked EP-mediated STAT3 inactivation. In addition, EP significantly decreased vascular endothelial growth factor (VEGF), one of STAT3 target genes at cellular and protein levels as well as disrupted in vitro tube formation assay. Moreover, EP significantly suppressed the growth of U266 cells inoculated in female BALB/c athymic nude mice and immunohistochemistry revealed that EP effectively reduced the expression of STAT3 and CD34 in tumor sections compared to untreated control. These findings suggest that EP can exert antitumor activity in multiple myeloma U266 cells partly with antiangiogenic activity targeting JAK2/STAT3 signaling pathway as a potent cancer preventive agent for treatment of multiple myeloma cells

Prospective relations between family conflict and adolescent maladjustment: security in the family system as a mediating process.

Science.gov (United States)

Cummings, E Mark; Koss, Kalsea J; Davies, Patrick T

2015-04-01

Conflict in specific family systems (e.g., interparental, parent-child) has been implicated in the development of a host of adjustment problems in adolescence, but little is known about the impact of family conflict involving multiple family systems. Furthermore, questions remain about the effects of family conflict on symptoms of specific disorders and adjustment problems and the processes mediating these effects. The present study prospectively examines the impact of family conflict and emotional security about the family system on adolescent symptoms of specific disorders and adjustment problems, including the development of symptoms of anxiety, depression, conduct problems, and peer problems. Security in the family system was examined as a mediator of these relations. Participants included 295 mother-father-adolescent families (149 girls) participating across three annual time points (grades 7-9). Including auto-regressive controls for initial levels of emotional insecurity and multiple adjustment problems (T1), higher-order emotional insecurity about the family system (T2) mediated relations between T1 family conflict and T3 peer problems, anxiety, and depressive symptoms. Further analyses supported specific patterns of emotional security/insecurity (i.e., security, disengagement, preoccupation) as mediators between family conflict and specific domains of adolescent adjustment. Family conflict was thus found to prospectively predict the development of symptoms of multiple specific adjustment problems, including symptoms of depression, anxiety, conduct problems, and peer problems, by elevating in in adolescent's emotional insecurity about the family system. The clinical implications of these findings are considered.

[The effect of self-reflection on depression mediated by hardiness].

Science.gov (United States)

Nakajima, Miho; Hattori, Yosuke; Tanno, Yoshihiko

2015-10-01

Previous studies have shown that two types of private self-consciousness result in opposing effects on depression; one of which is self-rumination, which leads to maladaptive effect, and the other is self-reflection, which leads to an adaptive effect. Although a number of studies have examined the mechanism of the maladaptive effect of self-rumination, only a few studies have examined the mechanism of the adaptive effect of self-reflection. The present study examined the process of how self-reflection affected depression adaptively, Based on the previous findings, we proposed a hypothetical model assuming that hardiness acts as a mediator of self-reflection. To test the validity of the model, structural equation modeling analysis was performed with the cross-sectional data of 155 undergraduate students. The results. suggest that the hypothetical model is valid. According to the present results and previous findings, it is suggested that self-reflection is associated with low levels of depression and mediated by "rich commitment", one component of hardiness.

[Effect of Adolescents' Abuse Experience on Suicidal Ideation: Focused on Moderated Mediation Effect of Self-esteem on Depression and Anxiety].

Science.gov (United States)

Kim, Ji Young; Lee, Kyunghee

2015-10-01

The purpose of this study was to examine the moderating mediation effect of self-esteem on the relations among adolescents' abuse experiences, depression and anxiety, and suicidal ideation. The participants were selected using secondary data from a population in the 2012 Korea Welfare Panel Survey (KOWEPS). Data were analyzed using SPSS 15.0 and SPSS Macro, and bootstrapping and hierarchical regression analysis were performed to analyze multilevel models. First, analysis of the mediating effect of the adolescents' abuse showed that there was significant mediating influence between suicidal ideation and depression and anxiety. Second, hierarchical regression analysis showed that self-esteem had significant mediation effect on depression and anxiety in adolescents' suicidal ideation. Third, SPSS Macro showed that self-esteem also significantly moderated the mediating effect of adolescents' abuse experiences on suicidal ideation through depression and anxiety. The study results suggest that in future research on adolescent's abuse experience, the risk of suicide in depression and anxiety scores should be selected through evaluation of each individual's self-esteem scale. Coping strategies with immediate early intervention should be suggested.

Microstructure-mediated Optical Effects in Southern African Snakes

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Singh Ishan

2017-01-01

Full Text Available The scales of the African Viper Bitis arietans were tested for optical effects. Spectral intensity was recorded at incident angles over the visible spectrum for dark, pale, and ventral scale regions. The lowest spectral intensity recordings were associated with scales which have the greatest level of micro-structuring. Our results indicate that scale appearance in B. arietans is a product of microstructure-mediated optical effects. The optical effect may play a role in improving the ecological performance of the snake in its natural environment.

Resource-Mediated Indirect Effects of Grassland Management on Arthropod Diversity

Science.gov (United States)

Simons, Nadja K.; Gossner, Martin M.; Lewinsohn, Thomas M.; Boch, Steffen; Lange, Markus; Müller, Jörg; Pašalić, Esther; Socher, Stephanie A.; Türke, Manfred; Fischer, Markus; Weisser, Wolfgang W.

2014-01-01

Intensive land use is a driving force for biodiversity decline in many ecosystems. In semi-natural grasslands, land-use activities such as mowing, grazing and fertilization affect the diversity of plants and arthropods, but the combined effects of different drivers and the chain of effects are largely unknown. In this study we used structural equation modelling to analyse how the arthropod communities in managed grasslands respond to land use and whether these responses are mediated through changes in resource diversity or resource quantity (biomass). Plants were considered resources for herbivores which themselves were considered resources for predators. Plant and arthropod (herbivores and predators) communities were sampled on 141 meadows, pastures and mown pastures within three regions in Germany in 2008 and 2009. Increasing land-use intensity generally increased plant biomass and decreased plant diversity, mainly through increasing fertilization. Herbivore diversity decreased together with plant diversity but showed no response to changes in plant biomass. Hence, land-use effects on herbivore diversity were mediated through resource diversity rather than quantity. Land-use effects on predator diversity were mediated by both herbivore diversity (resource diversity) and herbivore quantity (herbivore biomass), but indirect effects through resource quantity were stronger. Our findings highlight the importance of assessing both direct and indirect effects of land-use intensity and mode on different trophic levels. In addition to the overall effects, there were subtle differences between the different regions, pointing to the importance of regional land-use specificities. Our study underlines the commonly observed strong effect of grassland land use on biodiversity. It also highlights that mechanistic approaches help us to understand how different land-use modes affect biodiversity. PMID:25188423

Bayesian dynamic mediation analysis.

Science.gov (United States)

Huang, Jing; Yuan, Ying

2017-12-01

Most existing methods for mediation analysis assume that mediation is a stationary, time-invariant process, which overlooks the inherently dynamic nature of many human psychological processes and behavioral activities. In this article, we consider mediation as a dynamic process that continuously changes over time. We propose Bayesian multilevel time-varying coefficient models to describe and estimate such dynamic mediation effects. By taking the nonparametric penalized spline approach, the proposed method is flexible and able to accommodate any shape of the relationship between time and mediation effects. Simulation studies show that the proposed method works well and faithfully reflects the true nature of the mediation process. By modeling mediation effect nonparametrically as a continuous function of time, our method provides a valuable tool to help researchers obtain a more complete understanding of the dynamic nature of the mediation process underlying psychological and behavioral phenomena. We also briefly discuss an alternative approach of using dynamic autoregressive mediation model to estimate the dynamic mediation effect. The computer code is provided to implement the proposed Bayesian dynamic mediation analysis. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

DEFF Research Database (Denmark)

Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti

2011-01-01

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown...... the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture...... underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working...

Benthic macroinvertebrates and multiple stressors : quantification of the effects of multiple stressors in field, laboratory and model settings

NARCIS (Netherlands)

Peeters, E.T.H.M.

2001-01-01

Organisms are always exposed to several simultaneously operating stressors in nature. It appears that the combined effects of multiple stressors cannot be understood as a simple product of their individual effects. To understand how multiple stressors affect the composition and functioning

Partial Sleep Deprivation Attenuates the Positive Affective System: Effects Across Multiple Measurement Modalities.

Science.gov (United States)

Finan, Patrick H; Quartana, Phillip J; Remeniuk, Bethany; Garland, Eric L; Rhudy, Jamie L; Hand, Matthew; Irwin, Michael R; Smith, Michael T

2017-01-01

Ample behavioral and neurobiological evidence links sleep and affective functioning. Recent self-report evidence suggests that the affective problems associated with sleep loss may be stronger for positive versus negative affective state and that those effects may be mediated by changes in electroencepholographically measured slow wave sleep (SWS). In the present study, we extend those preliminary findings using multiple measures of affective functioning. In a within-subject randomized crossover experiment, we tested the effects of one night of sleep continuity disruption via forced awakenings (FA) compared to one night of uninterrupted sleep (US) on three measures of positive and negative affective functioning: self-reported affective state, affective pain modulation, and affect-biased attention. The study was set in an inpatient clinical research suite. Healthy, good sleeping adults (N = 45) were included. Results indicated that a single night of sleep continuity disruption attenuated positive affective state via FA-induced reductions in SWS. Additionally, sleep continuity disruption attenuated the inhibition of pain by positive affect as well as attention bias to positive affective stimuli. Negative affective state, negative affective pain facilitation, nor negative attention bias were altered by sleep continuity disruption. The present findings, observed across multiple measures of affective function, suggest that sleep continuity disruption has a stronger influence on the positive affective system relative to the negative affective affective system. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Effects of early language, speech, and cognition on later reading: A mediation analysis

Directory of Open Access Journals (Sweden)

Vanessa N Durand

2013-09-01

Full Text Available This longitudinal secondary analysis examined which early language and speech abilities are associated with school-aged reading skills, and whether these associations are mediated by cognitive ability. We analyzed vocabulary, syntax, speech sound maturity, and cognition in a sample of healthy children at age 3 years (N=241 in relation to single word reading (decoding, comprehension, and oral reading fluency in the same children at age 9 to 11 years. All predictor variables and the mediator variable were associated with the three reading outcomes. The predictor variables were all associated with cognitive abilities, the mediator. Cognitive abilities partially mediated the effects of language on reading. After mediation, decoding was associated with speech sound maturity; comprehension was associated with receptive vocabulary; and oral fluency was associated with speech sound maturity, receptive vocabulary, and syntax. In summary, all of the effects of language on reading could not be explained by cognition as a mediator. Specific components of language and speech skills in preschool made independent contributions to reading skills 6 to 8 years later. These early precursors to later reading skill represent potential targets for early intervention to improve reading.

Extending the Similarity-Attraction Effect: The Effects of When-Similarity in Computer-Mediated Communication

NARCIS (Netherlands)

Kaptein, M.C.; Castaneda, D.; Fernandez, N.; Nass, C.

2014-01-01

The feeling of connectedness experienced in computer-mediated relationships can be explained by the similarity-attraction effect (SAE). Though SAE is well established in psychology, the effects of some types of similarity have not yet been explored. In 2 studies, we demonstrate similarity-attraction

CRISPR/Cas9 mediates efficient conditional mutagenesis in Drosophila.

Science.gov (United States)

Xue, Zhaoyu; Wu, Menghua; Wen, Kejia; Ren, Menda; Long, Li; Zhang, Xuedi; Gao, Guanjun

2014-09-05

Existing transgenic RNA interference (RNAi) methods greatly facilitate functional genome studies via controlled silencing of targeted mRNA in Drosophila. Although the RNAi approach is extremely powerful, concerns still linger about its low efficiency. Here, we developed a CRISPR/Cas9-mediated conditional mutagenesis system by combining tissue-specific expression of Cas9 driven by the Gal4/upstream activating site system with various ubiquitously expressed guide RNA transgenes to effectively inactivate gene expression in a temporally and spatially controlled manner. Furthermore, by including multiple guide RNAs in a transgenic vector to target a single gene, we achieved a high degree of gene mutagenesis in specific tissues. The CRISPR/Cas9-mediated conditional mutagenesis system provides a simple and effective tool for gene function analysis, and complements the existing RNAi approach. Copyright © 2014 Xue et al.

Effective capacity of multiple antenna channels: Correlation and keyhole

KAUST Repository

Zhong, Caijun; Ratnarajah, Tharm; Wong, Kaikit; Alouini, Mohamed-Slim

2012-01-01

In this study, the authors derive the effective capacity limits for multiple antenna channels which quantify the maximum achievable rate with consideration of link-layer delay-bound violation probability. Both correlated multiple-input single

Lactoferricin mediates Anti-Inflammatory and Anti-Catabolic Effects via Inhibition of IL-1 and LPS Activity in the Intervertebral Disc†

Science.gov (United States)

Kim, Jae-Sung; Ellman, Michael B.; Yan, Dongyao; An, Howard S.; Kc, Ranjan; Li, Xin; Chen, Di; Xiao, Guozhi; Cs-Zabo, Gabriella; Hoskin, David W.; Buechter, D.D.; Van Wijnen, Andre J.; Im, Hee-Jeong

2013-01-01

The catabolic cytokine interleukin-1 (IL-1) and endotoxin lipopolysaccharide (LPS) are well-known inflammatory mediators involved in degenerative disc disease, and inhibitors of IL-1 and LPS may potentially be used to slow or prevent disc degeneration in vivo. Here, we elucidate the striking anti-catabolic and anti-inflammatory effects of bovine lactoferricin (LfcinB) in the intervertebral disc (IVD) via antagonism of both IL-1 and LPS-mediated catabolic activity using in vitro and ex vivo analyses. Specifically, we demonstrate the biological counteraction of LfcinB against IL-1 and LPS-mediated proteoglycan (PG) depletion, matrix-degrading enzyme production and enzyme activity in long-term (alginate beads) and short-term (monolayer) culture models using bovine and human nucleus pulposus (NP) cells. LfcinB significantly attenuates the IL-1 and LPS-mediated suppression of PG production and synthesis, and thus restores PG accumulation and pericellular matrix formation. Simultaneously, LfcinB antagonizes catabolic factor mediated induction of multiple cartilage-degrading enzymes, including MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, in bovine NP cells at both mRNA and protein levels. LfcinB also suppresses the catabolic factor-induced stimulation of oxidative and inflammatory factors such as iNOS, IL-6, and toll-like receptor-2 (TLR-2) and TLR-4. Finally, the ability of LfcinB to antagonize IL-1 and LPS-mediated suppression of PG is upheld in an en bloc intradiscal microinjection model followed by ex vivo organ culture using both mouse and rabbit IVD tissue, suggesting a potential therapeutic benefit of LfcinB on degenerative disc disease in the future. PMID:23460134

Lactoferricin mediates anti-inflammatory and anti-catabolic effects via inhibition of IL-1 and LPS activity in the intervertebral disc.

Science.gov (United States)

Kim, Jae-Sung; Ellman, Michael B; Yan, Dongyao; An, Howard S; Kc, Ranjan; Li, Xin; Chen, Di; Xiao, Guozhi; Cs-Szabo, Gabriella; Hoskin, David W; Buechter, Doug D; Van Wijnen, Andre J; Im, Hee-Jeong

2013-09-01

The catabolic cytokine interleukin-1 (IL-1) and endotoxin lipopolysaccharide (LPS) are well-known inflammatory mediators involved in degenerative disc disease, and inhibitors of IL-1 and LPS may potentially be used to slow or prevent disc degeneration in vivo. Here, we elucidate the striking anti-catabolic and anti-inflammatory effects of bovine lactoferricin (LfcinB) in the intervertebral disc (IVD) via antagonism of both IL-1 and LPS-mediated catabolic activity using in vitro and ex vivo analyses. Specifically, we demonstrate the biological counteraction of LfcinB against IL-1 and LPS-mediated proteoglycan (PG) depletion, matrix-degrading enzyme production, and enzyme activity in long-term (alginate beads) and short-term (monolayer) culture models using bovine and human nucleus pulposus (NP) cells. LfcinB significantly attenuates the IL-1 and LPS-mediated suppression of PG production and synthesis, and thus restores PG accumulation and pericellular matrix formation. Simultaneously, LfcinB antagonizes catabolic factor mediated induction of multiple cartilage-degrading enzymes, including MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, in bovine NP cells at both mRNA and protein levels. LfcinB also suppresses the catabolic factor-induced stimulation of oxidative and inflammatory factors such as iNOS, IL-6, and toll-like receptor-2 (TLR-2) and TLR-4. Finally, the ability of LfcinB to antagonize IL-1 and LPS-mediated suppression of PG is upheld in an en bloc intradiscal microinjection model followed by ex vivo organ culture using both mouse and rabbit IVD tissue, suggesting a potential therapeutic benefit of LfcinB on degenerative disc disease in the future. Copyright © 2013 Wiley Periodicals, Inc.

The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation

OpenAIRE

Malik, Sohail; Roeder, Robert G.

2010-01-01

The Mediator is an evolutionarily conserved, multiprotein complex that is a key regulator of protein-coding genes. In metazoan cells, multiple pathways that are responsible for homeostasis, cell growth and differentiation converge on the Mediator through transcriptional activators and repressors that target one or more of the almost 30 subunits of this complex. Besides interacting directly with RNA polymerase II, Mediator has multiple functions and can interact with and coordinate the action ...

Grandparental effects in marine sticklebacks: transgenerational plasticity across multiple generations.

Science.gov (United States)

Shama, L N S; Wegner, K M

2014-11-01

Nongenetic inheritance mechanisms such as transgenerational plasticity (TGP) can buffer populations against rapid environmental change such as ocean warming. Yet, little is known about how long these effects persist and whether they are cumulative over generations. Here, we tested for adaptive TGP in response to simulated ocean warming across parental and grandparental generations of marine sticklebacks. Grandparents were acclimated for two months during reproductive conditioning, whereas parents experienced developmental acclimation, allowing us to compare the fitness consequences of short-term vs. prolonged exposure to elevated temperature across multiple generations. We found that reproductive output of F1 adults was primarily determined by maternal developmental temperature, but carry-over effects from grandparental acclimation environments resulted in cumulative negative effects of elevated temperature on hatching success. In very early stages of growth, F2 offspring reached larger sizes in their respective paternal and grandparental environment down the paternal line, suggesting that other factors than just the paternal genome may be transferred between generations. In later growth stages, maternal and maternal granddam environments strongly influenced offspring body size, but in opposing directions, indicating that the mechanism(s) underlying the transfer of environmental information may have differed between acute and developmental acclimation experienced by the two generations. Taken together, our results suggest that the fitness consequences of parental and grandparental TGP are highly context dependent, but will play an important role in mediating some of the impacts of rapid climate change in this system. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

The Effects Of Self-Esteem on Academic Motivation: The Mediating Role of Automatic Thoughts

Directory of Open Access Journals (Sweden)

Cemaliye DIREKTOR

2017-06-01

Full Text Available The purpose of the present study is to investigate the mediational role of automatic thoughts on the association between self-esteem and academic motivation. Differences would be analyzed separated according to gender and faculty studied. Participants of the study are 210 undergraduate students (%42.4, 89 women; %57.6, 121 men selected randomly from counselling and intelligence teaching departments of University in Northern Cyprus. All permissions were taken. In order of the aim of self-esteem were assessed using ‘Rosenberg Self-Esteem Questionarie’’. In addition academic motivation was measured by ‘Academic Motivation Scale’ and ‘Automatic Thoughts Inventory’was used in measuring automatic thought levels of the participants. At this study relational screening analysis used, and mediation effect of automatic thoughts were analyzed using Baron and Kenny’s (1986 mediation analysis method. Partial mediation effect of amotivation subscale was proved among self-esteem and negative automatic thought. Evaluating the total effect and direct effect, it is indicated that, the difference is 28% of indirect effect value. Amotivation is related to self esteem and negative automatic thoughts

The Cascading Effects of Multiple Dimensions of Implementation on Program Outcomes: a Test of a Theoretical Model.

Science.gov (United States)

Berkel, Cady; Mauricio, Anne M; Sandler, Irwin N; Wolchik, Sharlene A; Gallo, Carlos G; Brown, C Hendricks

2017-12-14

This study tests a theoretical cascade model in which multiple dimensions of facilitator delivery predict indicators of participant responsiveness, which in turn lead to improvements in targeted program outcomes. An effectiveness trial of the 10-session New Beginnings Program for divorcing families was implemented in partnership with four county-level family courts. This study included 366 families assigned to the intervention condition who attended at least one session. Independent observers provided ratings of program delivery (i.e., fidelity to the curriculum and process quality). Facilitators reported on parent attendance and parents' competence in home practice of program skills. At pretest and posttest, children reported on parenting and parents reported child mental health. We hypothesized effects of quality on attendance, fidelity and attendance on home practice, and home practice on improvements in parenting and child mental health. Structural Equation Modeling with mediation and moderation analyses were used to test these associations. Results indicated quality was significantly associated with attendance, and attendance moderated the effect of fidelity on home practice. Home practice was a significant mediator of the links between fidelity and improvements in parent-child relationship quality and child externalizing and internalizing problems. Findings provide support for fidelity to the curriculum, process quality, attendance, and home practice as valid predictors of program outcomes for mothers and fathers. Future directions for assessing implementation in community settings are discussed.

Academic Achievement, Self-Concept and Depression in Taiwanese Children: Moderated Mediation Effect

Science.gov (United States)

Wu, Pei-Chen; Kuo, Shin-Ting

2015-01-01

The primary purpose of this study was to utilize a multidimensional perspective to examine whether children's self-concept served as a mediator between academic achievement and depression, and to further investigate whether this mediation effect was moderated by the ages of children. The participants consisted of 632 Taiwanese children in the…

Impulse purchases and trust: the mediating effect of stickiness and the mental budgeting account.

Science.gov (United States)

Wu, Jyh-Jeng; Chen, Ying-Hueih; Chien, Shu-Hua

2013-10-01

Impulse purchasing is a pervasive yet relatively little-discussed phenomenon. This study investigates the effect of impulse purchases on trust, as well as the mediating effect of stickiness and the mental budgeting account in the group buying context. Questionnaires were sent to group buying participants. The results show that impulse purchases have a positive effect on trust and that both stickiness and the mental budgeting account present a mediating effect.

Inflammation-mediated memory dysfunction and effects of a ketogenic diet in a murine model of multiple sclerosis.

Directory of Open Access Journals (Sweden)

Do Young Kim

Full Text Available A prominent clinical symptom in multiple sclerosis (MS, a progressive disorder of the central nervous system (CNS due to heightened neuro-inflammation, is learning and memory dysfunction. Here, we investigated the effects of a ketogenic diet (KD on memory impairment and CNS-inflammation in a murine model of experimental autoimmune encephalomyelitis (EAE, using electrophysiological, behavioral, biochemical and in vivo imaging approaches. Behavioral spatial learning deficits were associated with motor disability in EAE mice, and were observed concurrently with brain inflammation. The KD improved motor disability in the EAE model, as well as CA1 hippocampal synaptic plasticity (long-term potentiation and spatial learning and memory (assessed with the Morris Water Maze. Moreover, hippocampal atrophy and periventricular lesions in EAE mice were reversed in KD-treated EAE mice. Finally, we found that the increased expression of inflammatory cytokines and chemokines, as well as the production of reactive oxygen species (ROS, in our EAE model were both suppressed by the KD. Collectively, our findings indicate that brain inflammation in EAE mice is associated with impaired spatial learning and memory function, and that KD treatment can exert protective effects, likely via attenuation of the robust immune response and increased oxidative stress seen in these animals.

Diverse exocytic pathways for mast cell mediators.

Science.gov (United States)

Xu, Hao; Bin, Na-Ryum; Sugita, Shuzo

2018-04-17

Mast cells play pivotal roles in innate and adaptive immunities but are also culprits in allergy, autoimmunity, and cardiovascular diseases. Mast cells respond to environmental changes by initiating regulated exocytosis/secretion of various biologically active compounds called mediators (e.g. proteases, amines, and cytokines). Many of these mediators are stored in granules/lysosomes and rely on intricate degranulation processes for release. Mast cell stabilizers (e.g. sodium cromoglicate), which prevent such degranulation processes, have therefore been clinically employed to treat asthma and allergic rhinitis. However, it has become increasingly clear that different mast cell diseases often involve multiple mediators that rely on overlapping but distinct mechanisms for release. This review illustrates existing evidence that highlights the diverse exocytic pathways in mast cells. We also discuss strategies to delineate these pathways so as to identify unique molecular components which could serve as new drug targets for more effective and specific treatments against mast cell-related diseases. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

The effect of multiple blood-feeding on the longevity and insecticide resistant phenotype in the major malaria vector Anopheles arabiensis (Diptera: Culicidae).

Science.gov (United States)

Oliver, Shüné V; Brooke, Basil D

2014-08-23

Anopheles arabiensis is a major malaria vector in Africa. Adult females are likely to imbibe multiple blood meals during their lifetime. This results in regular exposure to potential toxins and blood-meal induced oxidative stress. Defence responses to these stressors may affect other factors of epidemiological significance, such as insecticide resistance and longevity. The aims of this study were to examine the effect of multiple blood-feeding on insecticide tolerance/resistance with increasing age, to assess the underlying biochemical mechanisms for the responses recorded, and to assess the effect of multiple blood-feeding on the life histories of adult females drawn from insecticide resistant and susceptible laboratory reared An. arabiensis. Laboratory reared An. arabiensis females from an insecticide resistant and an insecticide susceptible colony were offered either a single blood meal or multiple blood meals at 3-day intervals. Their tolerance or resistance to insecticide was then monitored by WHO bioassay four hours post blood-feeding. The biochemical basis of the phenotypic response was assessed by examining the effect of blood on detoxification enzyme activity and the effect of blood-meals on detoxification enzyme activity in ageing mosquitoes. Control cohorts that were not offered any blood meals showed steadily decreasing levels of insecticide tolerance/resistance with age, whereas a single blood meal significantly increased tolerance/resistance primarily at the age of three days. The expression of resistance/tolerance in those cohorts fed multiple blood meals generally showed the least variation with age. These results were consistent following exposure to DDT and pyrethroids but not to malathion. Multiple blood-meals also maintained the DDT and permethrin resistant phenotype, even after treatment females had stopped taking blood-meals. Biochemical analysis suggests that this phenotypic effect in resistant females may be mediated by the maintenance of

Helminths as governors of immune-mediated inflammation.

Science.gov (United States)

Elliott, David E; Summers, Robert W; Weinstock, Joel V

2007-04-01

Immune-mediated diseases (e.g. inflammatory bowel disease, asthma, multiple sclerosis and autoimmune diabetes) are increasing in prevalence and emerge as populations adopt meticulously hygienic lifestyles. This change in lifestyles precludes exposure to helminths (parasitic worms). Loss of natural helminth exposure removes a previously universal Th2 and regulatory immune biasing imparted by these organisms. Helminths protect animals from developing immune-mediated diseases (colitis, reactive airway disease, encephalitis and diabetes). Clinical trials show that exposure to helminths can reduce disease activity in patients with ulcerative colitis or Crohn's disease. This paper summarises work by multiple groups demonstrating that colonization with helminths alters immune reactivity and protects against disease from dysregulated inflammation.

Exploring the Relationship Between Social Anxiety and Bulimic Symptoms: Mediational Effects of Perfectionism Among Females

Science.gov (United States)

Menatti, Andrew R.; Weeks, Justin W.; Levinson, Cheri A.; McGowan, Maggie M.

2013-01-01

Previous findings indicate that social anxiety and bulimia co-occur at high rates; one mechanism that has been proposed to link these symptom clusters is perfectionism. We tested meditational models among 167 female undergraduates in which maladaptive evaluative perfectionism concerns (MEPC; i.e., critical self-evaluative perfectionism) mediated the relationship between social anxiety and bulimic symptoms. Results from a first model indicated that MEPC mediated the relationship between fear of public scrutiny and bulimia symptoms. This indirect effect was significant above and beyond the indirect effects of maladaptive body-image cognitions and perfectionism specific to pure personal standards. A second model was tested with MEPC mediating the relationship between social interaction anxiety and bulimia symptoms. Similar results were obtained; however, in this model, a significant direct effect remained after partialing out the indirect effect of the mediators. Theoretical implications are discussed. PMID:24932054

Proton pump inhibitors induce a caspase-independent antitumor effect against human multiple myeloma.

Science.gov (United States)

Canitano, Andrea; Iessi, Elisabetta; Spugnini, Enrico Pierluigi; Federici, Cristina; Fais, Stefano

2016-07-01

Multiple Myeloma (MM) is the second most common hematological malignancy and is responsive to a limited number of drugs. Unfortunately, to date, despite the introduction of novel drugs, no relevant increase in survival rates has been obtained. Proton pump inhibitors (PPIs) have been shown to have significant antitumor action as single agents as well as in combination with chemotherapy. This study investigates the potential anti-tumor effectiveness of two PPIs, Lansoprazole and Omeprazole, against human MM cells. We found that Lansoprazole exerts straightforward efficacy against myeloma cells, even at suboptimal concentrations (50 µM), while Omeprazole has limited cytotoxic action. The Lansoprazole anti-MM effect was mostly mediated by a caspase-independent apoptotic-like cytotoxicity, with only a secondary anti-proliferative action. This study provides clear evidence supporting the use of Lansoprazole in the strive against MM with an efficacy proven much higher than current therapeutical approaches and without reported side effects. It is however conceivable that, consistent with the results obtained in other human tumors, Lansoprazole may well be combined with existing anti-myeloma therapies with the aim to improve the low level of efficacy of the current strategies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effects of non-dissolved redox mediators on a hexavalent chromium bioreduction process

Directory of Open Access Journals (Sweden)

Jing Lian

2016-03-01

Full Text Available The effects of six non-dissolved redox mediators (RM immobilized in cellulose acetate beads on enhancing Cr(VI reduction by Mangrovibacter plantisponsor CR1 were investigated. In addition, the voltammetric behaviours and electron transfer capacities of the redox mediators were examined using electrochemical methods. Compared to the control beads, the Cr(VI bioreduction rate with 1-chloroanthraquinone cellulose acetate beads (1-CAQ/CA beads was increased up to 4.5-fold, which was mainly attributed to enhanced electron transfer by 1-CAQ. The redox mediators also improved the oxidation–reduction potential values of the Cr(VI bioreduction processes, which might assist in Cr(VI bioreduction. The role of the redox mediators was discussed based on the cyclic voltammetric characteristics (E0' of the redox mediators and the electrochemical impedance spectroscopy characteristics (Rct of the RM/CA beads. A linear correlation was found for the reaction constant k and the 1-CAQ concentration (C1-CAQ, which was k = 1.5674 C1-CAQ + 4.8506 (R2 = 0.9683. The Cr(VI bioreduction was affected by temperature, and the optimum pH for the Cr(VI bioreduction was 6.5. The results of repeated-batch operations showed that 1-CAQ/CA beads exhibited good stability and persistence. This study contributes to a better understanding of the effects of the redox mediator on Cr(VI bioreduction process and demonstrates its promising potential for environmental bioremediation applications.

Proactive sustainability strategy and corporate sustainability performance: The mediating effect of sustainability control systems.